Comparison in prostate cancer diagnosis with PSA 4-10 ng/mL: radiomics-based model VS. PI-RADS v2.1.

BACKGROUND: To evaluate accuracy of MRI-based radiomics in diagnosing prostate cancer (PCa) in patients with PSA levels between 4 and 10 ng/mL and compare it with the latest Prostate Imaging Reporting and Data System (PI-RADS v2.1) score. METHODS: 221 patients with prostate lesions and PSA levels in 4-10 ng/mL, including 154 and 67 cases in the training and validation groups. Pathological confirmation of all patients was accomplished by the use of MRI-TRUS fusion targeted biopsy or systematic transrectal ultrasound (TRUS) guided biopsy. 851 radiomic features were extracted from each lesion of ADC and T2WI images. The least absolute shrinkage and selection operator (LASSO) regression algorithm and logistic regression were employed to select features and build the ADC and T2WI model. The combined model was obtained based on the ADC and T2WI features. The clinical benefit and diagnostic accuracy of the three radiomics models and PI-RADS v2.1 score were evaluated. RESULTS: 10 radiomic features were ultimately selected from the ADC images, 13 from the T2WI images and 7 from the combined models. The ADC, T2WI and combined models achieved satisfactory diagnostic accuracy in the training [AUC:0.945 (ADC), 0.939 (T2WI), 0.979 (combined)] and validation groups [AUC: 0.942 (ADC), 0.943 (T2WI), 0.959 (combined)], which was significantly higher than those in PI-RADS v2.1 model (0.825 for training cohort and 0.853 for validation cohort). Compared with the PI-RADS v2.1 score, the three radiomics models generated superior PCa diagnostic performance in both the training (p = 0.002, p = 0.005, p < 0.001) and validation groups (p = 0.045, p = 0.035, p = 0.015). CONCLUSION: Radiomics based on ADC and T2WI images can better identify PCa in patients with PSA 4-10 ng/mL, and MRI-based radiomics significantly outperforms the PI-RADS v2.1 score. CLINICAL TRIAL NUMBER: Not applicable.

The diagnostic value of histogram analysis of DWI and DKI for the mismatch repair status of rectal adenocarcinoma.

Objectives: To compare the diagnostic value of histogram analysis derived from diffusion weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in differentiating the mismatch repair (MMR) status of rectal adenocarcinoma. Methods: DWI and DKI were performed in 124 patients with rectal adenocarcinoma, which were divided into deficient mismatch repair (dMMR) group and proficient mismatch repair (pMMR) group. The patients' general clinical information, pathology and image characteristics were compared. The histogram analysis of apparent diffusion coefficient (ADC), diffusion kurtosis (K) and diffusion coefficient (D)derived from DWI and DKI at b values of 1000 and 2000 s/mm2 were calculated. The diagnostic efficacy of quantitative parameters for MMR in rectal adenocarcinoma was compared. Results: The mean, 50th, 75th and 90th in ADC quantitative parameters of dMMR group were lower when the b value was 2000 s/mm2 (all P < 0.05). With b value of 1000 s/mm2, the 10th, 25th, and 50th in the dMMR group were lower, and the skewness was higher (all P < 0.05). D values (10th, 25th and 50th) derived from DKI quantitative parameters were lower in the dMMR group. The K values (75th, 90th and Kskewness) were higher in the dMMR group, while Kkurtosis was lower (all P < 0.05). The results of multivariate logistic regression analysis showed that ADC75th(b = 2000 s/mm2), ADCskewness (b = 1000 s/mm2) and Kskewness were the statistical significant parameters (P = 0.014, 0.036 and 0.002, respectively), and the AUC values were 0.713, 0.818 and 0.835, respectively. Conclusion: Histogram analysis derived from DWI and DKI can be good predictor of MMR. Kskewness is the strongest independent factor for predicting MMR.

Native T1 mapping-based radiomics diagnosis of kidney function and renal fibrosis in chronic kidney disease.

