bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammasomes and Pyroptosis of Liver Cells in Liver Fibrosis
Authors: Gan Can , Cai Qiuyu , Tang Chengwei , Gao Jinhang 
Published: May 2022

Inflammasomes are multiprotein complexes that can sense danger signals and activate caspase-1 to mediate pro-inflammatory cytokines release and pyroptotic cell death. There are two main canonical and non-canonical signaling pathways that trigger inflammasome activation. Inflammasomes are expressed and assembled in parenchymal and nonparenchymal cells in response to liver injury in the liver. Additionally, the hepatocytes, biliary epithelial cells (cholangiocytes), hepatic stellate cells (HSCs), hepatic macrophages, and liver sinusoidal endothelial cells (LSECs) contribute to liver fibrosis via different mechanisms. However, the underlying mechanism of the inflammasome and pyroptosis in these liver cells in liver fibrosis remains elusive. This review summarizes the activation and function of inflammasome complexes and then discusses the association between inflammasomes, pyroptosis, and liver fibrosis. Unlike other similar reviewers, we will focus on the effect of inflammasome activation and pyroptosis in the various liver cells during the development of liver fibrosis. We will also highlight the latest progress of pharmacological intervention in inflammasome-mediated liver fibrosis.
The Association Between Serum Complement 4 and Kidney Disease Progression in Idiopathic Membranous Nephropathy: A Multicenter Retrospective Cohort Study
Authors: Liu Jing , Zha Yang , Zhang Peng , He Peng , He Lijie 
Published: May 2022

IntroductionComplement system plays an important role in the pathogenesis of idiopathic membranous nephropathy (IMN), however, the relationship between serum complement 4 (C4) and kidney disease progression in IMN is unclear. This study aims to investigate the association of serum C4 level with the risk of kidney disease progression among patients with IMN.MethodsThe retrospective cohort assessed 1,254 participants with biopsy-proven IMN from three centers in Xi ‘an, Shaanxi Province, China. Baseline serum C4 levels were measured at renal biopsy. The association between baseline serum C4 and the risk of renal function progression, defined as a 30% decline in renal function or end stage renal disease, was evaluated in Cox proportional hazards models.ResultsA total of 328 patients with IMN and nephrotic proteinuria were eligible, and 11.3% (37/328) of them attained the renal function progression events after a median follow-up of 51 months (37-59 months). After adjustment for other confounders, a higher value of serum C4 was independently associated with a higher risk of renal function progression event with a hazard ratio (HR) of 4.76 (95% confidence interval [95% CI], 1.77-12.79) per natural log-transformed C4. In reference to the low level of C4, the adjusted HRs were 2.72 (95% CI, 1.02-7.24) and 3.65 (95% CI, 1.39-9.60), respectively, for the median and high levels of C4 (P for trend=0.008). Additionally, the results were robust and reliable in the sensitivity and subgroup analyses.ConclusionAmong patients with IMN and nephrotic proteinuria, serum C4 at renal biopsy is an independent predictor for kidney disease progression regardless of other confounders.
Harmonization of Multiple SARS-CoV-2 Reference Materials Using the WHO IS (NIBSC 20/136): Results and Implications
Authors: Windsor William Jonathan , Roell Yannik , Tucker Heidi , Cheng Chi-An , Suliman Sara , Peek Laura J. , Pestano Gary A. , Lee William T. , Zeichhardt Heinz , Lamb Molly M. , Kammel Martin , Wang Hui , Kedl Ross , Rester Cody , Morrison Thomas E. , Davenport Bennet J. , Carson Kyle , Yates Jennifer , Howard Kelly , Kulas Karen , Walt David R. , Dafni Aner , Taylor Daniel , Chu May 
Published: May 2022

