bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development of a Model for Appreciation Lessons in the Music Subject
Authors:   The Korean Society of Music Education Technology, Yoon Sungwon
Published: February 2024

The purpose of this study was to develop a lesson model for the appreciation domain in the music subject. For that purpose, the investigator examined appreciation lessons of music subject and made in inquiry into basic models to develop a lesson model. Based on them, the study generated the following results: first, it presented the components and mechanism of model development for appreciation lessons in the music subject; secondly, it presented a model for appreciation lessons in the music subject; and third, it provided a set of guidelines for its application to the music subject. The appreciation lesson model for the music subject developed in the study contained two-stage content for stepwise learning activities, the elements and strategies to increase the learning motivation of students, and the stages of practicing learning activities as an overall framework for the students and lessons here and now. The investigator made the following proposals for the smooth application of findings: first, teachers should understand the objectives of appreciation lessons in the music subject clearly and teach their students accordingly; secondly, they should always contemplate over the ways to motivate the students to learn; and finally, they should make use of best technologies in their lessons.
A Study on the Audition Pieces of Music Colleges for the Cello Majors from 2007 to 2017
Authors:   The Korean Society of Music Education Technology, Lee MyungJin
Published: February 2024

The purpose of this study is to analyze the audition requirements for the admission of the 8 music colleges for cello majors for last 10 years. In order to achieve this goal, 55 cello pieces were collected from 8 music colleges such as Kyunghee University, Seoul National University, Sookmyung Women’s University, Yonsei University, Ewha Womans University, Chungang University, Korea National University of Arts, and Hanyang University. Investigating the frequency of the repertoire presents that 8 music colleges are applying a uniform standard in their audition requirements. This results may illustrate that the cello audition repertoire is quite limited and many music colleges prefer to select the student in the early decision rather than the regular one.
Development of ‘Music Making Activities’ Teaching Materials for Elementary School Music Curriculum using Golden section and Fibonacci Sequence
Authors:   The Korean Society of Music Education Technology, Kwag Hyungyu
Published: February 2024

Among 6 capabilities suggested in the 2015 revised elementary school music curriculum, musical creativity · convergence thinking capability means the capability to make new and creative idea based on specialized knowledge and refinement in music field and to utilize musical information learnt or experienced by oneself in a convergent manner on various phenomena. It is required to develop not only new teachingㆍlearning method but also teaching materials in order to foster such capability. Therefore, this study developed teaching materials using Fibonacci sequence in order to apply to “music making activities“ in the ’expression’ field of the elementary school music curriculum. For this, investigation of relationships between music and mathematics was conducted from the aspect of theoretical background and examples of music were suggested using Golden section and Fibonacci sequence. It is expected that development of music making activities teaching materials to which mathematical conception was applied will be helpful for students without interest and confidence in music study to easily approach the study and also will be a small alternative to teachers who feel burden of guiding music making activities.
Action Plans of Music Education for Enhancing Core Competencies
Authors:   The Korean Society of Music Education Technology, Jang Gunjoo
Published: February 2024

The purpose of this study is to examine the action (implementation) plans in curriculum reorganization, teaching·learning methods and strategies, and education assessment in order to identify methods of improving music competencies. The result of this study is as follows. First, the curriculum reorganization included the process of setting goals and content configuration, actualizing and specifying music instruction in accordance with the achievement standards, planning teaching methods and materials, and assessment plans and tools.
Second, in teaching·learning methods, contents of music competencies needed to be reconstructed in accordance with lesson plans and implemented an appropriate courses and strategies. Therefore, this study presented subsequent reconfiguration examples and strategies of music lessons in elementary and middle schools.
Third, examples of various assessment tools including assessment perspective (viewpoints of assessment) and criteria, contents and time, and methods were suggested for the proper evaluation of the competency-based lesson plans and practices. Support systems suggested the flexible time operations and educational environments, appropriate teaching·learning methods for applying competency based music lessons, a variety of assessment tools and dissemination measures, such as process oriented assessment based on the achievement standards.
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Authors:   The Korean Society of Music Education Technology, Shin Jihae
Published: February 2024

전 세계의 교육자들은 교직에 적성을 가지고 있으며 능력 있는 학생들을 유인하는 것에 많은 관심을 기울이고 있다. 본 연구는 한국의 예비음악교사들이 교직을 선택하게 된 동기를 탐색하는데 목적을 두었다. 연구 목적에 따른 연구 질문은 다음과 같다. 첫째, 예비음악교사들은 언제 교사가 되기로 결심하였는가? 둘째, 예비음악교사들의 교직 선택에 영향을 준 인물은 누구인가? 셋째, 예비음악교사들의 교직 선택에 영향을 준 경험은 무엇인가? 넷째, 예비음악교사들의 교직 선택에 영향을 준 사건은 무엇인가? 다섯째, 예비음악교사들의 교직 선택에 영향을 준 동기 부여 요인은 무엇인가? 사범대학과 교육대학원에 재학 중인 173명의 예비음악교사들이 본 연구를 위한 설문지에 참여하였다. 연구 결과, 대다수의 참여자들은 대학교에 재학 중이거나 졸업 후에 음악교사가 되기로 결심하였고, 부모가 교직 선택에 영향을 준 중요한 인물이었다고 응답하였다. 또한 교직을 선택하는데 있어서 학교 앙상블이 중요한 경험이었고, 개인 레슨이 음악교사가 되기로 결심하는데 있어서 중요한 사건이었다. 마지막으로 응답자들은 교직 선택에 영향을 미친 동기 부여 요인으로 외재적이거나 이타적인 요인보다는 내재적 요인을 중요시 여겼다.
Analysis of Research Trends on Child Musicality
Authors:   The Korean Society of Music Education Technology, Kim JeeEan
Published: February 2024

