bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of Physical Fitness Level to Student Achievement Junior High School PGRI 08 Malang
Authors: Ramayandi Rian Ari , Kurniawan Rubbi , Budijanto Budijanto
Published: February 2023

Physical fitness and learning achievement is something that can not be separated, so it is necessary to do research to find out how far the relationship between the level of physical freshness to learning achievement. The test instrument uses the Indonesian physical fitness test which consists of five Tests, including the 50m running test, pull up test, sit up test, upright jump test, 1000m running test for men and 800m for women, while achievement data is taken from student Report Card values. The selected research subjects were seventh grade students of SMP PGRI 08 Malang as many as 15 people. The results showed that there is a significant relationship between the level of physical freshness with learning achievement with a coefficient (r2) obtained at 0.418 which means that physical freshness contributes 41.8% to student achievement, and the remaining 58.2% is influenced by other factors.
Survey of Physical Fitness Level on Ganthari Soccer Club Players in Malang City
Authors: Amir Mochamad Fatahilah , Sudarsono Sudarsono , Irawan Dedy , Susanto Ratno , Afandi Achmad
Published: February 2023

Football is a game played by 11 players. A player in playing football must have good health and fitness. If the player is sick or not fit, it will be difficult to achieve maximum performance, so fitness must be trained with exercises that are carried out continuously, programmed and planned. To be able to achieve good fitness, it is not only exercise but a regular lifestyle, for example maintaining a pattern of eating, drinking and resting time. The purpose of the study as data from the level of freshness of football players Ps. Ganthari Malang City. The research method is descriptive by using a survey. Descriptive research is research that describes certain symptoms, phenomena or events. The research subjects were PS Ganthari players, Malang City. In accordance with the research objectives, from this it can be concluded that the Physical Fitness Level of PS Ganthari players in Malang City. Based on the data that has been carried out the physical fitness test for PS Ganthari Malang City, the level of physical fitness is good, namely as many as 10 players with a level of 50%, moderate as many as 9 players or 45%, less that is as much as 1 player or 5%.
Students' Perceptions of Physical Education During the Covid-19 Pandemic at Junior High Schools in North Binjai District in 2020/2021
Authors: Siregar Aidilla Pratiwi , Hasibuan Sanusi
Published: February 2023

The purpose of the study was to examine the perceptions of students about how teachers conduct online learning with junior high school students in the district of North Binjai. The study included descriptive statistics. Data was collected from students in grades VII-IX using questionnaires and Google Forms. The subjects used in this study were junior high school students in North Binjai District in 2021, totaling 285 students. Data analysis using descriptive statistical analysis techniques with percentages and knowing the percentage of students filling out questionnaires is something that students need to know about online learning to students. This study aims to determine students' perceptions of Penjaskes online learning during the COVID-19 diSMP pandemic in North Binjai District. The population and sample in this study amounted to 285 students. The percentage of answers from junior high school students in North Binjai district was 73% strongly agreeing, 16% agreeing, 9% disagreeing, and 2% strongly disagreeing. The highest percentage of research results achieved is 73% of students answering "strongly agree," which is still not perfect because the expected value is 100% of students answering "strongly agree," but the goal of not meeting the target is not met. The overall research results in this study have a percentage of 75% in the good category. So it can be concluded from this study that students' perceptions of pen-and-paper online learning during the COVID-19 pandemic in junior high schools in North Binjai Sub-District run as desired.
Survey of Interest in Pencak Silat Extracurricular Training in Madrasah Aliyah Poncokusumo District Malang 2021/2022
Authors: Mughofar Mokhamad , Mushofi Yuskhil , Pradipta Anangga Widya
Published: February 2023

This research is to find out the size of the student's interest in pencak silat extracurricular at Madrasah Aliyah in the Poncokusumo district after the covid -19 pandemic, which was initially limited, then after Covid ended, the extras started again. Demands to maintain physical fitness by exercising, taking vitamins and adequate rest. In research, interest is defined as interest or liking for one thing or activity without coercion. To achieve a non-academic achievement goal, the extracurricular management from the school is to manage all matters relating to extracurricular activities. In this study using descriptive quantitative survey method using techniques in data collection, namely by using a questionnaire/questionnaire. Sampling of 20 students who attend Madrasah in Poncokusumo sub-district. This research uses quota sampling technique. The results showed interest in participating in extracurricular pencak silat 14 (70%) students had a high interest, and 4 (20%) students had a very high interest. The details on the indicators are intrinsic, namely 9 (45%) students have a very high category of interest in pencak silat and 9 (45%) students have a high category. On extrinsic indicators, 3 (15%) students have a very high interest in pencak silat and 15 (75%) students have a high interest in pencak silat.
Organizational System of Coaching Tennis Court Athletes in PELTI Lampung Province
Authors: Mutaqin Fikri Arif , Sugiyanto Sugiyanto , Utomo Tri Aprilijanto
Published: February 2023

