bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Plant based meat analogue
Authors: Mishal Siddhesh , Kanchan Shraddhar , Bhushette Pravin , Sonawane Sachin Kalidas
Published: March 2022

Plant-based meat analogue is a mimicked product that looks like animal meat along with nutritional qualities, beneficial health effects, and sensory characteristics. The main objective of this study was to formulate a meat analogue with similar nutritional and sensory characteristics as that of animal meat, which can potentially help with the shortcoming of meat to fulfil the demand. The process of one factor optimization optimized each selected ingredient of the meat analogue. Final base ingredients for meat analogue were selected, and the developed product was evaluated sensory using a nine-point hedonic scale. Desired treatment was selected based on the maximum index score obtained from nine points hedonic scale for ingredient optimization of jackfruit (26%), soy protein (26%), meat flavor (3%), and wheat gluten (4.3%). Physicochemical analysis of optimized plant-based-meat analogue was also conducted. The moisture content of the meat analogue was about 48.73%, the fat content - 2.46%, pH of raw product - 6%, cooking yield of product - 90.25%, diameter reduction of analogue - 3.86% and thickness reduction - 11.83%.
ANALISIS PERBANDINGAN ABNORMAL RETURN DAN TRADING VOLUME ACTIVITY SEBELUM DAN SESUDAH DIUMUMKANNYA KASUS PERTAMA COVID-19
Authors: Sahputra Arif , . Lindrianasari , Dharma Fitra , Amelia Yunia
Published: March 2022

ABSTRACT: The purpose of this study was to examine the information content of the announcement of the first Covid-19 case in Indonesia by looking at the differences in Abnormal Return and Trading Volume Activity both before and after the event. The method used in this research is an event study. The research period used was 6 stock exchange days, namely 3 days before and 3 days after the announcement of the first Covid-19 case in Indonesia. The statistical test used to test the hypothesis is the One Sample t-test and the Wilcoxon Signed Rank Test. The results of the One Sample t-test show that there are significant negative abnormal returns at t + 1 and t + 2 after the announcement event, which indicates that the Covid-19 pandemic has a negative impact on company operations. Meanwhile, the results of the Wilcoxon Signed Rank test show that there is a significant difference between the Abnormal Return before and after the announcement of the first Covid-19 case in Indonesia. However, the results of the Wilcoxon Signed Rank Test on Trading Volume Activity (TVA) show that there is no significant difference between before and after the announcement of the first Covid-19 case in Indonesia.

Keywords: Abnormal Return, Trading Volume Activity, Event Study, Covid-19

ABSTRAK: Tujuan dari penelitian ini adalah untuk menguji kandungan informasi dalam pengumuman kasus Covid-19 pertama di Indonesia, menganalisis perbedaan antara abnormal return dan volume perdagangan baik sebelum maupun sesudah peristiwa. Metode yang digunakan dalam penelitian ini adalah studi peristiwa. Periode penelitian yang digunakan adalah 6 hari bursa, masing-masing 3 hari sebelum dan 3 hari setelah pengumuman kasus Covid-19 pertama di Indonesia. Uji statistik yang digunakan untuk menguji hipotesis adalah uji One Sample dan uji Wilcoxon Signed Rank. Hasil uji One Sample menunjukkan bahwa terdapat abnormal return negatif yang signifikan pada t+1 dan t+2 setelah peristiwa pengumuman, yang mengindikasikan bahwa pandemi Covid-19 berdampak negatif terhadap operasional perusahaan. Sementara itu, hasil uji Wilcoxon Signed Rank menunjukkan terdapat perbedaan yang signifikan antara abnormal return sebelum dan sesudah pengumuman kasus Covid-19 pertama di Indonesia. Namun, hasil Wilcoxon Signed Rank Test pada Trading Volume Activity (TVA) menunjukkan tidak ada perbedaan yang signifikan antara sebelum dan sesudah pengumuman kasus Covid-19 pertama di Indonesia.

 Kata Kunci: Abnormal Return, Trading Volume Activity, Studi Peristiwa, Covid-19
PERUBAHAN HARGA SAHAM DILIHAT DARI FAKTOR FUNDAMENTAL PERUSAHAAN MAKANAN DAN MINUMAN
Authors: Veny Veny , Gunawan Yosepha
Published: March 2022

ABSTRACT: Fundamental analysis can be used by investors to estimate company performance, as well as to predict stock price movements. Investors can use fundamental analysis as a way to find out what is happening inside corporate to reduce investment risk. The purpose of this paper is to see how financial ratios such as DAR, DER, EPS, and PER as part of the solvency ratio and profitability ratio affect stock value movements of food and beverage companies. Food and beverage companies listed on the Stock Exchange are used as the population in this study, and 14 companies were selected from this population as research data. The 14 companies are companies that have published their complete financial statements during 2016-2019 and also reported their financial statements using the rupiah currency. The data used in this study is in the form of financial report data published through the IDX website. Panel data regression method will be used in this paper. The results of this test indicate that DAR has a negative and insignificant effect on stock prices and DER, EPS, and PER have a positive and insignificant effect on stock prices of food and beverage companies.

