scAnno: a deconvolution strategy-based automatic cell type annotation tool for single-cell RNA-sequencing data sets.

Undoubtedly, single-cell RNA sequencing (scRNA-seq) has changed the research landscape by providing insights into heterogeneous, complex and rare cell populations. Given that more such data sets will become available in the near future, their accurate assessment with compatible and robust models for cell type annotation is a prerequisite. Considering this, herein, we developed scAnno (scRNA-seq data annotation), an automated annotation tool for scRNA-seq data sets primarily based on the single-cell cluster levels, using a joint deconvolution strategy and logistic regression. We explicitly constructed a reference profile for human (30 cell types and 50 human tissues) and a reference profile for mouse (26 cell types and 50 mouse tissues) to support this novel methodology (scAnno). scAnno offers a possibility to obtain genes with high expression and specificity in a given cell type as cell type-specific genes (marker genes) by combining co-expression genes with seed genes as a core. Of importance, scAnno can accurately identify cell type-specific genes based on cell type reference expression profiles without any prior information. Particularly, in the peripheral blood mononuclear cell data set, the marker genes identified by scAnno showed cell type-specific expression, and the majority of marker genes matched exactly with those included in the CellMarker database. Besides validating the flexibility and interpretability of scAnno in identifying marker genes, we also proved its superiority in cell type annotation over other cell type annotation tools (SingleR, scPred, CHETAH and scmap-cluster) through internal validation of data sets (average annotation accuracy: 99.05%) and cross-platform data sets (average annotation accuracy: 95.56%). Taken together, we established the first novel methodology that utilizes a deconvolution strategy for automated cell typing and is capable of being a significant application in broader scRNA-seq analysis. scAnno is available at https://github.com/liuhong-jia/scAnno.

Deep learning radiomics under multimodality explore association between muscle/fat and metastasis and survival in breast cancer patients.

Sarcopenia is correlated with poor clinical outcomes in breast cancer (BC) patients. However, there is no precise quantitative study on the correlation between body composition changes and BC metastasis and survival. The present study proposed a deep learning radiomics (DLR) approach to investigate the effects of muscle and fat on distant metastasis and death outcomes in BC patients. Image feature extraction was performed on 4th thoracic vertebra (T4) and 11th thoracic vertebra (T11) on computed tomography (CT) image levels by DLR, and image features were combined with clinical information to predict distant metastasis in BC patients. Clinical information combined with DLR significantly predicted distant metastasis in BC patients. In the test cohort, the area under the curve of model performance on clinical information combined with DLR was 0.960 (95% CI: 0.942-0.979, P < 0.001). The patients with distant metastases had a lower pectoral muscle index in T4 (PMI/T4) than in patients without metastases. PMI/T4 and visceral fat tissue area in T11 (VFA/T11) were independent prognostic factors for the overall survival in BC patients. The pectoralis muscle area in T4 (PMA/T4) and PMI/T4 is an independent prognostic factor for distant metastasis-free survival in BC patients. The current study further confirmed that muscle/fat of T4 and T11 levels have a significant effect on the distant metastasis of BC. Appending the network features of T4 and T11 to the model significantly enhances the prediction performance of distant metastasis of BC, providing a valuable biomarker for the early treatment of BC patients.

Long-term warming increased carbon sequestration capacity in a humid subtropical forest.