The purpose of this study was to determine the organizational system for coaching tennis athletes at PELTI Lampung Province. This research is included in qualitative research. Sampling was done by purposive sampling to select research subjects. In this study, interviews, observations, and documentation were used to collect data. The interactive data analysis model was used in this study, which consisted of three parts: data reduction, data presentation, and conclusion drawing. Based on the results of the study, it can be concluded that the PELTI Lampung Province uses one form of organization, namely the single form. PELTI Lampung Province is led by one general chairman who oversees several coordinators, so that all decisions rest with the general chairman. Any activities that will be carried out by each division or member must be known and approved by the general chairman of the Lampung Province PELTI. The process and planning of activities are carried out by members of the Lampung Province PELTI so that the chairman only approves for reasons that are in accordance with the needs of the Lampung Province PELTI.
The Correlation of Height and Weight on Concentric Type of Muscle Endurance Malaysian Soccer Players from Sabah FC
Authors: Nidomuddin Muhammad , Pamungkas Hari , Yusuf Havid
Published: February 2023

One of the components of physical fitness includes calculating height and weight which are converted into body mass index (BMI) units. This method can determine the classification of body weight. Body mass index (BMI) numbers are used to indicate weight categories. Our body activities are inseparable from the role of our lower limbs. The base of the lower movement is the hip or pelvis. This research method uses correlation. In statistics, the term "correlation" is defined as the relationship and degree of relationship between two or more variables. The existence of a relationship and the level of this variable is important because by knowing the level of the existing relationship, the researcher will be able to develop it according to the research objectives. The researcher took the entire population as a sample, which consisted of 25 male soccer athletes from Sabah FC. data in the form of BMI test scores and concentric type muscle endurance, the scores were compiled, processed and analyzed for their significance using SPSS. The Pearson Correlation Test aims to determine the level of closeness of the relationship between variables stated by the correlation coefficient. From the results of the data above, it is known that the significance value is 0.000 <0.05. So, it can be said that the two variables are related or correlated. So that it can be interpreted that the two variables of BMI and concentric muscle endurance have a significant relationship with the performance of Sabah FC soccer athletes. It is proven that r count is greater than r table.
Development of Problem-Based Learning Photonovela Media
Authors: Wabo Oktaviani Koli , Lestari Purwaning Budi
Published: February 2023

This study aims to develop Problem Based Learning-based photonovela media and determine the feasibility of the media produced from Problem Based Learning-based photonovela development on the material of the VIII class human respiratory system. The type of this research is development research using the ADDIE model (Analysis, Design, Development, Implementation, and Evaluation). The subject of this research is class VIII students of SMP Negeri 2 Kodi Utara, the stages of development in this research are the analysis stage of defining ( Define), planning (Design) and stages of development (Development) Implementation (Implementation) and Evaluation (Evaluation) Data collection methods use validation, observation, and documentation. While the data analysis technique is based on the results of the validation, the results of the readability test. The results showed that the results of material expert validation with a percentage of 82% in the "very feasible" category, media expert validation with a percentage of 88% in the "very feasible" category, practitioner/field validation with a percentage of 98% in the "very feasible" category. , and the readability test with a percentage of 91% with the "very feasible" category. So it can be concluded that the problem-based learning media photonovela on the material of the human respiratory system class VIII is declared very feasible to use.
Cirrhosis: Reviewing the Literature and Future Perspectives
Authors: Verhelst Xavier , Geerts Anja , Van Vlierberghe Hans
Published: February 2023

Cirrhosis is the final stage of chronic liver disease and has many causes, including viral hepatitis, excessive alcohol intake, and non-alcoholic steatohepatitis. When decompensated cirrhosis develops, complications occur that affect quality of life and patient survival. Cirrhosis has a large burden of disease and is responsible for almost 2% of deaths in Europe. Cirrhotic patients are in need of early diagnosis and a careful follow-up for the prevention and detection of complications. The ultimate treatment for end-stage cirrhosis is liver transplantation. This review will cover clinical aspects of cirrhosis and uncover future trends in the care of these patients.
Definitions of Acute-On-Chronic Liver Failure: The Past, the Present, and the Future
Authors: Amathieu Roland , Al-Khafaji Ali
Published: February 2023

Acute-on-chronic liver failure (ACLF) is an entity used to define patients with liver cirrhosis presenting with acute decompensation. For over 20 years, ACLF has taken multiple definitions and/or classifications. Unfortunately, to date, there has not been a universally accepted definition/classification of this entity. In this short review, we discuss the definition evolution of ACLF, the strengths and weaknesses of the existing definitions and classifications, and finally the potential role of the ‘omic’ approaches for the diagnosis of this complex syndrome.
Storynomics Tourism Sebagai Strategi Dalam Pengembangan Kampung Paropo Sebagai Desa Wisata Budaya
Authors: Badollahi Muh Zainuddin , Anjarsari Hilda
Published: February 2023

Penelitian ini berkaitan dengan storynomics tourism sebagai startegi dalam pengembangan wisata pada kampung Paropo di Makassar, kampung ini merupakan kampung kesenian yang telah banyak menghasilkan seniman handal di kota Makassar. Kampung paropo juga merupakan kampung tua yang memiliki hubungan dengan kerajaan Gowa. Di kampung Paropo terdapat beberapa kesenian yang Populer antaralain Tari Kondobuleng, tari pepe pepeka ri makkah dan sinrili. pendekatan storynomics tourism pada kampung paropo dapat dilihat dari sejarah kampong dan kesenian yang masih dilestarikan hingga kini
Engineering Vibrio alginolyticus as a novel chassis for PHB production from starch
Authors: Li Hong-Fei , Tian Linyue , Lian Guoli , Fan Li-Hai , Li Zheng-Jun
Published: February 2023