Keywords: DAR, DER, EPS, PER, Stock Price

ABSTRAK: Analisis fundamental digunakan investor untuk memperkirakan kinerja perusahaan, serta untuk memprediksi pergerakan harga saham. Investor dapat menjadikan analisi fundamental sebagai salah satu cara untuk melihat apa yang terjadi dalam perusahaan untuk mengurangi resiko kerugian investasi yang akan ditanggungnya. Tujuan dari riset ini adalah untuk melihat bagaimana rasio keuangan seperti DAR, DER, EPS, dan PER sebagai bagian dari rasio solvabilitas dan rasio profitabilitas mempengaruhi pergerakan harga saham. Perusahaan makanan dan minuman yang terdaftar di BEI digunakan sebagai populasi dalam penelitian ini, dan dari populasi tersebut dipilih 14 perusahaan sebagai data penelitian. 14 perusahaan tersebut adalah perusahaan yang telah mempublikasikan laporan keuangannya secara lengkap selama tahun 2016-2019 dan juga melaporkan laporan keuangannya dengan menggunakan mata uang rupiah. Data yang digunakan dalam penelitian ini berupa data laporan keuangan yang dipublikasikan melalui website BEI. Metode regresi data panel akan digunakan dalam riset ini. Hasil pengujian ini menunjukkan bahwa DAR berpengaruh negatif dan tidak signifikan terhadap Harga saham dan DER, EPS, dan PER berpengaruh positif dan tidak signifikan terhadap harga saham perusahaan makanan dan minuman

Kata Kunci: DAR, DER, EPS, PER, Harga Saham
MATHEMATICAL MODELING OF FLAPPING WING MOVEMENTS WHEN INTERACTING WITH A RESISTING MEDIUM
Authors: Efimov Sergey , Emel'yanova Oksana , Yacun Sergey
Published: March 2022

The work objective. The paper deals with the issues of modeling biologically inspired movement of an unmanned flying platform (UFP) equipped with flapping wings. Special attention is paid to modeling the interaction of a flapping wing with a resisting air medium. Therefore, the study aim is mathematical modeling of the force which occurs when the wings interact with the resisting medium.

The problem to which the paper is devoted. To solve the problem is to make the mathematical model of the rotational motion of drone wing taking into account kinematic and dynamic features of two-coordinate rotation for various angle changing relative to the longitudinal and transverse axes.

Research methods. Methods of classical mechanics, theory of motion stability, optimal control, observations, parametric optimization were used to solve the problem.

The novelty of the work lies in the algorithms for changing the angles of wings rotation relative to the longitudinal and transverse axes, presented as smooth functions. A method for defining the reduced force arising during the wing movement is proposed. The dependences of the reduced force of wing-air interaction are obtained which provide the development of lifting and traction forces. These forces allow the drone to move in space along a given trajectory.

The study results. The modes of flapping wing motion are simulated and the dependences of instantaneous force values which the wing creates during movement are obtained. These forces allow the drone to move in space along a given trajectory. It is shown that the drone movement is controlled by changing the frequency and amplitude of the wing vibrations, as well as by changing the angle of theneutral line inclination relative to which the wing rotates.

Conclusions: a model of the reduced force arising from the flapping wing movement is proposed. Dependence graphs of the effective wing area (frontal area) for various parameters of changing rotation angles from time are constructed. Flapping wing motions of the aircraft is simulated. The range of parameters is defined at which the wing movement projections create horizontal F1x and lifting F1z forces at different values of area projections S1x, S1y, S1z.
Um estranho dia na vida do jovem Amadeus Gomes de Almeida
Authors: Firdauz Jorge
Published: March 2022

“Eu mesmo ando a me debater com estas afirmações. Como será que se percebe com clareza as escolhas nossas de cada dia? Como perceber antecipadamente as consequências futuras? Cada escolha pode se desdobrar em muitas consequências e nós nem nos apercebemos disto porque estamos muito pouco atentos aos nossos atos. Mas certas vezes parece que a vida já vem pronta para você vivê-la com apenas frívolas escolhas, como por exemplo, o que comer, o que beber, qual o filme ver; mas no fundamental não é bem assim... algumas vezes penso até que tudo já vem pronto só nos restando seguir. Eu digo que nós é que fazemos as escolhas, mas quantas vezes não me pego negando esta afirmação? Quantas vezes não me pego culpando deus ou o diabo pelo trabalho que tenho? Quantas vezes não sonho que um dia algum anjo virá com sua espada flamejante fazer justiça a mim e me libertará deste calvário? É difícil suportar sozinho as enormes possibilidades da escolha. Sartre dizia que o homem está condenado a ser livre".
Learning Progression–Based Assessments: A Systematic Review of Student and Teacher Uses
Authors: Harris Lois Ruth , Adie Lenore , Wyatt-Smith Claire
Published: March 2022

This systematic review examined evidence of the utility of learning progression (LP)–based assessments to inform teaching and student learning in classroom contexts. Fifty-nine studies met inclusion criteria and were analyzed against four research questions. Evidence highlighted their potential for supporting judgments about learning, informing instructional and learning decisions, and improving teacher learning and development. Although 23 studies measured student achievement, reporting positive overall effects, only 6 adopted the experimental designs necessary for causal claims. Using LP-based assessment for formative purposes was well supported. Limited evidence was found regarding summative and accountability uses. Findings show that LP-based assessment design and use requires trade-offs relating to standardization and scale. Teachers need opportunities for negotiation when making judgments and integrating LP-based assessments into existing curriculum and policy contexts. Future research should examine student use of LP assessments and find a balance between standardization and customization to meet the needs of diverse learners and local contexts.
A split-and-merge deep learning approach for phenotype prediction
Authors: Huang Wei-Heng , Wei Yu-Chung
Published: March 2022

