bluuebunny/crossref_metadata_2025 huggingface dataset:
THE IMPLEMENTATION OF PROJECT-BASED ASSIGNMENT IN ONLINE LEARNING DURING COVID-19
Authors: Yuliansyah Aldi , Ayu Mutiara
Published: March 2023

By implementation of online systems strategy indirectly forces teachers and students to master the uses of technology in learning process. Online learning is needed to facilitate the teacher delivering the material to students during the pandemic situation.  From this condition, it is suitable for teachers to implement Project Based Learning as it allows students to design, plan and carry out an extended project that produces a publicly exhibited output such as a product, publication or presentations Project Based Learning improves the students’ media research skills provides a real-world connection to context. The students conduct research using multiple information resources. By locating the resources themselves, their research skills develop and improve. Project Based Learning increases the students‟ collaboration. In the processing stages, students create and organize their own groups. They share knowledge and collaboratively construct their products. Through collaboration, they develop social communication skills and obtain multiple perspectives.
THE IMPORTANCE OF FAMILY MOTIVATION FOR STUDENT	TO STUDY ONLINE DURING THE COVID-19
Authors: Nadya Zesisca , Pustika Reza
Published: March 2023

Covid-19 is a new type of disease that first attacked the city of Wuhan in China, a virus that has spread from person to person and this virus began to enter Indonesia in early March 2019 which made Indonesia have to lockdown activities outside the home including education because this virus spreads, So that the learning process for all students continues, the Indonesian government enforces the teaching and learning process to be carried out online or commonly called E-learning. In online learning, of course, students need motivation to support the student learning process. Internal motivation and external motivation are very important for the online learning process during the Covid-19 pandemic. This study investigates whether internal motivation and external motivation are very important for students learning online from home, and investigates whether family influences student motivation. In order to study online well during the Covid-19 pandemic, the target of this research is the seventh semester of English students. Educational study program at the Universitas Teknokrat Indonesia. There were 30 students who took part in this research. through distributing link questionnaires to Universitas Teknokrat Indonesia students. Keywords: motivation, family, covid-19, online learning, E-Learning.
The Analysis of Game Usage for Senior High School Students to Improve Their Vocabulary Mastery
Authors: Yudha Hafidz Tresna , Mandasari Berlinda
Published: March 2023

Vocabulary plays an important role in learning English. Learning vocabulary in English is not easy, especially for students in vocational high school. In addition, they have special characteristics that are very different from adults. With emphasis on these different characteristics, it can be concluded that teachers who teach vocational learners have a challenging task to be able to motivate them in the learning process. In this case, teachers must be more creative and keep their students away from boredom while learning English vocabulary. They must prepare material to be given to students and also choose appropriate techniques to use. By doing these things, they can make students have a great interest in the learning process. They must be able to choose and use teaching techniques that can make the learning process more fun, interesting, and exciting for students. One such technique is to use games in the classroom. Using games can provide many benefits for teachers and students.This research aimed at identifying students’ improvement on their vocabulary mastery after learning English using game. The participant of this study is students of junior high school in Lampung province. Data gathered through questionnaire. The data then analyzed by using Creswell method. The result shows that using games in learning English vocabulary is very effective, because using games is very fun and matches the characteristics of children as learners.
STUDENTS’ DIFFICULTIES WITH SELF-DISCIPLINE DURING ONLINE CLASS
Authors: Ningsih Deski Yolan Septa Tenti , Sari Fatimah Mulya
Published: March 2023

The COVID-19 pandemic necessitates the government to take strict rules to prevent the spread of the virus. This condition bought about the transition from the offline learning process to online learning at every level of education across Indonesia. The main advantage of online learning is flexibility. This condition makes students possible to access online courses to learn and carry out assignments anytime and anywhere. Therefore, teaching and learning processes can be more practical and efficient. However, due to low self-discipline, the flexibility of time given by the lecturer triggers students to postpone in submitting their assignment and the majority tend to submit on or close to the deadline time. As a result, these conditions have implications for the effectiveness of the learning process in higher education. The purpose of this paper is to prove that self-discipline in the knowledge acquisition process is one of the most important factors in online learning. The research was conducted with a qualitative method. The instrument of this research was a questionnaire that was used to establish students’ opinions which were distributed by using google to collect the data. The questionnaire consists of 15 questions.  Keywords: Self-discipline, Online learning, Covid-19
STUDENT PROBLEMS IN ONLINE LEARNING: SOLUTIONS TO KEEP EDUCATION GOING ON
Authors: Erlangga Dion Tira
Published: March 2023

