A magnetic resonance imaging-based lymph node regression grading scheme for nasopharyngeal carcinoma after radiotherapy.

Background: Among patients with nasopharyngeal carcinoma (NPC), there is no established method to distinguish between patients with residual disease that may eventually progress and those who have achieved cured. We thus aimed to assess the prognostic value of magnetic resonance imaging (MRI)-based lymph node regression grade (LRG) in the risk stratification of patients with NPC following radiotherapy (RT). Methods: This study retrospectively enrolled 387 patients newly diagnosed with NPC between January 2010 and January 2013. A four-category MRI-LRG system based on the areal analysis of RT-induced fibrosis and residual tumor was established. Univariate analysis was performed using the Kaplan-Meier method, and comparisons were conducted via the log-rank test. Multivariate analyses were conducted using Cox regression models to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted P values. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: The sum of MRI-LRG scores (LRG-sum) was an independent prognostic factor for progression-free survival (PFS) (HR 2.50, 95% CI: 1.28-4.90; P<0.001). LRG-sum ≤9 and >9 showed a poorer 5-year PFS rate than did LRG-sum ≤2 (66.1%, 42.9%, and 77.6%, respectively; P<0.001). A survival clustering analysis-based decision tree model showed more complex interactions among LRG-sum and pretreatment and post-RT Epstein-Barr virus (EBV) DNA, yielding four patient clusters with differentiated disease progression risks (5-year PFS rates of 89.5%, 76.4%, 57.6%, and 27.8%, respectively), which showed better risk stratification than did post-RT EBV DNA alone (P<0.001). Conclusions: The MRI-LRG system adds prognostic information and is a potentially reliable, noninvasive means to stratify treatment modalities for patients with NPC.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Age and estimated glomerular filtration rate in Chinese older adults: a cohort study from 2014 to 2020.

Objectives: This study aimed to fill the data gap of the course of renal function decline in old age and explore changes in renal function across different health states with increasing age. Methods: This observational, retrospective, single-center cohort study included 5,112 Chinese older adults (3,321 men and 1,791 women, range 60-104 years). The individual rate of estimated glomerular filtration rate (eGFR) decline was analyzed using linear mixed-effects model to account for repeated measures over the years. Results: The median age was 66 years, median BMI was 24.56 kg/m2, and median eGFR was 89.86 mL/min.1.73 m2. For every 1-year increase in age, women's eGFR decreased by 1.06 mL/min/1.73 m2 and men's by 0.91 mL/min/1.73 m2. We observed greater age-related eGFR decline in men and women with high systolic blood pressure (SBP). Men with high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C), had greater age-related eGFR decline. In women, different BMI groups showed significant differences in age-related eGFR decline, with the highest decline in those with obesity. Additionally, participants with normal baseline eGFR had a faster age-related decline than those with low baseline eGFR. Conclusion: The eGFR declined linearly with age in Chinese older adults, with women exhibiting a slightly faster decline than men. Both men and women should be cautious of SBP. Older adults with normal baseline renal function experienced a faster eGFR decline. Men with high TG, LDL-C, and low HDL-C levels, as well as obese women, should be vigilant in monitoring renal function.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

Tailoring the Buried Interface by Dipolar Halogen-Substituted Arylamine for Efficient and Stable Perovskite Solar Cells.

Improving the quality of the buried interface is decisive for achieving stable and high-efficiency perovskite solar cells. Herein, we report the interface engineering by using dipolar 2,4-difluoro-3,5-dichloroaniline (DDE) as the adhesive between titanium dioxide (TiO2) and MAPbI3. By manipulation of the anchoring groups of DDE, this molecule not only passivated defects of TiO2 but also optimized the energy level alignment. Furthermore, the perovskite film on the modified TiO2 surface showed improved crystallinity, released residual stress, and reduced trap states. Therefore, these benefits directly contribute to achieving a power conversion efficiency of up to 22.10%. The unencapsulated device retained 90% of initial power conversion efficiencies (PCE) after continuous light illumination for 1000 h and 93% of initial PCE after exposure to air with a relative humidity of 30-40% for over 3000 h. Moreover, the performance of PSCs based on FA0.15MA0.85PbI3 has also increased from 20.48 to 23.51%. Our results demonstrate the effectiveness and universality of dipolar halogen-substituted arylamine (DDE) for enhancing PSC performance.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under it (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluated 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in >3,000 published studies. We found the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

Simultaneous quantification of mirabegron and vibegron in human plasma by HPLC-MS/MS and its application in the clinical determination in patients with tumors associated with overactive bladder.