Background: Phenotype prediction with genome-wide markers is a critical but difficult problem in biomedical research due to many issues such as nonlinearity of the underlying genetic mapping and high-dimensionality of marker data. When using the deep learning method in the small-n-large-p data, some serious issues occur such as over-fitting, over-parameterization, and biased prediction. Methods: In this study, we propose a split-and-merge deep learning method, named SM-DL method, to learn a neural network on the dimension reduce data by using the split-and-merge technique. Conclusions: Numerically, the proposed method has significant performance in phenotype prediction for a simulated example. A real example is used to demonstrate how the proposed method can be applied in practice.
Predicting Ischemic Stroke in Patients with Atrial Fibrillation Using Machine Learning
Authors: Jung Seonwoo , Song Min-Keun , Lee Eunjoo , Bae Sejin , Kim Yeon-Yong , Lee Doheon , Lee Myoung Jin , Yoo Sunyong
Published: March 2022

Background: Atrial fibrillation (AF) is a well-known risk factor for stroke. Predicting the risk is important to prevent the first and secondary attacks of cerebrovascular diseases by determining early treatment. This study aimed to predict the ischemic stroke in AF patients based on the massive and complex Korean National Health Insurance (KNHIS) data through a machine learning approach. Methods: We extracted 65-dimensional features, including demographics, health examination, and medical history information, of 754,949 patients with AF from KNHIS. Logistic regression was used to determine whether the extracted features had a statistically significant association with ischemic stroke occurrence. Then, we constructed the ischemic stroke prediction model using an attention-based deep neural network. The extracted features were used as input, and the occurrence of ischemic stroke after the diagnosis of AF was the output used to train the model. Results: We found 48 features significantly associated with ischemic stroke occurrence through regression analysis (p-value < 0.001). When the proposed deep learning model was applied to 150,989 AF patients, it was confirmed that the occurrence ischemic stroke was predicted to be higher AUROC (AUROC = 0.727 ± 0.003) compared to CHA2DS2-VASc score (AUROC = 0.651 ± 0.007) and other machine learning methods. Conclusions: As part of preventive medicine, this study could help AF patients prepare for ischemic stroke prevention based on predicted stoke associated features and risk scores.
Comprehensive Prediction of Lipocalin Proteins Using Artificial Intelligence Strategy
Authors: Zulfiqar Hasan , Ahmed Zahoor , Ma Cai-Yi , Khan Rida Sarwar , Grace-Mercure Bakanina Kissanga , Yu Xiao-Long , Zhang Zhao-Yue
Published: March 2022

Background: Lipocalin belongs to the calcyin family, and its sequence length is generally between 165 and 200 residues. They are mainly stable and multifunctional extracellular proteins. Lipocalin plays an important role in several stress responses and allergic inflammations. Because the accurate identification of lipocalins could provide significant evidences for the study of their function, it is necessary to develop a machine learning-based model to recognize lipocalin. Methods: In this study, we constructed a prediction model to identify lipocalin. Their sequences were encoded by six types of features, namely amino acid composition (AAC), composition of k-spaced amino acid pairs (CKSAAP), pseudo amino acid composition (PseAAC), Geary correlation (GD), normalized Moreau-Broto autocorrelation (NMBroto) and composition/transition/distribution (CTD). Subsequently, these features were optimized by using feature selection techniques. A classifier based on random forest was trained according to the optimal features. Results: The results of 10-fold cross-validation showed that our computational model would classify lipocalins with accuracy of 95.03% and area under the curve of 0.987. On the independent dataset, our computational model could produce the accuracy of 89.90% which was 4.17% higher than the existing model. Conclusions: In this work, we developed an advanced computational model to discriminate lipocalin proteins from non-lipocalin proteins. In the proposed model, protein sequences were encoded by six descriptors. Then, feature selection was performed to pick out the best features which could produce the maximum accuracy. On the basis of the best feature subset, the RF-based classifier can obtained the best prediction results.
Vitex negundo L. derived specialized molecules unveil the multi-targeted therapeutic avenues against COPD: a systems pharmacology approach
Authors: Adarshan Sivakumar , Muthuramalingam Pandiyan , Jeyasri Rajendran , Lakshmi Muthukannan Aishwarya , Sathishkumar Ramalingam , Pandian Shunmugiah Karutha , Shin Hyunsuk , Chen Jen-Tsung , Ramesh Manikandan
Published: March 2022

Introduction: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease caused by increasing breathing passage obstruction which completely disrupts human homeostasis. Some patients require lung transplantation or long-term oxygen therapy. COPD is one of the noxious diseases and its fourth leading cause of death around the globe. There is an immediate need for potential drug development to tackle this serious disease. Folk medicines are used to combat complex diseases that have shown effectiveness in the treatment of breathing diseases. Vitex negundo L. is an ethnobotanically important medicinal plant used for various ailments and modulates human cellular events. This shrub has diverse specialized metabolites and is being used as complementary medicine in various countries. Though systems-level understanding is there on the mode of action, the multi-target treatment strategy for COPD is still a bottleneck. Methods: In this investigation, systems pharmacology, cheminformatics, and molecular docking analyses were performed to unravel the multi-targeted mechanisms of V. negundo L. potential bioactives to combat COPD. Results: Cheminformatics analysis combined with the target mining process identified 86 specialized metabolites and their corresponding 1300 direct human receptors, which were further imputed and validated systematically. Furthermore, molecular docking approaches were employed to evaluate the potential activity of identified potential compounds. In addition, pharmacological features of these bioactives were compared with available COPD drugs to recognize potential compounds that were found to be more efficacious with higher bioactive scores. Conclusions: The present study unravels the druggable targets and identifies the bioactive compounds present in V. negundo L., that may be utilized for potential treatment against COPD. However, further in vivo analyses and clinical trials of these molecules are essential to deciphering their efficacy.
p62 Promotes Malignancy of Hepatocellular Carcinoma by Regulating the Secretion of Exosomes and the Localization of β-Catenin
Authors: Yang Weibang , Wei Jinxing , Lv Lihong , Xie Jiyan , Li Ang , Zheng Zhihua , Zhuo Wenfeng , Liu Peiqing , Min Jun
Published: March 2022

