bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving The Performance Employees Of Bogor Regency Regional Device Organization Through Improvement Employee Discipline, Work Climate, And Work Motivation
Authors: Istanawati Endah Wal
Published: February 2023

The purpose of this study is to examine the influence of improving employee discipline, work climate and work motivation on improving the performance of employees of regional device organizations in Bogor Regency. The research population is the executor in the Human Resources Staffing and Development Agency and the Bogor Regency Regional Secretariat as many as 290 people with a sample size of 169 people calculated using the Slovin formula with an error rate of 5%. Data collection for each variable studied using questionnaires with a rating scale. Data analysis techniques use descriptive statistical analysis techniques and inferential statistical analysis techniques. The data analysis in this study used the Partial Least Square Structural Equation Modelling (PLS SEM) method. The results showed: (a) Employee discipline variables have a positive and significant influence on motivational variables. (b) Employee discipline variables have a positive and significant influence on performance variables. (c) Work climate variables have a positive and significant influence on motivational variables. (d) Work climate variables have a positive and insignificant influence on performance variables. (e) Motivational variables have a positive and significant influence on performance variables. (f) The magnitude of the coefficient of parameters for discipline variables on performance through motivation is 0.054 which means there is a positive indirect influence of discipline on performance through motivation. Or it can be interpreted that the higher the value of discipline, the performance through motivation will increase as well. (g) The magnitude of the coefficient of parameters for the working climate variable on performance through motivation is 0.278 which means there is a positive indirect influence of discipline on performance through motivation. Or it can be interpreted that the higher the value of the work climate, the performance through motivation will increase as well.
Penerapan In House Training Untuk Meningkatkan Kompetensi Guru Tentang Konsep Matematika Di SMP Negeri 10 Bogor
Authors: Septiana Estiza
Published: February 2023

This research departs from the phenomenon that occurs in schools that the teacher's low understanding of the concept of Mathematics in the learning process. Therefore, a school principal needs to consider a strategy to increase teacher competency skills so that they can improve their abilities. This study aims to determine the effectiveness of the implementation of in-house training in improving teacher competence on the concept of Mathematics, to describe the process of increasing teacher competence about the concept of Mathematics through the implementation of in-house training activities, to measure the magnitude of the increase in teacher competence on the concept of Mathematics through the implementation of in-house training. The research was conducted at SMP Negeri 10 Bogor in the first semester of the 2019/2020 academic year. The results of this study indicate that by implementing in-house training can motivate teachers to improve their competence in understanding mathematical concepts. Before carrying out the in-house training, of the 5 Mathematics teachers, almost all of the teachers did not have the correct understanding of the concept of Mathematics learning. After the in-house training on the concept of learning Mathematics, there was an increase in the first cycle as many as 3 teachers (60%) became aware of the concept of Mathematics, as many as 1 person (20%) understood enough, and as many as 1 person (20%) did not understand. In the second cycle there was an increase to all teachers, as many as 5 people (100%) understood the concept of learning Mathematics. That the implementation of in-house training can improve the competence of teachers about the concept of Mathematics. Therefore, researchers suggest that the implementation of In house training in improving teacher competence should be socialized and used as an alternative in understanding Mathematics concepts for teachers in the Bogor City Education Office.
Upaya Mengatasi Kecemasan Peserta Didik Dalam Menghadapi Ujian Sekolah Melalui Penerapan Teknik Layanan Bimbingan Kelompok
Authors: Darwanto Darwanto
Published: February 2023

The purpose of this study was to determine the application of group guidance service techniques to overcome students' anxiety, to describe the process of efforts to overcome student anxiety, to measure the increase in efforts to overcome students' anxiety in dealing with school exams by applying group guidance service techniques in class IX of junior high school. The problem of this research is the high anxiety of students in facing the School Exam, therefore researchers will try to overcome this anxiety through the application of group guidance service techniques in the hope that students are able to overcome all the problems they experience in facing the School Exam. The method used is action research specifically on the problem of efforts to overcome student anxiety in facing school exams. The data collection technique used is filling out a questionnaire. Observation, interview. The tools used in this research are related to action planning, implementation process, as well as the results of the implementation of the action, the unit of guidance and counseling services in the field of tutoring and group guidance services. observation guidelines, to collect data at the time of the implementation of the good actions concerning the activities of teachers and students as research subjects. The results showed that the implementation of guidance and counseling action research with a group guidance service approach could reduce students' anxiety levels in facing the School Exam in class IX of Bogor City Junior High School. The existence of the ability of students in an effort to reduce the level of anxiety of students in facing school exams and is supported by the active involvement of students in the implementation of group guidance. The magnitude of the ability of students in an effort to reduce the level of anxiety of students in facing the School Exam is the lowest score in the pre-cycle, which is 70, decreasing to 39 in the first cycle and 22 in the second cycle. The highest value in the pre-cycle was 99, decreased to 78 in the first cycle and decreased again to 40 in the second cycle. The average in the pre-cycle was 81.50 in the first cycle changed to 56.71 in the second cycle and 31.43 in the second cycle. The completeness value becomes 100% because all students who are the subjects of the study have a score below or equal to the completeness target, which is 40.
Meningkatkan Kompetensi Guru Dalam Menyusun Kriteria Ketuntasan Minimal Melalui Metode Pendampingan Di SD Negeri Bojongkerta Kota Bogor
Authors: Sumiati Neneng
Published: February 2023