The spread of the Covid-19 virus that has swept across the world has changed various aspects of human life, one of which is the change of learning process that commonly occurs face to face in the classroom become online learning. Online learning is chosen as the solution to keep teaching and learning during this pandemic and this is done by various levels of education starting from primary school, middle school, high school, to college levels. The existence of cases of learning difficulties experienced by students during the Covid-19 pandemic made students do not understand the subject matter delivered by the teacher. This study aimed to find out some solutions of students' problem in the online learning process. Participants in this study were 25 English education students from a private university in Bandar Lampung. The researcher distributed a close ended questionnaire of 9 questions in the form of Google to collect data, and used qualitative data to illustrate the results of the questionnaire in data findings. The results of the study show that there were some problems faced by students in online learning included (1) students difficult to understanding materials, (2) students encounter technical difficulties, (3) limited internet quota, (4) poor communication, and (5) learning becomes less effective. The solutions that researcher has found to overcome the problems are namely (1) teachers or lecturers must implement face to face class twice a week, (2) teachers should use platforms with simpler operations in online learning, (3) teachers or lecturers should provide a material that is interactive, dynamic and attractive and (4) the government must extend the quota assistance for students.
THE CORRELATION BETWEEN SPEAKING CLASS ANXIETY AND STUDENTS’ ENGLISH PROFICIENCY
Authors: Dana Multi Yusan , Aminatun Dyah
Published: March 2023

Speaking is an essential skill that students should master because it requires oral communication such as, grammar, vocabulary, pronunciation, fluency, and comprehension. This study aims to determine the correlation between speaking class anxiety and their English skills. The participants in this study were sixth semester students majoring in English Education, Universitas Teknokrat Indonesia which consisted of 39 students. This research technique uses quantitative research. The research instrument was that students were asked to fill out a questionnaire about speaking anxiety which was distributed via a google form link and then the data would be analyzed with the help of SPSS 15.0 and Ms Excel 2007. The questionnaire was adopted from the Public Speaking Class Anxiety Scale (PSCA). The questionnaire contains 20 questions related to anxiety problems in speaking class with 5 scale criteria starting from strongly agree, agree, neutral, disagree and strongly disagree. From the result of the correlation between speaking anxiety and English proficiency scores, it can be concluded that students with high level of speaking anxiety had lower EPT scores than student with lower speaking anxiety level.
UNDERGRADUATE STUDENTS' MOTIVATION ON ENGLISH LANGUAGE LEARNING AT UNIVERSITAS TEKNOKRAT INDONESIA
Authors: Pranawengtias Wulandari
Published: March 2023

AbstractThe purpose of this research is to identify the factors that influence the learning motivation of Universitas Teknokrat Indonesia students. It also aims to reveal the motivational sub-factors that affect the student learning process. This study uses a qualitative research method  used questionnaire consisting of 2 intrinsic motivation factors and 3 extrinsic motivation factors, with a total of 30 questions. Questionnaire in the form of 5 Likert Scale. The sample amounted to 30 students from the majors in sports education, mathematics education, and English education. Data from the questionnaire were analyzed using statistical procedures and described descriptively. The results showed that extrinsic motivation contributed more to students' learning motivation (39.66) compared to intrinsic factors (36.1). The results also show that the extrinsic motivation factor; giving rewards and punishments (41.4) as well as the quality of lecturers and the teaching and learning process (40.0) are the two dominant factors that can increase students' learning motivation. Thus, these results have implications for what to pay attention to in language learning, especially in learning English. Therefore, the appropriateness of giving rewards or punishments for students and the quality of lecturers must be improved because it will increase student motivation in language learning.
THE CORRELATION BETWEEN STUDENTS' SELF-ESTEEM AND THEIR ENGLISH PROFICIENCY TEST RESULT
Authors: Gultom Septivana , Oktaviani Lulud
Published: March 2023

Nowadays, a wide range of professions around the world employs English as an International Language. Many people learn English to keep up with the worldwide advances in areas like education, technology, tourism, health, and economics. English is widely utilized in many facets of human life. English is additionally necessary for graduation. Students must pass the English proficiency test to graduate from university (EPT). Self-esteem, an essential component of personality, affects people's attitudes and behaviors. Self-esteem is frequently associated with good mental health, effective living, successful learning, and even a good quality of life. How people view themselves, whether favorably or unfavorably, is a measure of their self-esteem. Since self-esteem and academic performance are intertwined, the researchers want to know whether or not students' self-esteem correlates with their level of English proficiency. This study, which involved 38 participants from Universitas Teknokrat Indonesia, used the quantitative method. This study's conclusions showed a connection between students' self-esteem and their EPT score. The researchers conclude that students' self-esteem did have an impact on their EPT score, i.e., the greater their self-esteem, the higher their EPT score.
Overview of Asian clinical practice guidelines for the management of hepatocellular carcinoma: An Asian perspective comparison
Authors: Cho Yuri , Kim Bo Hyun , Park Joong-Won
Published: March 2023

Hepatocellular carcinoma (HCC) is highly prevalent and the third most common cause of cancer-related death in Asia. In contrast to the West, the main etiology of HCC in many Asian countries except Japan is chronic hepatitis B virus infection. Differences in the major causes of HCC lead to significant clinical and treatment differences. This review summarizes and compares guidelines on managing HCC from China, Hong Kong, Taiwan, Japan, and South Korea. From oncology and socio-economic perspectives, factors such as underlying diseases, staging methods, government policies, insurance coverage, and medical resources contribute to varying treatment strategies among countries. Furthermore, the differences in each guideline are fundamentally caused by the lack of incontrovertible medical evidence, and even existing results of clinical trials can be interpreted differently. This review will provide a complete overview of the current Asian guidelines for HCC in recommendations and in practice.
JUDGE'S EX OFFICIO AUTHORITY ON THE CASE OF TALAK -DIVORCE; MAQASID SHARIˋAH PERSPECTIVE
Authors: Fathurrohmah Fathurrohmah , Sadari Sadari
Published: March 2023