Mirabegron and vibegron, both newly identified beta-3 adrenergic agonists, have significantly improved the quality of life for patients suffering from overactive bladder. In order to comprehensively assess the plasma exposure levels of these agents, the development of a rapid and highly sensitive bioanalytical method becomes imperative. The primary objective of this study was to establish a robust high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the concurrent quantification of mirabegron and vibegron in human plasma. The analytes were extracted from a 100 µL plasma sample through protein precipitation, employing 300 µL of methanol. Subsequently, samples underwent separation and quantification using a Waters XBridge C18 column (2.1 × 100 mm, 3.5 µm), with a mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. The mass analysis was conducted using positive electrospray ionization (ESI+) operated in a multiple reaction monitoring (MRM) mode. The proposed method was meticulously validated in accordance with the guidelines set forth by the U.S. Food and Drug Administration (FDA) for bioanalytical method validation. The regression equations demonstrated exceptional linearity for both mirabegron (r² ≥ 0.994) and vibegron (r² ≥ 0.996) across the concentration range of 0.5 - 200 ng/mL. Furthermore, the assay exhibited accuracy (inter-day relative error ≤ 6.90%) and precision (inter-day coefficient of variation ≤ 8.88%). The average recoveries of the analytes were found to range from 81.94% to 102.02%, with mean matrix effects falling within the range of 89.77% to 110.58%. As a result, this method was deemed highly suitable for the precise determination of the concentrations of both mirabegron and vibegron in the context of therapeutic drug monitoring and bioequivalence studies.

Evaluating the clinical performance of SDC2/NDRG4 methylation for colorectal cancer detection.

Purpose: The performance and clinical accuracy of combined SDC2/NDRG4 methylation were evaluated in diagnosing colorectal cancer (CRC) and advanced adenoma. Methods: A total of 2333 participants were enrolled to assess the sensitivity and specificity of biomarkers in diagnosing CRC in a multicenter clinical trial through feces DNA methylation tests. Results: SDC2/NDRG4 methylation showed excellent performance for CRC detection in biomarker research and the real world. Its sensitivity for detecting CRC, early CRC and advanced adenoma were 92.06%, 91.45% and 62.61%, respectively. Its specificity was 94.29%, with a total coincidence rate of 88.28%. When interference samples were included, the specificity was still good (82.61%). Therefore, the SDC2/NDRG4 methylation test showed excellent performance in detecting CRC and advanced adenoma under clinical application.

Colorectal cancer (CRC) is one of the most malignant tumors of the digestive system and second only to breast cancer and lung cancer in terms of global incidence. Early CRCs are challenging to determine given their atypical nature. In contrast, late CRC symptoms are affected by the type, location and range of the lesion and complications. Therefore, CRC patients are generally diagnosed late, present with a high degree of malignancy, and have poor prognosis and 5-year survival rates. The current study therefore evaluated whether SDC2 and NDRG4 methylation could be used for diagnosis CRCs at an early stage and whether it has the potential to detect asymptomatic patients with adenomas. The findings presented herein will certainly help support the early diagnosis of CRC and precancerous lesions in clinical practice.

Oxide Ion Conduction in Ca-Doped Yb3Ga5O12 Garnet.

Developing oxide ion conductors with new structural families is important for many energy conversion and storage techniques. Herein, a series of Ca-doped Yb3Ga5O12 garnet-type materials are prepared through a traditional solid-state reaction method, with their oxide ion conduction properties being reported for the first time. The results revealed that Ca substitution for Yb would significantly improve the conductivity of Yb3Ga5O12 from 3.57 × 10-7 S/cm at 900 °C under air to 1.66 × 10-4 S/cm, with an oxide ion transporting number of ∼0.52. The oxygen vacancy defect formation energy (∼0.127 eV) and the local structure around an oxygen vacancy were studied by atomic-level static lattice simulations based on the interatomic potential method. The oxide ion conducting mechanism was studied by the bond-valence-based method, which revealed three-dimensional pathways for oxide ion migration in both the parent and Ca-doped structures. The simulated activation energy of oxide ion migration decreased slightly from ∼0.358 eV in the parent structure to 0.346 eV in the doped one. These discoveries in the Ca-doped Yb3Ga5O12 will stimulate extensive exploitation and fundamental research on garnet-type materials.