Citrullination is a protein PTM of arginine residues catalyzed by peptidylarginine deiminase. Protein citrullination has been detected in the CNS and associated with a number of neurological ...diseases. However, identifying citrullinated proteins from complex mixtures and pinpointing citrullinated residues have been limited. Using RP LC and high‐resolution MS, this study determined in vitro citrullination sites of glial fibrillary acid protein (GFAP), neurogranin (NRGN/RC3), and myelin basic protein (MBP) and in vivo sites in brain protein extract. Human GFAP has five endogenous citrullination sites, R30, R36, R270, R406, and R416, and MBP has 14 in vivo citrullination sites. Human NRGN/RC3 was found citrullinated at residue R68. The sequence of citrullinated peptides and citrullination sites were confirmed from peptides identified in trypsin, Lys‐C, and Glu‐C digests. The relative ratio of citrullination was estimated by simultaneous identification of citrullinated and unmodified peptides from Alzheimer's and control brain samples. The site occupancy of citrullination at the residue R68 of NRGN ranged from 1.6 to 9.5%. Compared to CID, higher‐energy collisional dissociation (HCD) mainly produced protein backbone fragmentation for citrullinated peptides. CID‐triggered HCD fragmentation is an optimal approach for the identification of citrullinated peptides in complex protein digests.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In recent years, sandwich-type rare earth tetrapyrrole derivatives, have attracted more and more attention as material for conductimetric sensors. They have not only great chemical stability and ...processability, but also flexible molecular structure, which is a key to adjustable semiconductor properties. In this mini review, we focus mainly on the development of tetrapyrrolato-rare earth sandwich-type complexes as the semiconducting active layer in the gas sensors published in the last ten years (2010–2020). The main part includes two sections. In the single component gas sensing of sandwich rare earth tetrapyrrole complexes, we describe the influence factors of the single-component semiconducting active layer on the sensing performance of tetrapyrrolato-rare earth sandwich-type complexes, including substituents, central metals and π-conjugate systems. In the multi-component gas sensors, the synergistic effect between tetrapyrrolato-rare earth sandwich-type complex and other materials on improving sensitivity and conductivity has been discussed briefly.
Excellent sensing properties of rare earth sandwich-type complexes can be achieved by a combination between the delicate molecular designed by adjusting the substituents, central coordination metal ions and extending π-conjugation systems, and facile film-built approaches. Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Objective The clinical distribution and drug resistance of Escherichia coli and Klebsiella pneumoniae in a hospital of Nanjing from 2020 to 2022 were analyzed in order to provide the basis for ...clinical rational use of antibiotics. Methods The distribution and drug resistance of Escherichia coli and Klebsiella pneumoniae specimens in Zhongda Hospital Southeast University from 2020 to 2022 were retrospectively analyzed. Results A total of 3 507, 4 323 and 4 806 pathogenic bacteria were detected from 2020 to 2022. There were 616, 748 and 840 strains of Escherichia coli , and 456, 631 and 757 strains of Klebsiella pneumoniae , with the total 3-year detection rate of 17.4% and 14.6%. There was a statistically significant difference in the constituent ratio of pathogenic bacteria between 2020 and 2022 (P＜0.01). From 2020 to 2022, the top three samples of pathogenic bacteria were sputum, blood and urine. From 2020 to 2022, the drug resistance rates of Escherichia coli to cefepime, ceftriaxone, cefazolin, gentamicin,
Temperature increase in the continuously narrowing interconnects accelerates the performance and reliability degradation of very large scale integration (VLSI). Thermal boundary resistance (TBR) ...between an interconnect metal and dielectric interlayer has been neglected or treated approximately in conventional thermal analyses, resulting in significant uncertainties in performance and reliability. In this study, we investigated the effects of TBR between an interconnect metal and dielectric interlayer on temperature increase of Cu, Co, and Ru interconnects in deeply scaled VLSI. Results indicate that the measured TBR is significantly higher than the values predicted by the diffuse mismatch model and varies widely from 1 × 10–8 to 1 × 10–7 m2 K W–1 depending on the liner/barrier layer used. Finite element method simulations show that such a high TBR can cause a temperature increase of hundreds of degrees in the future VLSI interconnect. Characterization of interface properties shows the significant importance of interdiffusion and adhesion in TBR. For future advanced interconnects, Ru is better than Co for heat dissipation in terms of TBR. This study provides a guideline for the thermal management in deeply scaled VLSI.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
•We developed and validated a fast, sensitive, and robust multiplex mycophenolic acid and antifungal assay.•Mass spectrometer conditions and assay sensitivities on Triple Quad 6500 and API 4000 ...instruments were compared and evaluated.•Considerations and advantages of mass spectrometry-based multiplex assay for therapeutic drug monitoring are discussed.