This article is the result of library research. This research is included in normative legal research. This research discussion aims to explain the basis of Islamic law on the judge’s ex officio authority of Nganjuk Religioun Court judges in judgement talak-divorce cases, number: 2033/Pdt.G/2017/PA.Ngj. Researcher analysis data by maqāsid sharī'ah theory. The findings of this study are that the use of ex efficio rights of the Nganjuk Religioun Court which does not follow civil procedural law has a strong Islamic legal basis. This argument is based on the maqāsid sharī'ah shāṭibi theory. The benefits that are guarded by the judge are in accordance with the al Dharūriyyāt category, especially hifz al nafs, namely the maintenance of the soul. The benefit of Dharāriyyāt is shown through the first data that the wife is proven not to be given her rights by her husband before the divorce is decided, so the judge considers ex officio authority; second, maintaining the rights of the ex-wife after the divorce even though the wife (the respondent) did not file a reconvention in the trial.

Keywords: judge’s ex officio authority, divorce-talak, sharia purpose.
The dark side of mRNA translation and the translation machinery in glioblastoma
Authors: Montiel-Dávalos Angélica , Ayala Yeniffer , Hernández Greco
Published: March 2023

Among the different types of cancer affecting the central nervous system (CNS), glioblastoma (GB) is classified by the World Health Organization (WHO) as the most common and aggressive CNS cancer in adults. GB incidence is more frequent among persons aged 45–55 years old. GB treatments are based on tumor resection, radiation, and chemotherapies. The current development of novel molecular biomarkers (MB) has led to a more accurate prediction of GB progression. Moreover, clinical, epidemiological, and experimental studies have established genetic variants consistently associated with the risk of suffering GB. However, despite the advances in these fields, the survival expectancy of GB patients is still shorter than 2 years. Thus, fundamental processes inducing tumor onset and progression remain to be elucidated. In recent years, mRNA translation has been in the spotlight, as its dysregulation is emerging as a key cause of GB. In particular, the initiation phase of translation is most involved in this process. Among the crucial events, the machinery performing this phase undergoes a reconfiguration under the hypoxic conditions in the tumor microenvironment. In addition, ribosomal proteins (RPs) have been reported to play translation-independent roles in GB development. This review focuses on the research elucidating the tight relationship between translation initiation, the translation machinery, and GB. We also summarize the state-of-the-art drugs targeting the translation machinery to improve patients’ survival. Overall, the recent advances in this field are shedding new light on the dark side of translation in GB.
Aurora kinases: Generators of spatial control during mitosis
Authors: Ali Aamir , Stukenberg P. Todd
Published: March 2023

Cell division events require regulatory systems to ensure that events happen in a distinct order. The classic view of temporal control of the cell cycle posits that cells order events by linking them to changes in Cyclin Dependent Kinase (CDK) activities. However, a new paradigm is emerging from studies of anaphase where chromatids separate at the central metaphase plate and then move to opposite poles of the cell. These studies suggest that distinct events are ordered depending upon the location of each chromosome along its journey from the central metaphase plate to the elongated spindle poles. This system is dependent upon a gradient of Aurora B kinase activity that emerges during anaphase and acts as a spatial beacon to control numerous anaphase/telophase events and cytokinesis. Recent studies also suggest that Aurora A kinase activity specifies proximity of chromosomes or proteins to spindle poles during prometaphase. Together these studies argue that a key role for Aurora kinases is to provide spatial information that controls events depending upon the location of chromosomes or proteins along the mitotic spindle.
Improvement of loperamide-hydrochloride-induced intestinal motility disturbance by Platycodon grandiflorum polysaccharides through effects on gut microbes and colonic serotonin
Authors: Hao Mengqi , Song Jing , Zhai Xiaohu , Cheng Nuo , Xu Cong , Gui Shuangying , Chen Juan
Published: March 2023

Constipation is a common gastrointestinal symptom characterized by intestinal motility disorder. The effects of Platycodon grandiflorum polysaccharides (PGP) on intestinal motility have not been confirmed. We established a rat model of constipation induced by loperamide hydrochloride to elucidate the therapeutic effect of PGP on intestinal motility disorder and to explore the possible mechanism. After PGP treatment (400 and 800 mg/kg) for 21 d, PGP clearly relieved gastrointestinal motility, including fecal water content, gastric emptying rate, and intestinal transit rate. Moreover, the secretion of motility-related hormones, gastrin and motilin, were increased. Enzyme-linked immunosorbent assay, western blot, immunohistochemistry, and immunofluorescence results confirmed that PGP significantly increased the secretion of 5-hydroxytryptamine (5-HT) and the expression of related proteins, such as tryptophan hydroxylase 1, 5-HT4 receptor, and transient receptor potential ankyrin 1. 16S rRNA gene sequencing showed that PGP significantly increased the relative abundance of Roseburia, Butyricimonas, and Ruminiclostridium, which were positively correlated with 5-HT levels. However, the relative abundance of Clostridia_UCG-014, Lactobacillus, and Enterococcus were decreased. PGP improved intestinal transport by regulating the levels of 5-HT, which interacts with the gut microbiota and the intestinal neuro-endocrine system, further affecting constipation. Overall, PGP is a potential supplement for the treatment of constipation.
Application of a core genome sequence typing (cgMLST) pipeline for surveillance of Clostridioides difficile in China
Authors: Wang Yuan Yuan , Xie Lu , Zhang Wen Zhu , Du Xiao li , Li Wen Ge , Bia Lu Lu , Cui Zhi Gang , Wu Yuan , Lu Jin Xing
Published: March 2023

