bluuebunny/crossref_metadata_2025 huggingface dataset:
Resiliency Assessment of Power Systems Using Deep Reinforcement Learning
Authors: Ibrahim Mariam , Alsheikh Ahmad , Elhafiz Ruba
Published: April 2022

Evaluating the resiliency of power systems against abnormal operational conditions is crucial for adapting effective actions in planning and operation. This paper introduces the level-of-resilience (LoR) measure to assess power system resiliency in terms of the minimum number of faults needed to produce a system outage (blackout) under sequential topology attacks. Four deep reinforcement learning (DRL)-based agents: deep Q-network (DQN), double DQN, the REINFORCE (Monte-Carlo policy gradient), and REINFORCE with baseline are used to determine the LoR. In this paper, three case studies based on IEEE 6-bus test system are investigated. The results demonstrate that the double DQN network agent achieved the highest success rate, and it was the fastest among the other agents. Thus, it can be an efficient agent for resiliency evaluation.
Baicalin Attenuates Continuous Activation of β-Catenin Induced by Lipopolysaccharide (LPS) and Depression Complicated by Infertility in Male Rats
Authors: Fan Rong , Dai Feng , Zhang Chunhu , Zhou Lu , Qiu Xinjian , Li Yunhui
Published: April 2022

Background. Baicalin (BA) is a potential candidate drug to inhibit depressive behavior. However, the mechanism of BA's role on depression complicated with male infertility (DCMI) is still unclear. This study aimed to investigate the role of BA in alleviating inflammatory factor-induced DCMI by regulating β-catenin. Methods. Firstly, we performed sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swim test (FST) in the chronic unpredictable mild stress (CUMS) + lipopolysaccharide (LPS) model rats to study the effect of BA on depressive behavior. The levels of neuropeptide Y (NPY), testosterone (T), and IL-1β, IL-6, TNF-α, IL-10, and IL-4 in the peripheral blood plasma of normal people, patients with depression, and patients with DCMI were measured. Then, the levels of IL-1β, IL-6, TNF-α, IL-10, IL-4, β-catenin in rat testis and peripheral blood and ANXA2, APP, SEMG1, and SEMG2 in seminal plasma proteins were examined. Moreover, the level of β-catenin in the testicular tissue was detected. LPS was used to treat Sertoli cells, and the level of β-catenin was detected. Finally, we evaluated the reproductive phenotype and sperm motility of rats. Results. BA (especially 100 mg/kg) could notably ameliorate depression-like behavior induced by CUMS + LPS. The levels of IL-4, IL-10, T, and NPY in depression patients, DCMI patients, and CUMS + LPS model rats elevated, while the levels of IL-1β, IL-6, and TNF-α were reduced. However, BA alleviated the changes in these factors. Moreover, BA alleviated male rat depression induced by CUMS + LPS. LPS upregulated β-catenin (NP) but could not adjust β-catenin (TP) level in rat Sertoli cells. BA relieved the symptoms of DCMI by regulating β-catenin. Furthermore, BA ameliorated the reproductive ability of depressed rats. Conclusion. BA modulated β-catenin in the relief of inflammatory factor-induced DCMI.
Efficacy and Safety of Zuojin Pill for the Treatment of Chronic Nonatrophic Gastritis: A Randomized Active-Controlled Clinical Trial
Authors: Wang Ruilin , Wang Yanling , Lu Zheng , Jing Jing , Wang Zhongxia , He Tingting , Tian Miao , Yuan Zongyang , Cui Yanfei , Rong Wenya , Ma Xiao , Zhao Yanling
Published: April 2022

Objective. Zuojin pill (ZJP) is used as the classical prescription for a wide variety of digestive diseases. However, there is a lack of direct evidence for its use in the treatment of chronic nonatrophic gastritis (CNG). In particular, there is a lack of rigorous trials of randomized controlled designs. In this study, a randomized active-controlled clinical trial was performed to verify the efficacy and safety of ZJP in detail. Methods. Patients with CNG were divided into the ZJP group and the Marzulene-S granule group. Patients were enrolled from September 2019 to February 2021 (ChiCTR2000040549). Endoscopy and histology scores were evaluated as the primary outcome measure. The Helicobacter pylori positive rate and the disappearance rate of symptoms were also measured to reflect the outcomes. Finally, adverse events were also calculated as the index of safety. Results. A total of 68 eligible patients were enrolled in this trial and randomly divided into two groups with baseline comparability. ZJP was able to improve the red plaques as well as bile reflux scores compared with Marzulene-S granule (

P
=
0.043

and

P
=
0.019

, respectively). Moreover, it also remarkably alleviated the active chronic inflammation score

P
=
0.043

. However, there was no difference between the Helicobacter pylori positivity rate

P
=
0.752

. The symptom scores of abdominal distension

P
=
0.004

, belching

P
=
0.010

, and loss of appetite

P
=
0.019

were alleviated by ZJP, but nausea and vomiting were not

P
=
0.616

. ZJP can also be considered safe with no obvious adverse effects. Conclusion. ZJP might decrease mucosal injury and alleviate symptoms in CNG. In addition, more large-scale clinical trials should be carried out to further confirm its clinical efficacy and safety.
Determination of B and T Cell Epitopes in Neospora caninum Immune Mapped Protein‐1 (IMP‐1): Implications in Vaccine Design against Neosporosis
Authors: Nazari Naser , Kordi Bahareh , Maleki Bahman , Shams Morteza , Azizi Esfandiar , Majidiani Hamidreza , Naserifar Razi
Published: April 2022