The purpose of this study is to present fundamental data for the research henceforth in the field of child musicality education, through the analysis of research trends. For this, 54 articles that were published during the last 14 years were selected and analyzed. The research trends were presented by year, content, research method, measurement scale, and date collecting method. Results on the analysis of research trends showed that the number of researches increased from 1 articles in 2003 to 10 articles in 2012, and the articles on the subject have proliferated into integrated research areas beyond the music education field. The greatest amount of research contents was on musical ability, particularly on 5-year old children. The most used research method was experimental research among the quantitative researches. The most used data analysis methods were by correlation analysis and regression analysis among survey researches. The PMMA(Gordon, 1986) measurement scale had the highest user rate. The most used data collection method was testing. The results showed that the study on the cognitive side and affective side of musicality was balanced in the contents of research. However, musicality has been principally measured as a musical ability. Overall, the research trends leaned more towards quantitative research, causing these significant implications of this research to be discussed.
Exploration of the Implementation Process of “Musicing” by Early Childhood Teachers
Authors:   The Korean Society of Music Education Technology, Bang EunYoung
Published: February 2024

The purpose of this study was to examine the implementation process of “musicing” among early childhood teachers in an effort to shed light on the content and method of their “musicing,” the changes of preschoolers experienced by them during the process and the educational significance of musicing in early childhood education. A collective case study was conducted after five early childhood teachers were selected. As for the method of the study, participant observation and interview were carried out, and the teachers were asked to keep a journal. Besides, activity footages and photograph materials were gathered. The collected data were analyzed by making a constant comparison analysis. The findings of the study were as follows: First, concerning the content and method of musicing, music activities that they conducted were extended in terms of both content and method, and a habit to attempt linking everything and every situation with music activities and integrating them was formed. There was a change in their teaching methods, and they made efforts to apply knowledge of music teaching methods. Second, the change of the preschoolers that the early childhood teachers experienced during the process of musicing were categorized into three: Young children who are outstanding musicians by instinct! Music activities in which every preschooler takes the initiative, and young children who actively get closer to their teachers to engage with them. Third, regarding the educational significance of musicing in early childhood education, musicing was a crucial channel to integrate early childhood curriculums. It created a classroom where the children enjoyed making musical expressions all the time, and it raised awareness of the importance of teacher roles in music activities. Finally, it accelerated the co-growth of the young children and the teachers. The findings of the study suggest that “musicing” could not only contribute to the development of young children’s music ability but be instrumental to early childhood education as an axis of it.
The relationship between Music Performance Anxiety and Trait Anxiety among College Music Majors
Authors:   The Korean Society of Music Education Technology, Bae Su Young
Published: February 2024

The purpose of this study was to examine the factors influencing Music Performance Anxiety(MPA) by analyzing the relationship between MPA and trait anxiety among college music majors by gender and major. The subjects were 170 college music majors who were enrolled in music department at two universities in Busan. MPA was measured by K-MPAS developed by Bae(2020) and trait anxiety was measured by STAI developed by Spielberger, Gorsuch, & Lushene(1970). The results are as follow: First, it was found that most of the students (89.4%) who participated in this study experienced MPA above the middle level, of which 47% experienced MPA above the upper level and 13.5% experienced the highest level. However, in terms of trait anxiety, most (81.8%) were found to be at a not very high level. These results indicate that MPA is a prevalent problem for college music major students, but it is an independent phenomenon that affects only a specific part of life, such as a performance situation. Second, according to gender, there was a significant difference in MPA (p< .01), but not in trait anxiety, and the level of MPA in female students was higher than that of male students. Third, according to major, there was a significant difference in MPA (p< .001), but not in trait anxiety, and string majors had the highest level of MPA and vocal majors had the lowest level of MPA. Fourth, it was found that, apart from gender and major variables, trait anxiety was a significant predictor of an individual s MPA. Based on these results, this study suggests that both personal and environmental factors are important to the MPA of college music major students.
Middle school students’ cultural and artistic activities Effects on self-esteem and happiness
Authors:   The Korean Society of Music Education Technology, Cho ung eun
Published: February 2024

