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OBJECTIVE: To assess the effects of colchicine, which has been shown to reduce the risks of coronary artery disease but scarcely studied in peripheral artery disease (PAD), on major adverse limb events (MALE) in patients with PAD. METHODS: This is a retrospective study based on a nationwide database. Patients who were diagnosed with PAD between 2010 and 2020 and prescribed with colchicine after the diagnosis of PAD were identified. Patients were then categorized into the colchicine or the control group according to drug use. Propensity score matching was performed to mitigate selection bias. Risks of MALE (including lower limb revascularization and nontraumatic amputation) and major adverse cardiovascular events were compared between the two groups. RESULTS: After patient selection and propensity score matching, there were 60,219 patients in both colchicine and control groups. After a mean follow-up of 4.5 years, the risk of MALE was significantly lower in the colchicine group compared with control (subdistribution HR, 0.75; 95% CI, 0.71 to 0.80), as were the incidence of both components of MALE, lower limb revascularization and major amputations. Colchicine treatment was also associated with lower risk of cardiovascular death. The lower risk of MALE observed with colchicine therapy was accentuated in the subgroup of patients receiving concomitant urate-lowering medications. CONCLUSION: In patients diagnosed with PAD, the use of colchicine is associated with lower risks of MALE and cardiovascular death. Anti-inflammatory therapy with colchicine may provide benefits in vascular beds beyond the coronary arteries.
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OBJECTIVES: To delineate the effects of exposure to air pollution on the risk of venous thromboembolism (VTE). BACKGROUND: The association between air pollution and arterial occlusive diseases has been well reported in the literature. VTE is the third most common acute cardiovascular syndrome; however, its relationship with exposure to air pollution has been controversial. METHODS: This study linked data from the Taiwan National Health Insurance Research Database with that from the Taiwan Environmental Protection Administration. Patients who were first admitted for VTE between January 1, 2001, and December 31, 2013, were analyzed. A time-stratified, case-crossover design was employed. Three different exposure periods were defined: exposure for 1 month, one quarter, and 1 year. Four control periods were designated for each exposure period. The association between exposure to air pollutants and the risk of VTE was tested using logistic regression analysis. Subgroup analyses were also performed, stratified by age, sex, type of VTE, the use of hormone therapy, and level of urbanization at the site of residence. RESULTS: Exposures to particulate matter (PM) smaller than 2.5 µm (PM2.5) and those smaller than 10 µm (PM10) were associated with higher risks of VTE, with longer exposures associated with higher risk. The concentration of PM2.5 exposure for 1 month was linearly associated with a greater risk of VTE up to 28.0 µg/m3, beyond which there was no association. PM2.5 exposure for one quarter or 1 year remained significantly associated with higher risks of VTE at higher concentrations. The increased risk in VTE associated with exposure to PM2.5 was more prominent in older patients and in patients not under hormone therapy. Similar results were observed for PM10 exposures. CONCLUSIONS: Exposure to PM, particularly PM2.5, leads to an increased risk of VTE, with possible accumulative effects. With increased PM production in industrializing countries, the effects of PM on VTE occurrence warrant further attention.
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The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.
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Neoplasias Urológicas , Humanos , Masculino , Feminino , Idoso , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Urológicas/patologia , Neoplasias Urológicas/cirurgia , Neoplasias Urológicas/mortalidade , Estadiamento de Neoplasias , Taiwan/epidemiologia , Nefroureterectomia , Idoso de 80 Anos ou maisRESUMO
Happiness has become one of the most important life goals worldwide. However, does valuing happiness lead to better well-being? This study investigates the effect of valuing happiness on well-being using a population-based longitudinal survey of Dutch adults (N = 8,331) from 2019 to 2023. Random-intercept cross-lagged panel models indicated that those who valued happiness generally exhibited higher well-being as manifested by life satisfaction, more positive affect, and less negative affect. However, increases in valuing happiness did not result in changes in life satisfaction 1 year later and had mixed emotional consequences (i.e., increasing both positive and negative affect). Additional analyses using fixed-effects models indicated that valuing happiness had contemporaneous positive effects on well-being. These findings indicate that endorsing happiness goals may have immediate psychological benefits but may not necessarily translate into long-term positive outcomes.