Vibrio alginolyticus LHF01 was engineered to efficiently produce poly-3-hydroxybutyrate (PHB) from starch in this study. Firstly, the ability of Vibrio alginolyticus LHF01 to directly accumulate PHB using soluble starch as the carbon source was explored, and the highest PHB titer of 2.06 g/L was obtained in 18 h shake flask cultivation. Then, with the analysis of genomic information of V. alginolyticus LHF01, the PHB synthesis operon and amylase genes were identified. Subsequently, the effects of overexpressing PHB synthesis operon and amylase on PHB production were studied. Especially, with the co-expression of PHB synthesis operon and amylase, the starch consumption rate was improved and the PHB titer was more than doubled. The addition of 20 g/L insoluble corn starch could be exhausted in 6-7 h cultivation, and the PHB titer was 4.32 g/L. To the best of our knowledge, V. alginolyticus was firstly engineered to produce PHB with the direct utilization of starch, and this stain can be considered as a novel host to produce PHB using starch as the raw material.
The interaction between microbiota and immune in intestinal inflammatory diseases: Global research status and trends
Authors: Liu Chuan , Su Wenhao , Tan Zongbiao , Zhang Jixiang , Dong Weiguo
Published: February 2023

Aims

This study aimed to conduct a bibliometric analysis of the relevant literature on the interaction between microbiota and immune in intestinal inflammatory diseases, and show its current status, hotspots, and development trends.

Methods

The related literature was acquired from the Web of Science Core Collection on October 12, 2022. Co-occurrence and cooperation relationship analysis of authors, institutions, countries, references, and keywords in the literature were carried out through CiteSpace 6.1.R3 software and the Online Analysis platform of Literature Metrology. At the same time, the relevant knowledge maps were drawn, and the keywords cluster analysis and emergence analysis were performed.

Results

3,608 related publications were included, showing that the number of articles in this field is increasing year by year. The results showed that Gasbarrini A and Sokol H were the authors with the highest cumulative number of articles with 25, and the institution with the most articles was Harvard University with 142 articles. The USA was far ahead in the article output, with 1,131 articles, and had a dominant role, followed by China with 707 articles. The journal Frontiers in Immunology contributed the most to this research field with 213 articles. In the cooperation network analysis, the USA, Harvard University, and Xavier RJ were the most widely collaborated country, institution, and author, respectively, which implied a high level of influence. Keywords analysis showed that there were 770 keywords, which were mainly classified as internal related diseases, such as “inflammatory bowel disease”, “irritable bowel syndrome”, “colorectal cancer”, and the mechanism of interaction of microbiota and immune, such as “intestinal microbiota”, “commensal microbiota”, “regulatory T cell”, “dendritic cell”, “barrier function”, “activation”, “anti-inflammatory properties”, “intestinal epithelium”, and “diversity”. Emerging analysis showed that future research hotspots and trends might be the short-chain fatty acid, gut dysbiosis, gut-liver axis, and fusobacterium nucleatum.

Conclusion

This research was the first bibliometric analysis of publications in the field of interaction between microbiota and immune in intestinal inflammatory diseases using visualization software and data information mining, and obtained the current status, hotspots, and development of this field, which provides a theoretical basis for its scientific research.
Rating gender stereotype violations: The effects of personality and politics
Authors: Hammond-Thrasher Stephanie , Järvikivi Juhani
Published: February 2023

The Gender Stereotype Effect in language comprehension refers to the increased processing load that occurs when comprehenders encounter linguistic information that is incongruent with their understanding of gender stereotypes; for example, upon encountering the pronoun he in the sentence The maid answered the phone because he heard it ring. We investigate the Stereotype Effect using appropriateness and correctness ratings and ask whether it is modulated by individual differences in participants' personality and political ideology. Results from this study indicate that the Stereotype Effect can be replicated in an offline paradigm and that the Effect is specific to a discourse character's gender: sentences describing male agents fulfilling stereotypical female roles were rated lower in both appropriateness and correctness than sentences describing female agents fulfilling stereotypical male roles. Further, more open, conscientious, liberal, and empathetic individuals were more sensitive to the character gender-specific effect, rating stereotype incongruent sentences, particularly female role-male pronoun pairings, lower than congruent ones. Overall, these results point to certain individual differences being associated with differences in the strength of stereotype perception, indicating the possibility that these individuals use more top-down language processing, where comprehenders higher on these scales might be able to make more use of extra-linguistic, sociocultural factors in their language comprehension. Additionally, the results indicate a character gender-based difference in sociocultural stereotypes.
Ox-LDL induced profound changes of small non-coding RNA in rat endothelial cells
Authors: Wang Yu , Liu Tianhua , Xiao Wenying , Bai Yanyan , Yue Dandan , Feng Liuliu
Published: February 2023

Introduction

Atherosclerosis (AS) is a common cardiovascular disease with a high incidence rate and mortality. Endothelial cell injury and dysfunction are early markers of AS. Oxidative low-density lipoprotein (Ox-LDL) is a key risk factor for the development of AS. Ox-LDL promotes endothelial cell apoptosis and induces inflammation and oxidative stress in endothelial cells. Small non-coding RNAs (sncRNAs) mainly include Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), microRNAs (miRNAs) and repeat-associated RNAs. Studies have shown that small non-coding RNAs play an increasingly important role in diseases.