Prevention of neosporosis is advantageous for cattle health and productivity. Previously, several vaccine candidates were nominated for vaccination against Neospora caninum. This study was premised on in silico evaluation of N. caninum IMP‐1 in order to determine its physicochemical features and immunogenic epitopes. We employed a wide array of network‐based tools for the prediction of antigenicity, allergenicity, solubility, posttranslational modification (PTM) sites, physicochemical properties, transmembrane domains and signal peptide, secondary and tertiary structures, and intrinsically disordered regions. Also, prediction and screening of potential continuous B cell peptides and those epitopes having stringent affinity to couple with mouse major histocompatibility complex (MHC) and cytotoxic T lymphocyte (CTL) receptors were accomplished. The protein had 393 residues with a molecular weight of 42.71 kDa, representing aliphatic index of 85.83 (thermotolerant) and GRAVY score of ‐0.447 (hydrophilic). There were 47 PTM sites without a signal peptide in the sequence. Secondary structure comprised mostly of extended strand and helices, followed by coils. The Ramachandran plot of the refined model showed 90.1%, 9.9%, 0.0%, and 0.0% residues in the favored, additional allowed, generously allowed, and disallowed regions, correspondingly. Additionally, various potential B cell (linear and conformational), CTL, and MHC binding epitopes were predicted for N. caninum IMP‐1. The findings of the present study could be further directed for next‐generation vaccine design against neosporosis.
Effects of Ruanmailing in Blocking Early Stages of Atherosclerosis by TNF-α Regulation via Kir2.1
Authors: Fan Liufang , Huang Xuanbin , Xue Wenjuan , Xie Weyan , Tong Ruxi , Chen Jinshui , Wu Tianmin
Published: April 2022

Objective. Ruanmailing oral solution consists of 16 herbs, has anti-lipid peroxidation activity, protects vascular endothelial cells, and improves vascular elasticity. It is an effective drug for the treatment of atherosclerosis (AS). The objective of this study was to investigate the mechanism underlying the antiatherosclerotic effects of Ruanmailing oral solution. Methods. Macrophages were isolated, cultured, and divided into the macrophage control; macrophage foam cell; and low-, medium-, and high-concentration Ruanmailing groups. Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay, and the expression levels of inward-rectifier potassium ion channel 2.1 (Kir2.1) and tumor necrosis factor (TNF)-α were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. Results. CCK-8 assay results showed that the tested concentrations of Ruanmailing solution did not affect macrophage proliferation. RT-PCR and Western blot assays indicated that TNF-α expression increased significantly with the formation of macrophage foam cells (P < 0.05). In addition, significant decreases in Kir2.1 and TNF-α expression were observed following treatment with various concentrations of Ruanmailing (P < 0.05). Conclusion. Based on the results, Ruanmailing affects macrophage foam cell formation by regulating Kir2.1 expression, which in turn reduces TNF-α expression and exerts antiatherosclerotic effects. These findings provide a scientific basis for the use of traditional Chinese medicine for AS treatment.
Physiological Response of the Freshwater Mussel Unio douglasiae in Microcystis aeruginosa Bloom Waters
Authors: Li Zhun , Kim Young-Hyo , Aldridge David C. , Kim Baik-Ho
Published: April 2022

In the present study, we evaluated the effects of different environments on the filtering rate (FR), mortality, and biodeposition (BD) of the freshwater mussel Unio douglasiae in bloom waters containing the toxic cyanobacterium Microcystis aeruginosa. The mean FR of 19 selected individuals (shell length, 5.0–9.8 cm) was 0.30 ± 0.03 L g−1 h−1 (range = 0.24–0.35 L g−1 h−1). Shell length was strongly correlated with both net and gross BD of mussels (P < 0.0001). The mean FR was higher in river water (0.405 ± 0.052 L g−1 h−1) than in lake water (0.304 ± 0.051 L g−1 h−1). In contrast, the BD of mussels was higher in RW (0.671 ± 0.609 mg g−1 h−1) than in LW (0.275 ± 0.027 mg g−1 h−1). For algal species, the FR of mussels ranged from 0.114 ± 0.024 to 0.553 ± 0.019 L g−1 h−1. The FR of U. douglasiae was higher in river water (mainly diatoms), whereas BD was higher in lake water (mainly Microcystis). U. douglasiae did not prefer toxic M. aeruginosa, which was significantly accumulated in pseudofaeces and faeces. The maximum FR of U. douglasiae in algal bloom water was recorded at a water temperature of 25°C and water depth of 50 cm. Moreover, the in situ mortality of U. douglasiae was strongly affected by water temperature and nitrogen concentration. Overall, U. douglasiae can enhance water quality in eutrophic areas by removing dominant cyanobacteria, although its removal efficiency depends on environmental parameters and site of introduction.
Coordinated Control Strategy of Short‐Turning Bus and Full‐Length Bus Based on Stable Headway
Authors: Liu Huasheng , Li Yu , Zhang Yanqiu , Li Jin , Wang Yi
Published: April 2022