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Although the benefits of sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) are well established, patients with hemodynamically significant mitral regurgitation (MR) were excluded from pivotal trials. We aimed to assess the effects of sacubitril/valsartan on survival in patients with HFrEF and concomitant significant MR. All patients from a single center who underwent echocardiography between June 2008 and December 2020, with a left ventricular ejection fraction (LVEF) of less than 40% and hemodynamically significant MR were recruited. Patients were categorized according to drug use and year of the index echocardiogram into the angiotensin receptor/neprilysin inhibitor (ARNI), non-ARNI before 2017, and non-ARNI after 2017 groups. Patients in the ARNI and non-ARNI after 2017 groups were compared directly, whereas patients in the non-ARNI before 2017 group were matched to the ARNI group in a 3:1 ratio. The outcome of interest was all-cause mortality. Death was compared between the groups using univariate and multivariate Cox proportional hazard models. After exclusion by criteria and matching, there remained 610 patients in the ARNI group, 434 in the non-ARNI after 2017 group, and 1,722 in the non-ARNI before 2017 group. During follow-up, all-cause mortality was significantly lower in the ARNI group compared with both non-ARNI after 2017 and non-ARNI before 2017 groups. Multivariate analysis of both pairs of comparison between groups found the use of ARNI to be significantly associated with increased survival. In patients with HFrEF and concomitant significant MR, treatment with sacubitril/valsartan was associated with lower risks of all-cause death.
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Cervical cancer is a significant public health concern, particularly in low- and middle-income countries where resources for prevention and treatment are limited. Routine screening, such as the Papanicolaou test (Pap smears) and human papillomavirus (HPV) testing, plays a crucial role in the early detection and prevention of cervical cancer. However, the participation rate in cervical cancer screening programs remains below optimal levels due to various factors. This study aimed to evaluate the reliability and acceptability of the HygeiaTouch Self Sampling Kit for Women in collecting vaginal samples for HPV typing, comparing the results with samples collected by physicians. The study included 1210 women aged 21-65 from three medical centers in Taiwan. The findings indicated that the self-sampling kit was as effective as physician-collected specimens in terms of obtaining valid samples and identifying HPV. The agreement between the two methods was 88%, with a κ value of 0.75. Furthermore, the study assessed the mechanical characteristics of the self-sampling applicator through tensile, bending, and torque tests, and determined that it was safe for intravaginal use. Additionally, the study evaluated the safety and satisfaction of self-sampling and found a low rate of adverse events (0.7%) and high levels of satisfaction (over 90%) among participants. Overall, we demonstrated that the HygeiaTouch Self Sampling Kit for Women is a reliable and acceptable device for HPV testing and cervical screening, providing a convenient, safe, and effective alternative for women.
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AIM: Glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are both recommended for patients with diabetes, yet their effects on the development or progression of diabetic retinopathy (DR) are largely unknown. METHODS: In this retrospective cohort study, data were collected from a nationwide database. Patients with diabetes who initiated treatment with a GLP1RA or SGLT2i between 1 May 2016 and 31 December 2017, were identified. Patients were divided into those with or without a previous diagnosis of DR and then categorized into the GLP1RA and the SGLT2i groups according to drug use. The primary outcome of interest in the DR group was the composite of new-onset proliferative DR, vitreous haemorrhage and tractional retinal detachment (RD). In the non-DR group, the primary outcome was the composite of newly diagnosed DR of any severity, vitreous haemorrhage and RD. RESULTS: In total, 97 413 patients were identified. After matching, 1517 patients were treated with a GLP1RA and 3034 with an SGLT2i in the DR cohort. In the non-DR cohort, 9549 initiated a GLP1RA and 19 098 initiated an SGLT2i. In patients with pre-existing DR, the incidence of any DR progression event was significantly higher in the GLP1RA group than the SGLT2i group (subdistribution hazard ratio 1.50, 95% confidence interval 1.01-2.23), primarily because of the increased risk of tractional RD. In patients without DR at baseline, the risks of all ocular outcomes were similar between the GLP1RA and SGLT2i groups. CONCLUSIONS: In patients with diabetes mellitus and established DR, GLP1RA treatment was associated with increased risks of DR progression compared with SGLT2i use.