Introduction

Clostridioides difficile (C. difficile) is a nosocomial bacterial pathogen that causes antibiotic-associated diarrhea mediated by cellular exotoxins secreted into the intestine during bacterial growth. Multilocus sequence typing (MLST) and PCR ribotyping are the main molecular typing for C. difficile. Whole genome sequencing (WGS) core genome multilocus sequence typing (cgMLST) was developed for genetic evolution and outbreak investigation of C. difficile with higher precision and accuracy.

Methods

A total of 699 whole (complete and draft) genome sequences of distinct C. difficile strains were used in this study to identify core gene set (2469 core genes) and the cgMLST scheme for the phylogeny analysis of C. difficile. This cgMLST pipeline was then carried the Chinese Pathogen Identification Net (China PIN) for surveillance of C. difficile in China. Within the China PIN, 195 WGS of C. difficile and an outbreak of CDI with 12 WGS of C. difficile were used to evaluate the cgMLST pipeline.

Results

The result displayed that mostly tested C. difficile isolates could be successfully divided into 5 classic clades and the outbreak event was also successfully identified.

Discussion

The results are meaningful and offer a practicable pipeline for a national-wide surveillance of C. difficile in China.
Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model
Authors: Lv Wei , Zhang Di , He Tian , Liu Yingying , Shao Limei , Lv Zhongping , Pu Xiaoping , Wang Yufang , Liu Ling
Published: March 2023

The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in mice. Here, we aimed to observe the changes in the tacrolimus-induced microbiome in a dextran sulfate sodium (DSS)-induced colitis mouse model and explore the possibility and efficacy of combination therapy with tacrolimus and the microbiome on colitis. Mice were divided into the control, DSS, tacrolimus monotherapy and tacrolimus plus Lactobacillus plantarum 550 (Lacto)-treated groups. The body weight, stool consistency, hematochezia and survival of mice were observed daily. Total RNA from colonic mucosa was extracted and subjected to transcriptome sequencing. Cecal contents were collected and the 16S rRNA sequencing was performed to characterize the gut microbiome and the ultrahigh- performance liquid chromatography-MS/MS (UHPLC-MS/MS) was used for targeted quantification of bile acids. The results confirmed that tacrolimus significantly ameliorated DSS-induced colitis in mice. Beneficial alterations of the gut microbiome characterized by a remarkable expansion of the genus Lactobacillus were induced by tacrolimus treatment. Oral supplementation with Lacto further improved the tacrolimus-mediated suppression of body weight loss in colitis, while the survival time of mice was further prolonged and the inflammation of colonic mucosa was obviously relieved. The immune and inflammation-related signaling pathways, including IFN-γ and IFN-α response, allograft rejection, IL2 STAT5 signaling and the inflammatory response pathways, were further downregulated in the tacrolimus plus Lacto cotreatment group. Cotreatment also improved the diversity of the gut microbiome and rescued the concentration of taurochenodeoxycholic acid (TCDCA) in colitis. The latter was positively correlated with the abundance of Lactobacillus but negatively related to the disease activity index score. Overall, our results indicated that Lactobacillus plantarum promoted the therapeutic effect of tacrolimus in experimental colitis, offering a promising strategy to combine tacrolimus and Lactobacillus in the treatment of colitis patients.
Different oscillatory rhythms anticipate failures in executive and arousal vigilance
Authors: Luna Fernando G. , Aguirre María Julieta , Martín-Arévalo Elisa , Ibáñez Agustín , Lupiáñez Juan , Barttfeld Pablo
Published: March 2023

Introduction

Vigilance is the challenging ability to maintain attention during long periods. When performing prolonged tasks, vigilance failures are often observed, reflecting a decrease in performance. Previous research has shown that changes in oscillatory rhythms are associated with states of vigilance loss. The present study aimed to investigate whether changes in different oscillatory rhythms anticipate failures in two vigilance components: (a) executive vigilance –necessary to detect infrequent critical signals– and (b) arousal vigilance –necessary to maintain a fast reaction to environmental stimuli without much control–.

Methods

37 young adults (age: M = 25.86; SD = 4.99) completed two experimental sessions in which high-density electroencephalography signal was recorded while they performed the Attentional Networks Test for Interactions and Vigilance – executive and arousal components, a task that simultaneously measures executive and arousal vigilance along with others attentional functions. Changes in delta, theta, alpha, beta, and gamma power before target onset were analyzed at the trial level in the executive and the arousal vigilance subtasks and as a function of the behavioral response.

Results

Changes in different oscillatory rhythms were observed prior to failures in executive and arousal vigilance. While increased alpha power in left occipital regions anticipated misses in the executive vigilance subtask, increased delta power in frontal-central regions anticipated very slow responses in the arousal vigilance subtask.