Background: p62 is a multi-domain protein and participates in a variety of cellular biological activities. p62 is also related to tumor malignancy. However, the underlying molecular mechanism of p62 regulating the progression of hepatocellular carcinoma (HCC) remains unclear. Methods: The expression levels of p62 in HCC tissues and adjacent non-tumor tissues were confirmed using the TCGA dataset and immunohistochemistry. Stable p62-overexpressing HepG2 cells and p62-knockdown MHCC97H cells were established with lentiviral vectors. Cell proliferation, migration, and invasion assays were carried out to investigate the role of p62 in HCC cells and HCC-derived exosomes. The relationship between p62 and β-catenin was investigated by immunofluorescence and co-immunoprecipitation assays. Male nude mice (BALB/c-nu/nu) were used to establish the xenograft tumors. Results: We found that p62 was significantly upregulated in HCC, and a high level of p62 indicated the promotion of malignancy including cell proliferation, migration, and invasion. Exosomes derived from p62-overexpressing HepG2 also demonstrated the ability to promote tumor malignancy. Immunofluorescence and co-immunoprecipitation assays indicated that p62 interacts with β-catenin and regulates the localization of β-catenin to affect the intercellular junction. p62 also promotes tumor growth of HCC and down-regulates the expression of β-catenin in vivo. Conclusions: The results of this study concluded that p62 promotes the malignancy of HCC by regulating the secretion of exosomes and the localization of β-catenin. These findings may provide new ideas for the diagnosis and treatment of HCC.
Comparative Proteomic and Metabolomic Analyses of Plasma Reveal the Novel Biomarker Panels for Thyroid Dysfunction
Authors: Xia Haodong , Li Yaohan , Liu Shengzhi , Han Haote , Zhou Chaoting , Wang Luyang , Jing Qiangan , Tian Jingkui , Tong Xiangmin , Wang Ying , Zhu Wei
Published: March 2022

Background: Thyroid dysfunction, including hypothyroidism (THO) and hyperthyroidism (THE), commonly arise from pathological processes in the thyroid gland. The current diagnosis of thyroid dysfunction varies because of the age and sex of the patients. The aim of this study was to explore novel candidate biomarker panels for hypothyroidism and hyperthyroidism screening with mass spectrometry and bioinformatics. Methods: Plasma samples were collected from 15 THE patients, 9 THO patients, and 15 healthy controls. Data Independent Acquisition(DIA)-based proteomic and untargeted metabolomic analyses were performed to identify novel biomarker panels for THO and THE patients. Finally, three candidate biomarkers were verified by ELISA in 34 samples. Results: A total of 2738 proteins and 6103 metabolites were identified, and 173 proteins and 2487 metabolites were found to be differentially expressed among the THE, THO and control groups. The results of the ensemble feature selection, K-means clustering and least absolute shrinkage and selection operator (LASSO) regression model showed that two proteins (C4-A and C3/C5 convertase) combined with two metabolites (L-arginine and L-proline), and proteins (APOL1 and ITIH4) combined with metabolites (cortisol, and cortisone) identified by plasma proteomics and metabolomics could help distinguish THO and THE patients from healthy controls, respectively. Conclusions: This study identified and verified two pairs of biomarker panels that can be used to distinguish THE and THO patients regardless of age and sex. Consequently, our findings represent a comprehensive analysis of thyroid dysfunction plasma, which is significant for clinical diagnosis.
A Yeast-Based Screening System for Differential Identification of Poisons and Suppressors of Human Topoisomerase I
Authors: Seddek Ahmed , Madeira Christian , Annamalai Thirunavukkarasu , Mederos Christopher , Tiwari Purushottam B. , Welch Aaron Z. , Tse-Dinh Yuk-Ching
Published: March 2022

Background: Inhibition of human topoisomerase I (TOP1) by camptothecin and topotecan has been shown to reduce excessive transcription of PAMP (Pathogen-Associated Molecular Pattern)-induced genes in prior studies, preventing death from sepsis in animal models of bacterial and SARS-CoV-2 infections. The TOP1 catalytic activity likely resolves the topological constraints on DNA that encodes these genes to facilitate the transcription induction that leads to excess inflammation. The increased accumulation of TOP1-DNA covalent complex (TOP1cc) following DNA cleavage is the basis for the anticancer efficacy of the TOP1 poisons developed for anticancer treatment. The potential cytotoxicity and mutagenicity of TOP1 targeting cancer drugs pose serious concerns for employing them as therapies in sepsis prevention. Methods: In this study we set up a novel yeast-based screening system that employs yeast strains expressing wild-type or a dominant lethal mutant recombinant human TOP1. The effect of test compounds on growth is monitored with and without overexpression of the recombinant human TOP1. Results: This yeast-based screening system can identify human TOP1 poisons for anticancer efficacy as well as TOP1 suppressors that can inhibit TOP1 DNA binding or cleavage activity in steps prior to the formation of the TOP1cc. Conclusions: This yeast-based screening system can distinguish between TOP1 suppressors and TOP1 poisons. The assay can also identify compounds that are likely to be cytotoxic based on their effect on yeast cell growth that is independent of recombinant human TOP1 overexpression.
Targeting the Key Enzymes of Abnormal Fatty Acid β-oxidation as a Potential Strategy for Tumor Therapy
Authors: Chen Hongdan , Yang Zeyu , Sun Yiceng , Yin Supeng , Tang Mi , Zhang Fan
Published: March 2022