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Circulating biomarkers play a pivotal role in personalized medicine, offering potential for disease screening, prevention, and treatment. Despite established associations between numerous biomarkers and diseases, elucidating their causal relationships is challenging. Mendelian Randomization (MR) can address this issue by employing genetic instruments to discern causal links. Additionally, using multiple MR methods with overlapping results enhances the reliability of discovered relationships. Here, we report an MR study using multiple methods, including inverse variance weighted, simple mode, weighted mode, weighted median, and MR-Egger. We use the MR-base resource (v0.5.6) from Hemani et al. 2018 to evaluate causal relationships between 212 circulating biomarkers (curated from UK Biobank analyses by Neale lab and from Shin et al. 2014, Roederer et al. 2015, and Kettunen et al. 2016 and 99 complex diseases (curated from several consortia by MRC IEU and Biobank Japan). We report novel causal relationships found by four or more MR methods between glucose and bipolar disorder (Mean Effect Size estimate across methods: 0.39) and between cystatin C and bipolar disorder (Mean Effect Size: -0.31). Based on agreement in four or more methods, we also identify previously known links between urate with gout and creatine with chronic kidney disease, as well as biomarkers that may be causal of cardiovascular conditions: apolipoprotein B, cholesterol, LDL, lipoprotein A, and triglycerides in coronary heart disease, as well as lipoprotein A, LDL, cholesterol, and apolipoprotein B in myocardial infarction. This Mendelian Randomization study not only corroborates known causal relationships between circulating biomarkers and diseases but also uncovers two novel biomarkers associated with bipolar disorder that warrant further investigation. Our findings provide insight into understanding how biological processes reflecting circulating biomarkers and their associated effects may contribute to disease etiology, which can eventually help improve precision diagnostics and intervention.
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Biomarcadores , Análise da Randomização Mendeliana , Humanos , Biomarcadores/sangue , Transtorno Bipolar/genética , Transtorno Bipolar/sangue , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/sangue , Fatores de Risco , Cistatina C/sangue , Cistatina C/genética , Gota/genética , Gota/sangueRESUMO
Background: Circulating biomarkers play a pivotal role in personalized medicine, offering potential for disease screening, prevention, and treatment. Despite established associations between numerous biomarkers and diseases, elucidating their causal relationships is challenging. Mendelian Randomization (MR) can address this issue by employing genetic instruments to discern causal links. Additionally, using multiple MR methods with overlapping results enhances the reliability of discovered relationships. Methods: Here we report an MR study using multiple methods, including inverse variance weighted, simple mode, weighted mode, weighted median, and MR Egger. We use the MR-base resource (v0.5.6)1 to evaluate causal relationships between 212 circulating biomarkers (curated from UK Biobank analyses by Neale lab and from Shin et al. 2014, Roederer et al. 2015, and Kettunen et al. 2016)2-4 and 99 complex diseases (curated from several consortia by MRC IEU and Biobank Japan). Results: We report novel causal relationships found by 4 or more MR methods between glucose and bipolar disorder (Mean Effect Size estimate across methods: 0.39) and between cystatin C and bipolar disorder (Mean Effect Size: -0.31). Based on agreement in 4 or more methods, we also identify previously known links between urate with gout and creatine with chronic kidney disease, as well as biomarkers that may be causal of cardiovascular conditions: apolipoprotein B, cholesterol, LDL, lipoprotein A, and triglycerides in coronary heart disease, as well as lipoprotein A, LDL, cholesterol, and apolipoprotein B in myocardial infarction. Conclusions: This Mendelian Randomization study not only corroborates known causal relationships between circulating biomarkers and diseases but also uncovers two novel biomarkers associated with bipolar disorder that warrant further investigation. Our findings provide insight into understanding how biological processes reflecting circulating biomarkers and their associated effects may contribute to disease etiology, which can eventually help improve precision diagnostics and intervention.
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OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.