Methods

We used ox-LDL to treat rat endothelial cells to simulate endothelial cell injury. The expression changes of sncRNA were analyzed by small RNA high-throughput sequencing, and the expression changes of piRNA, snoRNA, snRNA, miRNA and repeat-associated RNA were verified by quantitative polymerase chain reaction (qPCR).

Results

Small RNA sequencing showed that 42 piRNAs were upregulated and 38 piRNAs were downregulated in endothelial cells treated with ox-LDL. PiRNA DQ614630 promoted the apoptosis of endothelial cells. The snoRNA analysis results showed that 80 snoRNAs were upregulated and 68 snoRNAs were downregulated in endothelial cells with ox-LDL treatment, and snoRNA ENSRNOT00000079032.1 inhibited the apoptosis of endothelial cells. For snRNA, we found that 20 snRNAs were upregulated and 26 snRNAs were downregulated in endothelial cells with ox-LDL treatment, and snRNA ENSRNOT00000081005.1 increased the apoptosis of endothelial cells. Analysis of miRNAs indicated that 106 miRNAs were upregulated and 91 miRNAs were downregulated in endothelial cells with ox-LDL treatment, and miRNA rno-novel-136-mature promoted the apoptosis of endothelial cells. The repeat RNA analysis results showed that 4 repeat RNAs were upregulated and 6 repeat RNAs were downregulated in endothelial cells treated with ox-LDL.

Discussion

This study first reported the expression changes of sncRNAs in endothelial cells with ox-LDL treatment, which provided new markers for the diagnosis and treatment of endothelial cell injury.
The exploitation of crabs by Last Interglacial Iberian Neanderthals: The evidence from Gruta da Figueira Brava (Portugal)
Authors: Nabais Mariana , Dupont Catherine , Zilhão João
Published: February 2023

Hominin consumption of small prey has been much discussed over the past decades. Such resources are often considered to be unproductive in the Middle Paleolithic due to their limited meat yield and, hence, low energy return. However, ethnographic studies suggest that small prey—including shellfish—are a reliable, predictable and by no means marginal resource, and there is increasing evidence for their inclusion in hominin diets during the Middle Paleolithic and even earlier. Gruta da Figueira Brava features a MIS 5c-5b Neanderthal occupation that left behind substantial, human-accumulated terrestrial and marine faunal remains, capped by reworked levels that contain some naturally accumulated, recent Holocene material, namely the remains of small crab species and echinoderms. The brown crabCancer pagurus(Linnaeus, 1758) predominates in the intact Middle Paleolithic deposit, and reconstruction of its carapace width, based on regression from claw size, shows a preference for relatively large individuals. The detailed analysis of theCancer pagurusremains reveals that complete animals were brought to the site, where they were roasted on coals and then cracked open to access the flesh.
The association between self-monitoring of blood glucose and HbA1c in type 2 diabetes
Authors: Yuan Yanping , Zhou Xianghai , Jia Weiping , Zhou Jian , Zhang Fan , Du Jianling , Ji Linong
Published: February 2023

Aims

Fasting capillary blood glucose (FCG) and postprandial capillary blood glucose (PCG) both contribute to HbA1c in diabetes. Due to the collinearity between FCG and PCG, the HbA1c prediction model could not be developed with both FCG and PCG by linear regression. The study aimed to develop an HbA1c prediction model with both FCG and PCG to estimate HbA1c in type 2 diabetes.

Methods

A total of 1,642 patients with type 2 diabetes who had at least three FCG and three PCG measurements in the past 3 months were enrolled in the study. The mean of FCG (MEANFCG) and PCG (MEANPCG) were calculated for each patient. The patients were randomized into exploratory and validation groups. The former was used for developing HbA1c prediction models and the latter for performance evaluation.

Results

The new HbA1c prediction model using ridge regression expressed as HbA1c (%) = 0.320×MEANFCG (mmol/L) + 0.187×MEANPCG (mmol/L) + 2.979, R2 = 0.668. Compared to linear regression models developed with FCG, PCG, fasting plasma glucose (FPG), and 2-hour postprandial plasma glucose (2-h PPG), respectively, the new HbA1c prediction model showed the smallest mean square error, root mean square error, mean absolute error. The concordance correlation coefficient of the new HbA1c prediction model and the linear regression models with MEANFCG, MEANPCG, FPG or 2-h PPG were 0.810,0.773,0.749,0.715,0.672.