This study uses data from the Korean Children and Youth Integrated 2018 provided by the Korea Youth Policy Research Institute, and the effect of cultural and artistic activities on the self-esteem and happiness of middle school students in the middle of adolescence. Is to find out. Therefore, it is to confirm the effect of cultural and artistic activities, which play an important role in the formation of emotions in adolescence, on the self-esteem and happiness of middle school students. The analyzed sample is the contents of the middle school student panel of the Korean Children and Youth Panel Survey 2018 responding to cultural and artistic activities, self-esteem, and feelings of happiness, and the exogenous variables of cultural and artistic activities were limited to music and art. Excluded. As for the analysis method, a model of the structural equation was established, and the causal relationship between culture and art activities, self-esteem, and happiness of middle school students was confirmed. The programs used for the analysis are SPSS and LESREL.
As a result of the analysis, cultural and artistic activities of middle school students had a direct effect on self-esteem and happiness, and self-esteem was also related to happiness. However, contrary to expectations, cultural and artistic activities showed a negative effect in the path of happiness, and showed a positive effect through the mediation of self-esteem. These results suggest that middle school students need to discuss cultural and artistic activities in a variety of ways, and that participation in cultural and artistic activities should be activated for the development of healthy emotions in adolescence.
A Narrative Inquiry on Critical Life and Overcoming Process Faced by Freelance Early Childhood Music Instructors in the COVID-19 Situation
Authors:   The Korean Society of Music Education Technology, Bang Eun Young
Published: February 2024

This study was conducted for the purpose of a narrative inquiry on critical life and overcoming process that the freelance early childhood music instructors confronted in the COVID-19 situation. For this, the research participants were selected as five freelance early childhood music instructors who are being active in the after-school program at a kindergarten and a child care center where are located in Seoul Metropolis and Gyeonggi Province. The researcher carried out the 5-time individual interview and the 2-time group interview with the research participants from March through October in 2020. As a result of the research, the critical life faced by the freelance early childhood music instructors in the COVID-19 situation appeared to include the following: ‘feeeling anxiety about resumption of childhood music classes during a desperate situation,’ ‘having doubt about carrying an unstable job as a freelancer music instructor.’ The crisis overcoming process was indicated to include ‘sinking into the abyss, finding me in a crisis,’ ‘the weight of life, To be connected with the supportive colleagues,’ ‘What I have to conquer in the end, Seeking a way out.’ The results of this study have a big implication in that arranged an opportunity of sympathizing with critical life encountered by freelance early childhood music instructors who struggle to get over a tough situation while striving not to give up the reward and expectation of own choice even in the face of difficulties, and of recognizing the need to prepare a social support system in order to prevent the leakage of early childhood music education professionals.
Potensi Interaksi Obat Pada Peresepan Obat Peroral Pasien Dewasa Rawat Inap Diabetes Mellitus Tipe 2 Dengan Komorbiditas Hipertensi Di RSUD Dr. Moewardi Surakarta
Authors: Yesi Yesi Susianti , Prawistya Sari Agnes , Rahardjoputro Rolando
Published: February 2024

Diabetes mellitus termasuk dalam penyakit kronis (menahun) yang diderita pasien selama hidupnya penyakit ini berdampak pada sumber manusia dan melonjaknya biaya kesehatan. Hipertensi termasuk dalam penyakit silent killer karena hampir tidak memiliki gejala awal apabila terdapat gejala sering dianggap sebagai gangguan biasa, dapat mengakibatkan efek yang fatal yaitu kematian. Penyebab diabetes mellitus tipe 2 disertai hipertensi yaitu retensi natrium ginjal yang menyebabkan ekspansi volume, peningkatan resistensi vaskular yang disebabkan karena kurangnya vasodilatasi yang diperantarai nitric oxide dan peningkatan stimulasi simpatetik karena hiperinsulinemia. Penelitian ini bertujuan untuk mengetahui gambaran potensi interaksi obat pada peresepan obat peroral pasien rawat inap diabetes mellitus tipe 2 dengan komorbiditas hipertensi di RSUD Dr. Moewardi Surakarta. Penelitian ini merupakan penelitian non eksperimental dengan rancangan pendekatan depskritif. Pengambilan data dilakukan secara retrospektif. Data penelitian diambil dari rekam medis pasien diabetes mellitus tipe 2 dengan komorbiditas hipertensi di instalasi rawat inap di RSUD Dr. Moewardi Surakarta tahun 2022. Hasil penelitian berdasarkan karakteristik responden menunjukkan jenis kelamin yang terbanyak adalah perempuan dibandingkan laki-laki, perempuan sebanyak 61 (61%) sedangkan laki- laki sebanyak 39 (39%). Berdasarkan hasil dari 100 catatan rekam medis pasien diabetes mellitus tipe 2 dengan komorbiditas hipertensi di instalasi rawat inap di RSUD Dr. Moewardi Surakarta tahun 2022 terdapat 64% pasien memiliki kriteria mayor sebanyak 0%, moderate sebanyak 64%, minor sebanyak 0% potensi interaksi obat diabetes mellitus tipe 2 dengan komorbiditas hipertensi.
What Multi-Level Solutions Can Enhance the Financial Literacy of Healthcare Professionals in Kenya?
Authors: Mtula Fiona-Hope A. , Son Barbara , Wambalaba Francis
Published: February 2024