BackgroundThere is an urgent need for harmonization between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology platforms and assays prior to defining appropriate correlates of protection and as well inform the development of new rapid diagnostic tests that can be used for serosurveillance as new variants of concern (VOC) emerge. We compared multiple SARS-CoV-2 serology reference materials to the WHO International Standard (WHO IS) to determine their utility as secondary standards, using an international network of laboratories with high-throughput quantitative serology assays. This enabled the comparison of quantitative results between multiple serology platforms.MethodsBetween April and December 2020, 13 well-characterized and validated SARS-CoV-2 serology reference materials were recruited from six different providers to qualify as secondary standards to the WHO IS. All the samples were tested in parallel with the National Institute for Biological Standards and Control (NIBSC) 20/136 and parallel-line assays were used to calculate the relevant potency and binding antibody units.ResultsAll the samples saw varying levels of concordance between diagnostic methods at specific antigen–antibody combinations. Seven of the 12 candidate materials had high concordance for the spike-immunoglobulin G (IgG) analyte [percent coefficient of variation (%CV) between 5 and 44%].ConclusionDespite some concordance between laboratories, qualification of secondary materials to the WHO IS using arbitrary international units or binding antibody units per milliliter (BAU/ml) does not provide any benefit to the reference materials overall, due to the lack of consistent agreeable international unit (IU) or BAU/ml conversions between laboratories. Secondary standards should be qualified to well-characterized reference materials, such as the WHO IS, using serology assays that are similar to the ones used for the original characterization of the WHO IS.
Evidence for Dopamine Abnormalities Following Acute Methamphetamine Exposure Assessed by Neuromelanin-Sensitive Magnetic Resonance Imaging
Authors: Tang Fei , Liu Hui , Zhang Xiao Jie , Zheng Hui Hui , Dai Yong Ming , Zheng Li Yun , Yang Wen Han , Du Yan Yao , Liu Jun 
Published: May 2022

BackgroundNeuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a newly developed MRI technique that provides a non-invasive way to indirectly measure of dopamine (DA) function. This study aimed to determine NM concentrations in brain regions following acute methamphetamine (MA) administration using NM-MRI and to explore whether NM-MRI can be used as a biomarker of DA function in non-neurodegenerative diseases.MethodsBaseline NM-MRI, T1-weighted and T2-weighted images were acquired from 27 rats before drug/placebo injection. The control group (n = 11) received acute placebo (Normal saline), while the experimental group (n = 16) received acute MA. NM-MRI scans were performed 5, 30, 60 and 90 min after injection. Regions of interest (ROIs), including the caudate putamen (CP), nucleus accumbens (NAc), hippocampus (HIP), substantia nigra (SN) and crus cerebri (CC), were manually drawn by an experienced radiologist. NM-MRI signal intensity in five brain regions at different time points (baseline and 5, 30, 60, and 90 min) were analyzed.ResultsIn both the control and experimental groups, at each time point (baseline and 5, 30, 60, and 90 min), the SN exhibited significantly higher NM-MRI signal intensity than the other brain regions (P &lt; 0.05). In addition, acute MA administration resulted in a continuous upward trend in NM-MRI signal intensity in each brain region over time. However, there was no such trend over time in the control group. The NM-MRI signal intensity of SN in the experimental group was significantly higher at the 60 and 90 min compared with that in the control group (P values were 0.042 and 0.042 respectively). Within experimental group, the NM-MRI signal intensity of SN was significantly higher at the 60 and 90 min compared with that before MA administration (P values were 0.023 and 0.011 respectively). Increased amplitudes and rates of NM-MRI signal intensity were higher in the SN than in other brain regions after MA administration.ConclusionOur results indicated that NM was mainly deposited in the SN, and the conversion of DA to NM was most significant in the SN after acute MA exposure. Increased DA release induced by acute MA exposure may lead to increased accumulation of NM in multiple brain regions that can be revealed by NM-MRI. NM-MRI may serve as a powerful imaging tool that could have diverse research and clinical applications for detecting pathological changes in drug addiction and related non-neurodegenerative diseases.
Screening of the TMEM151A Gene in Patients With Paroxysmal Kinesigenic Dyskinesia and Other Movement Disorders
Authors: Ma Ling-Yan , Han Lin , Niu Meng , Chen Lu , Yu Ya-Zhen , Feng Tao 
Published: May 2022

BackgroundParoxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by recurrent involuntary movements usually triggered by sudden movements. Mutations in the TMEM151A gene were found to be the causative factor of PKD in recent studies. It has also been revealed that loss-of-function is the mechanism by which TMEM151A mutations cause PKD.MethodsTo investigate the genetic basis of PKD and broaden the clinical spectrum of the TMEM151A mutations, we recruited 181 patients of Chinese origin with movement disorders (MDs), including 39 PRRT2-negative PKD, 3 paroxysmal exercise-induced dyskinesia (PED), 2 paroxysmal non-kinesigenic dyskinesia (PNKD), 127 isolated dystonia, 8 choreas, and 2 myoclonus-dystonia syndromes. Whole-exome sequencing was applied to identify their possible disease-causing mutations. Then, Sanger sequencing was performed for validation and co-segregation analysis. Genetic analysis was also performed on additional family members of patients with TMEM151A mutations. Clinical manifestations of all PKD cases with mutations in TMEM151A reported, so far, were reviewed.ResultsTwo novel variants of the TMEM151A gene (NM_153266.4, NP_694998.1), c.627_643dup (p.A215Gfs*53) and c.627delG (p.L210Wfs*52), were identified in 2 patients with PKD by whole-exome sequencing and further Sanger sequencing. Both variants were inherited by the patients from their respective mothers. No mutation of the TMEM151A gene was found in the other type of movement disorders. In reviewing the clinical presentation of TMEM151A-related PKD, no statistically significant difference in the age of onset, family history, duration of attacks, laterality, and phenotype was found between genders. More male patients received treatment and had a good response. A higher proportion of female patients did not receive any treatment, possibly because they had a milder condition of the disease.ConclusionsThis study further validated the role of TMEM151A in PKD. Future studies on protein function will be needed to ascertain the pathogenesis of TMEM151A in PKD.
eIF6 as a Promising Diagnostic and Prognostic Biomarker for Poorer Survival of Cutaneous Melanoma
Authors: Zhang Fangyingnan , Waheed Saquib , Armato Ubaldo , Wu Jun , Zhang Chao , Li Zhibin 
Published: May 2022

BackgroundSkin cutaneous melanoma (SKCM) is the deadliest skin cancer and has the most rapidly increasing incidences among all cancer types. Previous research elucidated that melanoma can only be successfully treated with surgical abscission in the early stage. Therefore, reliable and specific biomarkers are crucial to melanoma diagnosis since it often looks like nevi in the clinical manifestations. Moreover, identifying key genes contributing to melanoma progression is also highly regarded as a potential strategy for melanoma therapy. In this respect, translation initiator eIF6 has been proved as a pro-tumor factor in several cancers. However, the role of eIF6 in the skin cutaneous melanoma progression and its potential as a prognostic marker is still unexplored.MethodsThe immunochemical analysis of clinical specimens were served to assess eIF6 expression levels. Gene Expression Profiling Interactive Analysis (GEPIA) database consultations allowed us to find the survival rates of the eIF6-overexpressed patients. eIF6 cellular effects were evaluated in an eIF6-overexpressed A375 cell line constructed with a lentivirus. The analysis of down-stream effectors or pathways was conducted using C-Bioportal and STRING databases.ResultsOur results revealed that eIF6 was highly over-expressed in melanomas compared to normal skin specimens, and thus the abnormally high level of eIF6 can be a diagnostic marker for melanoma. The in silica analysis indicated that patients with eIF6 over-expression had lower survival rates than that low-expression in SKCM. Meanwhile, similar results also could be found in the other four types of cancers. In vitro, over-expression of eIF6 increased the proliferation and migration of melanoma cells. Correspondingly, pan-cancer clustering analysis indicated the expression level of intermediate filament proteins was correlated with that of eIF6 expression. In our study, all over-expressed keratin proteins, in accordance with over-expressed eIF6, had a negative correlation with melanoma prognosis. Moreover, the decreased methylation level of keratin genes suggested a new potential regulation mode of eIF6.ConclusionsThe up-regulated eIF6 could be a potential diagnostic and prognostic biomarker of melanoma. This study also provides insights into the potential role of eIF6 in pan-cancer epigenetic regulation.
Combined Radiomic and Visual Assessment for Improved Detection of Lung Adenocarcinoma Invasiveness on Computed Tomography Scans: A Multi-Institutional Study
Authors: Vaidya Pranjal , Bera Kaustav , Linden Philip A. , Gupta Amit , Rajiah Prabhakar Shantha , Jones David R. , Bott Matthew , Pass Harvey , Gilkeson Robert , Jacono Frank , Hsieh Kevin Li-Chun , Lan Gong-Yau , Velcheti Vamsidhar , Madabhushi Anant 
Published: May 2022