Under the condition of dynamically collecting vehicle operation information, bus dynamic dispatching is an effective means to stabilize the vehicle operation according to the traffic plan and improve the stability of the system by giving real‐time response and continuous dynamic control to the vehicle running state. Speed control does not increase the extra parking time at the station, does not waste parking resources, does not significantly prolong the waiting time of passengers at the station, and is more easily accepted by passengers. In this paper, by using the speed control method, the problem of how to realize the coordinated control between the short‐turning bus and the full‐length bus is studied in order to stabilize that the headway between the full‐length buses is equal to the departure interval, and the headway between the short‐turning bus and the full‐length bus is equal to the expected headway. The problem of ensuring the coordinated and stable operation of the short‐turning bus and the full‐length bus is studied. The result of an example shows that the coordinated control strategy can make the whole system run more stable.
Image Aided Recognition of Wireless Capsule Endoscope Based on the Neural Network
Authors: Lu Bin
Published: April 2022

Wireless capsule endoscopy is an important method for diagnosing small bowel diseases, but it will collect thousands of endoscopy images that need to be diagnosed. The analysis of these images requires a huge workload and may cause manual reading errors. This article attempts to use neural networks instead of artificial endoscopic image analysis to assist doctors in diagnosing and treating endoscopic images. First, in image preprocessing, the image is converted from RGB color mode to lab color mode, texture features are extracted for network training, and finally, the accuracy of the algorithm is verified. After inputting the retained endoscopic image verification set into the neural network algorithm, the conclusion is that the accuracy of the neural network model constructed in this study is 97.69%, which can effectively distinguish normal, benign lesions, and malignant tumors. Experimental studies have proved that the neural network algorithm can effectively assist the endoscopist’s diagnosis and improve the diagnosis efficiency. This research hopes to provide a reference for the application of neural network algorithms in the field of endoscopic images.
Risk Evaluation of Urban Integrated Pipe Corridor Operation and Maintenance Based on Improved AHP‐CIM Model
Authors: Wang Shuai , Fu Shaochuan
Published: April 2022

In order to scientifically and objectively evaluate the risk in the operation and maintenance process of the urban integrated pipe corridor, and then prevent the occurrence of urban integrated pipe corridor operation and maintenance accidents, this paper combines AHP analysis and CIM model to propose a new model for the risk assessment of pipe corridors: AHP‐CIM model, and uses the model to conduct a verification of the operation and maintenance risk evaluation of the Beijing Tongzhou Canal Core Area North Ring Tunnel Integrated Pipe Corridor. Using a combination of qualitative and quantitative methods, the risk factors in the operation and maintenance process of the integrated urban pipe corridor were first identified and their weights determined, and then the CIM model was used to calculate the probability distribution of the levels of risk factors at each level of the hierarchical model, and finally the risk assessment set of the risk probability distribution of this integrated pipe corridor was obtained. The results show that the overall O&M risk level of this integrated pipe corridor is high, and its probability is 69.47%.
Adaptive Alleviation for Popularity Bias in Recommender Systems with Knowledge Graph
Authors: Wei Feng , Chen Shuyu , Jin Jie , Zhang Shuai , Zhou Hongwei , Wu Yingbo
Published: April 2022

Recommender systems are known to suffer from the popularity bias problem: popular items are recommended frequently, and nonpopular ones rarely, if at all. Prior studies focused on tackling this issue by increasing the number of recommended nonpopular (long-tail) items. However, these methods ignore the users’ personal popularity preferences and increase the exposure rate of the nonpopular items indiscriminately, which may hurt the user experience because different users have diverse interests in popularity. In this work, we propose a novel debias framework with knowledge graph (AWING), which adaptively alleviates popularity bias from the users’ perspective. Concretely, we explore fine-grained preferences (including popularity preference) behind a user-item interaction by using the heterogeneous graph transformer over the knowledge graph embedded with popularity nodes and endow the preferences with explicit semantics. Based on this idea, we can manipulate how much popularity preference affects recommendation results and improves the exposure rate of nonpopular items while considering the popularity preferences of different users. Experiments on public datasets show that the proposed method AWING can effectively alleviate popularity bias and ensure the user experience at the same time. The case study further demonstrates the feasibility of AWING on the explainable recommendation task.
Process Optimization for Acid Hydrolysis and Characterization of Bioethanol from Leftover Injera Waste by Using Response Surface Methodology: Central Composite Design
Authors: Bekele Bayu Abreham , Abeto Amibo Temesgen , Beyan Surafel Mustefa
Published: April 2022

In this study, leftover injera waste from the southwestern parts of Ethiopia was used as a raw material for bioethanol production. The conversion of this biomass into ethanol involved processing techniques, which include hydrolysis, fermentation, and distillation. This research focuses on determining optimal parameters that are temperature, acid concentration, and hydrolyzing time in a hydrolysis stage. Using response surface analysis, the suggested model is quadratic and has three independent factors, which had significant effects on the yield of ethanol. In this analysis, the temperature and hydrolyzing time had a positive relationship with the yield of ethanol whereas acid concentration had a negative relation. The optimum yield of ethanol obtained was 79.07%. The yield optimized in g/g was 29.99, which was obtained at a temperature of 109.99°C, at an acid concentration of 1.00%, and hydrolyzing time of 49.59 minutes. For this analysis, the mathematical model equation was developed and the R2 value was 99.9% and its desirability was 0.8867. The property of ethanol was characterized by the many parameters used in different standardization. The density, viscosity, flammability, boiling points, and pH were determined as 0.803 gcm−3, 1.1 cP, 14°C, 80°C, and 6.65, respectively.
Prediction of the Mechanism of Shaoyao Gancao Decoction in the Treatment of Alopecia Areata by Network Pharmacology and Its Preliminary Verification Study
Authors: Lv Shuying , Wang Lei , Duan Yuhang , Huang Dan , Yang Dingquan
Published: April 2022