Tropical and subtropical forests play a crucial role in global carbon (C) pools, and their responses to warming can significantly impact C-climate feedback and predictions of future global warming. Despite earth system models projecting reductions in land C storage with warming, the magnitude of this response varies greatly between models, particularly in tropical and subtropical regions. Here, we conducted a field ecosystem-level warming experiment in a subtropical forest in southern China, by translocating mesocosms (ecosystem composed of soils and plants) across 600 m elevation gradients with temperature gradients of 2.1°C (moderate warming), to explore the response of ecosystem C dynamics of the subtropical forest to continuous 6-year warming. Compared with the control, the ecosystem C stock decreased by 3.8% under the first year of 2.1°C warming; but increased by 13.4% by the sixth year of 2.1°C warming. The increased ecosystem C stock by the sixth year of warming was mainly attributed to a combination of sustained increased plant C stock due to the maintenance of a high plant growth rate and unchanged soil C stock. The unchanged soil C stock was driven by compensating and offsetting thermal adaptation of soil microorganisms (unresponsive soil respiration and enzyme activity, and more stable microbial community), increased plant C input, and inhibitory C loss (decreased C leaching and inhibited temperature sensitivity of soil respiration) from soil drying. These results suggest that the humid subtropical forest C pool would not necessarily diminish consistently under future long-term warming. We highlight that differential and asynchronous responses of plant and soil C processes over relatively long-term periods should be considered when predicting the effects of climate warming on ecosystem C dynamics of subtropical forests.

Remodeling the Electronic Structure of Metallic Nickel and Ruthenium via Alloying in a Molecular Template for Sustainable Hydrogen Evolution.

The reasonably constructed high-performance electrocatalyst is crucial to achieve sustainable electrocatalytic water splitting. Alloying is a prospective approach to effectively boost the activity of metal electrocatalysts. However, it is a difficult subject for the controllable synthesis of small alloying nanostructures with high dispersion and robustness, preventing further application of alloy catalysts. Herein, we propose a well-defined molecular template to fabricate a highly dispersed NiRu alloy with ultrasmall size. The catalyst presents superior alkaline hydrogen evolution reaction (HER) performance featuring an overpotential as low as 20.6 ± 0.9 mV at 10 mA·cm-2. Particularly, it can work steadily for long periods of time at industrial-grade current densities of 0.5 and 1.0 A·cm-2 merely demanding low overpotentials of 65.7 ± 2.1 and 127.3 ± 4.3 mV, respectively. Spectral experiments and theoretical calculations revealed that alloying can change the d-band center of both Ni and Ru by remodeling the electron distribution and then optimizing the adsorption of intermediates to decrease the water dissociation energy barrier. Our research not only demonstrates the tremendous potential of molecular templates in architecting highly active ultrafine nanoalloy but also deepens the understanding of water electrolysis mechanism on alloy catalysts.

IKKα aggravates renal fibrogenesis by positively regulating the Wnt/ß-catenin pathway.

AKI (acute kidney injury) with maladaptive repair plays exacerbated role in renal fibrosis characterized by tubulointerstitial fibrosis. Previously, we reported that IKKα contributed to kidney regeneration and inhibited inflammation. Here, we first identified the role and mechanism of IKKα on TGF-ß1-induced fibrosis in human tubular epithelial cells and fibrotic kidneys. IKKα was up-regulated in kidney tubular epithelium in unilateral ureteral obstruction (UUO) and unilateral ischemic reperfusion injury (UIRI) mice. Immunohistochemical staining showed that IKKα was positively correlated with the extent of kidney fibrosis in tissue biopsies from chronic kidney disease (CKD) patients. Compared with wild-type controls, Ksp-IKKα-/- mice exhibited inactivated Wnt/ß-catenin pathway, decreased serum creatinine and interstitial fibrosis in the kidney after IRI. In TGF-ß1-stimulated human tubular epithelial cells, IKKα overexpression enhanced ß-catenin nuclear translocation. Blocking IKKα by siRNA specifically suppressed ß-catenin activation and downstream profibrotic genes such as fibronectin and α-smooth muscle actin (α-SMA). Taken together, our study demonstrated that IKKα aggravated renal fibrogenesis by activating Wnt/ß-catenin signalling pathway, providing a new target for the treatment of kidney fibrosis.

Association between IL-38 and inflammatory indicators in patients with bacterial pneumonia.