Conclusion

We have developed a new HbA1c prediction model with both FCG and PCG, which showed better prediction ability and good agreement.
Seasonal changes in endoplasmic reticulum stress and ovarian steroidogenesis in the muskrats (Ondatra zibethicus)
Authors: Lu Wenjing , Gao Qingjing , Wei Jinlan , Xie Wenqian , Zhang Haolin , Yuan Zhengrong , Han Yingying , Weng Qiang
Published: February 2023

Many studies have shown roles for endoplasmic reticulum stress (ERS)/unfolded protein response (UPR) signaling cascades with ovarian folliculogenesis, and oocyte maturation. In this study, we investigated seasonal changes in ERS and ovarian steroidogenesis in the muskrats (Ondatra zibethicus) during the breeding season (BS) and non-breeding season (NBS). There were noticeable seasonal variations in the weight and size of muskrat ovaries with values higher in the BS than that in NBS. The circulating luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17β-estradiol, and progesterone of the female muskrats were higher during the BS. The RNA-seq data of ovaries during different seasons revealed 2580 differentially expressed genes, further analysis showed a prominent enrichment of ERS-related pathways and ovarian steroidogenesis pathway. Immunohistochemical results showed that GRP78 and steroidogenic enzymes (P450scc, 3β-HSD, P450c17, and P450arom) existed in the various kinds of cells in muskrat ovaries during the BS and NBS. In ovaries from the BS, the mRNA levels of P450scc, P450arom, P450c17, and 3β-HSD were considerably higher. Furthermore, the expression levels of oxidative stress-related genes (SOD2, CAT, and GPX1) and UPR signal genes (Bip/GRP78, ATF4, ATF6, and XBP1s) were increased strikingly higher during the BS in comparison with the NBS. However, the mRNA levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and caspase-3 had no considerable difference between the BS and NBS. Taken together, these results suggested that UPR signaling associated with the seasonal changes in ovarian steroidogenesis is activated in the BS and the delicate balance in redox regulation is important for seasonal reproduction in the muskrats.
Empirical study on green development of marine economy driven by marine scientific and technological innovation and its influencing factors
Authors: Wu Fan , Cui Fengxiang , Liu Tao
Published: February 2023

In this study, the green development of marine economy driven by marine scientific and technological innovation is empirically studied and the influencing factors are analyzed. The results show that the development of marine science and technology is significantly positively correlated with the green development of marine economy as a whole, and each input variable has a promoting effect on economic development, but with varied degree of effect. The analysis on the growth models of “Circum-Bohai Sea Economic Zone,” “Yangtze River Delta Economic Zone” and “Pearl River Delta Economic Zone” shows that at present, science and technology in each marine economic zone play an obvious role in promoting economic development, and each input variable plays a different role in promoting the green development of regional marine economy. With the help of threshold panel model, the influences of five factors, namely opening to the outside world, government investment, financial development, human capital and technology investment, on the green development of marine economy driven by marine scientific and technological innovation are investigated, and it is concluded that all kinds of external influencing factors will interfere with the role of marine scientific and technological innovation and achieve the effect of promoting or restricting it.
White blood cells and coronary heart disease: A mendelian randomization study
Authors: Zhao Qiuping , Liu Rongmei , Chen Hui , Yang Xiaomo , Dong Jiajia , Bai Minfu
Published: February 2023

Background: The causal direction and magnitude of the associations between blood cell count and coronary heart disease (CHD) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between blood cell count and CHD using Mendelian randomization (MR).

Methods: In this two-sample MR study, we identified independent blood cell count associated genetic variants from a genome-wide association studies (GWAS) among European ancestry individuals. Summary level data of CHD was obtained from a GWAS consisting of 547261 subjects. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and outlier test (MR-PRESSO) were conducted to investigate the associations between blood cell and CHD.

Results: Among all cardiovascular outcomes of interest, blood cell counts were only associated with CHD. Our findings indicated that white blood cell count and neutrophil cell count were significantly associated with increased risk of CHD [odds ratio (OR) = 1.07, 95% confidence interval (CI), 1.01–1.14; OR = 1.09, 1.02–1.16). However, there was no significant association between monocyte cell count, basophil cell count, lymphocyte cell count, eosinophil cell count, and CHD (p > 0.05). The results after excluding outliers were consistent with main results and the sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, p > 0.05).

Conclusion: Our MR study suggested that greater white blood cell count and neutrophil cell count were associated with a higher risk of CHD. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.
iPoLNG—An unsupervised model for the integrative analysis of single-cell multiomics data
Authors: Zhang Wenyu , Lin Zhixiang
Published: February 2023

Single-cell multiomics technologies, where the transcriptomic and epigenomic profiles are simultaneously measured in the same set of single cells, pose significant challenges for effective integrative analysis. Here, we propose an unsupervised generative model, iPoLNG, for the effective and scalable integration of single-cell multiomics data. iPoLNG reconstructs low-dimensional representations of the cells and features using computationally efficient stochastic variational inference by modelling the discrete counts in single-cell multiomics data with latent factors. The low-dimensional representation of cells enables the identification of distinct cell types, and the feature by factor loading matrices help characterize cell-type specific markers and provide rich biological insights on the functional pathway enrichment analysis. iPoLNG is also able to handle the setting of partial information where certain modality of the cells is missing. Taking advantage of GPU and probabilistic programming, iPoLNG is scalable to large datasets and it takes less than 15 min to implement on datasets with 20,000 cells.
Comparative functional analysis of macrophage phagocytosis in Dagu chickens and Wenchang chickens
Authors: Zhang Jin , Wang Qiao , Li Qinghe , Wang Zixuan , Zheng Maiqing , Wen Jie , Zhao Guiping
Published: February 2023