Financial literacy is a crucial asset within the human capital pool, whether individuals are working within or outside the hospital setting. Professionals in various fields benefit from financial literacy, and the main recipients include individuals, the broader economy, businesses, and the overall financial system. In the context of medical professionals, the expectation is often that they make informed business decisions and effectively manage healthcare facilities. However, a notable challenge is the potential lack of essential skills in financial literacy among these professionals. In Kenya, a considerable number of healthcare professionals face a deficiency in financial literacy skills, hindering their ability to proficiently handle even small businesses in private practices and oversee financial matters in hospital departments, both in public and private healthcare facilities. Consequently, the objective of this study is to present healthcare professionals with a roadmap to identify and address gaps to enhance their financial literacy. A survey was conducted from June to July 2023, involving 339 doctors, including medical doctors, dentists, and pharmacists. The findings were interesting concerning gender performance and global comparisons. Unlike previous studies, female doctors demonstrated a higher financial knowledge, behavior, and attitude, suggesting a well-rounded financial proficiency compared to their male counterparts. At the global level, the descriptive analysis revealed strong financial knowledge, positive attitudes, and prudent financial behaviors among the Kenyan participating doctors compared to the OECD global averages. For example, unlike the OECD global average of 52.5% in financial knowledge and literacy, the findings for the Kenyan counterparts stood at 77%; while the OECD global average for financial attitude was 70%, that of the Kenyan counterparts was at 75%; and compared to the OECD global average of prudent financial behavior of 59%, that of the Kenyan counterparts was 69%. It seems that socio-demographic factors, coupled with financial knowledge, attitudes, and behaviors, intricately influence the financial literacy of healthcare professionals. The findings highlight the importance of implementing multi-level solutions to enhance overall financial literacy among healthcare professionals. These solutions include tailored financial programs, self-paced online courses with interactive elements, and the integration of financial literacy into medical undergraduate and postgraduate training curricula. Keywords: healthcare professionals, financial literacy, Kenya, multi-level solutions
A Pilot Study Showing Fluconazole and Flucytosine Activities against Candida glabrata are Affected by Low pH: Implications for the Treatment of Recurrent Vulvovaginal Candidiasis
Authors: Khan Ziauddin , Ahmad Suhail , Asadzadeh Mohammad
Published: February 2024

Background: Candida albicans (C. albicans) and Candida glabrata (C. glabrata) are mainly associated with vulvovaginal candidiasis (VVC). Management of VVC caused by C. glabrata is particularly challenging due to its inherent reduced susceptibility to fluconazole. In this prospective laboratory-based cohort study, we investigated the effect of pH on in vitro susceptibility of Candida spp. isolates to fluconazole and flucytosine. Methods: Vaginal isolates of C. glabrata, C. albicans, Candida tropicalis (C. tropicalis) and Candida parapsilosis (C. parapsilosis) were tested for susceptibility to fluconazole and flucytosine by Epsilometer test (ETEST) strips on Roswell Park Memorial Institute (RPMI) 1640 medium at pH 7.0 and pH 4.5. Minimum inhibitory concentrations (MICs) were read after 24 h at 35 °C. Results were interpreted according to the European Committee on Antimicrobial Susceptibility testing (EUCAST) guidelines. Results: Mean fluconazole MICs (µg/mL) at pH 4.5 were significantly higher than those at pH 7.0 for C. glabrata (82.55 ± 100.32 versus 14.96 ± 7.71, respectively, p = 0.001) and C. albicans (1.32 ± 7.98 versus 0.96 ± 1.35, respectively, p = 0.017) isolates. A similar effect was not observed with C. tropicalis and C. parapsilosis isolates. In contrast, mean MICs against flucytosine were reduced at pH 4.5 compared to pH 7.0 for all four Candida spp. isolates, with this reduction being statistically significant for C. glabrata and C. parapsilosis isolates. Conclusions: Our data show that the therapeutic efficacy of fluconazole against C. glabrata and C. albicans is reduced at lower (normal vaginal) pH values while the activity of flucytosine is enhanced. Therefore, flucytosine may serve as an effective alternative for the treatment of VVC and recurrent VVC caused by C. glabrata and other Candida spp.
Efficacy of Fractional CO2 Laser Versus Intravaginal Estrogen for Controlling the Genitourinary Syndrome of Menopause (GSM) Especially Sexual Dysfunctions—A Systematic Review and Meta-Analysis
Authors: Luo Can , Yue Fuping , Mei Ling , Chen Yueyue , Niu Xiaoyu
Published: February 2024

Background: Fractional CO2 laser (FCL) has been gradually used in the management of genitourinary syndrome of menopause (GSM) in recent years, but the results remain uncertain. We aimed to estimate the efficacy and safety of FCL as a novel treatment for controlling the GSM, especially sexual dysfunction, compared with intravaginal estrogen. Methods: The following digital databases were searched, including PubMed, Web of Science, Cochrane Library, and Embase. All the studies were limited to randomized controlled trials (RCTs). Included literatures must be in English, without limitation about region and race. The pooled dates were analyzed by Review Manger version 5.4 (Cochrane Collaboration’s Information Management System, London, UK). Results: 3 RCTs were included, which involved 160 patients, 79 of whom received FCL treatment, 81 received intravaginal estrogen treatments. This meta-analysis results showed no statistical significance existed in improving the patient’s vaginal health index (VHI) (mean difference (MD) = 0.59; 95% confidence interval (95% CI): –1.07~2.25; p = 0.49) after FCL treatment. In terms of the female sexual function index (FSFI) total scores, we observed no improvement without statistical significance (MD = –0.13; 95% CI: –3.32~3.06; p = 0.94). Furthermore, all the FSFI domains showed no statistical significance. No serious complications were reported in all included trials. Conclusions: FCL therapy was an interesting and novel treatment for menopausal female sexual dysfunction. However, no statistical evidence existed, which recommended that FCL was superior to intravaginal estrogen. Our results will be confirmed by high-quality and multicentric RCTs in the future.
Effect of Autologous Platelet-Rich Plasma Therapy on the Pregnancy Outcomes of Women with Repeated Implantation Failure: A Systematic Review and Meta-Analysis
Authors: Ma Tingting , Pu Yan
Published: February 2024