BACKGROUND: IL-38, a recently discovered cytokine of IL-1 family, exerts immunoregulatory activities in multi-type inflammatory diseases. However, its expression level and underlying clinical importance for IL-38 in respiratory bacterial infections remain unknown. METHODS: Thirty-five patients with bacterial pneumonia and twenty age- and gender- matched healthy individuals were enrolled in the study to determine serum IL-38 concentrations by ELISA. Then, the correlation between serum IL-38 levels and clinical features were analyzed and ROC curve was used to evaluate the potential diagnostic value for bacterial infections. In vitro, LPS-stimulated human respiratory epithelial cell model was employed to explore immunomodulatory mechanism of IL-38 in pulmonary infections. RESULTS: Elevated serum levels of IL-38 were determined in patients with bacterial pneumonia when compared with healthy controls. In addition, serum IL-38 levels were negatively correlated with clinical inflammation parameters, including WBC count, CRP, PCT and proinflammatory IL-6 and IL-8. In vitro, we demonstrated that recombinant IL-38 was able to remarkably inhibit expression of proinflammatory IL-6, IL-8, IL-1ß and TNF-α as well as adhesion molecule ICAM-1, which were partially mediated by attenuated activation of STAT3 and NF-κB signal cascades in BEAS-2B cells. Furthermore, we identified the diagnostic efficiency of IL-38 in discriminating patients with bacterial pneumonia from healthy individuals. CONCLUSIONS: Our study indicates higher serum IL-38 levels in patients with bacterial pneumonia are involved in anti-inflammatory activities in respiratory infections revealing a critical role of IL-38 in attenuating excessive pulmonary inflammation against exogenous pathogens. More importantly, IL-38 exhibited a potential novel biomarker for bacterial pneumonia. Thus, our data may provide useful insights for both clinical and basic research for bacterial pneumonia diagnosis.

Resolving the influence of lignin on soil organic matter decomposition with mechanistic models and continental-scale data.

Confidence in model estimates of soil CO2 flux depends on assumptions regarding fundamental mechanisms that control the decomposition of litter and soil organic carbon (SOC). Multiple hypotheses have been proposed to explain the role of lignin, an abundant and complex biopolymer that may limit decomposition. We tested competing mechanisms using data-model fusion with modified versions of the CN-SIM model and a 571-day laboratory incubation dataset where decomposition of litter, lignin, and SOC was measured across 80 soil samples from the National Ecological Observatory Network. We found that lignin decomposition consistently decreased over time in 65 samples, whereas in the other 15 samples, lignin decomposition subsequently increased. These "lagged-peak" samples can be predicted by low soil pH, high extractable Mn, and fungal community composition as measured by ITS PC2 (the second principal component of an ordination of fungal ITS amplicon sequences). The highest-performing model incorporated soil biogeochemical factors and daily dynamics of substrate availability (labile bulk litter:lignin) that jointly represented two hypotheses (C substrate limitation and co-metabolism) previously thought to influence lignin decomposition. In contrast, models representing either hypothesis alone were biased and underestimated cumulative decomposition. Our findings reconcile competing hypotheses of lignin decomposition and suggest the need to precisely represent the role of lignin and consider soil metal and fungal characteristics to accurately estimate decomposition in Earth-system models.

Clinical feature and disease outcome in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder: a Chinese study.