Phagocytosis of macrophages constitutes a powerful barrier to innate immunity. Differences in the phagocytic function of macrophages among chicken breeds have rarely been reported, and the molecular mechanisms underlying phagocytosis remain poorly understood. This study compared functional difference of macrophages in Dagu chickens, originated in Zhuanghe, Liaoning Province, China, and Wenchang chickens, originated from Hainan Island in the South China Sea, and explored the potential molecular mechanisms by integrated analysis of mRNA expression profiles of macrophages and whole genome sequencing. Immunological parameters in peripheral blood indicated that Dagu chickens were more resistant to Salmonella challenge at 28 days old. Phagocytosis index and phagocytosis rate of macrophages displayed Dagu chickens performed a significantly higher phagocytic ability of macrophages at 14 and 28 days old. Furthermore, comparative analysis of mRNA expression profiles of macrophages of two breeds at 28 days old revealed that 1136 differentially expressed genes (DEGs), and 22 DEGs (e.g., H2AFZ, SNRPA1, CUEDC2, S100A12) were found to be hub genes regulating phagocytosis by participating in different immunological biological signaling pathways. In addition, many DEGs and hub genes were under strong differentiation in genome between two breeds, the H2AFZ gene was an intersection of DEGs and hub genes. These results provided a comprehensive functional comparison and transcriptomic profiles of macrophages in Chinese native chicken breeds, and deepened our understanding of the genetic mechanism of innate immunity.
IgA Nephropathy: Pleiotropic impact of Epstein-Barr virus infection on immunopathogenesis and racial incidence of the disease
Authors: Mestecky Jiri , Julian Bruce A. , Raska Milan
Published: February 2023

IgA nephropathy (IgAN) is an autoimmune disease in which poorly galactosylated IgA1 is the antigen recognized by naturally occurring anti-glycan antibodies, leading to formation of nephritogenic circulating immune complexes. Incidence of IgAN displays geographical and racial disparity: common in Europe, North America, Australia, and east Asia, uncommon in African Americans, many Asian and South American countries, Australian Aborigines, and rare in central Africa. In analyses of sera and cells from White IgAN patients, healthy controls, and African Americans, IgAN patients exhibited substantial enrichment for IgA-expressing B cells infected with Epstein-Barr virus (EBV), leading to enhanced production of poorly galactosylated IgA1. Disparities in incidence of IgAN may reflect a previously disregarded difference in the maturation of the IgA system as related to the timing of EBV infection. Compared with populations with higher incidences of IgAN, African Americans, African Blacks, and Australian Aborigines are more frequently infected with EBV during the first 1-2 years of life at the time of naturally occurring IgA deficiency when IgA cells are less numerous than in late childhood or adolescence. Therefore, in very young children EBV enters “non-IgA” cells. Ensuing immune responses prevent infection of IgA B cells during later exposure to EBV at older ages. Our data implicate EBV-infected cells as the source of poorly galactosylated IgA1 in circulating immune complexes and glomerular deposits in patients with IgAN. Thus, temporal differences in EBV primo-infection as related to naturally delayed maturation of the IgA system may contribute to geographic and racial variations in incidence of IgAN.
Non-coding RNAs targeting NF-κB pathways in aquatic animals: A review
Authors: Zhao Tanjun , Zou Yang , Yan Hanyu , Chang Yaqing , Zhan Yaoyao
Published: February 2023

Nuclear factor-kappa B (NF-κB) pathways have a close relationship with many diseases, especially in terms of the regulation of inflammation and the immune response. Non-coding RNAs (ncRNAs) are a heterogeneous subset of endogenous RNAs that directly affect cellular function in the absence of proteins or peptide products; these include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), etc. Studies on the roles of ncRNAs in targeting the NF-κB pathways in aquatic animals are scarce. A few research studies have confirmed detailed regulatory mechanisms among ncRNAs and the NF-κB pathways in aquatic animals. This comprehensive review is presented concerning ncRNAs targeting the NF-κB pathway in aquatic animals and provides new insights into NF-κB pathways regulatory mechanisms of aquatic animals. The review discusses new possibilities for developing non-coding-RNA-based antiviral applications in fisheries.
Immunogenicity of SARS-CoV-2 mRNA intramuscular vaccination in patients with muscular disorders
Authors: Kasai Ryousuke , Funato Michinori , Maruta Kanako , Yasuda Kunihiko , Minatsu Hiroshi , Ito Junji , Takahashi Kazuhiro
Published: February 2023

Backgrounds

Little clinical data is available on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with muscular disorders (MDs). The immunogenicity of SARS-CoV-2 vaccines against MDs, in particular, remains unknown. Thus, this study aimed to confirm the immunogenicity and safety of the SARS-CoV-2 vaccine against MDs.

Methods

All participants were vaccinated with two doses of mRNA vaccines (BNT162b2, Pfizer-BioNTech). The serum samples were collected from each patient on the day of second dose of vaccination, and then, consecutively, after one month, three months, and six months. Anti-SARS-CoV-2 IgG levels were determined using the Abbott SARS-CoV-2 IgG II Quant assay.