Background: A major challenge in reproductive medicine is repeated implantation failure (RIF). Possible benefits of platelet-rich plasma (PRP) for pregnancy outcomes are still uncertain, and more evidence is required to properly evaluate this. The current meta-analysis was therefore carried out to assess the impact of intrauterine PRP infusion on pregnancy outcomes in women with RIF. Methods: Various databases (Web of Science, PubMed, Cochrane Library, Embase) were screened for English-language papers that investigated the effect of PRP treatment on pregnancy outcomes in RIF women who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). This effect was analyzed in both frozen-thawed and fresh cycles. These studies involved randomized controlled trial (RCT) and quasi-experimental (non-randomized experimental) studies, but excluded case-control, case series, self-control, cross-sectional studies. The Newcastle-Ottawa Scale was employed to determine study quality. Risk ratios (RRs) were calculated for dichotomous outcome variables, and weighted mean difference (WMD) with 95% confidence interval (95% CI) for continuous outcome variables. These were performed under fixed- or random-effect models. Results: This meta-analysis evaluated 15 articles from the literature. Improved pregnancy outcomes were observed in RIF women who received PRP, including higher rates of implantation, clinical pregnancy and live birth compared to control patients. Conclusions: The results of this study indicate that PRP could be a useful treatment strategy for RIF patients and those with a thin endometrium. Additional large RCTs are required to identify the subpopulation of women who could derive the maximum benefit from PRP.
What Obstetricians Need to Know about Crohn’s Disease—A Narrative Review
Authors: Danciu Bianca Mihaela , Marincaş Augustin Marian , Ciocîrlan Mihai , Simionescu Anca Angela
Published: February 2024

Objective: Crohn’s disease (CD) is an immune-mediated inflammatory bowel disease (IBD), which comprises an idiopathic aberrant systemic and local inflammatory response. This response is a result of unknown interactions between the luminal content and the intestinal wall. This article is a review of the current state of knowledge providing information to help obstetricians to manage patients with CD, and to understand the particularities of these patients, with emphasis during pregnancy and postpartum, including recommendation for the birthing methods. It is important to explain the usefulness of the pursue of treatment during pregnancy, taking into consideration the drugs allowed during pregnancy, and addressing the challenges that CD may pose in addition to the physiological adaptations of pregnancy. Mechanism: As both an obstetrician and a gastroenterologist, this topic can be approach from two distinct perspectives. Firstly, how CD influences fertility and pregnancy, and secondly, an exploration on how hormonal changes and immune system tolerance during pregnancy probably influences CD. Findings in Brief: Data shows that pregnancy outcomes are influenced by the clinical course of CD at the time of conception. Latent disease prior to conception is associated with uneventful pregnancies and favorable neonatal outcomes, comparable to general population. Conversely, an active disease during pregnancy and ileal localization can be associated with prematurity, stillbirth, and small-for-gestational age (SGA) infants. A high risk of preeclampsia was reported in pregnancy with severe CD and oral or systemic corticosteroids administration. Optimal management approach involves a multidisciplinary team consisting of an obstetrician, gastroenterologist, and surgeon. Thiopurines and biologic agents are considered safe during pregnancy and breastfeeding. In infants with CD, alteration in the composition of the maternal microbiome may contribute to the systemic inflammation and to influence the transmission of an altered microbiota to the infants. This suggests that modulating the early microbiome can be an effective strategy to reduce cases of CD. Conclusions: Healthcare practitioners and patients must be aware that CD patients can have a successful pregnancy and a healthy infant. A multidisciplinary team can provide supportive care and help address significant information to adapt the treatment plan, and to monitor pregnancy.
The Large Ectodomain of APP Prevents APP from being Directly Cleaved by γ-Secretase
Authors: Li Yuan , Li Hejie , Liang Wenping , Li Yu , Wang Zhe
Published: February 2024

Background: Alzheimer’s disease (AD) is characterized by the deposition of amyloid-β peptide (Aβ) in the brain. Aβ is produced by sequential β- and γ-secretase cleavages of amyloid precursor protein (APP). Clinical trials targeting β- and γ-secretases have all failed, partly because of the strong side effects. The aims of this work were to determine if the direct cleavage of APP by γ-secretase inhibits Aβ production, and to identify γ-cleavage-inhibiting signals within APP that can be targeted to prevent Aβ generation without inhibiting any enzyme. Methods: An APP mutant mimicking secreted APPγ was overexpressed in cells to test β-cleavage and Aβ production. APP deletion and truncation mutants were overexpressed in cells to identify the γ-secretase-inhibiting domain. The intracellular transport of the mutants was examined using immunofluorescence. Co-immunoprecipitation was performed to investigate the molecular mechanisms. Results: The APP N-terminal fragment mimicking the direct γ-cleavage product was not cleaved by beta-secretase 1 to produce detectable Aβ. However, in cells, the C-terminal fragments of APP longer than the last 116 residues could not be cleaved by γ-secretase in cells. No deletion mutant was cleaved by γ-secretase. C99, the direct precursor of Aβ, was no longer a γ-secretase substrate when green fluorescent protein was fused to its N-terminus. The large ectodomains prevented access to γ-secretase. Conclusions: Enabling the direct γ-cleavage of APP is a new and valid strategy to reduce Aβ. However, APP does not inhibit γ-cleavage via a specific inhibitory sequence in the ectodomain. Other methods to fulfill the strategy may benefit AD prevention and therapy.
Analysis of TLR2 in Primary Endocrine Resistant of Breast Cancer
Authors: Wang Yunmei , Wang Guangxi , Wang Xiang , Yang Jiao , Shen Yanwei , Zhao Bin , Yang Jin
Published: February 2024