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.
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.
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.
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.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
•Patients who are unsuitable for chemoembolization could progress with extrahepatic spread or vascular invasion after initial chemoembolization monotherapy.•A radiomics signature based on the machine ...learning algorithm was identified.•The signature combined with clinicoradiologicial predictors could predict TACE-unsuitable patients.•The combined model showed improved predictive performance compared with the model without radiomics signature.•The combined model could stratify patients into three strata with a low, intermediate, or high risk in training and external testing sets.
Due to the high heterogeneity of hepatocellular carcinoma (HCC), patients with non-advanced disease who are unsuitable for initial transarterial chemoembolization (TACE) monotherapy may have the potential to develop extrahepatic spread or vascular invasion. We aimed to develop and independently validate a radiomics-based model for predicting which patients will develop extrahepatic spread or vascular invasion after initial TACE monotherapy (EVIT).
This retrospective study included 256 HCC patients (training set: n = 136; testing set: n = 120) who underwent TACE as initial therapy between April 2007 and June 2018. Clinicoradiological predictors were selected using multivariate logistic regression and a clinicoradiological model was constructed. The radiomic features were extracted from contrast-enhanced computed tomography (CT) images and a radiomics signature was constructed based on a machine learning algorithm. A combined model integrated clinicoradiological predictor and radiomics signature was developed. The predictive performance of the two models was evaluated and compared based on its discrimination, calibration, and clinical usefulness.
In the training set, 34 (25.0%) patients were confirmed to have EVIT, whereas 26 (21.7%) patients in the testing set had EVIT. When the radiomics signature was added, the combined model showed improved discrimination performance compared to the clinicoradiological model (area under the curves AUCs 0.911 vs. 0.772 in the training set; AUCs 0.847 vs. 0.746 in the testing set) and could divide HCC patients into three strata of low, intermediate, or high risk in the two sets. Decision curve analysis demonstrated that the two models were clinically useful, and the combined model provided greater benefits for discriminating patients than the clinicoradiological model.
This study presents a model that integrates clinicoradiological predictors and CT-based radiomics signature that could provide a preoperative individualized prediction of EVIT in patients with HCC.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Background: An accurate measurement of the glomerular filtration rate (GFR) is essential for detecting renal insufficiency in living kidney donors. Iohexol is a “near-ideal” exogenous filtration ...marker for GFR measurements that has attracted increasing interest in clinical practice because it is non-toxic, non-radioactive, readily available, and easy to measure. In this study, we aimed to set up a laboratory test to conveniently assess the plasma clearance of iohexol in living kidney donors. Methods: A workflow was established in the institution’s infusion clinic to administer iohexol and to collect three timed blood samples from renal transplant donors. Iohexol was thereafter measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The serum proteins were precipitated and the supernatant containing iohexol was diluted prior to the LC-MS/MS analysis. The LC-MS/MS method was developed on a Thermo Vanquish UHPLC coupled with a TSQ Endura triple quadruple mass spectrometer with a total run time of 2.5 min. The analytical performance of the method was assessed. Results: The LC-MS/MS method demonstrated a good analytical performance. To calculate the iohexol clearance rate and the GFR, automated data integration and a result calculation were accomplished by using a custom Python script. Automated result reporting was achieved using a laboratory informatics system (LIS) vendor’s direct media interface. Conclusions: We developed and implemented a laboratory test to assess the plasma clearance of iohexol. A workflow was established in the hospital to reliably measure the GFR in living kidney donors, with a potential to be further expanded into other areas where an accurate GFR measurement is needed.