The purpose of this study was to improve the teacher's ability to develop minimum completeness criteria through mentoring for elementary school teachers in Bojongkerta, South Bogor District, Bogor City. The method used in this research is Action Research which consists of 2 (two) cycles, and each cycle consists of: Planning, Implementation, Observation, and Reflection. Based on the results of action research that Mentoring can Improve Teachers' Ability in Developing Minimum Completeness Criteria for Teachers at SDN Bojongkerta, South Bogor District, Bogor City. Furthermore, the researcher recommends: (1) Principals who have the same difficulty can apply Mentoring to improve the ability to develop Minimum Completeness Criteria for Guided Teachers. (2) In order to obtain maximum results, intensive and sustainable individual assistance can be applied. This research can provide benefits, especially: (1) For teachers, an effective method can be found in compiling minimum criteria for completeness, (2) for school principals to increase their role as supervisors so that they can improve teacher abilities, (3) for schools to determine the direction of learning achievement in learning. one school year.
Upaya Meningkatkan Hasil Belajar Siswa Dalam Memahami Unsur-Unsur Intrinsik Cerpen Melalui Metode Jigsaw Pada Siswa SMPN 1 Kota Bogor
Authors: Husnaeni Dedi
Published: February 2023

This study aims to identify and describe the increase in Literature Learning Outcomes in Understanding the Intrinsic Elements of Short Stories through the Jigsaw Method for Junior High School Students. The background problem is that students' ability to understand short stories is still not good. This problem can be reduced by using the Jigsaw method. This Classroom Action Research was conducted in two cycles by taking the setting at Junior High School Students (SMP Negeri 1) Bogor City class IX-E with a total of 37 students as a sample. The sample was given a test instrument listening to the reading of short stories in order to obtain an intrinsic element appreciation test score. The conclusion of this study is the average ability of students in Pre-Cycle 57. In Cycle I the level of achievement was still low with an average score of 71 and the number of students who completed 22 people so that the percentage of completeness only reached 71%. In Cycle II it was classified as good with an average score of 82 and the number of students who completed reached 28 people so that the percentage of completeness reached 87%. This proves that there is an increase in the ability to understand the intrinsic elements of short stories through the Jigsaw method. This means that the Jigsaw method is relatively effective in an effort to improve the ability to understand the intrinsic elements of short stories that are read to class IX-F students of Junior High School Students (SMP Negeri 1) Bogor City.
Meningkatkan Hasil Belajar Siswa Kelas VIII SMP Negeri 19 Kota Bogor Melalui Penggunaan Media Simulasi Virtual PhET Pada Pelajaran Ipa Materi Getaran
Authors: Kurniawati Wiwin
Published: February 2023

The purpose of this study was to determine the increase in student learning outcomes regarding the subject matter of Vibration of Science in class VIII of SMP Negeri 19 Bogor City Even Semester of the 2021/2022 Academic Year through the use of PhET Virtual Simulation Media. The method used is a class action research method consisting of two cycles. In the first cycle, learning was carried out using the PhET Virtual Simulation Media, while in the second cycle, the enhanced PhET Virtual Simulation Media was used. In each cycle consists of four stages of research namely planning, implementation of action, observation, and reflection. The research data were analyzed using a comparative descriptive followed by reflection. Comparative descriptive is done by comparing the initial condition data, cycle 1 and cycle 2, both for learning outcomes. The results of this study indicate that: First, the use of PhET Virtual Simulation Media can improve student learning outcomes about Vibration material in science subjects in class VIII. It is proven that the percentage of student learning outcomes has increased from the initial condition the average daily test score was 68.91 in cycle I to 75.37 and in cycle II to 82.29 or in the final condition it increased by 19.42% from the initial condition. It is proven that the percentage of students' learning completeness increased from the initial condition of 61.11% in cycle I to 91.67% in cycle II or in the final condition it increased by 50.01% from the initial condition.
Analisis Bimbingan Belajar Siswa Berkesulitan Membaca
Authors: Suchyadi Yudhie
Published: February 2023