BACKGROUND: To identify factors associated with relapse risk and disability in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHOD: Between 2016 and 2021, 186 patients with MOGAD were included in the study. Factors associated with a relapsing course, annualised relapse rate (ARR), recurrent relapses under different maintenance treatments and unfavourable disability outcome were analysed. RESULTS: MOGAD affects women (53.8%) slightly more often than men. After a median disease duration of 51.0 months, 60.2% (112/186) relapsed, with an overall ARR of 0.5. The ARR (0.6 vs 0.4, p=0.049), median Expanded Disability Status Scale (EDSS) score (1 (range 0-9.5) vs 1 (range 0-3.5), p=0.005) and Visual Functional System Score (VFSS) (0 (range 0-6) vs 0 (range 0-3), p=0.023) at last visit were higher in adults than in children, and time to first relapse was shorter in adults than in children (4.1 (range 1.0-111.0) vs 12.2 (range 1.3-266.8) months, p=0.001). Myelin oligodendrocyte glycoprotein antibody (MOG-ab) persistence over 1 year was associated with a relapsing course (OR 7.41, 95% CI 2.46 to 22.33, p=0.000), while timely maintenance therapy was associated with a lower ARR (p=0.008). More than four attacks (OR 4.86, 95% CI 1.65 to 14.28, p=0.004) and poor recovery from the first attack (OR 75.28, 95% CI 14.45 to 392.05, p=0.000) were associated with an unfavourable outcome (EDSS score ≥2 including VFSS ≥2). CONCLUSIONS: The results underscored the importance of timely maintenance treatment to prevent further relapses, especially in adult patients with persistently positive MOG-ab and unsatisfactory recovery from the onset attack.

Causal associations between prodromal infection and neuromyelitis optica spectrum disorder: A Mendelian randomization study.

BACKGROUND AND PURPOSE: Prodromal infections are associated with neuromyelitis optica spectrum disorder (NMOSD), but it remains unclear which type of infection has a causal association with NMOSD. We aimed to explore the causal associations between four herpesvirus infections (chickenpox, cold sores, mononucleosis and shingles) and NMOSD, as well as between other types of infections and NMOSD. METHODS: For data on infections, we used the genome-wide association study (GWAS) summary statistics from the 23andMe cohort. For outcomes, we used the GWAS data of participants of European ancestry, including 215 NMOSD patients (132 anti-aquaporin-4 antibody [AQP4-ab]-positive patients and 83 AQP4-ab-negative patients) and 1244 normal controls. Single-nucleotide polymorphism (SNP) identification and two-sample Mendelian randomization (MR) analyses were then performed. RESULTS: In the 23andMe cohort, we identified one SNP for chickenpox (rs9266089 in HLA-B gene), one SNP for cold scores (rs885950 in the POU5F1 gene), one SNP for mononucleosis (rs2596465 in the HCP5 gene), and three SNPs for shingles (rs2523591 in the HLA-B gene; rs7047299 in the IFNA21 gene; rs9260809 in the MICD gene). The association between cold sores and AQP4-ab-positive NMOSD reached statistical significance (odds ratio [OR] 745.318; 95% confidence interval [CI] 22.176, 25,049.53 [p < 0.001, Q < 0.001]). The association between shingles and AQP4-ab-positive NMOSD was also statistically significant (OR 21.073; 95% CI 4.271, 103.974 [p < 0.001, Q < 0.001]). No significant association was observed between other infections and AQP4-ab-positive or AQP4-ab-negative NMOSD. CONCLUSION: These findings suggest there are positive associations between cold sores and shingles and AQP4-ab-positive NMOSD, indicating there may be causal links between herpes simplex virus and varicella-zoster virus infection and AQP4-ab-positive NMOSD.

Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from the FREEDOMS II study.