Objective. To explore the mechanism of Shaoyao Gancao decoction (SGD) in treatment of alopecia areata (AA) by network pharmacology and animal experiments. Methods Based on the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), the components and targets of SGD were determined. Then, the related targets of AA were retrieved from DrugBank, GeneCards, OMIM, and DisGeNET databases. The intersection of drug targets and disease targets was determined, and the key targets of the protein-protein interaction network were obtained with the String database. Gene Ontology (GO) biological process enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of potential key targets were carried out using the DAVID database using AutoDock for molecular docking verification. Finally, the key pathway was validated by animal experiments. Results. A total of 102 active components, 212 predicted targets, and 812 AA disease-related targets were obtained. Topological analysis yielded 45 key targets of SGD in the treatment of AA, including IL-6, PTGS2, TNF, VEGFA, CCL2, IL-1B, CXCL8, CASP3, MPO, and IL-10. There were 324 GO entries obtained through GO biological process enrichment analysis, and 20 pathways were obtained through KEGG pathway enrichment analysis, involving the PI3K-Akt signaling pathway, osteoclast differentiation, and Jak-STAT signaling pathway. The molecular docking results showed effective ingredients (quercetin, kaempferol, and 7-methoxy-2-methyl isoflavone) have good docking results with targets (IL-6, PTGS2, and TNF). The results of animal experiments showed that SGD can effectively upregulate the expression of PI3K and AKT proteins. Conclusion. This is the first in-depth study on the mechanism of SGD’s treatment effect in AA using network pharmacology, and preliminary animal experiments verified that it is closely related to the PI3K/AKT signaling pathway. This finding may provide a new basis for SGD’s clinical application in AA.
Upregulation of Synuclein‐γ and Snai1 Contributes to Poor Clinical Prognosis in Oral Squamous Cell Carcinoma Patients
Authors: Yang Jie , Pan Yangyang , Peng Lu , Zhang Licui , Zhao Juan , Zheng Zhihong , Zheng Jun , Xu Xiaoli , Zeng Yan
Published: April 2022

Synuclein‐γ (SNCG) and Snai1 play an important role in the occurrence and development of different types of malignant tumors. However, the association between SNCG and Snai1 and the effect of their combination on oral squamous cell carcinoma (OSCC) are unknown. The purpose of this study was to assess the expression of SNCG and Snai1 in OSCC tissues and their role in the genesis, development, diagnosis, and prognosis of OSCC. In this study, we first analyzed the Gene Expression Omnibus (GEO) database to determine the expression of SNCG and Snai1 in OSCC. And we also evaluated the correlation between the expression of SNCG and Snai1 and clinical pathological parameters in OSCC from The Cancer Genome Atlas (TCGA) database. Then, the expression of SNCG and Snai1 in OSCC and its adjacent tissues in our experimental cohort were detected by qRT‐PCR, Western blot, and immunohistochemistry, and the relationship between their expression and clinical pathological parameters were analyzed. At the same time, the correlation between the expression of SNCG and Snai1 was analyzed from the TCGA, GEO database, and our experimental cohort. Next, the ROC curves were constructed to explore the diagnostic value of SNCG and Snai1 in OSCC. Finally, the survival curves were drawn, and the univariate and multivariate Cox regression analyses were performed to determine the prognostic value of SNCG and Snai1 in OSCC. The study found that SNCG and Snai1 were highly expressed in OSCC tissues. The expression of SNCG was related to the differentiation of OSCC, while that of Snai1 was related to the T stage, lymph node metastasis, clinical stage, and differentiation. Besides, the expression of SNCG in OSCC was positively correlated with that of Snai1. In addition, we also found that SNCG and Snai1 could well distinguish OSCC patients from normal people; especially, the combined diagnosis of SNCG and Snai1 had a better effect, with a specificity up to 96.67%. Moreover, SNCG‐negative/Snai1‐negative OSCC patients had the best prognosis. Multivariate analysis displayed that SNCG‐positive expression was an independent risk factor for prognosis in OSCC patients. The results of this study strongly suggested that SNCG and Snai1 might have a cooperative effect in the occurrence and development of OSCC. They may become new markers for the diagnosis and prognosis of OSCC.
Public Opinion Guidance and Communication Mechanism Innovation of Public Health Events Based on the Multitask Learning Network in the Internet Era
Authors: Lian Shaoying , Li Zhi
Published: April 2022

In order to improve the public opinion guidance ability for public health events in the Internet era, and improve the the problems of the traditional public opinion guidance mechanism, we analyze the public opinion guidance and communication mechanism based on the Internet era, and analyze the guidance software and software system, and related technical requirements? subsequently, the efficiency analysis of the public opinion guidance and communication mechanism of the multitask learning network was conducted; the results show that the public opinion guidance and communication mechanism of public health events based on the multitask learning network can effectively improve the diagnostic and early warning ability and diagnostic accuracy of the public opinion fermentation in public health emergencies, reduce the difficulty of guiding the public opinion fermentation of public health emergencies, and effectively improve the success rate of guidance for such events. In the Internet era, the public opinion guidance and communication mechanism based on the multitask learning network has improved the public opinion guidance ability for public health events, and it provides a research direction for the development of the network public opinion guidance system for unconventional public health emergencies in the future.
Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome
Authors: Chen Peixian , Tang Yan , He Weixin , Yang Ruixuan , Lan Zhien , Chen Ruirong , Zhang Peidong
Published: April 2022