ObjectiveThe timing and nature of surgical intervention for semisolid abnormalities are dependent upon distinguishing between adenocarcinoma-in-situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (INV). We sought to develop and evaluate a quantitative imaging method to determine invasiveness of small, ground-glass lesions on computed tomography (CT) chest scans.MethodsThe study comprised 268 patients from 4 institutions with resected (&lt;=3 cm) semisolid lesions with confirmed histopathological diagnosis of MIA/AIS or INV. A total of 248 radiomic texture features from within the tumor nodule (intratumoral) and adjacent to the nodule (peritumoral) were extracted from manually annotated lung nodules of chest CT scans. The datasets were randomly divided, with 40% of patients used for training and 60% used for testing the machine classifier (Training DTrain, N=106; Testing, DTest, N=162).ResultsThe top five radiomic stable features included four intratumoral (Laws and Haralick feature families) and one peritumoral feature within 3 to 6 mm of the nodule (CoLlAGe feature family), which successfully differentiated INV from MIA/AIS nodules with an AUC of 0.917 [0.867-0.967] on DTrain and 0.863 [0.79-0.931] on DTest. The radiomics model successfully differentiated INV from MIA cases (&lt;1 cm AUC: 0.76 [0.53-0.98], 1-2 cm AUC: 0.92 [0.85-0.98], 2-3 cm AUC: 0.95 [0.88-1]). The final integrated model combining the classifier with the radiologists’ score gave the best AUC on DTest (AUC=0.909, p&lt;0.001).ConclusionsAddition of advanced image analysis via radiomics to the routine visual assessment of CT scans help better differentiate adenocarcinoma subtypes and can aid in clinical decision making. Further prospective validation in this direction is warranted.
Initiation of Tocilizumab or Baricitinib Were Associated With Comparable Clinical Outcomes Among Patients Hospitalized With COVID-19 and Treated With Dexamethasone
Authors: Wong Carlos K. H. , Lau Kristy T. K. , Au Ivan C. H. , Xiong Xi , Chung Matthew S. H. , Leung Belle Y. C. , Lau Eric H. Y. , Cowling Benjamin J. 
Published: May 2022

Objectives: This retrospective cohort study aims to explore head-to-head clinical outcomes and complications associated with tocilizumab or baricitinib initiation among hospitalized COVID-19 patients receiving dexamethasone.Methods: Among 10,445 COVID-19 patients hospitalized between January 21st 2020 and January 31st 2021 in Hong Kong, patients who had received tocilizumab (n = 165) or baricitinib (n = 76) while on dexamethasone were included. Primary study outcome was time to clinical improvement (at least one score reduction on WHO clinical progression scale). Secondary outcomes were disease progression, viral dynamics, in-hospital death, hyperinflammatory syndrome, and COVID-19/treatment-related complications. Hazard ratios (HR) of event outcomes were estimated using Cox regression models.Results: The initiation of tocilizumab or baricitinib had no significant differences in time to clinical improvement (HR = 0.86, 95%CI 0.57-1.29, p = 0.459), hospital discharge (HR = 0.85, 95%CI 0.57-1.27, p = 0.418), recovery without the need for oxygen therapy (HR = 1.04, 95%CI 0.64-1.67, p = 0.883), low viral load (HR = 1.49, 95%CI 0.85-2.60, p = 0.162), and positive IgG antibody (HR = 0.97, 95%CI 0.61-1.54, p = 0.909). Time to viral clearance (HR = 1.94, 95%CI 1.01-3.73, p = 0.048) was shorter in the tocilizumab group with marginal significance, compared to that of baricitinib. Meanwhile, the two treatment modalities were not significantly different in their associated risks of in-hospital death (HR = 0.63, 95%CI 0.29-1.35, p = 0.233), severe liver injury (HR = 1.15, 95%CI 0.43-3.08, p = 0.778), acute renal failure (HR = 2.33, 95%CI 0.61-8.82, p = 0.213), hyperinflammatory syndrome (HR = 2.32, 95%CI 0.87-6.25, p = 0.091), thrombotic and bleeding events (HR = 1.39, 95%CI 0.32-6.00, p = 0.658), and secondary infection (HR = 2.97, 95%CI 0.62-14.31, p = 0.173).Conclusion: Among hospitalized patients with moderate-to-severe COVID-19 on background dexamethasone, the initiation of tocilizumab or baricitinib had generally comparable effects on time to clinical improvement, hospital discharge, recovery, low viral load, and positive IgG antibody; risks of in-hospital death, hepatic and renal complications, hyperinflammatory syndrome, thrombotic and bleeding events, and secondary infection. On the other hand, tocilizumab users might achieve viral clearance slightly faster than baricitinib users. Further studies and clinical trials are needed to confirm our findings regarding the evaluation of tocilizumab and baricitinib in COVID-19 patients with different disease severities, at varying stages or timing of drug initiation, and considering the concomitant use of other therapeutics.
Development and Validation of a Deep-Learning Model to Detect CRP Level from the Electrocardiogram
Authors: Jiang Junrong , Deng Hai , Liao Hongtao , Fang Xianhong , Zhan Xianzhang , Wu Shulin , Xue Yumei 
Published: May 2022