Results

We evaluated 75 individuals, including 42 patients with MDs and 33 patients with non-muscular disorders (non-MDs). Non-MD patients primarily include those with severe motor and intellectual disabilities. The median age of the patients was 32 years (range 12–64 years). After one and three months following the second immunization, patients with MDs had lower antibody responses. Furthermore, three months following the second immunization, the proportion of high responders among patients with MDs decreased significantly compared to that among patients without MDs (p-value of less than 0.01). No serious adverse events were observed in patients with or without MDs.

Conclusion

Intensity and latency of antibody response were suppressed in patients with MDs. Although MDs may be a key contributor in predicting the antibody response to SARS-CoV-2 vaccination, SARS-CoV-2 immunization in MDs needs extensive research.
Murine scald models characterize the role of neutrophils and neutrophil extracellular traps in severe burns
Authors: Elrod Julia , Lenz Moritz , Kiwit Antonia , Armbrust Lina , Schönfeld Lavinia , Reinshagen Konrad , Pagerols Raluy Laia , Mohr Christoph , Saygi Ceren , Alawi Malik , Rohde Holger , Herrmann Martin , Boettcher Michael
Published: February 2023

Introduction

Severe burns cause unique pathophysiological alterations especially on the immune system. A murine scald model was optimized as a basis for the understanding of immunological reactions in response to heat induced injury. The understanding of the roles of neutrophil extracellular traps (NETs) and DNases will support the development of new surgical or pharmacological strategies for the therapy of severe burns.

Methods

We studied C57BL/6 mice (n=30) and employed four scalding protocols with varying exposure times to hot water. An additional scald group with a shorter observational time was generated to reduce mortality and study the very early phase of pathophysiology. At 24h or 72h, blood was drawn and tissue (wound, liver, lung, spleen) was analyzed for the presence of NETs, oxidative stress, apoptosis, bacterial translocation, and extracellular matrix re-organization. In addition, we analyzed the transcriptome from lung and liver tissues.

Results

Exposure to hot water for 7s led to significant systemic and local effects and caused considerable late mortality. Therefore, we used an observation time of 24h in this groups. To study later phases of burns (72h) an exposure time of 6s is optimal. Both conditions led to significant disorganization of collagen, increased oxidative stress, NET formation (by immunodetection of H3cit, NE, MPO), apoptosis (cC3) and alterations of the levels of DNase1 and DNase1L3. Transcriptome analysis revealed remarkable alterations in genes involved in acute phase signaling, cell cohesion, extracellular matrix organization, and immune response.

Conclusion

We identified two scald models that allow the analysis of early (24h) or late (72h) severe burn effects, thereby generating reproducible and standardized scald injuries. The study elucidated the important involvement of neutrophil activity and the role of NETs in burns. Extensive transcriptome analysis characterized the acute phase and tissue remodeling pathways involved in the process of healing and may serve as crucial basis for future in-depth studies.
Discovering hematoma-stimulated circuits for secondary brain injury after intraventricular hemorrhage by spatial transcriptome analysis
Authors: Zhang Le , Badai Jiayidaer , Wang Guan , Ru Xufang , Song Wenkai , You Yujie , He Jiaojiao , Huang Suna , Feng Hua , Chen Runsheng , Zhao Yi , Chen Yujie
Published: February 2023

Introduction

Central nervous system (CNS) diseases, such as neurodegenerative disorders and brain diseases caused by acute injuries, are important, yet challenging to study due to disease lesion locations and other complexities.

Methods

Utilizing the powerful method of spatial transcriptome analysis together with novel algorithms we developed for the study, we report here for the first time a 3D trajectory map of gene expression changes in the brain following acute neural injury using a mouse model of intraventricular hemorrhage (IVH). IVH is a common and representative complication after various acute brain injuries with severe mortality and mobility implications.

Results

Our data identified three main 3D global pseudospace-time trajectory bundles that represent the main neural circuits from the lateral ventricle to the hippocampus and primary cortex affected by experimental IVH stimulation. Further analysis indicated a rapid response in the primary cortex, as well as a direct and integrated effect on the hippocampus after IVH stimulation.

Discussion

These results are informative for understanding the pathophysiological changes, including the spatial and temporal patterns of gene expression changes, in IVH patients after acute brain injury, strategizing more effective clinical management regimens, and developing novel bioinformatics strategies for the study of other CNS diseases. The algorithm strategies used in this study are searchable via a web service (www.combio-lezhang.online/3dstivh/home).
Heat shock protein 90 inhibitor RGRN-305 potently attenuates skin inflammation
Authors: Ben Abdallah Hakim , Seeler Sabine , Bregnhøj Anne , Ghatnekar Gautam , Kristensen Lasse S. , Iversen Lars , Johansen Claus
Published: February 2023

Introduction

Chronic inflammatory skin diseases may have a profound negative impact on the quality of life. Current treatment options may be inadequate, offering an unsatisfactory response or side effects. Therefore, ongoing efforts exist to identify novel effective and safe treatments. Heat shock protein (HSP) 90 is a chaperone that promotes the activity of a wide range of client proteins including key proinflammatory molecules involved in aberrant inflammation. Recently, a proof-of-concept clinical trial of 13 patients suggested that RGRN-305 (an HSP90 inhibitor) may be an oral treatment for psoriasis. However, HSP90 inhibition may be a novel therapeutic approach extending beyond psoriasis to include multiple immune-mediated inflammatory skin diseases.