In recent decades, many serious respiratory infections have broken out all over the world, including SARS-CoV, MERS, and COVID-19. They are characterized by strong infectivity, rapid disease progression, high mortality, and poor prognosis. Excessive immune system activation results in cytokine hypersecretion, which is an important reason for the aggravation of symptoms, and can spread throughout the body leading to systemic multiple organ dysfunction, namely, cytokine release syndrome (CRS). Although many diseases related to CRS have been identified, the mechanism of CRS is rarely mentioned clearly. This review is intended to clarify the pathogenetic mechanism of CRS in the deterioration of related diseases, describe the important signaling pathways and clinical pathophysiological characteristics of CRS, and provide ideas for further research and development of specific drugs for corresponding targets to treat CRS.
Renal Replacement Therapy for Patients Requiring Extracorporeal Membrane Oxygenation: A Multicenter International Survey
Authors: Thy Michael , Augustin Pascal , Tran-Dinh Alexy , Montravers Philippe , de Tymowski Christian
Published: April 2022

Introduction: Patients receiving extracorporeal membrane oxygenation (ECMO) often require renal replacement therapy (RRT). The challenge of inserting a dialysis catheter (DC) could be solved by direct connection of RRT lines on an ECMO circuit (DCRE) without published guidelines. This study aimed to describe the practice of RRT in patients on ECMO, including the DCRE as well as the perception and concerns related to this technique. Methods: An international survey was worldwide sent via email to professionals involved in the management of ECMO. Respondents always or often performing RRT via the ECMO circuit were classified in the ECMO group, and those using a DC were classified in the DC group. Results: From March 2019 to October 2019, 298 participants answered the questionnaire from 46 different countries. Only 28% were working in pediatric departments. Among the 165 participants commonly performing RRT in patients on ECMO, 100 (61%) performed mainly RRT via the ECMO circuit, and 65 (39%) performed RRT via DC. Pediatric practice and a longer experience were the only noticeable characteristics of the ECMO group. The most reported concern regarding DCRE was the risk of air embolism (n = 84, 28%), but the most encountered problem was unmanageable pressure alarms in RRT devices. Conclusion: The present study showed significant heterogeneity in RRT practices in patients on ECMO. The lower experience of the DC group, the high rates of concerns toward DCRE, and pressure alarm issues suggested that protocols and training may overcome reluctance and technical difficulties.
Dermoscopic Features of Actinic Cheilitis and Other Common Inflammatory Cheilitis: A Multicentric Retrospective Observational Study by the International Dermoscopy Society
Authors: Jha Abhijeet Kumar , Sławińska Martyna , Vinay Keshavamurthy , Akay Bengu Nisa , Kamińska-Winciorek Grażyna , Sobjanek Michał , Zeeshan Md , Singh Anupama , Ankad Balachandra S. , Bhat Yasmeen Jabeen , Lallas Aimilios , Apalla Zoe , Zalaudek Iris , Errichetti Enzo
Published: April 2022

Background: Clinical differentiation between different cheilitis variants may be difficult. Application of mucoscopy, in addition to clinical background, could provide additional diagnostic clues facilitating initial patient management. Objectives: To determine mucoscopic clues differentiating actinic cheilitis from the main forms of inflammatory cheilitis, including eczematous cheilitis, discoid lupus erythematosus, and lichen planus of the lips. Methods: This was a retrospective, multicenter study being a part of an ongoing project “Mucoscopy – an upcoming tool for oral mucosal disorders” under the aegis of the International Dermoscopy Society. Cases included in the current study were collected via an online call published on the IDS website (www.dermoscopy-ids.org) between January 2019 and December 2020. Results: Whitish-red background was found in actinic cheilitis as well as in cheilitis due to discoid lupus erythematous and lichen planus. Polymorphous vessels were more likely to be seen in actinic cheilitis compared to other causes of cheilitis. White scales, ulceration, and blood spots predominated in actinic cheilitis and lichen planus, whereas yellowish scales typified eczematous and discoid lupus erythematous cheilitis. Radiating white lines although most common in lichen planus patients were also seen in actinic cheilitis. Conclusion: Despite differences in the frequency of mucoscopic structures, we have not found pathognomonic features allowing for differentiation between analyzed variants of cheilitis.
Protocadherin B9 Is Associated with Human Esophageal Squamous Cell Carcinoma Progression
Authors: Fujiki Yuto , Ishikawa Akira , Akabane Shintaro , Mukai Shoichiro , Maruyama Ryota , Yamamoto Yuji , Kido Aya , Katsuya Narutaka , Taniyama Daiki , Sentani Kazuhiro , Oue Naohide , Yasui Wataru
Published: April 2022

Introduction: Esophageal cancer is the sixth leading cause of cancer-related death worldwide. However, molecular targeted therapy and novel therapeutic targets are needed for esophageal squamous cell cancer (ESCC). In a previous study, we reported that protocadherin (PCDH) B9 plays an important role in several cancers. Therefore, in this study, we examined the clinical significance of PCDHB9 expression in ESCC. Methods: PCDHB9 expression was examined using immunohistochemistry in 128 cases and using quantitative reverse transcription-polymerase chain reaction in 16 cases of ESCC. PCDHB9 function in ESCC cells was examined using RNA interference. Results: High PCDHB9 expression was identified in 5 of 16 (31.3%). In total, 51 (40%) ESCC cases showed strong PCDHB9 expression, whereas nonneoplastic mucosa rarely showed its expression. High PCDHB9 expression was significantly associated with T classification, N grade, and stage in ESCC. In ESCC cell lines, PCDHB9 knockdown affected cell growth, migration, and adhesion. Further, the expression of integrin (ITG) A3, ITGA4, ITGA5, ITGB1, ITGB6, vimentin, snail family transcriptional repressor 1, and cadherin 2 (NCAD) was significantly reduced and cadherin 1 was significantly increased in PCDHB9 knockdown ESCC cells. Conclusion: These results suggest that PCDHB9 plays a tumor-promoting role and is a potential biomarker and therapeutic target in ESCC.
Gender Differences in Mental Health, Quality of Life, and Caregiver Burden among Informal Caregivers during the Second Wave of the COVID-19 Pandemic in Germany: A Representative, Population-Based Study
Authors: Zwar Larissa , König Hans-Helmut , Hajek André
Published: April 2022