The purpose of this study was to investigate the feasibility of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) image-based radiomics in differentiating bone metastases from ...benign bone lesions in patients with tumors.
A total of 192 lesions from 132 patients (134 in the training group, 58 in the validation group) diagnosed with vertebral bone metastases or benign bone lesions were enrolled. All images were evaluated and diagnosed independently by two physicians with more than 20 years of diagnostic experience for qualitative classification, the images were imported into MaZda software in Bitmap (BMP) format for feature extraction. All radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation algorithms after the process of normalization and correlation analysis. Based on these selected features, two models were established: The CT model and SPECT model (radiomics features were derived from CT and SPECT images, respectively). In addition, a combination model (ComModel) combined CT and SPECT features was developed in order to better evaluate the predictive performance of radiomics models. Subsequently, the diagnostic performance between each model was separately evaluated by a confusion matrix.
There were 12, 13, and 18 features contained within the CT, SPECT, and ComModel, respectively. The constructed radiomics models based on SPECT/CT images to discriminate between bone metastases and benign bone lesions not only had high diagnostic efficacy in the training group (AUC of 0.894, 0.914, 0.951 for CT model, SPECT model, and ComModel, respectively), but also performed well in the validation group (AUC; 0.844, 0.871, 0.926). The AUC value of the human experts was 0.849 and 0.839 in the training and validation groups, respectively. Furthermore, both SPECT model and ComModel show higher classification performance than human experts in the training group (
= 0.021 and
= 0.001, respectively) and the validation group (
= 0.037 and
= 0.007, respectively). All models showed better diagnostic accuracy than human experts in the training group and the validation group.
Radiomics derived from SPECT/CT images could effectively discriminate between bone metastases and benign bone lesions. This technique may be a new non-invasive way to help prevent unnecessary delays in diagnosis and a potential contribution in disease staging and treatment planning.
The purpose of this study was to explore the application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) image radiomics in the identification of spine ...multiple myeloma (MM) and bone metastasis (BM), and whether this method could improve the classification diagnosis performance compared with traditional methods.
This retrospective study collected a total of 184 lesions from 131 patients between January 2017 and January 2021. All images were visually evaluated independently by two physicians with 20 years of experience through the double-blind method, while the maximum standardized uptake value (SUVmax) of each lesion was recorded. A total of 279 radiomics features were extracted from the region of interest (ROI) of CT and PET images of each lesion separately by manual method. After the reliability test, the least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation were used to perform dimensionality reduction and screening of features. Two classification models of CT and PET were derived from CT images and PET images, respectively and constructed using the multivariate logistic regression algorithm. In addition, the ComModel was constructed by combining the PET model and the conventional parameter SUVmax. The performance of the three classification diagnostic models, as well as the human experts and SUVmax, were evaluated and compared, respectively.
A total of 8 and 10 features were selected from CT and PET images for the construction of radiomics models, respectively. Satisfactory performance of the three radiomics models was achieved in both the training and the validation groups (Training: AUC: CT: 0.909, PET: 0.949, ComModel: 0.973; Validation: AUC: CT: 0.897, PET: 0.929, ComModel: 0.948). Moreover, the PET model and ComModel showed significant improvement in diagnostic performance between the two groups compared to the human expert (Training:
= 0.01 and
= 0.001; Validation:
= 0.018 and
= 0.033), and no statistical difference was observed between the CT model and human experts (
= 0.187 and
= 0.229, respectively).
The radiomics model constructed based on 18F-FDG PET/CT images achieved satisfactory diagnostic performance for the classification of MM and bone metastases. In addition, the radiomics model showed significant improvement in diagnostic performance compared to human experts and PET conventional parameter SUVmax.
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.
MD/MC simulations elucidate the intricate relationships among structure, dynamics, and properties, enhancing comprehension of how polymer chain behaviors impact relevant properties. They provide insights into tailoring vitrimer properties on a macro scale. Concurrently, DFT calculations delve deeper into chemical nuances, aiding in the design of bond exchange mechanisms and fine‐tuning reaction kinetics.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