Analysis of Student Guidance with Difficulty Reading. Qualitative research with a descriptive study approach. Thesis of Elementary School Teacher Education Study Program, Faculty of Teacher Training and Education, Pakuan University, Bogor, 2020. The objective is to describe the forms of learning difficulties to read, factors of reading difficulties and tutoring for students with reading difficulties. The subjects of this study were 3 students of class IIIA & IIIB Cimayang State Elementary School 01. The research was carried out in the odd semester of the 2020-2021 school year. In collecting data, researchers used observation, interview and documentation methods. Researchers used credibility, transferability, dependability, and confirmability tests to obtain data validity. The results showed that the form of reading difficulty students could not distinguish letters that were almost the same shape, students did not recognize diphthong and digraphs, students stammered reading syllables, students could not read words, could not pronounce letters in one sentence and still spell letters. The factors that cause student reading difficulties are students lack of interest in reading, the family environment lack of parental attention to their children's learning activities at home, lack of enthusiasm for students in learning, teaching methods and media used by teachers when the teaching and learning process is inadequate does not vary, disturbances in health. Guidance for students having difficulty learning to read at SD Negeri Cimayang 01 is still not optimal. The role of the school in providing guidance for students with difficulty learning to read is also not optimal. In addition, the ability of students to have difficulty learning to read in overcoming their learning difficulties is still lacking.
Teaching U.S. Constitutional Design: The Case of the "Genovian Revolution"
Authors: Anson Ian
Published: February 2023

Instructors often lament that their students possess a distorted understanding of the U.S. Constitution. Students often initially fail to appreciate how power, group interests, and conflictual processes have shaped American political institutions and their long-term effects. To foster a view of U.S. Constitutional design that better reflects the core insights of contemporary political science, I introduce a two-week constitutional convention simulation that centers on the fictional Principality of Genovia. Working in groups, students assume roles within various segments of Genovian society who seek democratic representation following the sudden abdication of their autocratic prince. The simulation is designed to foreshadow key concepts in American government and politics. It also provides a collaborative, active learning environment. In a pre-post survey instrument, I test the effectiveness of the Genovian simulation in fostering key learning outcomes vis-a-vis several other classroom modules, finding that the Genovian exercise is beneficial to students on several dimensions.
Teaching Information Literacy in General Education Using Conspiracy Theories
Authors: Kelly Jarrod
Published: February 2023

Introductory coursework in political science, particularly courses that also satisfy general education requirements, have historically focused on imparting substantive knowledge within a subfield. I propose that political scientists may want to rethink approaches to general education to reflect the modern informational environment. While the internet and other communication technologies make information about politics and government more accessible, this has the unintended consequence of facilitating a more rapid, and often more consequential, spread of mis-/dis-information. Therefore, I posit that undergraduate courses, particularly those aimed at non-majors, should offer an increased focus on fostering students political information literacy skills. In this paper, I will describe my approach to designing and implementing a general education course on mis-/dis-information centered around conspiracy theories. I also present some preliminary findings on changes in students beliefs regarding conspiracy theories before and after they completed the course.
In vitro screening of anti-methanogenic additives for use in Australian grazing systems
Authors: Parra Mariano C. , Forwood Daniel L. , Chaves Alex V. , Meale Sarah J.
Published: February 2023

Despite considerable effort to develop and optimise additives to reduce methane emissions from cattle, little information on additive effectiveness exists for cattle under grazing scenarios. As the majority of Australian cattle production occurs on grazing land it is pertinent to report on the use of additives under simulated conditions. The current study evaluated the addition of nine additives to Rhodes grass hay under in vitro conditions, to estimate their impact on methane (CH4), gas production, and rumen fermentation parameters (volatile fatty acids, rumen pH and in vitro dry matter digestibility [IVDMD]). Citral extract at 0.1% of rumen media decreased all CH4 production parameters, but reduced gas production and digestibility, compared to a 100% hay control. Similarly, Sandalwood essential oil decreased CH4 production at 48 h, IVDMD and gas production, compared to the control. Biochar + nitrates at 5 and 8% DM, and Biochar + Asparagopsis at 5% DM decreased cumulative CH4 production (15.6%, 25.9%, 23.8%, respectively; P < 0.01), compared to the control. No changes in IVDMD and gas production were observed. As such, the biochar additives were considered the most promising additives from those evaluated with a substrate designed to replicate Australian grazing systems.
The monkeypox diagnosis, treatments and prevention: A review
Authors: Khattak Saadullah , Rauf Mohd Ahmar , Ali Yasir , Yousaf Muhammad Tufail , Liu Zhihui , Wu Dong-Dong , Ji Xin-Ying
Published: February 2023

The world is currently dealing with a second viral outbreak, monkeypox, which has the potential to become an epidemic after the COVID-19 pandemic. People who reside in or close to forest might be exposed indirectly or at a low level, resulting in subclinical disease. However, the disease has lately emerged in shipped African wild mice in the United States. Smallpox can cause similar signs and symptoms to monkeypox, such as malaise, fever, flu-like signs, headache, distinctive rash, and back pain. Because Smallpox has been eliminated, similar symptoms in a monkeypox endemic zone should be treated cautiously. Monkeypox is transmitted to humans primarily via interaction with diseased animals. Infection through inoculation via interaction with skin or scratches and mucosal lesions on the animals is conceivable significantly once the skin barrier is disrupted by scratches, bites, or other disturbances or trauma. Even though it is clinically unclear from other pox-like infections, laboratory diagnosis is essential. There is no approved treatment for human monkeypox virus infection, however, smallpox vaccination can defend counter to the disease. Human sensitivity to monkeypox virus infection has grown after mass vaccination was discontinued in the 1980s. Infection may be prevented by reducing interaction with sick patients or animals and reducing respiratory exposure among people who are infected.
Shifts and importance of viable bacteria in treatment of DSS-induced ulcerative colitis mice with FMT
Authors: Liu Jinglong , Lin Hao , Cao Man , Lin Tan , Lin Aiqiang , Xu Wei , Wang Han , He Jianquan , Li Yuantao , Tang Hailing , Zhang Bangzhou
Published: February 2023

Background and Aims

Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease.