Introduction: This study aimed to compare the mental health, quality of life, and caregiving burden between male and female informal caregivers of older adults (≥60 years) during the second wave of the COVID-19 pandemic in Germany. Methods: The sample consisted of 301 female and 188 male informal caregivers of older adults in need of care (≥60 years). Data were used from a cross-sectional study in March 2021 that questioned a representative sample of adults aged 40 years and older from Germany. Information on informal care provision, mental health (depressive and anxiety symptoms), caregiving burden, and quality of life was assessed for the period between December 2020 and March 2021. Regression analyses, adjusted for (1) the sociodemographic background and health of the caregivers, (2) the caregiving time and caregiving tasks, and (3) the perception of impairment and danger posed by the pandemic, were conducted. Results: Findings of the fully adjusted model indicated a higher level of anxiety and lower quality of life among female caregivers, compared to male caregivers. Gender differences in depression and caregiver burden were not significant in analyses that controlled for care tasks and time. Moderator analyses indicated that gender differences in caregiver’s anxiety levels were influenced by the danger perceived to be posed by the pandemic: among men the danger to the care recipient, and among women the danger to themselves, increased anxiety. Conclusion: Female informal caregivers were more negatively affected than male informal caregivers during the pandemic, as indicated by higher levels of anxiety and lower quality of life. Gender differences in anxiety depended on the perceived danger posed by the pandemic. Thus, policy and pandemic measures should focus on gender-specific support of female caregivers who seem to be particularly vulnerable during the pandemic. More caregiver-specific support and information around protecting themselves and their care recipients are recommended. Also, further research on gender differences in care performance and their relation to psychosocial health outcomes is recommended.
A Chilean Experience of Telestroke in a COVID-19 Pandemic Year
Authors: Delfino Carlos , Mazzon Enrico , Cavada Gabriel , Muñoz Venturelli Paula , Brunser Alejandro M. , Jurado Díaz Felipe , Cisternas Lorena Lara , Rocha Jiménez Diego , Arévalo Valdivia Mirya , Rojas Torres Diego , Mansilla Eloy
Published: April 2022

Background and Purpose: Telemedicine for stroke patients’ care (telestroke [TS]) has grown notably in recent decades and may offer advantages during health crisis. Hospital admissions related to stroke have decreased globally during the COVID-19 pandemic, but scarce information is available regarding the effect of COVID-19 in TS. Using a population-based TS registry, we investigated the impact of the first year of the COVID-19 pandemic throughout our TS network in Santiago, Chile. Methods: Stroke codes evaluated after the onset of COVID-19 restrictions in Chile (defined as March 15, 2020) were compared with those evaluated in 2019. We analyzed differences between number of stroke codes, thrombolysis rate, stroke severity, and time from the stroke onset to hospital admission. Results: We observed that the number of stroke codes and the number of patients undergoing reperfusion therapy did not change significantly (p = 0.669 and 0.415, respectively). No differences were found with respect to the median time from the stroke onset to admission (p = 0.581) or in National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.055). The decision-making-to-needle time was significantly shorter in the COVID-19 period (median 5 min [IQR 3–8], p < 0.016), but no significant changes were found at the other times. Conclusions: This study demonstrates the potential of adapting TS to extreme situations such as the COVID-19 pandemic, as well as the importance of establishing networks that facilitate patient access to quality treatments.
Antibody and Cellular-Based Therapies for Pediatric Acute Lymphoblastic Leukemia: Mechanisms and Prospects
Authors: Li Wei , Zhang Yayu , Kankala Ranjith Kumar , Zou Liang , Chen Zhoujiang
Published: April 2022

Background: Acute lymphoblastic leukemia (ALL) is one of the most commonly diagnosed cancers in children. Despite enormous efforts to treat ALL over the past decade, the intensity of conventional chemotherapeutic strategies has reached the tolerance limit. Among various recently developed therapeutic approaches, antibody and cellular-based therapies showed less toxicity and better curative effect. Summary: Due to advanced mechanistic actions, these innovative therapies have provided durable responses and long-term survival in eradicating pediatric ALL, especially patients with refractory/relapsed ALL. Owing to these aspects, herein, we emphasize the mechanisms of action and application status of antibodies targeting tumor antigens, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells. Key Messages: The significant prospects and challenges are discussed, highlighting the innovative immunotherapies to deal with ALL. Together, this review will summarize the progress of antibody and cellular-based therapies for pediatric ALL, which may promote further research on antibody-based biopharmaceutics.
Dose Modification of Etoposide plus Platinum in Elderly Patients with Extensive-Disease Small-Cell Lung Cancer
Authors: Kim Hyera , Choi Ehyun , Heo Mi Hwa , Kim Jin Young , Park Keon Uk
Published: April 2022