Background: Previous clinical studies have suggested that Toll-like receptor (TLR)2 had predictive function for endocrine resistance in HER2-positive breast cancer (BCa). Nevertheless, it remains unclear whether TLR2 would relate to development of endocrine therapy resistance in triple-positive breast cancer (TPBC). Methods: Bioinformatic analysis of TLR2 was carried out through a database. Ten tumor tissues were obtained from TPBC patients who underwent surgery, with five patients displaying primary resistance to tamoxifen (TAM) with the remaining 5 being sensitive. Different levels of proteins were identified through mass spectrometry analysis and confirmed through reverse transcription polymerase chain reaction (RT-PCR) and western blot. TAM-resistant cell lines (BT474-TAM) were established by continuous exposure to TAM, and TAM resistance was assessed via IC50. Additionally, TLR2 mRNA was analyzed through western blot and RT-PCR in BT474, BT474-TAM, MCF-7, and MCF10A cells. Furthermore, TLR2-specific interference sequences were utilized to downregulate TLR2 expression in BT474-TAM cells to elucidate its role in TAM resistance. Results: TLR2 had a correlation with decreased relapse-free survival in BCa patients from the GSE1456-GPL96 cohort, and it was involved in cancer development predominantly mediated by MAPK and PI3K pathways. TLR2 protein expression ranked in the top 5 proteins within the TAM-resistant group, and was 1.9 times greater than that in the sensitive group. Additionally, TLR2 mRNA and protein expression increased significantly in the established TAM-resistant BT474/TAM cell lines. The sensitivity of TAM was restored upon TLR2 downregulation in BT474/TAM cells. Conclusions: TLR2 might have a therapeutic value as it was involved in the TAM resistance in TPBC, with potential to be a marker for primary endocrine resistance.
Metabolic Landscape of Osteosarcoma: Reprogramming of Lactic Acid Metabolism and Metabolic Communication
Authors: Wang Linbang , Dou Xinyu , Xie Linzhen , Zhou Xuchang , Liu Yu , Liu Jingkun , Liu Xiaoguang
Published: February 2024

Background: Lactic acid, previously regarded only as an endpoint of glycolysis, has emerged as a major regulator of tumor invasion, growth, and the tumor microenvironment. In this study, we aimed to explore the reprogramming of lactic acid metabolism relevant to osteosarcoma (OS) microenvironment by decoding the underlying lactic acid metabolic landscape of OS cells and intercellular signaling alterations. Methods: The landscape of OS metabolism was evaluated using single-cell gene expression data, lactic acid metabolism clustering, and screening of the hub genes in lactic acid metabolism of OS samples using transcriptome data. The role of the hub gene NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 6 (NDUFAF6) was validated with in vitro studies and patient experiments. Results: Single-cell RNA sequencing data validated a lactic acid metabolismhigh subcluster in OS. Further investigation of intercellular communications revealed a unique metabolic communication pattern between the lactic acid metabolismhigh subcluster and other subclusters. Next, two lactic acid metabolic reprogramming phenotypes were defined, and six lactic acid metabolism-related genes (LRGs), including the biomarker NDUFAF6, were screened in OS. In vitro studies and patient experiments confirmed that NDUFAF6 is a crucial lactic acid metabolism-associated gene in OS. Conclusions: The patterns of lactic acid metabolism in OS suggested metabolic reprogramming phenotypes relevant to the tumor microenvironment (TME) and identified NDUFAF6 as an LRG prognostic biomarker.
Recent Advancements in the Atopic Dermatitis Mechanism
Authors: Savva Maria , Papadopoulos Nikolaos G , Gregoriou Stamatis , Katsarou Spyridoula , Papapostolou Niki , Makris Michael , Xepapadaki Paraskevi
Published: February 2024