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Anaerobic biodegradation rates (half-lives) of organic chemicals are pivotal for environmental risk assessment and remediation. Traditional experimental evaluation, constrained by prolonged, oxygen-free conditions, struggles to keep pace with emerging contaminants. Data-driven machine learning (ML) models serve as promising complements. However, reported quantitative structure-biodegradation relationships or ML models on anaerobic biodegradation are mostly based on small data sets (<100 records) and neglect experimental conditions, usually achieving compromised predictions. This work aimed to develop ML models for predicting the biodegradation half-lives of organic pollutants in anaerobic environments (i.e., sediment/soil and sludge). Focusing on important features of both chemicals and experimental conditions, we first curated two data sets, one for sediment/soil (SED) and the other for sludge (SLD), covering 978 records for 206 chemicals from the literature, and then conducted a meta-analysis. Next, we built a binary classification (half-life of 30 days as the cutoff) model with an accuracy of 81% and a regression model with R2 of 0.56 for SED based on LightGBM (80% and 0.31 for SLD based on Extra tree, respectively). The model interpretations underscored the significance of experimental conditions (e.g., temperature and inoculum dosage), as evidenced by their high feature importance, and the models were found to correctly capture the effects of chemical substructures, for example, branched structures and aromatic rings prolonged half-lives while methyl group and ortho-substitution on rings shortened half-lives. The applicability domains of the models were also defined, resulting in reasonable prediction for the half-lives of 41% (SED) or 67% (SLD) of over 4000 persistent, bioaccumulative, and toxic chemicals. Overall, this study pioneers ML models for predicting the anaerobic degradation half-lives, offering valuable support for future evaluation and implementation of chemical anaerobic biodegradation.
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Biodegradação Ambiental , Aprendizado de Máquina , Esgotos , Anaerobiose , Sedimentos Geológicos/química , Compostos Orgânicos/metabolismoRESUMO
BACKGROUND: Surgical resection (SR) is the main treatment for small bowel adenocarcinoma (SBA), but it increases metabolic demand, systemic inflammation, and digestive dysfunction, resulting in major impacts on the postoperative outcomes of patients. This study, we aimed to investigate the role of the postoperative prognostic nutritional index (PNI), a surrogate marker of inflammation and nutrition, in patients with SBA after resection. METHODS: From June 2014 to March 2022, 44 consecutive patients who underwent SR for SBA in Taipei Veterans General Hospital were retrospectively reviewed. Factors associated with survival including PNI were analyzed. RESULTS: PNI decreased in patients after SR for SBA (median change: -1.82), particularly in those who underwent Whipple operation or developed postoperative pancreatic fistula. Postoperative PNI < 45.2 best predicted overall survival (OS) (AUROC: 0.826, p = 0.001). Patients with lower postoperative PNI had significantly worse OS compared to those higher postoperative values (median OS: 19.3 months vs. not reached, p < 0.001). Low postoperative PNI (hazard ratio [HR]: 11.404, p = 0.002), tumoral lymphovascular invasion (HR: 8.023, p = 0.012), and adjuvant chemotherapy (HR: 0.055, p = 0.002) were independent risk factors for OS. Postoperative PNI also significantly predicted recurrence-free survival independent of lymphovascular invasion and adjuvant chemotherapy (HR: 6.705, p = 0.001). CONCLUSION: PNI commonly decreases in patients with SBA who undergo Whipple surgery or develop postoperative pancreatic fistula. Postoperative PNI independently predicts survival and may serve as a clinical marker to optimize patient outcomes.
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We conducted a retrospective population-based, matched cohort study using the National Health Insurance Research Database to estimate healthcare resource utilisation (HRU) and costs in patients with newly diagnosed AL amyloidosis in Taiwan. Cases were matched 10:1 by age, sex, and area of residence to patients without AL amyloidosis (comparators) randomly selected from the database during the same time period. Annual all-cause HRU and costs for 3 years were quantified. AL amyloidosis-attributable costs were obtained by subtracting all-cause HRU costs incurred by comparators from cases. The mean age of all patients was 60.78 years and 59.07% were male. Co-morbidities were more frequent in cases than comparators. By 6 months after diagnosis, 12.1% of cases had died versus 0.9% of comparators. In the first year, cases had 103% more outpatient visits, 177% more emergency room visits, were hospitalised 4-times more frequently, and spent 5.5-times more days in hospital than comparators, and total healthcare costs were > sixfold higher. Costs incurred during the first year after diagnosis accounted for 55% of the 3-year cumulative cost. High HRU costs associated with delayed diagnosis and end-organ damage indicate a need for earlier diagnosis and more effective treatments for AL amyloidosis.