Fatty acid metabolism has attracted extensive attention for its key role in the occurrence and development of tumors. Fatty acids not only participate in the biosynthesis of phospholipids in the membrane to overcome the demand for rapidly proliferating membrane lipids but also provide ATP, signaling molecules, and NADPH through β-oxidation to maintain tumor survival and growth. However, the specific role of fatty acid β-oxidation in tumors and the description of multiple potential targets in this process are not comprehensive and systematic. Therefore, this review summarizes the function of fatty acid β-oxidation in tumors and studies of key enzymes that catalyze related reactions in various stages to improve the overall understanding of fatty acid β-oxidation and search for novel tumor treatment strategies and ideas.
Machine learning on thyroid disease: a review
Authors: Lee Kwang-Sig , Park Hyuntae
Published: March 2022

This study reviews the recent progress of machine learning for the early diagnosis of thyroid disease. Based on the results of this review, different machine learning methods would be appropriate for different types of data for the early diagnosis of thyroid disease: (1) the random forest and gradient boosting in the case of numeric data; (2) the random forest in the case of genomic data; (3) the random forest and the ensemble in the case of radiomic data; and (4) the random forest in the case of ultrasound data. Their performance measures varied within 64.3–99.5 for accuracy, 66.8–90.1 for sensitivity, 61.8–85.5 for specificity, and 64.0–96.9 for the area under the receiver operating characteristic curve. According to the findings of this review, indeed, the following attributes would be important variables for the early diagnosis of thyroid disease: clinical stage, marital status, histological type, age, nerve injury symptom, economic income, surgery type [the quality of life 3 months after thyroid cancer surgery]; tumor diameter, symptoms, extrathyroidal extension [the local recurrence of differentiated thyroid carcinoma]; RNA feasures including ADD3-AS1 (downregulation), MIR100HG (downregulation), FAM95C (downregulation), MORC2-AS1 (downregulation), LINC00506 (downregulation), ST7-AS1 (downregulation), LOC339059 (downregulation), MIR181A2HG (upregulation), FAM181A-AS1 (downregulation), LBX2-AS1 (upregulation), BLACAT1 (upregulation), hsa-miR-9-5p (downregulation), hsa-miR-146b-3p (upregulation), hsa-miR-199b-5p (downregulation), hsa-miR-4709-3p (upregulation), hsa-miR-34a-5p (upregulation), hsa-miR-214-3p (downregulation) [papillary thyroid carcinoma]; gut microbiota RNA features such as veillonella, paraprevotella, neisseria, rheinheimera [hypothyroidism]; and ultrasound features, i.e., wreath-shaped feature, micro-calcification, strain ratio [the malignancy of thyroid nodules].
Role of cytokine storm in coronavirus infections: culprit or accomplice?
Authors: Xu Rongpeng , Liu Cunming , Xu Xiaolin , Hu Yimin , Zhu Bin , Yang Chun
Published: March 2022

At present, there are seven known types of human coronaviruses (HCoVs), which can be further divided into two categories: low pathogenic and highly pathogenic. The low pathogenic HCoVs infect the upper respiratory tract, mainly causing mild, cold-like respiratory diseases. By contrast, highly pathogenic HCoVs mainly infect the lower respiratory tract and cause fatal types of pneumonia, which include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as the recent outbreak of coronavirus disease 2019 (COVID-19). Highly pathogenic HCoV infection has a high morbidity and mortality, which is usually related to the strong immune response induced by highly proinflammatory cytokines, which is also known as “cytokine storm”. Therefore, it is particularly important to explore the role of cytokine storm in the process of highly pathogenic HCoV infection. We review the epidemiological and clinical manifestations of highly pathogenic HCoV infection, and reveal the pathology of cytokine storm and its role in the process of highly pathogenic HCoV infection.
Long-Term Ultrastructural Outcomes of Autologous Transplantation of Retinal Pigment Epithelium—Partial Thickness Choroid (RPE-PTC) Sheet in Rabbits
Authors: Ding Xue , Zhang Taoran , Hong Ying , Chang Xin , Li Ying , Ma Zhizhong , Hu Yuntao
Published: March 2022

Background: To observe the ultrastructural outcomes of autologous transplantation of retinal pigment epithelium-partial-thickness choroidal (RPE-PTC) sheets in rabbits after 6 months. Methods: Eighteen pigmented rabbits were used in this study. Among them, nine rabbits were used for autologous transplantation of RPE-PTC sheets. Tissue sections were observed under a transmission electron microscope for one, three, and six months after transplantation, respectively. Results: One, three, and six months after the autologous transplantation of RPE-PTC sheets, the inner and outer segments of photoreceptor cells were arranged regularly, and the connection between the inner and outer segments was normal. The inner structure of the RPE cells and tight junctions among them remained normal. Phagocytosis of outer segment of photoreceptor cells could also be observed in RPE cells. The structure of the Bruch’s membrane appeared loose, rather than being dense as normal, and it was undulated after one and three months, while it became dense after six months. The graft and the bed were healed well, the boundary was unclear, and the graft was vascularized after one, three, and six months, respectively. Conclusions: Our findings revealed that the RPE-PTC sheets could quickly rebuild blood vessels, thereby maintaining the normal physiological functions of RPE cells, as well as the survival and functional status of photoreceptor cells for a long-time.
Effects of Mitochondrial Dynamics in the Pathophysiology of Obesity
Authors: Wang Jinling , Lin Xiufu , Zhao Ningning , Dong Guanping , Wu Wei , Huang Ke , Fu Junfen
Published: March 2022