Atopic dermatitis (AD) is a recurrent, chronic, inflammatory, itchy skin disorder that affects up to 20% of the pediatric population and 10% of the adult population worldwide. Onset typically occurs early in life, and although cardinal disease features are similar across all ages, different age groups and ethnicities present distinct clinical characteristics. The disease imposes a significant burden in all health-related quality of life domains, both in children and adults, and a substantial economic cost both at individual and national levels. The pathophysiology of AD includes a complex and multifaceted interplay between the impaired dysfunctional epidermal barrier, genetic predisposition, and environmental contributors, such as chemical and/or biological pollutants and allergens, in the context of dysregulated TH2 and TH17 skewed immune response. Regarding the genetic component, the loss of function mutations encoding structural proteins such as filaggrin, a fundamental epidermal protein, and the more recently identified variations in the epidermal differentiation complex are well-established determinants resulting in an impaired skin barrier in AD. More recently, epigenetic factors have facilitated AD development, including the dysbiotic skin microbiome and the effect of the external exposome, combined with dietary disorders. Notably, the interleukin (IL)-31 network, comprising several cell types, including macrophages, basophils, and the generated cytokines involved in the pathogenesis of itch in AD, has recently been explored. Unraveling the specific AD endotypes, highlighting the implicated molecular pathogenetic mechanisms of clinically relevant AD phenotypes, has emerged as a crucial step toward targeted therapies for personalized treatment in AD patients. This review aims to present state-of-the-art knowledge regarding the multifactorial and interactive pathophysiological mechanisms in AD.
Applications of Circulating Tumor DNA in Myelodysplastic Syndromes and Acute Myeloid Leukemia: Promises and Challenges
Authors: Xue Yuhang , Xia Xuejiao , Liu Xin , Zheng Yanhua , Gu Hongcang , Wang Xiaoxue
Published: February 2024

The term ‘liquid biopsy’ has become widely used by clinicians with the development of non-invasive diagnostic and monitoring techniques for malignancies. Liquid biopsy can provide genetic information for early diagnosis, risk stratification, treatment selection and postoperative follow-up. In the era of personalized medicine, liquid biopsy is an important research direction. In recent years, research on circulating tumour DNA (ctDNA) in hematological malignancies has also made great progress. This review provides an overview of the current understanding of circulating tumour DNA in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Additionally, recent advancements in the monitoring of minimal/measurable residual disease (MRD) through ctDNA are discussed.
The Use of Human Platelet Lysate as a Coating Substance for Adipose-Derived Stem Cell Expansion
Authors: Tragoonlugkana Patcharapa , Chitchongyingcharoen Narong , Pruksapong Chatchai , Hassan Shirmeela , Ngamkham Kamolchanok , Kamprom Witchayapon , Supokawej Aungkura
Published: February 2024

Background: Large-scale production of mesenchymal stromal cells is essential for sufficient therapeutic doses in regenerative medicine. However, long-term cultivation encounters limited cell growth and cellular aging. Therefore, an alternative cell culture approach that promotes proliferation and attenuates cell senescence is required. Human platelet lysate (HPL) is a potent supplement for in vitro cell expansion. Applying HPL as a coating material can potentially improve mesenchymal stromal cell cultures. Method: To examine the capacity of HPL, it was used to pre-coat a tissue culture plate for in vitro adipose-derived mesenchymal stromal cell expansion. Alterations in biological features of adipose-derived stem cells (ADSCs) were investigated, including cell adhesion assays, cell proliferation, population doubling time, and cellular senescence. Results: ADSCs cultured on HPL-coated plates significantly increased cell adhesion rate, shortened population doubling time, and stimulated cell growth. The senescent cells were significantly decreased in ADSCs cultured in an HPL-coated plate, and the expression levels of senescence-associated genes, including p16, p21, and p53, were downregulated. Furthermore, Western blotting analysis revealed that HPL was enriched with fibronectin and vitronectin, essential cell adhesive proteins. Conclusions: HPL was effectively used as a coating material for ADSC expansions. Cellular cultivation on the HPL coating is an alternative approach for producing mesenchymal stromal cells.
A Comprehensive Prognostic and Immune Infiltration Analysis of RBM4 in Pan-Cancer
Authors: Ding Jia-Jun , Wu Jie , Bian Hai-Lei , Zong Yi , Lu Bing , Ni Li
Published: February 2024

Background: Aberrant splicing has been closely associated with human cancer, though the precise underlying mechanisms linking the two remain not fully understood. Investigating the role of splicing factors in cancer progression may aid in the development of targeted therapies for dysregulated splicing, thereby opening up new avenues for cancer treatment. RNA-binding motif 4 (RBM4) has been identified as a critical participant in the condensin II complex, which is involved in chromosome condensation and stabilization during mitosis. Its significance in tumors is currently gaining attention. The genetic characteristics of RBM4 suggest its potential to elucidate the malignant progression of tumors in a broader context, encompassing various types of cancer, known as pan-cancer. Methods: This study aims to comprehensively explore the potential function of RBM4 in pan-cancer by leveraging existing databases such as The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Results: RBM4 is found to be overexpressed in almost all tumors and exhibits significant prognostic and diagnostic efficacy. The correlation between RBM4 and immune signatures, including immune cell infiltration and immune checkpoint genes, indicates that RBM4 could serve as a guiding factor for immunotherapy. Conclusions: As a member of the pan-oncogene, RBM4 has the potential to become a biomarker and therapeutic target for various malignant tumors, offering novel possibilities for precision medicine.
Handwriting Movement Abnormalities in Older Adults with Silent Cerebral Small Vessel Disease—A Preliminary Study
Authors: Zhao Hongyi , Chi Liyi , Teulings Hans-Leo , Xia Cuiqiao , Huang Yonghua
Published: February 2024