Background: Elderly patients with extensive-disease small-cell lung cancer (ED-SCLC) have a high risk of chemotherapy toxicity due to multiple comorbidities and poor performance status. Although dose modification is often used to avoid toxicity in elderly patients with ED-SCLC, there is little data on the effect of initial dose-reduced chemotherapy on survival outcomes. Methods and Patients: We retrospectively reviewed 100 elderly patients (≥70 years) with ED-SCLC who received first-line etoposide plus platinum chemotherapy between January 2006 and December 2020. Results: The median age was 74 years. Eighty-nine patients (89%) had a history of smoking, and 38 (38%) had chronic lung disease. Thirty-four patients (34%) received dose-reduced etoposide plus platinum in the first cycle. The dose-reduced group had significantly higher age, lower body mass index, and poor Eastern Cooperative Oncology Group Performance Score. There were no significant differences in survival outcomes between the dose-reduced and full-dose chemotherapy (median overall survival [OS], 4.9 vs. 6.5 months, p = 0.440; median progression-free survival [PFS], 3.7 vs. 4.6 months, p = 0.272). In multivariate analyses, DR in the first cycle (hazard ratio 0.519, 95% CI: 0.269–1.000, p = 0.050) was significantly associated with OS. Following a subgroup analysis of 59 patients who received minimum four cycles, no significant differences in survival outcomes between the two groups (median OS, 10.9 vs. 9.4 months, p = 0.817; median PFS, 6.3 vs. 6.5 months, p = 0.902) were noted. Conclusions: The dose-reduced chemotherapy with first-line etoposide plus platinum had non-inferior survival outcomes compared to the full-dose chemotherapy in elderly patients with ED-SCLC.
Ser joven andino quechua cerca y lejos de sus comunidades de origen
Authors: Mendoza-Zapata Rossana
Published: April 2022

(analítico)La investigación se pregunta cómo las y los «jóvenes» procedentes de comunidades quechuas surandinas del Perú construyen su «ser joven» en contextos de imposición neocolonial/neoliberal y, a la vez, de resistencias cerca y lejos de sus lugares de origen. Se realizó desde la postura decolonial con la metodología investigación-acción participativa adaptada al mundo de jóvenes de comunidades de Apurímac, Huancavelica y Ayacucho. Se constata que son afectados por imposiciones de la sociedad nacional, que a través de servicios y políticas públicas les proyectan una manera homogénea y hegemónica de ser joven que tiende a distanciarlos de sus familias y comunidades. La crianza en su cosmovisión será fuente de sus resistencias y les permitirá recuperar sus raíces por la vía de la lengua originaria y de la espiritualidad andina.
Palabras clave: Población indígena; joven; quechua; colonialismo; modernización; investigación participativa.
Major Vault Protein Prevents Atherosclerotic Plaque Destabilization by Suppressing Macrophage ASK1-JNK Signaling
Authors: Liu Qingling , Pan Junlu , Bao Linrui , Xu Chunxiang , Qi Yu , Jiang Bin , Wang Dongdong , Zhu Xudong , Li Xiaoyu , Zhang Hanwen , Bai Hui , Yang Qing , Ma Junqing , Wiemer Erik A.C. , Ben Jingjing , Chen Qi
Published: April 2022

Background:

Macrophages are implicated in atherosclerotic plaque instability by inflammation and degradation of extracellular matrix. However, the regulatory mechanisms driving these macrophage-associated processes are not well understood. Here, we aimed to identify the plaque destabilization-associated cytokines and signaling pathways in macrophages.

Methods:

The atherosclerotic models of myeloid-specific MVP (major vault protein) knockout mice and control mice were generated. Atherosclerotic instability, macrophage inflammatory signaling, and active cytokines released by macrophages were examined in vivo and in vitro by using cellular and molecular biological approaches.

Results:

MVP deficiency in myeloid cells exacerbated murine plaque instability by increasing production of both MMP (matrix metallopeptidase)-9 and proinflammatory cytokines in artery wall. Mechanistically, expression of MMP-9 was mediated via ASK1 (apoptosis signal-regulating kinase 1)-MKK-4 (mitogen-activated protein kinase kinase 4)-JNK (c-Jun N-terminal kinase) signaling in macrophages. MVP and its α-helical domain could bind with ASK1 and inhibit its dimerization and phosphorylation. A 62 amino acid peptide (MVP-[686–747]) in the α-helical domain of MVP showed a crucial role in preventing macrophage MMP-9 production and plaque instability.

Conclusions:

MVP may act as an inhibitor for ASK1-JNK signaling-mediated MMP-9 production in macrophages and, thereby, attenuate unstable plaque formation. Our findings suggest that suppression of macrophage ASK1-JNK signaling may be a useful strategy antagonizing atherosclerotic diseases.
2021 Jeffrey M. Hoeg Award Lecture: Defining the Role of Efferocytosis in Cardiovascular Disease: A Focus on the CD47 (Cluster of Differentiation 47) Axis
Authors: Jarr Kai-Uwe , Kojima Yoko , Weissman Irving L. , Leeper Nicholas J.
Published: April 2022