Methods

This study aimed to investigate (i) the anti-inflammatory effects and mechanisms of HSP90 inhibition and (ii) the feasibility of topical RGRN-305 administration (new route of administration) in models of inflammation elicited by 12-O-tetradecanoylphorbol-13-acetate (TPA) in primary human keratinocytes and mice (irritative dermatitis murine model).

Results/Discussion

In primary human keratinocytes stimulated with TPA, a Nanostring® nCounter gene expression assay demonstrated that HSP90 inhibition with RGRN-305 suppressed many proinflammatory genes. Furthermore, when measured by quantitative real-time polymerase chain reaction (RT-qPCR), RGRN-305 significantly reduced the gene expression of TNF, IL1B, IL6 and CXCL8. We next demonstrated that topical RGRN-305 application significantly ameliorated TPA-induced skin inflammation in mice. The increase in ear thickness (a marker of inflammation) was significantly reduced (up to 89% inhibition). In accordance, RT-qPCR of the ear tissue demonstrated that RGRN-305 robustly reduced the gene expression of proinflammatory markers (Tnf, Il1b, Il6, Il17A and Defb4). Moreover, RNA sequencing revealed that RGRN-305 mitigated TPA-induced alterations in gene expression and suppressed genes implicated in inflammation. Lastly, we discovered that the anti-inflammatory effects were mediated, at least partly, by suppressing the activity of NF-κB, ERK1/2, p38 MAPK and c-Jun signaling pathways, which are consistent with previous findings in other experimental models beyond skin inflammation. In summary, HSP90 inhibition robustly suppressed TPA-induced inflammation by targeting key proinflammatory cytokines and signaling pathways. Our findings suggest that HSP90 inhibition may be a novel mechanism of action for treating immune-mediated skin disease beyond psoriasis, and it may be a topical treatment option.
Utility of monocyte HLA-DR and rationale for therapeutic GM-CSF in sepsis immunoparalysis
Authors: Joshi Ila , Carney Walter P. , Rock Edwin P.
Published: February 2023

Sepsis, a heterogeneous clinical syndrome, features a systemic inflammatory response to tissue injury or infection, followed by a state of reduced immune responsiveness. Measurable alterations occur in both the innate and adaptive immune systems. Immunoparalysis, an immunosuppressed state, associates with worsened outcomes, including multiple organ dysfunction syndrome, secondary infections, and increased mortality. Multiple immune markers to identify sepsis immunoparalysis have been proposed, and some might offer clinical utility. Sepsis immunoparalysis is characterized by reduced lymphocyte numbers and downregulation of class II human leukocyte antigens (HLA) on innate immune monocytes. Class II HLA proteins present peptide antigens for recognition by and activation of antigen-specific T lymphocytes. One monocyte class II protein, mHLA-DR, can be measured by flow cytometry. Downregulated mHLA-DR indicates reduced monocyte responsiveness, as measured by ex-vivo cytokine production in response to endotoxin stimulation. Our literature survey reveals low mHLA-DR expression on peripheral blood monocytes correlates with increased risks for infection and death. For mHLA-DR, 15,000 antibodies/cell appears clinically acceptable as the lower limit of immunocompetence. Values less than 15,000 antibodies/cell are correlated with sepsis severity; and values at or less than 8000 antibodies/cell are identified as severe immunoparalysis. Several experimental immunotherapies have been evaluated for reversal of sepsis immunoparalysis. In particular, sargramostim, a recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF), has demonstrated clinical benefit by reducing hospitalization duration and lowering secondary infection risk. Lowered infection risk correlates with increased mHLA-DR expression on peripheral blood monocytes in these patients. Although mHLA-DR has shown promising utility for identifying sepsis immunoparalysis, absence of a standardized, analytically validated method has thus far prevented widespread adoption. A clinically useful approach for patient inclusion and identification of clinically correlated output parameters could address the persistent high unmet medical need for effective targeted therapies in sepsis.
Function and regulation of cGAS-STING signaling in infectious diseases
Authors: Du Yang , Hu Zhiqiang , Luo Yien , Wang Helen Y. , Yu Xiao , Wang Rong-Fu
Published: February 2023

The efficacious detection of pathogens and prompt induction of innate immune signaling serve as a crucial component of immune defense against infectious pathogens. Over the past decade, DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signaling adaptor stimulator of interferon genes (STING) have emerged as key mediators of type I interferon (IFN) and nuclear factor-κB (NF-κB) responses in health and infection diseases. Moreover, both cGAS-STING pathway and pathogens have developed delicate strategies to resist each other for their survival. The mechanistic and functional comprehension of the interplay between cGAS-STING pathway and pathogens is opening the way for the development and application of pharmacological agonists and antagonists in the treatment of infectious diseases. Here, we briefly review the current knowledge of DNA sensing through the cGAS-STING pathway, and emphatically highlight the potent undertaking of cGAS-STING signaling pathway in the host against infectious pathogenic organisms.