Chronic kidney disease (CKD) raises major concerns for global public health as it is characterized by high prevalence, low awareness, high healthcare costs, and poor prognosis. Therefore, our study prospectively established and validated native T1 mapping-based radiomics models for the prediction of renal fibrosis and renal function in patients with CKD. Moreover, the area under the receiver operating characteristic curve (AUC) and diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate its performance. Thus, our results show that radiomics based on native T1 mapping images can better identify renal function and renal fibrosis in patients with CKD and outperform conventional T1 mapping parameters of ΔT1 and T1%, thus providing more information for CKD management and clinical decision-making.

Polyphenol-stabilized coacervates for enzyme-triggered drug delivery.

Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Here we report a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, we develop size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. We discover a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery.

Therapeutic drug monitoring of mycophenolic acid and azole antifungals on two distinct LC-MS/MS instruments.

Background: As an active metabolite of a commonly prescribed immunosuppressant, mycophenolic acid (MPA) levels are often monitored to prevent organ rejection following a transplant. Triazoles are often prescribed for treatment of invasive fungal infections in immunocompromised patients. Due to the variability in individual pharmacokinetics and drug-drug interactions, therapeutic drug monitoring is recommended for triazole antifungals. A multiplex LC-MS/MS assay has been developed that can quantify both MPA and triazole drugs in serum. Methods: A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument. Results: The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4-48 µg/mL for MPA, 0.1-12 µg/mL for posaconazole, and 0.2-24 µg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 µg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems. Conclusion: A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.

Colorimetric sensing for translational applications: from colorants to mechanisms.

Colorimetric sensing offers instant reporting via visible signals. Versus labor-intensive and instrument-dependent detection methods, colorimetric sensors present advantages including short acquisition time, high throughput screening, low cost, portability, and a user-friendly approach. These advantages have driven substantial growth in colorimetric sensors, particularly in point-of-care (POC) diagnostics. Rapid progress in nanotechnology, materials science, microfluidics technology, biomarker discovery, digital technology, and signal pattern analysis has led to a variety of colorimetric reagents and detection mechanisms, which are fundamental to advance colorimetric sensing applications. This review first summarizes the basic components (e.g., color reagents, recognition interactions, and sampling procedures) in the design of a colorimetric sensing system. It then presents the rationale design and typical examples of POC devices, e.g., lateral flow devices, microfluidic paper-based analytical devices, and wearable sensing devices. Two highlighted colorimetric formats are discussed: combinational and activatable systems based on the sensor-array and lock-and-key mechanisms, respectively. Case discussions in colorimetric assays are organized by the analyte identities. Finally, the review presents challenges and perspectives for the design and development of colorimetric detection schemes as well as applications. The goal of this review is to provide a foundational resource for developing colorimetric systems and underscoring the colorants and mechanisms that facilitate the continuing evolution of POC sensors.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Inter-coat protein loading of active ingredients into Tobacco mild green mosaic virus through partial dissociation and reassembly of the virion.

Chemical pesticide delivery is a fundamental aspect of agriculture. However, the extensive use of pesticides severely endangers the ecosystem because they accumulate on crops, in soil, as well as in drinking and groundwater. New frontiers in nano-engineering have opened the door for precision agriculture. We introduced Tobacco mild green mosaic virus (TMGMV) as a viable delivery platform with a high aspect ratio and favorable soil mobility. In this work, we assess the use of TMGMV as a chemical nanocarrier for agriculturally relevant cargo. While plant viruses are usually portrayed as rigid/solid structures, these are "dynamic materials," and they "breathe" in solution in response to careful adjustment of pH or bathing media [e.g., addition of solvent such as dimethyl sulfoxide (DMSO)]. Through this process, coat proteins (CPs) partially dissociate leading to swelling of the nucleoprotein complexes-allowing for the infusion of active ingredients (AI), such as pesticides [e.g., fluopyram (FLP), clothianidin (CTD), rifampicin (RIF), and ivermectin (IVM)] into the macromolecular structure. We developed a "breathing" method that facilitates inter-coat protein cargo loading, resulting in up to ~ 1000 AIs per virion. This is of significance since in the agricultural setting, there is a need to develop nanoparticle delivery strategies where the AI is not chemically altered, consequently avoiding the need for regulatory and registration processes of new compounds. This work highlights the potential of TMGMV as a pesticide nanocarrier in precision farming applications; the developed methods likely would be applicable to other protein-based nanoparticle systems.