Discussion

The present results further support an empirical dissociation at the neural level between executive and arousal vigilance. Changes in alpha –in left occipital regions– and delta –in frontal-central regions– power might be identified as different brain states associated with loss in vigilance components when performing prolonged tasks.
A three-year prospective cohort study evaluating implant stability utilising the Osstell® and Periotest™ devices
Authors: Reynolds Ian , Winning Lewis , Polyzois Ioannis
Published: March 2023

Objectives

To investigate implant stability measurements from two different devices and at three different time points in order to determine their level of correlation. To also evaluate the influence of a range of clinical characteristics on the values produced by the devices at these three time points.

Materials & Methods

Measurements were recorded at implant placement (T1), implant exposure (T2) and at 3 years from implant placement (T3). A range of clinical data was collected including patient demographics and site characteristics. Stability measurements and clinical characteristics were recorded for 29 patients and 68 dental implants at T1, subsequent stability measurements were recorded for 67 implants at T2 and 58 implants at T3. Correlation testing between the Osstell® and Periotest™ devices was carried out utilising Spearman's rank correlation for each time point. Analysis of the difference between clinical factors and stability measurements was compared using Kruskal-Wallis test for each variable and time point.

Results

A single dental implant failed shortly after second stage surgery for an overall survival rate of 98% during the study timeline. The median ISQ value was 73.25 (IQR 67–75) at T1 and 74 (IQR 70.5–77) at T3. The median Periotest value was −4 (IQR −6, −2) at T1 and −6 (IQR −7, −5) at T3. The range of ISQ values observed was 50 (39–89) ISQ at T1 and decreased to 21 (61–82) ISQ at T3. The Periotest values ranged from 37 (29 to −8) at T1 and decreased to 6 (−2 to −8) at T3. A weak to moderate correlation was observed between mean ISQ and Periotest values across time points T1, T2 and T3, (r = −0.26, p = 0.05), (r = −0.35, p < 0.01) and (r = −0.28, p = 0.04) respectively.

Conclusions

Based on the results of this study there was a weak to moderate level of correlation between values recorded between the two measurement devices at implant placement, implant exposure and three years following placement. For both the Osstell® and Periotest™ a narrowing of the range of stability values was observed from T1 to T3. In general, Periotest™ seemed to be more sensitive in highlighting differences in measurements affected by local conditions.
Evaluation of the predictive values of collapse and necrotic lesion boundary for osteonecrosis of the femoral head prognosis
Authors: Fan Yinuo , Liu Xuejie , Zhong Yuan , Zhang Jiahao , Liu Yuhao , Fang Hanjun , He Wei , Zhou Chi , Chen Zhenqiu
Published: March 2023

Objective

Osteonecrosis of the femoral head (ONFH) is a disabling and intractable orthopedic disease largely affecting young and middle-aged groups. Current standard of treatment relies on the collapse of femoral head as a predictor for prognosis. However, a wide range of variability in repair potentials is observed in patients with femoral head collapse. Therefore, the present study aimed to evaluate the accuracy of femoral head collapse as a predictor and to propose the necrotic lesion boundary as a novel yet reliable measure for ONFH prognosis.

Methods

A retrospective cross-sectional study was conducted at the First Affiliated Hospital of Guangzhou University of Chinese Medicine, 203 hips with ONFH from 134 patients were included. The occurrences and progression of femoral head collapse were recorded. Necrosis lesion boundary was quantified and classified for each case based on anteroposterior view intact ratio (APIR) and the frog-leg view intact ratio (FLIR) as independent variables. Dependent variables were defined as progressive collapse or terminal collapse for Association Research Circulation Osseous (ARCO) stage II and III respectively. Logistic regression analysis, Receiver Operating Characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis was performed and results were interpreted.

Results

Out of the 106 hips in ARCO stage II, 31 hips collapsed with further progression, while 75 hips had no collapse or collapse with repair of the necrotic areas. Out of the 97 hips in ARCO stage IIIA, the collapse continued to progress in 58 hips while the necrotic areas were repaired in 39 hips. Logistic regression analysis demonstrated that both APIR and FLIR, were independent risk factors. Further ROC curve analysis indicated that the cutoff values of APIR and FLIR could be considered as indications for evaluating the prognosis of ONFH. Contrary to the traditional view of poor prognosis after femoral head collapse, K-M survival analysis demonstrated a high value of APIR and FLIR for ONFH prognosis.

Conclusion

The present study found that the occurrence of collapse is an oversimplified predictor for ONFH prognosis. The collapse of the femoral head in ONFH does not predict a poor prognosis. The necrosis lesion boundary has a high value in predicting ONFH prognosis and informing clinical treatment strategies.
Fire blight rootstock infections causing apple tree death: A case study in high-density apple orchards with Erwinia amylovora strain characterization
Authors: Aćimović Srđan G. , Santander Ricardo Delgado , Meredith Christopher L. , Pavlović Žaklina M.
Published: March 2023