Methods

We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota.

Results

We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group.

Conclusion

We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.
Fresh takes on five health data sharing domains: Quality, privacy, equity, incentives, and sustainability
Authors: Guerrini Christi J. , Majumder Mary A. , Robinson Jill O. , Cook-Deegan Robert , Blank Matthew , Bollinger Juli , Geary Janis , Gutierrez Amanda M. , Shrikant Maya , McGuire Amy L.
Published: February 2023

As entities around the world invest in repositories and other infrastructure to facilitate health data sharing, scalable solutions to data sharing challenges are needed. We conducted semi-structured interviews with 24 experts to explore views on potential issues and policy options related to health data sharing. In this Perspective, we describe and contextualize unconventional insights shared by our interviewees relevant to issues in five domains: data quality, privacy, equity, incentives, and sustainability. These insights question a focus on granular quality metrics for gatekeeping; challenge enthusiasm for maximalist risk disclosure practices; call attention to power dynamics that potentially compromise the patient's voice; encourage faith in the sharing proclivities of new generations of scientists; and endorse accounting for personal disposition in the selection of long-term partners. We consider the merits of each insight with the broad goal of encouraging creative thinking to address data sharing challenges.
The C-FEWS framework: Supporting studies of climate-induced extremes on food, energy, and water systems at the regional scale
Authors: Vörösmarty Charles J. , Melillo Jerry M. , Wuebbles Donald J. , Jain Atul K. , Ando Amy W. , Chen Mengye , Tuler Seth , Smith Richard , Kicklighter David , Corsi Fabio , Fekete Balazs , Miara Ariel , Bokhari Hussain H. , Chang Joseph , Lin Tzu-Shun , Maxfield Nico , Sanyal Swarnali , Zhang Jiaqi , Vignoles Daniel
Published: February 2023

Climate change continues to challenge food, energy, and water systems (FEWS) across the globe and will figure prominently in shaping future decisions on how best to manage this nexus. In turn, traditionally engineered and natural infrastructures jointly support and hence determine FEWS performance, their vulnerabilities, and their resilience in light of extreme climate events. We present here a research framework to advance the modeling, data integration, and assessment capabilities that support hypothesis-driven research on FEWS dynamics cast at the macro-regional scale. The framework was developed to support studies on climate-induced extremes on food, energy, and water systems (C-FEWS) and designed to identify and evaluate response options to extreme climate events in the context of managing traditionally engineered (TEI) and nature-based infrastructures (NBI). This paper presents our strategy for a first stage of research using the framework to analyze contemporary FEWS and their sensitivity to climate drivers shaped by historical conditions (1980–2019). We offer a description of the computational framework, working definitions of the climate extremes analyzed, and example configurations of numerical experiments aimed at evaluating the importance of individual and combined driving variables. Single and multiple factor experiments involving the historical time series enable two categories of outputs to be analyzed: the first involving biogeophysical entities (e.g., crop production, carbon sequestered, nutrient and thermal pollution loads) and the second reflecting a portfolio of services provided by the region’s TEI and NBI, evaluated in economic terms. The framework is exercised in a series of companion papers in this special issue that focus on the Northeast and Midwest regions of the United States. Use of the C-FEWS framework to simulate historical conditions facilitates research to better identify existing FEWS linkages and how they function. The framework also enables a next stage of analysis to be pursued using future scenario pathways that will vary land use, technology deployments, regulatory objectives, and climate trends and extremes. It also supports a stakeholder engagement effort to co-design scenarios of interest beyond the research domain.
Epigenetic clocks derived from western samples differentially reflect Taiwanese health outcomes
Authors: Lin Wan-Yu
Published: February 2023

Introduction: Several epigenetic clocks have been developed, with five measures of epigenetic age acceleration (EAA) especially receiving extensive investigations: HannumEAA, IEAA, PhenoEAA, GrimEAA, and DunedinPACE. These epigenetic clocks were mainly developed by individuals of European or Hispanic ancestry. It remains unclear whether they can reflect disease morbidity and physiological conditions in Asian populations.

Methods: I here investigated five measures of EAA of 2,474 Taiwan Biobank participants with DNA methylation data. Using logistic regressions, I sequentially regressed various health outcomes on each of the five measures of EAA while adjusting for chronological age, sex, body mass index, the number of smoking pack-years, drinking status, regular exercise, educational attainment, and six cell-type proportions.