BACKGROUND AND PURPOSE: The aim was to evaluate the potential of retinal nerve fiber layer thickness (RNFLT) measured with optical coherence tomography in predicting disease progression in relapsing-remitting multiple sclerosis (RRMS). METHODS: Analyses were conducted post hoc of this 24-month, phase III, double-blind study, in which RRMS patients were randomized (1:1:1) to once daily oral fingolimod 0.5 mg, 1.25 mg or placebo. The key outcomes were the association between baseline RNFLT and baseline clinical characteristics and clinical/imaging outcomes up to 24 months. Change of RNFLT with fingolimod versus placebo within 24 months and time to retinal nerve fiber layer (RNFL) thinning were evaluated. RESULTS: Altogether 885 patients were included. At baseline, lower RNFLT was correlated with higher Expanded Disability Status Scale score (r = -1.085, p = 0.018), lower brain volume (r = 0.025, p = 0.006) and deep gray matter volume (r = 0.731, p < 0.0001), worse visual acuity (r = -19.846, p < 0.0001) and longer duration since diagnosis (r = -0.258, p = 0.018). At month 12, low baseline RNFLT (<86 µm) versus high baseline RNFLT (≥99 µm) was associated with a greater brain volume loss (percentage change -0.605% vs. -0.315%, p = 0.035) in patients without optic neuritis history. At month 24, low baseline RNFLT versus high baseline RNFLT was associated with a higher number of new or newly enlarged T2 lesions (mean number 4.0 vs. 2.8, p = 0.014) and a higher risk of subsequent RNFL thinning (hazard ratio 2.55; 95% confidence interval 1.84-3.53; p < 0.001). The atrophy of the RNFL in the inferior quadrant was alleviated with fingolimod 0.5 mg versus placebo at month 24 (Δ(least squares mean) = 1.8, p = 0.047). CONCLUSION: Retinal nerve fiber layer thickness could predict disease progression in RRMS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00355134, https://clinicaltrials.gov/ct2/show/NCT00355134.

Acidity of Soil and Water Decreases in Acid-Sensitive Forests of Tropical China.

Acid deposition in China has been declining since the 2000s. While this may help mitigate acidification in forest soils and water, little is known about the recovery of soils and water from previous severe acidification in tropical China. Here, we assessed the chemistry of mineral soils, water, and acid gases (SO2 and NOx) from three successional forest types in tropical China from 2000 to 2022. Our results showed that soil pH increased synchronously from 3.9 (2000-2015) to 4.2 (2016-2022) across all three forest types, with exchangeable acid initially decreasing and thereafter stabilizing. Surface and ground water pH also gradually increased throughout the monitoring period. Soil pH recovery was stronger in the primary than in the planted forest. However, soil pH recovery lagged behind the increase in rainfall pH by approximately a decade. The recovery of soil pH was likely related to the positive effects of the dissolution of Al/Fe-hydroxysulfate mineral and subsequent sulfur desorption on soil acid-neutralizing capacity, increased soil organic matter, and climate warming, but was likely moderated by increased exchangeable aluminum and potentially proton-producing hydroxysulfate mineral dissolution that caused the lagged soil pH recovery. Surface and ground water pH recovery was attributed to increased water acid-neutralizing capacity. Our study reports the potential for the recovery of acidified soil and water following decreased acid deposition and provides new insights into the functional recovery of acid-sensitive forests.

Development and validation of a nomogram prediction model for hypertension-diabetes comorbidity based on chronic disease management in the community.

PURPOSE: ​Develop and validate a nomogram prediction model for hypertension-diabetes comorbidities based on chronic disease management in the community. PATIENTS AND METHODS: The nomogram prediction model was developed in a cohort of 7200 hypertensive patients at a community health service center in Hongshan District, Wuhan City. The data were collected from January 2022 to December 2022 and randomly divided into modeling and validation groups at a 7:3 ratio. The Lasso regression model was used for data dimensionality reduction, feature selection, and clinical test feature construction. Multivariate logistic regression analysis was used to build the prediction model. RESULTS: The application of the nomogram in the verification group showed good discrimination, with an AUC of 0.9205 (95% CI: 0.8471-0.9527) and a good calibration effect. Decision curve analysis demonstrated that the predictive model was clinically useful. CONCLUSION: This study presents a nomogram prediction model that incorporates age, waist-height ratio and elevated density lipoprotein cholesterol (HDL-CHOLESTEROL), which can be used to predict the risk of codeveloping diabetes in hypertensive patients.

Pectoralis muscle predicts distant metastases in breast cancer by deep learning radiomics.