A devastating outcome of fire blight in apple trees is the infection of rootstock, which leads to canker development. Fire blight cankers are infected zones of dead bark on perennial branches, trunk, or rootstock that develop after fire blight pathogen Erwinia amylovora invades wood. Cankers can girdle the trunk, branches and rootstock leading to tree death and production losses, especially significant in high-density orchards. An accurate diagnosis of trunk and rootstock blight is a top challenge for apple growers because fire blight cankers can be visually misdiagnosed with cankers caused by less frequent Oomycete and fungal pathogens (e.g., Phytophthora spp., Botryosphaeria dothidea, B. obtusa, Valsa mali). In addition, detecting E. amylovora in apple rootstocks is essential because this pathogen also causes asymptomatic infections. Accurate fire blight diagnosis is necessary to inform the complete removal of infected trees from the orchard and help replanting efforts while preventing further pathogen dissemination. To determine apple tree losses caused by fire blight rootstock infections, PCR was used to detect E. amylovora in symptomatic and asymptomatic rootstocks for two years. Rootstock canker incidence and tree death were rated in selected infection foci on seven commercial apple orchards in New York. Each infection focus consisted of central rootstock-blighted tree and the nearest surrounding edge trees showing no rootstock blight. E. amylovora strains collected from these seven orchards and other orchards in New York were characterized. In the first year, most of the orchards showed E. amylovora detection rates of 10.7 – 45.3% in asymptomatic rootstocks on the edge trees immediately surrounding visibly infected i.e. rootstock-blighted central trees. One year later, 20.8 – 56.3% cankered rootstocks were detected on the edge trees and from zero to 35.4% dead edge trees were recorded. However, the PCR from sampled edge rootstocks one year later showed no pathogen detections. E. amylovora rootstock strains showed slight variability in enzymatic activity, copper sensitivity, virulence, and exopolysaccharide production. These results elucidate the role and importance of rootstock infections for apple tree survival, the presence of latent fire blight infections, and the valuable utility of molecular detection methods to assist apple tree removal after epidemics.
Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study
Authors: Cao Guangming , Hua Dingchao , Li Jinfeng , Zhang Xuefang , Zhang Zhiqiang , Zhang Bei , Bei Ting , Cui Lina , Chen Shiqing , Wang Shuzhen , Zhu Lei
Published: March 2023

Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8+ T cells (P = 0.033), CD20+ B cells (P = 0.023), CD56 NK cells (P = 0.041), PD-1+ cells (P = 0.042), and PD-L1+CD68+ macrophages (P = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20+ cells (P = 0.046) and in the M1/M2 ratio (P = 0.038) as well as fewer tumors showing increase in the infiltration of CD56bright cells (P = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8+ cells was positively associated with longer progression-free survival (PFS) (P = 0.011) and overall survival (OS) (P = 0.048). Post-NACT CD20+ and CD163+ macrophages (M2) infiltrates were associated with prolonged (P = 0.005) and shortened PFS (P = 0.021), respectively. Increase in the density of CD4+ T cells was predictive for longer PFS (P = 0.022) and OS (P = 0.023). In the multivariate analysis, high density of CD8+ cells pre-NACT (P = 0.042) were independently associated with improved OS.
Role of the inflammasome in insulin resistance and type 2 diabetes mellitus
Authors: Lu Shen , Li Yanrong , Qian Zhaojun , Zhao Tiesuo , Feng Zhiwei , Weng Xiaogang , Yu Lili
Published: March 2023

The inflammasome is a protein complex composed of a variety of proteins in cells and which participates in the innate immune response of the body. It can be activated by upstream signal regulation and plays an important role in pyroptosis, apoptosis, inflammation, tumor regulation, etc. In recent years, the number of metabolic syndrome patients with insulin resistance (IR) has increased year by year, and the inflammasome is closely related to the occurrence and development of metabolic diseases. The inflammasome can directly or indirectly affect conduction of the insulin signaling pathway, involvement the occurrence of IR and type 2 diabetes mellitus (T2DM). Moreover, various therapeutic agents also work through the inflammasome to treat with diabetes. This review focuses on the role of inflammasome on IR and T2DM, pointing out the association and utility value. Briefly, we have discussed the main inflammasomes, including NLRP1, NLRP3, NLRC4, NLRP6 and AIM2, as well as their structure, activation and regulation in IR were described in detail. Finally, we discussed the current therapeutic options-associated with inflammasome for the treatment of T2DM. Specially, the NLRP3-related therapeutic agents and options are widely developed. In summary, this article reviews the role of and research progress on the inflammasome in IR and T2DM.
Fibrinogen-like protein 1 promotes liver-resident memory T-cell exhaustion in hepatocellular carcinoma
Authors: Yang Changjie , Qian Qiwei , Zhao Yudong , Huang Bingyuan , Chen Ruilin , Gong Qiyu , Ji Hao , Wang Chenchen , Xia Lei , You Zhengrui , Zhang Jianjun , Chen Xiaosong
Published: March 2023

Background and aims

The key role of tissue-resident memory T (TRM) cells in the immune regulation of hepatocellular carcinoma (HCC) has been investigated and reported, but the regulatory mechanism of tumor microenvironment on TRM cells is still unclear. Lymphocyte activating gene 3 (LAG-3) is a promising next-generation immune checkpoint that is continuously expressed due to persistent antigen exposure in the tumor microenvironment. Fibrinogen-like protein 1 (FGL1) is a classical ligand of LAG-3 and can promote T cell exhaustion in tumors. Here, we excavated the effect of FGL1-LAG3 regulatory axis on TRM cells in HCC.