Obesity has become an urgent and serious public health challenge with an overwhelming increase over the decades worldwide. The rate of obese children and adolescents has recently accelerated, especially in China. Obesity is closely related to unbalanced cellular energy metabolism. Mitochondria, as the main organelles of energy metabolism, play an important role in the pathophysiology of obesity. Recent researches have revealed that mitochondrial dynamics with constant fission and fusion, can alter mitochondrial structure, organelle connections, ROS production, neuronal activity, and OXPHOS system as well as adipose tissue thermogenesis, which ultimately lead to obesity. In this review, we will update the latest findings about mitochondrial fission/fusion related GTPase proteins and discuss the effects of mitochondrial dynamics in the pathophysiology of obesity.
Energy drink consumption: a rising public health issue
Authors: Kaur Amandeep , Yousuf Hamza , Ramgobin-Marshall Devyani , Jain Rahul , Jain Rohit
Published: March 2022

Energy drink (ED) consumption has become a growing public health issue over the past few decades. Despite claims of being safe and beneficial, EDs have been linked to particularly fatal outcomes associated with the cardiovascular system which include atrial and ventricular arrhythmias, myocardial infarctions, cardiomyopathies, and sudden cardiac death. Large quantities of caffeine, taurine, sugars, and B-vitamins may be contributing to these outcomes by increasing the heart rate, blood pressure (BP), and contractility of the heart in addition to prolonging the QTc. There is still a substantial amount of unknown information on EDs that warrants more research and a dire need for age regulations, transparency of ingredients, clear labeling of adverse effects, and most importantly, education of consumers.
Remifentanil versus Dexmedetomidine in Cardiac Surgery Patients with Noninvasive Ventilation Intolerance: Protocol for the REDNIVI Trial
Authors: Luo Ming-hao , Hao Guang-wei , Liu Kai , Yin Kanhua , Yu Shen-Ji , Wang Huan , Su Ying , Luo Jing-chao , Wei Yong-qi , Wang Yu-hang , Pan Wen-qi , Tu Guo-wei , Luo Zhe
Published: March 2022

Background: Respiratory failure is one of the most common complications following cardiac surgery. Although noninvasive ventilation (NIV) has been an effective treatment, it has a high rate of intolerance. Both remifentanil and dexmedetomidine are used as sedatives in cardiac surgery (CS) patients with NIV intolerance. However, no randomized controlled trials have compared the effects of these drugs in relieving the intolerance. Methods: REDNIVI will be a multicenter, prospective, single-blind, randomized controlled trial carried out in six clinical sites in China. Subjects with NIV intolerance will be randomized to receive remifentanil or dexmedetomidine in a ratio of 1:1. Primary outcomes of intolerance remission rate at different timings (15 minutes, 1, 3, 6, 12, 24, 36, 48, 60, 72 hours after initiation of treatment) and 72 h average remission rate will be determined. In addition, secondary outcomes such as mortality, duration of intensive care unit (ICU) stay, duration of mechanical ventilation (MV), the need for endotracheal intubation, hemodynamic changes, and delirium incidence will also be determined. Conclusions: This trial will provide evidence to determine the effects of remifentanil and dexmedetomidine in patients with NIV intolerance after cardiac surgery. Clinical Trial Registration: This study has been registered on ClinicalTrials.gov (NCT04734418).
The role of surgery for secondary mitral regurgitation and heart failure in the era of transcatheter mitral valve therapies
Authors: Noly Pierre-Emmanuel , Pagani Françis D. , Obadia Jean-Fançois , Bouchard Denis , Bolling Steven F. , Ailawadi Gorav , Tang Paul C.
Published: March 2022

The approach to the management of mitral valve (MV) disease and heart failure (HF) has dramatically changed over the last decades. It is well recognized that severe mitral regurgitation secondary to ischemic or non-ischemic cardiomyopathy is associated with an excess risk of mortality. Understanding the impact of the surgical treatment modality on mortality outcomes has been difficult due to the broad spectrum of secondary mitral regurgitation (SMR) phenotypes and lack of randomized surgical clinical trials. Over the last 30 years, surgeons have failed to provide compelling evidence to convince the medical community of the need to treat SMR in patients with severe HF. Therefore, the surgical treatment of SMR has never gained uniform acceptance as a significant option among patients suffering from SMR. Recent evidence from randomized trials in a non-surgical eligible patients treated with transcatheter therapies, has provided a new perspective on SMR treatment. Recently published European and American guidelines confirm the key role of percutaneous treatment of SMR and in parallel, these guidelines reinforce the role of mitral valve surgery in patients who require surgical revascularization. Complex mitral valve repair combining subvalvular apparatus repair along with annuloplasty seems to be a promising approach in selected patients in selected centers. Meanwhile, mitral valve replacement has become the preferred surgical strategy in most patients with advanced heart failure and severe LV remodeling or high risk of recurrent mitral regurgitation. In this comprehensive review, we aimed to discuss the role of mitral surgery for SMR in patients with heart failure in the contemporary era and to provide a practical approach for its surgical management.
Learning from Controversy and Revisiting the Randomized Trials of Secondary Mitral Regurgitation
Authors: Fiore Antonio , Avtaar Singh Sanjeet Singh , Nappi Francesco
Published: March 2022