Results: Except for IEAA, all measures of EAA reflected the obesity of Taiwanese (p < 4.0E-4). Diabetes was reflected by DunedinPACE (p = 5.4E-6) and GrimEAA (p = 5.8E-5). Moreover, DunedinPACE was associated with dyslipidemia, including hypertriglyceridemia (p = 1.1E-5), low high-density lipoprotein cholesterol (HDL-C) (p = 4.0E-5), and high triglyceride to HDL-C ratio (p = 1.6E-7).

Discussion: This is one of the first studies to show that epigenetic clocks (developed by individuals of European or Hispanic ancestry) can reflect Taiwanese physiological conditions. DunedinPACE was associated with more Taiwanese health outcomes than the other four measures of EAA.
Comprehensive analysis reveals signal and molecular mechanism of mitochondrial energy metabolism pathway in pancreatic cancer
Authors: Yang Hong , Cui Ye , Zhu YuMing
Published: February 2023

Pancreatic cancer (PAAD) is one of the most malignant tumors with the worst prognosis. The abnormalities in the mitochondrial energy metabolism pathway are intimately correlated with the occurrence and progression of cancer. For the diagnosis and treatment of pancreatic cancer, abnormal genes in the mitochondrial energy metabolism system may offer new targets and biomarkers. In this study, we compared the dysregulated mitochondrial energy metabolism-associated pathways in PAAD based on pancreatic cancer samples in the Cancer Genome Atlas (TCGA) database and normal pancreas samples from the Genotype Tissue Expression project (GTEx) database. Then identified 32 core genes of mitochondrial energy metabolism pathway-related genes (MMRG) were based on the gene set enrichment analysis (GSEA). We found most of these genes were altered among different clinical characteristic groups, and showed significant prognostic value and association with immune infiltration, suggesting critical roles of MMRG involve tumor genesis of PAAD. Therefore, we constructed a four-gene (LDHA, ALDH3B1, ALDH3A1, and ADH6) prognostic biomarker after eliminating redundant factors, and confirming its efficiency and independence. Further analysis indicated the potential therapeutic compounds based on the mitochondrial energy metabolism-associated prognostic biomarker. All of the above analyses dissected the critical role of mitochondrial energy metabolism signaling in pancreatic cancer and gave a better understanding of the clinical intervention of PAAD.
Immune checkpoints expression patterns in early-stage triple-negative breast cancer predict prognosis and remodel the tumor immune microenvironment
Authors: Zhang Jinguo , Jin Hongwei , Pan Shuaikang , Han Chaoqiang , Sun Qingqing , Han Xinghua
Published: February 2023

Background

Currently, targeting immune checkpoint molecules holds great promise for triple-negative breast cancer (TNBC). However, the expression landscape of immune checkpoint genes (ICGs) in TNBC remains largely unknown.

Method

Herein, we systematically investigated the ICGs expression patterns in 422 TNBC samples. We evaluated the ICGs molecular typing based on the ICGs expression profile and explored the associations between ICGs molecular subtypes and tumor immune characteristics, clinical significance, and response to immune checkpoint inhibitors (ICIs).

Results

Two ICGs clusters and two ICGs-related gene clusters were determined, which were involved in different survival outcomes, biological roles and infiltration levels of immune cells. We established a quantification system ICGs riskscore (named IRS) to assess the ICGs expression patterns for individuals. TNBC patients with lower IRS were characterized by increased immune cell infiltration, favorable clinical outcomes and high sensitivity to ICIs therapy. We also developed a nomogram model combining clinicopathological variables to predict overall survival in TNBC. Genomic feature analysis revealed that high IRS group presented an increased tumor mutation burden compared with the low IRS group.

Conclusion

Collectively, dissecting the ICGs expression patterns not only provides a new insight into TNBC subtypes but also deepens the understanding of ICGs in the tumor immune microenvironment.
The role of TNF-α in the fate regulation and functional reprogramming of mesenchymal stem cells in an inflammatory microenvironment
Authors: Li Weiqiang , Liu Qianqian , Shi Jinchao , Xu Xiang , Xu Jinyi
Published: February 2023

Mesenchymal stem cells (MSCs) are pluripotent stem cells with multidirectional differentiation potential and strong immunomodulatory capacity. MSCs have been widely used in the treatment of injured, inflammatory, and immune-related diseases. Resting MSCs lack differentiation and immunomodulatory ability. Instead, they rely on microenvironmental factors to: 1) stimulate and regulate their expression of specific cell growth factors, chemokines, immunomodulatory factors, or receptors; or 2) direct their differentiation into specific tissue cells, which ultimately perform tissue regeneration and repair and immunomodulatory functions. Tumor necrosis factor (TNF)-α is central to the creation of an inflammatory microenvironment. TNF-α regulates the fate and functional reprogramming of MSCs, either alone or in combination with a variety of other inflammatory factors. TNF-α can exert opposing effects on MSCs, from inducing MSC apoptosis to enhancing their anti-tumor capacity. In addition, the immunomodulation and osteogenic differentiation capacities of MSCs, as well as their exosome or microvesicle components vary significantly with TNF-α stimulating concentration, time of administration, or its use in combination with or without other factors. Therefore, this review discusses the impact of TNF-α on the fate and functional reprogramming of MSCs in the inflammatory microenvironment, to provide new directions for improving the immunomodulatory and tissue repair functions of MSCs and enhance their therapeutic potential.
Enhancing the functionality of self-assembled immune signals using chemical crosslinks
Authors: Ackun-Farmmer Marian , Jewell Christopher M.
Published: February 2023