BACKGROUND: Sarcopenia is associated with a poor prognosis in patients with breast cancer (BC). Currently, there are few quantitative assessments carried out between muscle biomarkers and distant metastasis using existing methods. PURPOSE: To assess the predictive value of the pectoralis muscle for BC distant metastasis, we developed a deep learning radiomics nomogram model (DLR-N) in this study. MATERIAL AND METHODS: A total of 493 patients with pathologically confirmed BC were registered. Image features were extracted from computed tomography (CT) images for each patient. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors for distant metastasis. The DLR-N was built based on independent prognostic factors and CT images to predict distant metastases. The model was assessed in terms of overall performance, discrimination, calibration, and clinical value. Finally, the predictive performance of the model was validated using the testing cohort. RESULTS: The developed DLR-N combined multiple radiomic features and clinicopathological factors and demonstrated excellent predictive performance. The C-index of the training cohort was 0.983 (95% confidence interval [CI] = 0.969-0.998) and the C-index of the testing cohort was 0.948 (95% CI = 0.917-0.979). Decision curve analysis (DCA) showed that patients could benefit more from incorporating multimodal radiomic features into clinicopathological models. CONCLUSIONS: DLR-N verified that there were biomarkers at the level of the fourth thoracic vertebra (T4) that affected distant metastasis. Multimodal prediction models based on deep learning could be a potential method to aid in the prediction of distant metastases in patients with BC.

Serum Cystatin C within 24 hours after admission: a potential predictor for acute kidney injury in Chinese patients with community acquired pneumonia.

BACKGROUND: Acute kidney injury (AKI) is common in patients with community-acquired pneumonia (CAP), and is associated with poor prognosis. Therefore, in this study, we evaluated whether AKI in Chinese patients with CAP could be well predicted by serum Cystatin C within 24 h after admission. METHODS: Univariate and multivariate logistic regression analyses were used to investigate independent factors of AKI in patients with CAP. RESULTS: Totally, 2716 patients with CAP were included in this study. 766 (28%) patients developed AKI. After multivariate logistic regression analysis, serum Cystatin C (odds ratio [OR] 4.27, 95% confidence interval [CI] 3.36-5.44; p < 0.001) was an independent factor for AKI in patients with CAP. Serum Cystatin C had an area under the receiver operating characteristic curve (AUC) of 0.81 for predicting AKI, with an optimal cutoff value of 1.37 mg/L, computing 68% sensitivity, 80% specificity. Furthermore, serum Cystatin C within 24 h after admission still had a good and stable prediction efficiency for AKI in various subgroups (age, gender, hypertension, diabetes, coronary artery disease, cardiac insufficiency, cerebrovascular disease, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, and tumor, albumin, anemia, platelet count, white blood cell count, and uric acid, confusion, uremia, respiratory rate, blood pressure, and age 65 years or older [CURB-65] score, acute respiratory failure, intensive care unit admission, and mechanical ventilation) of patients with CAP (AUCs: 0.69-0.84). CONCLUSION: Serum Cystatin C within 24 h after admission appears to be a good biomarker for predicting AKI in Chinese patients with CAP.

Monocyte to high density lipoprotein ratio in patients with acute kidney injury after cardiac surgery.

BACKGROUND: The Monocyte to high density lipoprotein ratio (MHR) has been postulated as a novel parameter associated with adverse renal and cardiovascular outcomes. In this study we investigated the association of MHR with cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS: In this retrospective study, we analyzed the data pertaining to 1505 patients undergoing cardiopulmonary bypass (CPB) surgery. The CSA-AKI, which was defined using Kidney Disease Improving Global Outcomes criteria. Concurrently, a retrospective scan of patient files was conducted and information relevant to nephropathy such as the level of their serum creatinine (SCr), Blood urea nitrogen (BUN), uric acid (UA), serum cystatin C (Cys-C), total cholesterol (TC), triglycerides (TG), glucose and MHR, ejection fraction, CPB duration time, and other indicators. RESULTS: About 1505 patients were studied of whom 195 developed AKI. MHR was significantly higher in the AKI patients (p = 0.001). In multivariate logistic regression analysis, MHR, UA, Cys-C, age, glucose, and history of chronic kidney disease or hypertension were independently correlated with CSA-AKI. CONCLUSIONS: As a laboratory index, the elevated MHR is convenient, independent, and a useful predictor for CSA-AKI.