Until recently, conventional mitral valve surgery has been the treatment of choice even in secondary mitral regurgitation. Recent evidence, however, advocates the use of transcatheter edge-to-edge mitral valve repair (TEER) of the mitral valve. This has been reflected by the change in guidelines of the American College of Cardiology/American Heart Association. We reviewed the literature to shed light on the risks and benefits of all interventions, surgical, transcatheter and guideline-directed medical therapy. Secondary mitral regurgitation occurs due to an imbalance between closing forces and tethering forces. Given the pathology extends beyond the valve alone, treatment should be directed at restoring the geometrical shape of the left ventricle alongside the valve. Myocardial revascularization plays a pivotal role in preventing recurrence. The role of papillary muscle approximation in addition to restrictive mitral annuloplasty should be considered in a select group of patients. We also reviewed the current literature on TEERs from the COAPT and Mitra-FR trials while highlighting the concept of proportionate/disproportionate MR which may help identify which patients benefit from mitral valve restoration. Treatment of this condition will require robust randomized trials alongside the use of state-of-the-art imaging technologies available with the full complement of the multidisciplinary team to ensure the best outcomes for each patient.
Current Opinions on New-Onset Left Bundle Branch Block after Transcatheter Aortic Valve Replacement and the Search for Physiological Pacing
Authors: Zhang Jiefang , Pan Yiwen , Wang Bei , Fu Guosheng
Published: March 2022

Transcatheter aortic valve replacement possesses a high validity for patients with aortic stenosis who are considered high risk for aortic valve replacement surgery, nowadays it is also considered for patients with intermediate risk or even lower risk in certain situations. The incidence of new conduction abnormalities remains to be a tough problem, in particular, left bundle branch block. New-onset left bundle branch block is a major concern despite improvements in valve technology, and it may affect postoperative prognosis. Understanding the anatomical relationship between the conduction system and the aortic root, clarify factors related to the procedure, devices, and patients, might help to reduce the conduction abnormalities. Physiological pacing has emerged as a reasonable pacing strategy for patients with cardiac insufficiency post-valve replacement, especially combined with left bundle branch block. The purpose of this review is to summarize the current opinion on the incidence of new-onset left bundle branch block associated with transcatheter aortic valve replacement, to offer insights into its anatomical and procedural causes, clinical consequences, and more importantly, the prospect of applying physiological pacing as a therapeutic method for these patients.
Comparison of Different Thoracic Aortic Wall Characteristics for Assessment of Disease Activity in Takayasu Arteritis: A Quantitative Study with 3.0 T Magnetic Resonance Imaging
Authors: Zhang Nan , Pan Lili , Liu Jiayi , Li Yu , Xu Lei , Sun Zhonghua , Wang Zhenchang
Published: March 2022

Background: Determination of disease activity in Takayasu arteritis (TAK) is crucial for clinical management but challenging. The value of different magnetic resonance imaging (MRI) characteristics for the assessment of disease activity remains unclear. This study investigated the imaging findings of the thoracic aortic wall and elasticity by using a comprehensive 3.0 T MRI protocol. Methods: We prospectively enrolled 52 consecutive TAK patients. TAK activity was recorded according to the ITAS2010. All the patients underwent thoracic aortic MRI. The luminal morphology of the thoracic aorta and its main branches were quantitatively evaluated using a contrast-enhanced magnetic resonance angiography (MRA) sequence. The maximum wall thickness of the thoracic aorta, postcontrast enhancement ratio, and aortic wall edema were analyzed in each patient through pre- and post-enhanced T1-weighted and T2-weighted imaging. Pulse-wave velocity (PWV) of the thoracic aorta was calculated using a four-dimensional flow technique. Results: The majority of the 52 patients had type V disease (34.62%, 18/52). Among all the MRI indicators of the thoracic aorta, the area under the curve was the largest for the maximal wall thickness (0.804, 95% confidence interval [CI] = 0.667–0.941). The maximal wall thickness (93.33%, 95% CI = 68.1%–99.8%) exhibited the highest sensitivity with a cutoff value of 3.12 mm. Wall edema (84.00%, 95% CI = 63.9%–95.5%) presented the highest specificity. A positive correlation was noted between PWV and patients’ age (r = 0.54, p < 0.001), disease duration (r = 0.52, p < 0.001), and the maximum wall thickness (r = 0.45, p = 0.001). Conclusions: MRI enabled the comprehensive assessment of aortic wall morphology and functional markers for TAK disease activity. Aortic maximal wall thickness was the most accurate indicator of TAK activity. The early phase was superior to the delay phase for aortic wall enhancement analysis for assessing TAK activity.
The Severity of Obstructive Sleep Apnea Increases the Risk of Arteriosclerosis
Authors: Tang Biwen , Bai Yaya , Zhao Jiehui , Yang Hui , Avolio Alberto , Zuo Junli
Published: March 2022