Methods

The function and phenotype of intrahepatic CD8+ TRM cells in 35 HCC patients were analyzed using multicolor flow cytometry. Using a tissue microarray of 80 HCC patients, we performed the prognosis analysis. Moreover, we investigated the suppressive effect of FGL1 on CD8+ TRM cells both in in vitro induction model and in vivo orthotopic HCC mouse model.

Results

There was an increase in LAG3 expression in CD8+ TRM cells in end-stage HCC; moreover, FGL1 levels were negatively correlated with CD103 expression and related to poor outcomes in HCC. Patients with high CD8+ TRM cell proportions have better outcomes, and FGL1-LAG3 binding could lead to the exhaustion of CD8+ TRM cells in tumors, indicating its potential as a target for immune checkpoint therapy of HCC. Increased FGL1 expression in HCC may result in CD8+ TRM cell exhaustion, causing tumor immune escape.

Conclusions

We identified CD8+TRM cells as a potential immunotherapeutic target and reported the effect of FGL1-LAG3 binding on CD8+ TRM cell function in HCC.
Plasmodium falciparum infection coinciding with the malaria vaccine candidate BK-SE36 administration interferes with the immune responses in Burkinabe children
Authors: Tiono Alfred B. , Palacpac Nirianne Marie Q. , Bougouma Edith Christiane , Nebie Issa , Ouédraogo Alphonse , Houard Sophie , Arisue Nobuko , D’Alessio Flavia , Horii Toshihiro , Sirima Sodiomon B.
Published: March 2023

Background

A vaccine targeting the erythrocyte stages of Plasmodium falciparum could play a role in preventing clinical disease. BK-SE36 is a promising malaria vaccine candidate that has shown a good safety profile and immunological responses during field evaluations. It was observed that repeated natural infections could result in immune tolerance against SE36 molecule.

Methods

The primary trial was conducted to assess the safety and immunogenicity of the BK-SE36 in two cohorts of children aged 25-60 months (Cohort 1) and 12-24 months (Cohort 2). Immunization was at full dose (1.0 mL) administered at 0, 1, and 6 months. Blood samples were collected before each vaccination for immunological assessments and detection of Plasmodium falciparum infection by microscopy. Blood samples were further collected one month post each vaccination to evaluate immunogenicity.

Results

Of seventy-two (72) subjects that have received BK-SE36 vaccination, 71 had available blood smears during vaccination days. One month post Dose 2, the geometric mean of SE36 antibodies was 263.2 (95% CI: 178.9-387.1) in uninfected individuals compared to 77.1 (95% CI: 47.3-125.7) in infected participants. The same trend was observed one-month post booster dose. Participants uninfected at the time of booster vaccination had significantly higher GMTs compared to those who were infected (424.1 (95% CI: 301.9-595.8) vs. 92.8 (95% CI: 34.9-246.6), p = 0.002. There was a 14.3 (95% CI: 9.7-21.1) and 2.4 (95% CI: 1.3-4.4) fold-change, respectively, in uninfected and infected participants between one-month post Dose 2 and booster. The difference was statistically significant (p < 0.001).

Conclusion

Concomitant infection by P. falciparum during BK-SE36 vaccine candidate administration is associated with reduced humoral responses. However, it is to be noted that the BK-SE36 primary trial was not designed to investigate the influence of concomitant infection on vaccine-induced immune response and should be interpreted cautiously.

Trial registration

WHO ICTRP, PACTR201411000934120.
Exploring SARS-CoV-2 and Plasmodium falciparum coinfection in human erythrocytes
Authors: López-Farfán Diana , Irigoyen Nerea , Gómez-Díaz Elena
Published: March 2023

The co-occurrence and the similarities between malaria and COVID-19 diseases raise the question of whether SARS-CoV-2 is capable of infecting red blood cells and, if so, whether these cells represent a competent niche for the virus. In this study, we first tested whether CD147 functions as an alternative receptor of SARS-CoV-2 to infect host cells. Our results show that transient expression of ACE2 but not CD147 in HEK293T allows SARS-CoV-2 pseudoviruses entry and infection. Secondly, using a SARS-CoV-2 wild type virus isolate we tested whether the new coronavirus could bind and enter erythrocytes. Here, we report that 10,94% of red blood cells had SARS-CoV-2 bound to the membrane or inside the cell. Finally, we hypothesized that the presence of the malaria parasite, Plasmodium falciparum, could make erythrocytes more vulnerable to SARS-CoV-2 infection due to red blood cell membrane remodelling. However, we found a low coinfection rate (9,13%), suggesting that P. falciparum would not facilitate the entry of SARS-CoV-2 virus into malaria-infected erythrocytes. Besides, the presence of SARS-CoV-2 in a P. falciparum blood culture did not affect the survival or growth rate of the malaria parasite. Our results are significant because they do not support the role of CD147 in SARS-CoV-2 infection, and indicate, that mature erythrocytes would not be an important reservoir for the virus in our body, although they can be transiently infected.
Cross-sectional association between systemic metal concentrations and immune markers in patients with total joint arthroplasty
Authors: Peterson Stephanie M. , O’Byrne Thomas J. , Brennan Peter C. , Jannetto Paul J. , Pavelko Kevin D. , Lewallen David G. , Vassilaki Maria , Maradit Kremers Hilal
Published: March 2023