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Custos de Cuidados de Saúde , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Taiwan/epidemiologia , Idoso , Amiloidose de Cadeia Leve de Imunoglobulina/economia , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Amiloidose de Cadeia Leve de Imunoglobulina/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Hospitalização/economia , Adulto , ComorbidadeRESUMO
BACKGROUND: Several studies suggest an "obesity paradox," associating obesity with better cardiovascular outcomes in patients with type 2 diabetes mellitus (DM) or aortic stenosis (AS) compared to normal or underweight individuals. This study explores the impact of body mass index (BMI) on diabetic patients with AS. METHODS: Between 2014 and 2019, patients with DM who underwent echocardiography were analyzed. Outcomes included all-cause mortality, cardiovascular, and non-cardiovascular death. Patients were categorized as underweight, normal weight, or obese based on BMI (<18.5, 18.5 to 27, and >27 kg/m2, respectively). RESULTS: Among 74,835 DM patients, 734 had AS. Normal weight comprised 65.5% (n=481), underweight 4.1% (N=30), and 30.4% were obese. Over a 6-year follow-up, underweight patients had significantly higher all-cause mortality (HR 1.96, 95% CI 1.22 - 3.14, p = 0.005), while obese patients had significantly lower mortality (HR 0.79, 95% CI 0.68 - 0.91, p=0.001) compared to the normal group. Regarding etiologies, underweight patients had a higher risk of non-cardiovascular death (HR 2.47, 95% CI 1.44-4.25, p = 0.001), while obese patients had a lower risk of cardiovascular death (HR 0.66, 95% CI 0.50-0.86, p=0.003). Subgroup analysis showed a consistent trend without significant interaction. CONCLUSIONS: BMI significantly impacts mortality in DM patients with AS. Being underweight is associated with worse non-cardiovascular death, while obesity is linked to improved cardiovascular death outcomes.
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Estenose da Valva Aórtica , Índice de Massa Corporal , Diabetes Mellitus Tipo 2 , Obesidade , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Idoso , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/complicações , Obesidade/complicações , Obesidade/mortalidade , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Fatores de Risco , Ecocardiografia , Magreza/complicações , Magreza/mortalidadeRESUMO
Flexible electronics, like electronic skin (e-skin), rely on stretchable conductive materials that integrate diverse components to enhance mechanical, electrical, and interfacial properties. However, poor biocompatibility, bacterial infections, and limited compatibility of functional additives within polymer matrices hinder healthcare sensors' performance. This study addresses these challenges by developing an antibacterial hydrogel using polyvinyl alcohol (PVA), konjac glucomannan (KGM), borax (B), and flower-shaped silver nanoparticles (F-AgNPs), referred as PKB/F-AgNPs hydrogel. The developed hydrogel forms a hierarchical network structure, with a tensile strength of 96 kPa, 83% self-healing efficiency within 60 minutes, and 128% cell viability in Cell Counting Kit-8 (CCK-8) assays, indicating excellent biocompatibility. It also shows strong antibacterial efficacy against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). Blue light irradiation enhances its antibacterial activity by 1.3-fold for E. coli and 2.2-fold for S. aureus. The hydrogel's antibacterial effectiveness is assessed by monitoring changes in electrical conductivity, providing a cost-effective alternative to traditional microbial culture assays. The PKB/F-AgNPs hydrogel's flexibility and electrical conductivity enable it to function as strain sensors for detecting body movements and facial expressions. This antibacterial hydrogel underscores its potential for future human-machine interfaces and wearable electronics.