Background: Obstructive sleep apnea (OSA) is a common disorder worldwide. It is associated with myocardial remodeling and arteriosclerosis in patients with hypertension. Our study investigated the relationship between OSA severity and arteriosclerosis and blood pressure in an Asian population. Methods: We enrolled 365 subjects from July 2018 to December 2020 at Ruijin Hospital. We recorded data from the medical history and collected blood samples from all participants. We performed 24-hour ambulatory Blood Pressure (BP) monitoring and Carotid-femoral pulse wave velocity (cf-PWV) measurements. Overnight polysomnography (PSG) was performed using Respironics Alice PDxSleepware. Results: PSG was performed in a total of 365 subjects; mean age of 49.1 ± 12.8 years and Body Mass Index (BMI) 28.1 ± 3.8 kg/m2. The majority (89.3%) were male. The office systolic BP was significantly higher in the moderate to severe group than mild OSA group (148 ± 21 mmHg vs 139 ± 19 mmHg, p < 0.01). The subjects with moderate to severe OSA presented higher cf-PWV values than those in the mild group (10.03 ± 3.67 m/s vs 7.62 ± 1.48 m/s, p < 0.01). BMI was significantly higher in the moderate to severe than the mild OSA groups (28.3 ± 4.0 kg/m2 vs 27.5 ± 3.2 kg/m2, p < 0.05). The Pearson correlation showed that the apnea-hypopnea index (AHI) was significantly and positively correlated with cf-PWV (r = 0.217, p < 0.01), Age (r = 0.148, p < 0.01), BMI (r = 0.228, p < 0.01) and HbA1c (r = 0.172, p < 0.01). After adjusting for age, BMI, low density lipoprotein cholesterin (LDL-c), FGB, AHI, estimated Glomerular Filtration Rate (eGFR), Night BP, office diastolic BP and Day BP in Logistic regression model, AHI (OR = 1.03, 95% CI: 1.01–1.05) and office diastolic pressure (OR = 1.04, 95% CI: 1.00–1.08) and age (OR = 1.12, 95% CI: 1.06–1.19) were independent risk factors for arteriosclerosis. Conclusions: The severity of OSA was positively correlated with pulse wave velocity. AHI, office BP and age were independent risk factors for arteriosclerosis.
Aortic Root Dilatation in Hypertensive Patients with Left Ventricular Hypertrophy–Application of A New Multivariate Predictive Model. The Life Study
Authors: Lilja-Cyron Alexander , Bang Casper N. , Gerdts Eva , Larstorp Anne C. , Kjeldsen Sverre E. , Julius Stevo , Okin Peter M. , Wachtell Kristian , Devereux Richard B.
Published: March 2022

Background: Available nomograms to predict aortic root (AoR) diameter for body surface area have limitations. The purpose of this study was to evaluate the use of a new multivariate predictive model to identify AoR dilatation in hypertensive patients with left ventricular hypertrophy. Methods: 943 of 961 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic sub-study had the necessary baseline characteristics and echocardiographic 2D measurements of AoR size to be included. Results: Predicted AoR (Sinus of Valsalva) diameter was 1.519 + (age [years] × 0.010) + (height [cm] × 0.010) – (gender [1 = M, 2 = F] × 0.247), and a measured AoR diameter exceeding the 97.5-percentile of this estimate was considered dilated. Measured AoR diameter was larger in men than in women (3.75 vs. 3.48 cm, p < 0.001) and AoR diameter predicted by the model was larger than predicted by nomogram (3.52 vs. 3.28 cm, p < 0.001). Using the multivariate model to identify patients with AoR dilatation, the prevalence was 13.7% in men and 12.3% in women (p = 0.537). There was consensus of AoR phenotype (normal/dilated) between model and nomogram in 92.8% of the patients. In multivariate logistic regression, AoR dilatation by model definition was predicted by presence of aortic regurgitation (OR 2.67, p < 0.001) and SD increase in age (OR 0.75, p = 0.023), pulse pressure (OR 0.64, p < 0.001), left ventricular mass index (OR 1.36, p = 0.08) and stroke volume (OR 1.45, p = 0.002), but not by body weight. Conclusions: Using the proposed model the prevalence of AoR dilatation was equal in men and women and the model seems to address the effects of gender, age and body size on AoR size. Clinical Trial Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00338260.
Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) do not Increase the Risk of Hepatic Impairment in Patients with Non-Valvular Atrial Fibrillation: Insights from Multi-Source Medical Data
Authors: Gu Zhi-Chun , Wang Jia , Zhang Chi , Zhao Bin , Li Zhi-Ling
Published: March 2022

Background: There is controversy over whether non-vitamin K antagonist oral anticoagulants (NOACs) use increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation (NVAF). We conducted a comprehensive assessment using multi-source medical data. Methods: We first performed a systematic search of the PubMed, Embase, and Cochrane Library databases (through 11 August 2021) for randomised controlled trials (RCTs) and real-world studies (RWSs) that reported hepatic impairment events in patients with NVAF administered NOACs or vitamin K antagonists (VKAs) therapy. The primary outcomes were hepatic impairment identified by diagnostic liver injury (DLI) or abnormal liver enzyme (ALE). The secondary outcome was hepatic failure. Relative risks (RRs) for RCTs and adjusted hazard ratios (aHRs) for RWSs were calculated separately using random-effects models. We also conducted a disproportionality analysis by extracting reports of hepatic impairment associated with NOACs from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reporting odds ratios (RORs) were calculated to identify the statistical associations between NOACs and hepatic impairment. Scenario analyses were further performed to eliminate event- and drug-related competition bias. Results: A total of 559,873 patients from five RCTs and four RWSs were included in the pooled analysis. For RCTs, NOACs use was not associated with an increased risk of DLI (RR: 0.96, 95% confidence intervals (CI): 0.73–1.28) or ALE (RR: 0.91, 95% CI: 0.69–1.19) compared with VKAs. The merged results of RWSs also showed a similar risk of DLI (aHR: 0.88, 95% CI: 0.72–1.09) or ALE (aHR: 0.91, 95% CI: 0.82–1.00) between NOACs and VKAs. The results of hepatic failure were in accordance with the primacy outcomes. Analyses of individual NOACs did not significantly affect the results. Insights from the FAERS database failed to detect hepatic impairment signals for overall NOACs agents (ROR: 0.34, 95% CI: 0.32–0.37). Scenario analyses confirmed the primary results. Conclusions: Insights from multi-source medical data confirmed that NOACs use was not associated with an increased risk of hepatic impairment in patients with NVAF.