Warming drives sustained plant phosphorus demand in a humid tropical forest.

Phosphorus (P) is often one of the most limiting nutrients in highly weathered soils of humid tropical forests and may regulate the responses of carbon (C) feedback to climate warming. However, the response of P to warming at the ecosystem level in tropical forests is not well understood because previous studies have not comprehensively assessed changes in multiple P processes associated with warming. Here, we detected changes in the ecosystem P cycle in response to a 7-year continuous warming experiment by translocating model plant-soil ecosystems across a 600-m elevation gradient, equivalent to a temperature change of 2.1°C. We found that warming increased plant P content (55.4%) and decreased foliar N:P. Increased plant P content was supplied by multiple processes, including enhanced plant P resorption (9.7%), soil P mineralization (15.5% decrease in moderately available organic P), and dissolution (6.8% decrease in iron-bound inorganic P), without changing litter P mineralization and leachate P. These findings suggest that warming sustained plant P demand by increasing the biological and geochemical controls of the plant-soil P-cycle, which has important implications for C fixation in P-deficient and highly productive tropical forests in future warmer climates.

Preoperative PDW levels predict pulmonary metastasis in patients with hepatocellular carcinoma.

BACKGROUND: In hepatocellular carcinoma (HCC), pulmonary metastasis (PM) after hepatectomy is associated with poor clinical outcomes. The crucial phases of tumour cell proliferation, angiogenesis, and metastasis all entail platelet activation. In HCC, platelet distribution width (PDW) suggests platelet size changes and predicts a worse prognosis. The aim of this study was to assess the association between PDW and PMs in HCC patients receiving hepatectomy. MATERIAL/METHODS: From January 2013 to December 2015, a cohort of patients who underwent hepatectomy for HCC at the Harbin Medical University Cancer Hospital in China were retrospectively evaluated. The relationship between PDW levels and clinical and demographic parameters was examined. To investigate the relationships between predicted factors and PM, a competing risk model was used. From January 2016 to December 2018, a validation cohort of 109 patients from the First Affiliated Hospital of Harbin Medical University was studied independently. RESULTS: In the primary cohort, 19 out of 214 patients had postoperative PMs. In HCC patients with PM, PDW levels were lower than in those without PM. There was a significant difference in the cumulative incidence of 2-year PM between the high-PDW and low-PDW groups after controlling for competing risk events (death prior to the development of PM) (p < 0.001). In addition, PDW was also found to be an independent predictor for PM in a multivariable competing risk analysis. The results were externally validated in another cohort. CONCLUSIONS: In HCC, preoperative PDW is significantly associated with PM. PDW could be a biomarker for post-operative PM in HCC patients.

Late onset neuromyelitis optica spectrum disorder with anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies.