Background: The features of cerebral small vessel disease (CSVD) range from occurrence of asymptomatic radiological markers to symptomatic characteristics that include cognitive deficits and gait decline. The aim of the present study was to examine whether handwriting movement is abnormal in older people with CSVD through handwriting and drawing tasks using digitized handwriting kinematic assessment technology. Methods: Older subjects (n = 60) were grouped according to Fazekas score, with 16 in the Severe CSVD group, 12 in the Non-severe group and 32 in the Healthy group. Kinematic data were recorded and analyzed during handwriting and drawing tasks: signature; writing of Chinese characters (“正” and “永”); and Archimedes’ spiral drawing. Results: The Severe CSVD group showed lower velocity and higher tortuosity during signature writing, lower velocity of stroke #4 of “正” and vertical size of “永” than did the Non-severe and Healthy groups. Both Severe CSVD and Non-severe CSVD subjects displayed higher average normalized jerk than did the Healthy group. Partial correlation analysis adjusting for age, gender, education, and mini-mental state evaluation (MMSE) showed that CSVD burden was positively associated with tortuosity of signature and average normalized jerk of Archimedes’ spiral, and was negatively associated with velocity of strokes #3 and #4 of “正”, as well as vertical size of “永”. Conclusions: Older adults with CSVD showed abnormal handwriting movement. And the handwriting abnormalities captured by digitized handwriting analysis were correlated with CSVD severity in users of simplified Chinese characters.
Increased Extracellular Water in Normal-Appearing White Matter in Patients with Cerebral Small Vessel Disease
Authors: Man Shuqian , Chen Songkuan , Xu Zhihua , Zhang Hongxia , Cao Zhenyu
Published: February 2024

Background: Microcirculatory variations have been observed in the normal-appearing white matter (NAWM) of individuals affected by cerebral small vessel disease (CSVD). These variations collectively possess the potential to trigger neuroinflammation and edema, ultimately leading to an elevation in extracellular fluid (ECF). Nevertheless, the specific alterations in ECF within the NAWM of CSVD patients have remained inadequately understood. Methods: We reviewed the clinical and imaging characteristics of a cohort comprising 129 patients diagnosed with CSVD to investigate alterations in the ECF within NAWM. The severity of CSVD was assessed by total CSVD magnetic resonance (MR) score according to the four imaging markers, namely perivascular space, lacunar infarction, white matter hyperintensities and cerebral microbleed. ECF was evaluated by the parameter free water (FW), ranging from 0 to 1 generated from diffusion tensor imaging. Results: Significant differences in NAWM FW were observed in relation to the total CSVD MR score (p < 0.05). Patients with a total CSVD MR score of 0 exhibited significantly lower NAWM free water (FW) values compared to those with a score greater than 0 (p < 0.05). Similarly, patients with a total CSVD MR score of 1 also demonstrated notably lower NAWM FW values than those with a score greater than 1 (p < 0.05). After conducting multivariate regression analysis, age and total CSVD MR score was independently associated with FW in NAWM (p < 0.001). Further, the total CSVD MR score served as a partial mediator in the relationship between age and FW in the NAWM among patients with CSVD. Conclusions: ECF in NAWM is increased in CSVD patients, even during the early course of CSVD.
Coronary Microvascular Function Assessment using the Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients with ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Li Ming , Peng Xi , Zheng Naixin , Ai Hu , Zhao Ying , Li Hui , Yang Guojian , Tang Guodong , Sun Fucheng , Zhang Huiping
Published: February 2024

Background: Studies reporting the status of coronary microvascular function in the infarct-related artery (IRA) after primary percutaneous coronary intervention (PCI) remain limited. This study utilized the coronary angiography-derived index of microcirculatory resistance (caIMR) to assess coronary microvascular function in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. Methods: We used the FlashAngio system to measure the caIMR after primary PCI in 157 patients with STEMI. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite endpoint encompassing cardiac mortality, target vessel revascularization, and rehospitalization due to congestive heart failure (CHF), myocardial infarction (MI), or angina. Results: Approximately 30% of patients diagnosed with STEMI and who experienced successful primary PCI during the study period had a caIMR in the IRA of >40. The caIMR in the IRA was significantly higher than in the reference vessel (32.9 ± 15.8 vs. 27.4 ± 11.1, p < 0.001). The caIMR in the reference vessel of the caIMR >40 group was greater than in the caIMR ≤40 group (30.9 ± 11.3 vs. 25.9 ± 10.7, p = 0.009). Moreover, the caIMR >40 group had higher incidence rates of MACEs at 3 months (25.5% vs. 8.3%, p = 0.009) and 1 year (29.8% vs. 13.9%, p = 0.04), than in the caIMR ≤40 group, which were mainly driven by a higher rate of rehospitalization due to CHF, MI, or angina. A caIMR in the IRA of >40 was an independent predictor of a MACE at 3 months (hazard ratio (HR): 3.459, 95% confidence interval (CI): 1.363–8.779, p = 0.009) and 1 year (HR: 2.384, 95% CI: 1.100–5.166, p = 0.03) in patients with STEMI after primary PCI. Conclusions: Patients with STEMI after primary PCI often have coronary microvascular dysfunction, which is indicated by an increased caIMR in the IRA. An elevated caIMR of >40 in the IRA was associated with an increased risk of adverse outcomes in STEMI patients undergoing primary PCI.