Probing Protein Corona Formation around Gold Nanoparticles: Effects of Surface Coating.

There has been much interest in integrating various inorganic nanoparticles (nanoscale colloids) in biology and medicine. However, buildup of a protein corona around the nanoparticles in biological media, driven by nonspecific interactions, remains a major hurdle for the translation of nanomedicine into clinical applications. In this study, we investigate the interactions between gold nanoparticles and serum proteins using a series of dihydrolipoic acid (DHLA)-based ligands. We employed gel electrophoresis combined with UV-vis absorption and dynamic light scattering to correlate protein adsorption with the nature and size of the ligand used. For instance, we found that AuNPs capped with DHLA alone promote nonspecific protein adsorption. In comparison, capping AuNPs with polyethylene glycol- or zwitterion-appended DHLA essentially prevents corona formation, regardless of ligand charge and size. Our results highlight the crucial role of surface chemistry and core material in protein corona formation and offer valuable information for the design of colloidal nanomaterials for biological applications.

Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.

Peptide-Driven Proton Sponge Nano-Assembly for Imaging and Triggering Lysosome-Regulated Immunogenic Cancer Cell Death.

Triggering lysosome-regulated immunogenic cell death (ICD, e.g., pyroptosis and necroptosis) with nanomedicines is an emerging approach for turning an "immune-cold" tumor "hot"-a key challenge faced by cancer immunotherapies. Proton sponge such as high-molecular-weight branched polyethylenimine (PEI) is excellent at rupturing lysosomes, but its therapeutic application is hindered by uncontrollable toxicity due to fixed charge density and poor understanding of resulted cell death mechanism. Here, a series of proton sponge nano-assemblies (PSNAs) with self-assembly controllable surface charge density and cell cytotoxicity are created. Such PSNAs are constructed via low-molecular-weight branched PEI covalently bound to self-assembling peptides carrying tetraphenylethene pyridinium (PyTPE, an aggregation-induced emission-based luminogen). Assembly of PEI assisted by the self-assembling peptide-PyTPE leads to enhanced surface positive charges and cell cytotoxicity of PSNA. The self-assembly tendency of PSNAs is further optimized by tuning hydrophilic and hydrophobic components within the peptide, thus resulting in the PSNA with the highest fluorescence, positive surface charge density, cell uptake, and cancer cell cytotoxicity. Systematic cell death mechanistic studies reveal that the lysosome rupturing-regulated pyroptosis and necroptosis are at least two causes of cell death. Tumor cells undergoing PSNA-triggered ICD activate immune cells, suggesting the great potential of PSNAs to trigger anticancer immunity.

Endostar acts as a pneumonitis protectant in patients with locally advanced non-small cell lung cancer receiving concurrent chemoradiotherapy.

BACKGROUND: CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients. METHODS: This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP. RESULTS: There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC. CONCLUSIONS: When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.

New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis.

Background and Aims: Several first-line immune checkpoint inhibitor (ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma (uHCC). This network meta-analysis (NMA) aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC. Methods: A comprehensive literature search was performed in various databases from database inception to May 2022. The phase 3 trials evaluating first-line single-agent ICIs, molecular-target agents (MTAs), or their combinations in uHCC were included. The main endpoints were overall survival (OS) and progression-free survival (PFS). Pooled effect estimates were calculated using a random effects model within the frequentist framework. Subgroup analyses based on etiology were also conducted. Results: Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were included. OS with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305 [hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.80-1.68] and camrelizumab plus apatinib (HR: 1.06; 95% CI: 0.75-1.51). The combination therapies, apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS, had higher P-score than single-agent MTAs or ICIs. The survival benefits were associated with a high risk of adverse events leading to treatment discontinuation. The proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages (R2=0.8039, p=0.0155). Conclusion: This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC. The optimal treatment algorithms should consider efficacy, safety, and etiology.