A key feature of atherogenesis is the accumulation of diseased and dying cells within the lesional necrotic core. While the burden of intraplaque apoptotic cells may be driven in part by an increase in programmed cell death, mounting evidence suggests that their presence may primarily be dictated by a defect in programmed cell removal, or efferocytosis. In this brief review, we will summarize the evidence suggesting that inflammation-dependent changes within the plaque render target cells inedible and reduce the appetite of lesional phagocytes. We will present the genetic causation studies, which indicate these phenomena promote lesion expansion and plaque vulnerability, and the interventional data which suggest that these processes can be reversed. Particular emphasis is provided related to the antiphagocytic CD47 (cluster of differentiation 47) do not eat me axis, which has emerged as a novel antiatherosclerotic translational target that is predicted to provide benefit independent of traditional cardiovascular risk factors.
Pharmacological Targeting of the CCL2/CCR2 Axis for Atheroprotection: A Meta-Analysis of Preclinical Studies
Authors: Živković Luka , Asare Yaw , Bernhagen Jürgen , Dichgans Martin , Georgakis Marios K.
Published: April 2022

Background:

The CCL2 (CC-chemokine ligand 2)/CCR2 (CC-chemokine receptor 2) axis governs monocyte recruitment to atherosclerotic lesions. Genetic and epidemiological studies show strong associations of CCL2 levels with atherosclerotic disease. Still, experimental studies testing pharmacological inhibition of CCL2 or CCR2 in atheroprone mice apply widely different approaches and report variable results, thus halting clinical translation.

Methods:

We systematically searched the literature for studies employing pharmacological CCL2/CCR2 blockade in atheroprone mice and meta-analyzed their effects on lesion size and morphology.

Results:

In a meta-analysis of 14 studies testing 11 different agents, CCL2/CCR2 blockade attenuated atherosclerotic lesion size in the aortic root or arch (
g
=−0.75 [−1.17 to −0.32],
P
=6×10
−
4
; N=171/171 mice in experimental/control group), the carotid (
g
=−2.39 [−4.23 to −0.55],
P
=0.01; N=24/25), and the femoral artery (
g
=−2.38 [−3.50 to −1.26],
P
=3×10
−
5
; N=10/10). Furthermore, CCL2/CCR2 inhibition reduced intralesional macrophage accumulation and increased smooth muscle cell content and collagen deposition. The effects of CCL2/CCR2 inhibition on lesion size correlated with reductions in plaque macrophage accumulation, in accord with a prominent role of CCL2/CCR2 signaling in monocyte recruitment. Subgroup analyses showed comparable efficacy of different CCL2- and CCR2-inhibitors in reducing lesion size and intralesional macrophages. The quality assessment revealed high risk of detection bias due to lack of blinding during outcome assessment, as well as evidence of attrition and reporting bias.

Conclusions:

Preclinical evidence suggests that pharmacological targeting of CCL2 or CCR2 might lower atherosclerotic lesion burden, but the majority of existing studies suffer major quality issues that highlight the need for additional high-quality research.
Abstract 003: Contextual- And Personal-level Social Determinants Of Health And Real-world Adoption Of Novel Treatments For Improving Cardiovascular Outcomes In Type 2 Diabetes
Authors: Guo Jingchuan , Hu Hui , Zheng Yi , Guo Yi , Chen Aokun , Magnani Jared W , Hernandez Inmaculada , O'Neal LaToya , Shenkman Elizabeth , Bian Jiang
Published: April 2022

Background:
The two novel antidiabetic drugs (
ADD
), sodium-glucose cotransporter-2 inhibitors (
SGLT2i
) and glucagon-like peptide-1 receptor agonists (
GLP1a
), have shown distinctive cardiovascular benefits. However, prior studies have found racial disparities in the initiation of SGLT2i/GLP1a, suggesting that, despite their potential, the real-world utilization of these therapies may exacerbate health inequities. Our study was aimed to understand how contextual and personal-level social determinants of health (
SDoH
) interact and drive inequities in access to these novel agents.

Methods:
Using electronic health records (
EHR
) from the University of Florida Health system, we assembled a cohort of type 2 diabetes (
T2D
) who initiated a second line ADD in 2015-2020. The T2D cohort was spatiotemporally linked to a set of 79 contextual SDoH documenting social and built environment at census tract level. Normalization transformation was conducted for these variables, as needed. We applied an exposome-wide association study (
ExWAS
) approach to identify key contextual SDoH associated with SGTL2i/GLP1a initiation vs. other second line ADD. We identified patients’ marital status, as proxy of social support, among other personal-level SDoH from clinical notes via a natural language processing pipeline. We applied logistic regression and adjusted for clinical factors to determine the effect of contextual SDoH on SGLT2i/GLP1a initiation across racial groups and by personal-level SDoH.

Results:
Of 2,563 study patients, 57% were females, 42% were Blacks, and the mean age was 59 (13) years. We identified three contextual SDoH factors that were statistically significantly associated with lower likelihood of SGLT2i/GLP1a initiation: neighborhoods with limited food access, with more long-term vacant houses, and with less group quarters (e.g., living in nursing facilities and group homes). In the subgroup analysis by race, neighborhoods with limited food access (
p
=.025) and having less group quarter (
p
=.028) are barriers to initiate newer ADD only in White patients, while living in neighborhoods having more vacant houses was a risk factor of the newer drug initiation only in Black patients (
p
<.001). When subgrouped by marital status, living in a place with less group quarters was a risk factor of non-initiation of SGLT2i/GLP1a only in those being unmarried (
p
=.027), while living in a place having more vacant addresses was a risk factor of non-initiation only in those being married (
p
<.001).

Conclusion:
We identified novel contextual SDoH associated with lower initiation of novel cardioprotective drugs in patients with T2D. The effect of contextual SDOH in such treatment initiation varies across racial groups and by marital status.