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We introduce Get Free Copy (https://getfreecopy.com), a web-based platform designed to streamline the search for biomedical literature across major repositories like arXiv, bioRxiv, medRxiv, and PubMed Central (PMC). Addressing challenges posed by paywalls and fragmented databases, it offers a unified interface for efficient retrieval of free, legitimate copies of biomedical literature. The platform's implementation involves a Node.js backend and dynamic front-end display, enhancing accessibility and research efficiency. As an open-source project, Get Free Copy represents a significant contribution to the open-access movement, inviting global researcher collaboration for further development.
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Knowing odor sensory attributes of odorants lies at the core of odor tracking when addressing waterborne odor issues. However, experimental determination covering tens of thousands of odorants in authentic water is not pragmatic due to the complexity of odorant identification and odor evaluation. In this study, we propose the first machine learning (ML) model to predict odor perception/threshold aiming at odorants in water, which can use either molecular structure or MS2 spectra as input features. We demonstrate that model performance using MS2 spectra is nearly as good as that using unequivocal structures, both with outstanding accuracy. We particularly show the model's robustness in predicting odor sensory attributes of unidentified chemicals by using the experimentally obtained MS2 spectra from nontarget analysis on authentic water samples. Interpreting the developed models, we identify the intricate interaction of functional groups as the predominant influence factor on odor sensory attributes. We also highlight the important roles of carbon chain length, molecular weight, etc., in the inherent olfactory mechanisms. These findings streamline the odor sensory attribute prediction and are crucial advancements toward credible tracking and efficient control of off-odors in water.
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Aprendizado de Máquina , Odorantes , Água , Água/química , Espectrometria de MassasRESUMO
A microfluidic immuno-biosensor detection system consisting of a microfluidic spectrum chip and a micro-spectrometer detection device is presented for the rapid point-of-care (POC) detection and quantification of high-sensitivity C-reactive protein (hs-CRP) in urine. The detection process utilizes a highly specific enzyme-linked immunosorbent assay (ELISA) method, in which capture antibodies and detection antibodies are pre-deposited on the substrate of the microchip and used to form an immune complex with the target antigen. Horseradish peroxidase (HRP) is added as a marker enzyme, followed by a colorimetric reaction using 3,3',5,5'-tetramethylbenzidine (TMB). The absorbance values (a.u.) of the colorimetric reaction compounds are measured using a micro-spectrometer device and used to measure the corresponding hs-CRP concentration according to the pre-established calibration curve. It is shown that the hs-CRP concentration can be determined within 50 min. In addition, the system achieves recovery rates of 93.8-106.2% in blind water samples and 94.5-104.6% in artificial urine. The results showed that the CRP detection results of 41 urine samples from patients with chronic kidney disease (CKD) were highly consistent with the conventional homogeneous particle-enhanced turbidimetric immunoassay (PETIA) method's detection results (R2 = 0.9910). The experimental results showed its applicability in the detection of CRP in both urine and serum. Overall, the results indicate that the current microfluidic ELISA detection system provides an accurate and reliable method for monitoring the hs-CRP concentration in point-of-care applications.
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Técnicas Biossensoriais , Proteína C-Reativa , Ensaio de Imunoadsorção Enzimática , Sistemas Automatizados de Assistência Junto ao Leito , Proteína C-Reativa/análise , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica , ColorimetriaRESUMO
Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals. The majority of neutralizing antibody clones lose or exhibit reduced activities against Beta, Delta, and Omicron variants. Nevertheless, a portion of anti-RBD antibody clones that develops after a primary series or booster dose of COVID-19 vaccination exhibit broad neutralization against emerging Omicron BA.2, BA.4, BA.5, BQ.1.1, XBB.1.5 and XBB.1.16 variants. These broadly neutralizing antibodies share genetic features including a conserved usage of the IGHV3-53 and 3-9 genes and recognize three clustered epitopes of the RBD, including epitopes that partially overlap the classically defined set identified early in the pandemic. The Fab-RBD crystal and Fab-Spike complex structures corroborate the epitope grouping of antibodies and reveal the detailed binding mode of broadly neutralizing antibodies. Structure-guided mutagenesis improves binding and neutralization potency of antibody with Omicron variants via a single amino-substitution. Together, these results provide an immunological basis for partial protection against severe COVID-19 by the ancestral strain-based vaccine and indicate guidance for next generation monoclonal antibody development and vaccine design.