Cardiac substructures dosimetric predicts cardiac toxicity and prognosis in esophageal squamous cell cancer treated by radiotherapy.

PURPOSE: To look into the relationship between cardiac substructures (CS) dosimetric parameters and cardiac events (CE) or overall survival (OS) in patients undergoing radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: A retrospective study included 350 patients with ESCC receiving definitive chemoradiotherapy or radiotherapy (d-CRT/d-RT) or neoadjuvant chemoradiotherapy (NCRT) from March 2013 to May 2022. Our study examined the adverse cardiac events of any grade or G3+, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Competing risk analysis and Cox regression analysis were used to assess the relationship between CS doses and CEs or OS. RESULTS: 201 (57.4 %) patients received any grade CEs over a median follow-up time of 22.50 months (IQR, 12.40-45.60), and 24 (6.86 %) patients suffered G3+ CEs. On landmark analysis, patients with any grade CEs had significantly lower OS (P = 0.003). Multivariable analysis revealed that any grade CEs were predicted by the dose of CSs in all populations. In addition, for G3+ cardiac events, arrhythmic and small probability of cardiac events, LAD V20 ((HR: 1.02, 95 % CI: 1.00-1.03, P = 0.012; HR: 1.01, 95 % CI: 1.00-1.02, P = 0.005; HR; 1.01, 95 % CI: 1.00-1.02, P = 0.012) was also an independent predictive factor. LAD V50 (HR: 1.07, 95 % CI: 1.03-1.10, P <0.001) predicted pericardium effusion events. Moreover, the multivariable analysis revealed that OS was predicted by LAD V30 (HR: 1.03; 95 % CI, 1.01-1.05, P = 0.015). CONCLUSIONS: In the population of ESCC patients receiving RT, we showed that the CS factors had a substantial predictive value for the various types and grades of CEs. The elevated radiation dose of LAD was a significant contributor to a higher rate of cardiac events and a worse prognosis.

Molar excess of coordinating N-heterocyclic carbene ligands triggers kinetic digestion of gold nanocrystals.

There has been much interest in evaluating the strength of the coordination interactions between N-heterocyclic carbene (NHC) molecules and transition metal ions, nanocolloids and surfaces. We implement a top-down core digestion test of Au nanoparticles (AuNPs) triggered by incubation with a large molar excess of poly(ethylene glycol)-appended NHC molecules, where kinetic dislodging of surface atoms and formation of NHC-Au complexes progressively take place. We characterize the structure and chemical nature of the generated PEG-NHC-Au complexes using 1D and 2D 1H-13C NMR spectroscopy, supplemented with matrix assisted laser desorption/ionization mass spectrometry, and transmission electron microscopy. We further apply the same test using thiol-modified molecules and find that though etching can be measured the kinetics are substantially slower. We discuss our findings within the classic digestion of transition metal ores and colloids induced by interactions with sodium cyanide, which provides an insight into the strength of coordination between the strong σ-donating (soft Lewis base) NHC and Au surfaces (having a soft Lewis acid character), as compared to gold-to-gold covalent binding.

Next-Generation Vitrimers Design through Theoretical Understanding and Computational Simulations.

Vitrimers are an innovative class of polymers that boast a remarkable fusion of mechanical and dynamic features, complemented by the added benefit of end-of-life recyclability. This extraordinary blend of properties makes them highly attractive for a variety of applications, such as the automotive sector, soft robotics, and the aerospace industry. At their core, vitrimer materials consist of crosslinked covalent networks that have the ability to dynamically reorganize in response to external factors, including temperature changes, pressure variations, or shifts in pH levels. In this review, the aim is to delve into the latest advancements in the theoretical understanding and computational design of vitrimers. The review begins by offering an overview of the fundamental principles that underlie the behavior of these materials, encompassing their structures, dynamic behavior, and reaction mechanisms. Subsequently, recent progress in the computational design of vitrimers is explored, with a focus on the employment of molecular dynamics (MD)/Monte Carlo (MC) simulations and density functional theory (DFT) calculations. Last, the existing challenges and prospective directions for this field are critically analyzed, emphasizing the necessity for additional theoretical and computational advancements, coupled with experimental validation.