Background: C-reactive protein (CRP), as a non-specific inflammatory marker, is a predictor of the occurrence and prognosis of various arrhythmias. It is still unknown whether electrocardiographic features are altered in patients with inflammation.Objectives: To evaluate the performance of a deep learning model in detection of CRP levels from the ECG in patients with sinus rhythm.Methods: The study population came from an epidemiological survey of heart disease in Guangzhou. 12,315 ECGs of 11,480 patients with sinus rhythm were included. CRP &gt; 5mg/L was defined as high CRP level. A convolutional neural network was trained and validated to detect CRP levels from 12 leads ECGs. The performance of the model was evaluated by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, and balanced F Score (F1 score).Results: Overweight, smoking, hypertension and diabetes were more common in the High CRP group (p &lt; 0.05). Although the ECG features were within the normal ranges in both groups, the high CRP group had faster heart rate, longer QTc interval and narrower QRS width. After training and validating the deep learning model, the AUC of the validation set was 0.86 (95% CI: 0.85–0.88) with sensitivity, specificity of 89.7 and 69.6%, while the AUC of the testing set was 0.85 (95% CI: 0.84–0.87) with sensitivity, specificity of 90.7 and 67.6%.Conclusion: An AI-enabled ECG algorithm was developed to detect CRP levels in patients with sinus rhythm. This study proved the existence of inflammation-related changes in cardiac electrophysiological signals and provided a noninvasive approach to screen patients with inflammatory status by detecting CRP levels.
Seasonal Shifts in the Morphological Traits of Bloom-Forming Cyanobacteria in Lake Chaohu, China
Authors: Meng Yangyang , Zhang Min , Yang Zhen , Shi Xiaoli , Yu Yang , Shi Limei 
Published: May 2022

Harmful cyanobacterial blooms in eutrophic water bodies pose a major threat to the environment and to human health. The morphological functional traits of cyanobacteria play important roles in maintaining their competitive advantages. To explore the regulatory mechanisms of the morphological functional traits of different bloom-forming cyanobacteria, we performed a one-year-long phytoplankton survey from November 2016 to October 2017 in Lake Chaohu, China. The colony size and cell diameter of the dominant cyanobacteria were measured, and their relationships were analyzed. The results showed that Dolichospermum flos-aquae and Microcystis aeruginosa were the dominant cyanobacteria in the lake. Microcystis was the dominant species during the summer; the growth of Dolichospermum growth surpassed that of Microcystis, and Dolichospermum became the dominant species in the late autumn, winter and spring. From winter to spring, the colony size of Dolichospermum decreased from 222.25 μm to 10.51 μm, and the individual cell diameter increased from 6.5 μm to 7.4 μm. From summer to autumn, Dolichospermum showed enlarged colony sizes and reduced cell diameters. The Microcystis colony size increased from 83.71 μm in the spring to 196.71 μm in the summer and autumn, while cells diameter remained essentially at 3–4 μm from March to October in Lake Chaohu. The relationship between colony size and cell diameter in Dolichospermum was significantly positive, while that of Microcystis was not significant. These results suggest that Dolichospermum may maintain biomass through a trade-off between cell diameter and colony size, and that a flexible morphological regulatory mechanism exists. This study seeks to improve our understanding of how bloom-forming cyanobacteria maintain their dominance by regulating their morphological traits.
A Linear-Arc Composite Beam Piezoelectric Energy Harvester Modeling and Finite Element Analysis
Authors: Zhang Xuhui , Guo Yan , Zhu Fulin , Chen Xiaoyu , Tian Hao , Xu Hengtao 
Published: May 2022

To improve the output performance of the piezoelectric energy harvester, this paper proposed the design of a linear-arc composite beam piezoelectric energy harvester (PEH-C). First the nonlinear restoring force model of a composite beam was obtained by the numerical simulation method. Afterwards, the corresponding coupled governing equations were derived by using the generalized Hamilton principle, laying the foundation for subsequent in-depth research. After this, a finite element simulation was performed in the COMSOL software to simulate the output voltage, stress distribution, and resonance frequency of the PEH-C under different curvatures. In this way, the effect of curvature change on the PEH-C was analyzed. Finally, the PEH-C with a curvature of 40 m−1 was prepared, and an experimental platform was built to verify the correctness of the relevant analysis. The results showed that the resonant frequency of the PEH-C can be changed by changing the curvature, and that the stress on the composite beam will increase after the arc segment is introduced. When the curvature of the PEH-C was 40 m−1, the open-circuit output voltage was 44.3% higher than that of the straight beam.