BACKGROUND AND PURPOSE: This study aimed to evaluate the clinical characteristics and prognosis of late onset (≥50 years) neuromyelitis optica spectrum disorder (LO-NMOSD), and compare them with those of early onset (<50 years) NMOSD (EO-NMOSD) and NMOSD with various antibody serostatuses. METHODS: From January 2015 to December 2020, 360 anti-aquaporin 4 antibody (AQP4-ab)-positive and 130 anti-myelin oligodendrocyte glycoprotein antibody (MOG-ab)-positive patients presented to the Huashan Hospital, China. We retrospectively reviewed their medical records, including the Expanded Disability Status Scale (EDSS) score at each visit and the annualized relapse rate (ARR). Prognostic outcomes included the time to first relapse, blindness, motor dysfunction, severe motor dysfunction, and death. Correlations between the age at onset, lesion location, and clinical parameters were analyzed. RESULTS: This study included 122 (24.9%) patients with LO-NMOSD, 101 with AQP4-ab and 21 with MOG-ab. Compared with EO-NMOSD patients, those with LO-NMOSD had higher EDSS scores and more frequent disease onset with transverse myelitis, blindness, motor dysfunction, and severe motor dysfunction. Compared with LO-NMOSD patients with MOG-ab, those with AQP4-ab had a worse prognosis. Age at disease onset had a significantly positive correlation with EDSS score at the last follow-up of all NMOSD patients, but a negative correlation with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up) in NMOSD patients with AQP4-ab. CONCLUSIONS: Patients with LO-NMOSD, especially those with AQP4-ab, had a worse prognosis compared with patients with EO-NMOSD. Age at disease onset and antibody serostatus predicted blindness and motor dysfunction.

Efficacy and safety of azathioprine, mycophenolate mofetil, and reduced dose of rituximab in neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: Data regarding the efficacy and safety of currently widely available preventive therapies in neuromyelitis optica spectrum disorder (NMOSD) are needed. We compared the efficacy and safety of azathioprine (AZA), mycophenolate mofetil (MMF), and reduced dose of rituximab (RTX) in NMOSD based on a large multicenter retrospective cohort. METHODS: Patients with aquaporin 4 (AQP4) antibody-positive NMOSD with AZA (n = 167), MMF (n = 131), or RTX (n = 55) as initial preventive treatment were included. The main outcome was the occurrence of relapse after the initiation of immunotherapy. Secondary outcomes were annual relapse rate, disability accumulation, drug persistence, and adverse events. RESULTS: The median follow-up time of the 353 patients was 30.3 months. The regimen of RTX was 100 mg on Day 1 and 500 mg on Day 2, followed by 500 mg every 6 months. The proportions of patients with concomitant steroid therapy at baseline were 96.4%, 95.4%, and 76.4% in the AZA, MMF, and RTX groups. Risk of relapse was significantly reduced in patients treated with RTX compared with those treated with AZA (hazard ratio [HR] = 4.40, 95% confidence interval [CI] = 1.41-13.80, p = 0.011) or MMF (HR = 5.20, 95% CI = 1.60-16.86, p = 0.006) after adjusting for potential confounding variables. Drug discontinuations were less likely on RTX than AZA (HR = 2.22, 95% CI = 1.34-3.66, p = 0.002). RTX exhibited lower incidence of adverse events (32.7%) than AZA (62.3%, p < 0.001). CONCLUSIONS: We provide Class III evidence that reduced dose of RTX is superior to AZA and MMF as initial treatment to reduce the risk of relapse and is better tolerated than AZA in Chinese patients with AQP4 antibody-positive NMOSD.

Quenching and Electrical Current Poling Effect on Improved Ferroelectric and Piezoelectric Properties in BiFeO3-Based High-Temperature Piezoceramics.

The effects of quenching on the structural, electrical, dielectric, ferroelectric (FE), and piezoelectric properties are investigated systematically in the 0.85BiFe1-xCrxO3-0.15BaTi1-xMnxO3 (0 ≤ x ≤ 0.03) ceramics. Optimal piezoelectricity and FE Curie temperature are obtained through optimized quenching rate and temperature. Quenching effect on piezoelectricity is especially significant for the samples near morphotropic phase boundaries (MPB), which can be ascribed to quenching-induced changes in phase ratio (rhombohedral and tetragonal phase) and domain structure/defect dipole orientation. Moreover, a new poling method, that is, cooling the sample at a constant dc current across FE TC, is established to improve the piezoelectricity. This work not only reveals the possible mechanism of quenching effect on the improved piezoelectricity in the BFO-based piezoceramics (especially near the MPB) but also suggests an electric current poling strategy for improving piezoelectricity by suppressing the defect dipole effects in BFO-based and even other piezoelectrics.