Self-Assembled Homopolymeric Spherulites from Small Molecules in Solution.

Polymeric spherulites are typically formed by melt crystallization: spherulitic growth in solution is rare and requires complex polymers and dilute solutions. Here, we report the mild and unique formation of luminescent spherulites at room temperature via the simple molecule benzene-1,4-dithiol (BDT). Specifically, BDT polymerized into oligomers (PBDT) via disulfide bonds and assembled into uniform supramolecular nanoparticles in aqueous buffer; these nanoparticles were then dissolved back into PBDT in a good solvent (i.e., dimethylformamide) and underwent chain elongation to form spherulites (rPBDT) in 10 min. The spherulite geometry was modulated by changing the PBDT concentration and reaction time. Due to the step-growth polymerization and reorganization of PBDT, these spherulites not only exhibited robust structure but also showed broad clusterization-triggered emission. The biocompatibility and efficient cellular uptake of the spherulites further underscore their value as traceable drug carriers. This system provides a new pathway for designing versatile superstructures with value for hierarchical assembly of small molecules into a complicated biological system.

Valence-driven colorimetric detection of norovirus protease via peptide-AuNP interactions.

We report here a colorimetric method for rapid detection of norovirus based on the valence-driven peptide-AuNP interactions. We engineered a peptide sequence named K1 with a cleavage sequence in between two lysine residues. The positively charged lysine groups aggregated the negatively charged nanoparticles leading to a purple color change. There was a red color when the cleavage sequence was digested by the Southampton norovirus 3C-like protease (SV3CP)-a protease involved in the life cycle of Human norovirus (HNV). The limit of detection was determined to be 320 nM in Tris buffer. We further show that the sensor has good performance in exhaled breath condensate, urine, and faecal matter. This research provides a potential easy and quick way to selectively detect HNV.

Identification of novel biomarkers for the prediction of subclinical coronary artery atherosclerosis in patients with rheumatoid arthritis: an exploratory analysis.

BACKGROUND: Cardiovascular (CV) risk estimation calculators for the general population underperform in patients with rheumatoid arthritis (RA). The purpose of this study was to identify relevant protein biomarkers that could be added to traditional CV risk calculators to improve the capacity of coronary artery calcification (CAC) prediction in individuals with RA. In a second step, we quantify the improvement of this prediction of CAC when these circulating biomarkers are added to standard risk scores. METHODS: A panel of 141 serum and plasma proteins, which represent a broad base of both CV and RA biology, were evaluated and prioritized as candidate biomarkers. Of these, 39 proteins were selected and measured by commercial ELISA or quantitative mass spectroscopy in 561 individuals with RA in whom a measure of CAC and frozen sera were available. The patients were randomly split 50:50 into a training/validation cohort. Discrimination (using area under the receiver operator characteristic curves) and re-classification (through net reclassification improvement and integrated discrimination improvement calculation) analyses were performed first in the training cohort and replicated in the validation cohort, to estimate the increase in prediction accuracy for CAC using the ACA/AHA (American College of Cardiology and the American Heart Association) score with, compared to without, addition of these circulating biomarkers. RESULTS: The model containing ACC/AHA score plus cytokines (osteopontin, cartilage glycoprotein-39, cystatin C, and chemokine (C-C motif) ligand 18) and plus quantitative mass spectroscopy biomarkers (serpin D1, paraoxonase, and clusterin) had a statistically significant positive net reclassifications index and integrated discrimination improvement for the prediction of CAC, using ACC/AHA score without any biomarkers as the reference category. These results were confirmed in the validation cohort. CONCLUSION: In this exploratory analysis, the addition of several circulating CV and RA biomarkers to a standard CV risk calculator yielded significant improvements in discrimination and reclassification for the presence of CAC in individuals with RA.