Multiple sclerosis (MS) is an autoimmune disease that develops when dysfunctional autoreactive lymphocytes attack the myelin sheath in the central nervous system. There are no cures for MS, and existing treatments are associated with unwanted side effects. One approach for treating MS is presenting distinct immune signals (i.e., self-antigen and immunomodulatory cues) to innate and adaptive immune cells to engage multiple signaling pathways involved in MS. We previously developed immune polyelectrolyte multilayer (iPEM) complexes built through layer-by-layer deposition of self-antigen - myelin oligodendrocyte glycoprotein (MOG) - and toll-like receptor antagonist, GpG to treat MS. Here, glutaraldehyde-mediated stable cross-links were integrated into iPEMs to load multiple classes of therapeutics. These cross-linked iPEMs maintain their immunological features, including the ability of GpG to blunt toll-like-receptor 9 signaling and MOG to expand T cells expressing myelin-specific T cell receptors. Lastly, we show that these functional assemblies can be loaded with a critical class of drug - mTOR inhibitors - associated with inducing regulatory T cells. These studies demonstrate the ability to incorporate small molecule drugs in reinforced self-assembled immune signals juxtaposed at high densities. This precision technology contributes new technologies that could drive antigen-specific immune response by simultaneously modulating innate and adaptive immunity.
Regulatory effects of IRF4 on immune cells in the tumor microenvironment
Authors: Lu Jing , Liang Taotao , Li Ping , Yin Qingsong
Published: February 2023

The tumor microenvironment (TME) is implicated in tumorigenesis, chemoresistance, immunotherapy failure and tumor recurrence. Multiple immunosuppressive cells and soluble secreted cytokines together drive and accelerate TME disorders, T cell immunodeficiency and tumor growth. Thus, it is essential to comprehensively understand the TME status, immune cells involved and key transcriptional factors, and extend this knowledge to therapies that target dysfunctional T cells in the TME. Interferon regulatory factor 4 (IRF4) is a unique IRF family member that is not regulated by interferons, instead, is mainly induced upon T-cell receptor signaling, Toll-like receptors and tumor necrosis factor receptors. IRF4 is largely restricted to immune cells and plays critical roles in the differentiation and function of effector cells and immunosuppressive cells, particularly during clonal expansion and the effector function of T cells. However, in a specific biological context, it is also involved in the transcriptional process of T cell exhaustion with its binding partners. Given the multiple effects of IRF4 on immune cells, especially T cells, manipulating IRF4 may be an important therapeutic target for reversing T cell exhaustion and TME disorders, thus promoting anti-tumor immunity. This study reviews the regulatory effects of IRF4 on various immune cells in the TME, and reveals its potential mechanisms, providing a novel direction for clinical immune intervention.
FcγRI FG-loop functions as a pH sensitive switch for IgG binding and release
Authors: Lu Jinghua , Spencer Matthew , Zou Zhongcheng , Traver Maria , Brzostowski Joseph , Sun Peter D.
Published: February 2023

Understanding the molecular mechanism underlying the hierarchic binding between FcγRs and IgG antibodies is critical for therapeutic antibody engineering and FcγR functions. The recent determination of crystal structures of FcγRI-Fc complexes, however, resulted in two controversial mechanisms for the high affinity receptor binding to IgG. Here, we describe high resolution structures of a bovine FG-loop variant of FcγRI in complex with the Fc fragment of IgG1 crystallized in three different conditions at neutral pH, confirming the characteristic FG loop-Fc interaction is critical to the high affinity immunoglobulin binding. We showed that the FcγRI D2-domain FG-loop functioned as a pH-sensing switch for IgG binding. Further live cell imaging of FcγRI-mediated internalization of immune complexes showed a pH sensitive temporal-spatial antibody-antigen uptake and release. Taken together, we demonstrate that the structures of FcγRI-Fc crystallized at neutral and acidic pH, respectively, represent the high and low affinity binding states of the receptor for IgG uptake and release. These results support a role for FcγRI in antigen delivery, highlight the importance of Fc glycan in antibody binding to the high affinity receptor and provide new insights to future antibody engineering.
Stochastic processes drive the soil fungal communities in a developing mid-channel bar
Authors: Ye Fei , Hong Yiguo , Yi Xuemei , Sun Zhaohong , Wu Jiapeng , Wang Yu
Published: February 2023