Total joint arthroplasty (TJA) implants are composed of metal components. Although they are regarded safe, the long-term immunological effects of chronic exposure to the specific implant materials are unknown. We recruited 115 hip and/or knee TJA patients (mean age 68 years) who provided a blood draw for measurement of chromium, cobalt, titanium concentrations, inflammatory markers and systemic distribution of immune cells. We examined differences between the immune markers and the systemic concentrations of chromium, cobalt and titanium. CD66-b neutrophils, early natural killer cells (NK), and eosinophils were present in higher percentages in patients with chromium and cobalt concentrations greater than the median. The opposite pattern was observed with titanium where the percentages of CD66-b neutrophils, early NK, and eosinophils were higher in patients with undetectable titanium. Cobalt concentrations were positively correlated with a higher percentage of gamma delta T cells. Both chromium and cobalt concentrations were positively correlated with higher percentages of plasmablasts. Titanium concentrations were positively correlated with higher CD4 effector memory T cells, regulatory T cell count and Th1 CD4 helper cells. In this exploratory study, we observed altered distribution of immune cells in TJA patients with elevated systemic metal concentrations. Although these correlations were not strong, these exploratory findings warrant further investigation into the role of increased metals circulating in blood and its role in immune modulation.
Protective anti-tumor vaccination against glioblastoma expressing the MHC class II transactivator CIITA
Authors: Celesti Fabrizio , Gatta Andrea , Shallak Mariam , Chiaravalli Anna Maria , Cerati Michele , Sessa Fausto , Accolla Roberto S. , Forlani Greta
Published: March 2023

Glioblastoma is the most malignant tumor of the central nervous system. Current treatments based on surgery, chemotherapy, and radiotherapy, and more recently on selected immunological approaches, unfortunately produce dismal outcomes, and less than 2% of patients survive after 5 years. Thus, there is an urgent need for new therapeutic strategies. Here, we report unprecedented positive results in terms of protection from glioblastoma growth in an animal experimental system after vaccination with glioblastoma GL261 cells stably expressing the MHC class II transactivator CIITA. Mice injected with GL261-CIITA express de novo MHC class II molecules and reject or strongly retard tumor growth as a consequence of rapid infiltration with CD4+ and CD8+ T cells. Importantly, mice vaccinated with GL261-CIITA cells by injection in the right brain hemisphere strongly reject parental GL261 tumors injected in the opposite brain hemisphere, indicating not only the acquisition of anti-tumor immune memory but also the capacity of immune T cells to migrate within the brain, overcoming the blood–brain barrier. GL261-CIITA cells are a potent anti-glioblastoma vaccine, stimulating a protective adaptive anti-tumor immune response in vivo as a consequence of CIITA-driven MHC class II expression and consequent acquisition of surrogate antigen-presenting function toward tumor-specific CD4+ Th cells. This unprecedented approach for glioblastoma demonstrates the feasibility of novel immunotherapeutic strategies for potential application in the clinical setting.
Non-coding RNA alterations in extracellular vesicles from bronchoalveolar lavage fluid contribute to mechanical ventilation-induced pulmonary fibrosis
Authors: Tang Ri , Hu Yue , Mei Shuya , Zhou Yang , Feng Jinhua , Jin Tao , Dai Bo , Xing Shunpeng , Gao Yuan , Xu Qiaoyi , He Zhengyu
Published: March 2023

Objective

For respiratory failure patients, mechanical ventilation (MV) is a life-saving therapy to maintain respiratory function. However, MV could also cause damage to pulmonary structures, result in ventilator-induced lung injury (VILI) and eventually progress to mechanical ventilation-induced pulmonary fibrosis (MVPF). Mechanically ventilated patients with MVPF are closely related to increased mortality and poor quality of life in long-term survival. Thus, a thorough understanding of the involved mechanism is necessary.

Methods

We used next-generation sequencing to identify differentially expressed non-coding RNAs (ncRNAs) in BALF EVs which were isolated from Sham and MV mice. Bioinformatics analysis was conducted to identify the engaged ncRNAs and related signaling pathways in the process of MVPF.

Results

We found 1801 messenger RNAs (mRNA), 53 micro RNAs (miRNA), 273 circular RNAs (circRNA) and 552 long non-coding RNAs (lncRNA) in mice BALF EVs of two groups, which showed significant differential expression. TargetScan predicted that 53 differentially expressed miRNAs targeted 3105 mRNAs. MiRanda revealed that 273 differentially expressed circRNAs were associated with 241 mRNAs while 552 differentially expressed lncRNAs were predicated to target 20528 mRNAs. GO, KEGG pathway analysis and KOG classification showed that these differentially expressed ncRNA-targeted mRNAs were enriched in fibrosis related signaling pathways and biological processes. By taking the intersection of miRNAs target genes, circRNAs target genes and lncRNAs target genes, we found 24 common key genes and 6 downregulated genes were confirmed by qRT-PCR.

Conclusions

Changes in BALF-EV ncRNAs may contribute to MVPF. Identification of key target genes involved in the pathogenesis of MVPF could lead to interventions that slow or reverse fibrosis progression.