Intricate associations between rhizosphere microbial communities and plants play a critical role in developing and maintaining of soil ecological functioning. Therefore, understanding the assembly patterns of rhizosphere microbes in different plants and their responses to environmental changes is of great ecological implications for dynamic habitats. In this study, a developing mid-channel bar was employed in the Yangtze River to explore the assembly processes of rhizosphere fungal communities among various plant species using high-throughput sequencing-based null model analysis. The results showed a rare significant variation in the composition and alpha diversity of the rhizosphere fungal community among various plant species. Additionally, the soil properties were found to be the primary drivers instead of plant species types. The null model analysis revealed that the rhizosphere fungal communities were primarily driven by stochastic processes (i.e., undominated processes of ecological drift), and the predominance varied with various plant species. Moreover, the assembly processes of rhizosphere fungal communities were significantly related to the changes in soil properties (i.e., soil total carbon, total nitrogen, organic matter, and pH). The co-occurrence network analysis revealed that many keystone species belonged to unclassified fungi. Notably, five network hubs were almost unaffected by the measured soil properties and aboveground plant traits, indicating the effect of stochastic processes on the rhizosphere fungal community assembly. Overall, these results will provide insights into the underlying mechanisms of fungal community assembly in the rhizosphere soils, which are significant for maintaining the functional stability of a developing ecosystem.
Soil fungal community characteristics vary with bamboo varieties and soil compartments
Authors: Guo Wen , Zhang Jian , Li Mai-He , Qi Lianghua
Published: February 2023

Soil fungi play an important role in nutrient cycling, mycorrhizal symbiosis, antagonism against pathogens, and organic matter decomposition. However, our knowledge about the community characteristics of soil fungi in relation to bamboo varieties is still limited. Here, we compared the fungal communities in different soil compartments (rhizosphere vs. bulk soil) of moso bamboo (Phyllostachys edulis) and its four varieties using ITS high-throughput sequencing technology. The fungal α diversity (Shannon index) in bulk soil was significantly higher than that in rhizosphere soil, but it was not affected by bamboo variety or interactions between the soil compartment and bamboo variety. Soil compartment and bamboo variety together explained 31.74% of the variation in fungal community diversity. Soil compartment and bamboo variety were the key factors affecting the relative abundance of the major fungal taxa at the phylum and genus levels. Soil compartment mainly affected the relative abundance of the dominant fungal phylum, while bamboo variety primarily influenced the dominant fungal genus. Network analysis showed that the fungal network in rhizosphere soil was more complex, stable, and connected than that in bulk soil. A FUNGuild database analysis indicated that both soil compartment and bamboo variety affect fungal functions. Our findings provide new insights into the roles of both soil compartments and plant species (including variety) in shaping soil fungal communities.
Advances in the oral microbiota and rapid detection of oral infectious diseases
Authors: Xiao Xuan , Liu Shangfeng , Deng Hua , Song Yuhan , Zhang Liang , Song Zhifeng
Published: February 2023

Several studies have shown that the dysregulation of the oral microbiota plays a crucial role in human health conditions, such as dental caries, periodontal disease, oral cancer, other oral infectious diseases, cardiovascular diseases, diabetes, bacteremia, and low birth weight. The use of traditional detection methods in conjunction with rapidly advancing molecular techniques in the diagnosis of harmful oral microorganisms has expanded our understanding of the diversity, location, and function of the microbiota associated with health and disease. This review aimed to highlight the latest knowledge in this field, including microbial colonization; the most modern detection methods; and interactions in disease progression. The next decade may achieve the rapid diagnosis and precise treatment of harmful oral microorganisms.
The mechanism of sudden unexpected death in epilepsy: A mini review
Authors: Sun Xinyi , Lv Yehui , Lin Jian
Published: February 2023

Sudden unexpected death in epilepsy (SUDEP) is defined as a sudden, unexpected, non-traumatic, non-drowning death in a person with epilepsy. SUDEP is generally considered to result from seizure-related cardiac dysfunction, respiratory depression, autonomic nervous dysfunction, or brain dysfunction. Frequency of generalized tonic clonic seizures (GTCS), prone posture, and refractory epilepsy are considered risk factors. SUDEP has also been associated with inherited cardiac ion channel disease and severe obstructive sleep apnea. Most previous studies of SUDEP mechanisms have focused on cardiac and respiratory dysfunction and imbalance of the neural regulatory system. Cardiac-related mechanisms include reduction in heart rate variability and prolongation of QT interval, which can lead to arrhythmias. Laryngospasm and amygdala activation may cause obstructive and central apnea, respectively. Neural mechanisms include impairment of 5-HT and adenosine neuromodulation. The research to date regarding molecular mechanisms of SUDEP is relatively limited. Most studies have focused on p-glycoprotein, catecholamines, potassium channels, and the renin-angiotensin system, all of which affect cardiac and respiratory function.
Smaller baseline subcortical infarct volume predicts good outcomes in patients with a large core in early acute ischemic stroke after endovascular treatment
Authors: Gu Yiming , Ding Yasuo , Hang Yu , Cao Yuezhou , Jia Zhenyu , Zhao Linbo , Liu Ying , Liu Sheng
Published: February 2023

Background

Patients with acute ischemic stroke (AIS) and a large core may benefit from endovascular treatment (EVT) in the early time window.

Purpose

To examine the prognostic factors for good outcomes in patients with a large core (70–130 ml) after EVT.

Materials and methods

We retrospectively reviewed 40 patients who met the criteria from October 2019 to April 2021. Based on the modified Rankin Score (mRS) at 90 days, the patients were divided into a good outcome group (mRS 0–2) and a poor outcome group (mRS 3–6). Baseline and procedural characteristics were collected for unilateral and multivariate regression analyses to explore the factors that influence good outcomes. In particular, the infarct territories were quantified as subcortical infarct volume (SIV) and cortical infarct volume (CIV).

Results

Of the 40 patients included, good outcomes were observed in 11 (27.5%) patients. Younger age, smaller SIV and larger mismatch volume were noted in the good outcome group than in the poor outcome group (all P < 0.05). Multivariate logistic regression analysis showed that only a smaller SIV [odds ratio (OR) 0.801; 95% CI 0.644–0.996; P = 0.046] was an independent predictor for good outcomes. The receiver operating characteristic curve indicated a moderate value of SIV for predicting good outcomes, with an area under the receiver operating characteristic curve of 0.735 (95% CI 0.572–0.862; P = 0.007).

Conclusion

Subcortical infarct volume was a potential useful predictor of good outcomes in patients with a large core after EVT in the early time window.
Prognostic analysis of telangiectatic osteosarcoma of the extremities
Authors: Zhong Wei , Luo Wei , Lin Zili , Wu Ziyi , Yuan Yuhao , He Yizhe
Published: February 2023

Background and objectives

Telangiectatic osteosarcoma (TOS) is a rare but highly malignant subtype of osteosarcoma. Although surgical treatment is the primary treatment modality for osteosarcoma, evidence on the benefits of different surgical methods in patients with TOS is lacking. This study aimed to compare the effects of different surgical and adjuvant treatments on overall survival of TOS, and the association of patient demographics, oncological characteristics, and socioeconomic status on treatment outcomes.

Method

This retrospective study selected the most common TOS cases of the extremities registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1989 to 2019. Univariate and multivariate Cox regression models were used to analyze all prognostic factors, and Kaplan-Meier analyses were performed for disease-specific treatment factors of survival.

Result

A total of 127 patients were included in the analysis. The average age at initial diagnosis was 20.09 years. In univariate analyses, the absence of metastasis at initial diagnosis, limb-salvage surgery, adjuvant chemotherapy, and no regional lymph node dissection were associated with a lower risk of death. Multivariate analysis further showed that the presence or absence of distant metastasis and regional lymph node dissection, implementation of adjuvant chemotherapy, and choice of surgical method were independent predictors of prognosis.

Conclusion

Distant metastasis and regional lymph node dissection are associated with poorer outcomes in TOS, and amputation has no better prognosis than limb salvage surgery. Compared with conventional chemotherapy, neoadjuvant chemotherapy did not significantly improve the prognosis of TOS.
Asthma with recurrent middle lobe syndrome in children: Clinical features and lung function patterns
Authors: Feng Yong , Yu Haoting , Liu Xin , Chen Ning , Shang Yunxiao , Zhang Han
Published: February 2023

Background

Middle lobe syndrome (MLS) is a complication of childhood asthma. This study aimed to compare the clinical features and lung function between asthmatic children with recurrent MLS and transient right middle lobe (RML) and/or lingula atelectasis.

Methods

This study retrospectively analyzed asthmatic children with RML and/or lingula atelectasis between 2010 and 2020 using data from the pediatric pulmonary department. According to the episodes of atelectasis, children were divided into recurrent (≥2 episodes) and non-recurrent (only 1 episode) MLS groups, to compare clinical features and lung function. Spirometry during acute asthma exacerbation and stable stages were recorded, and variations were calculated.

Results

A total of 35 children with asthma and RML and/or lingula atelectasis were included, 15 of whom had recurrent MLS. The recurrent MLS group had a higher proportion of girls, infections, family allergy history, severe asthma, severe exacerbation, and higher levels of total IgE than the non-recurrent MLS group (P < 0.05). The recurrent MLS group had a significantly higher % predicted and z-scores for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), a greater proportion of high FEV1 and higher variations in FEV1 and FVC than that in the non-recurrent group (P < 0.05). After excluding children with mild to moderate asthma in the recurrent MLS group, the differences in clinical features disappeared, but the results regarding lung function remained similar, when compared to severe asthma patients without RML and/or lingula atelectasis.

Conclusions

Childhood asthma with recurrent MLS has more frequent severe asthma and exacerbation but high lung function and variations.