bluuebunny/crossref_metadata_2025 huggingface dataset:
SÖZLEŞMELERDE AMAÇ VE GENEL AHLAKA AYKIRILIK DEĞERLENDİRMESİ
Authors: ATEŞ Derya , SÜLEYMANLAR Gülin
Published: December 2022

Bu çalışma, sözleşme amacının genel ahlak kuralları denetimine tabi tutulması yönünden bir değerlendirmeyi içermektedir. Değerlendirme Türk ve İsviçre Hukukları yönünden doktrin ve yargı kararları esas alınarak genişletilmiş olup öncelikle sözleşme özgürlüğüne bağlı olarak Türk Borçlar Kanunu m. 26 ve m. 27 hükümleri ile “sözleşmenin içeriği” kavramı detaylandırılmaktadır. Çalışmada geniş anlamda sözleşme içeriğine dahil olan sözleşmenin amacı ve sınırları da özel olarak ortaya konulmaktadır. Zira bilhassa taraflara ait saik ve sözleşmenin sebebi (causa) yönünden sözleşmenin amacı ile var olan farkların ortaya konulması önem taşımaktadır. Belirlenen amaç doğrultusunda sözleşmelerde genel ahlaka aykırılık denetimi yapacak olan hâkimin hangi esasları incelemesi gerektiği özel olarak vurgulandıktan sonra sözleşmenin doğrudan ve dolaylı amacı kavramları açıklanmakta ve amacı genel ahlâka aykırı sözleşmeler ile genel ahlâka aykırı amaçla düzenlenen soyut borç ikrarları bakımından denetimin kapsamı belirlenmektedir. Amacı genel ahlâka aykırı sözleşmeler yönünden denetimin kapsamı incelenirken borçlandırıcı işlemler ve tasarruf işlemleri arasındaki ayrıma da işaret edilmektedir. Soyut borç ikrarları yönünden ise Türk Borçlar Kanunu m. 81 hükmü çerçevesinde bir değerlendirmeye de yer verilmektedir.
Chinese Language Structure From a Korean Perspective Consideration: Focusing on the Chinese Active Verbs Syntax
Authors:   The Korean Society of Culture and Convergence, Lee Seung- Hee
Published: December 2022

The purpose of this study is to examine the connection between the semantic function and grammatical structure of the Chinese word “activity verb” in the category above. This is an attempt to explain the Chinese active verb syntax, which was difficult to understand due to the grammatical structure of the Korean language, with the commercial characteristics of the verb. Therefore, words that do not match the Chinese language structure are not searched. This paper shows that the qualities inherently shared by verbs in language structure are at work. In line with this, it is suggested that Korean speakers can solve the questions faced by the Chinese grammar structure by looking at the commercial characteristics of verbs and considering the constraints and semantic changes of Chinese active verbs. Furthermore, it is possible to explain why some grammatical phenomena are always described as having two or more meanings depending on the commercial characteristics of the active verb.
Cultural Intermediation Experience of Sports Professionals in the Process of Glocalization Advertising of Multinational Corporation
Authors:   The Korean Society of Culture and Convergence, Kim Eonhye , Chang Ik Young , Lee Wonmi , Park Seulki , Song Minkyu
Published: December 2022

The purpose of this study is to examine how Nike, the main body of global media, and the autonomy of local Sports Professionals in the production of glocalized advertisements for multinational companies, are balanced, and to explore the role and limitations of sports workers as cultural intermediaries. The study's findings are listed below. First, the study participants participated in the production of glocalization advertisements for Nike, a multinational corporation, from an outsider called a sports expert to an insider called a cultural intermediaries. Second, Participants in the study were found to carry out cultural mediation activities such as changing sports, simplifying physical activities, and sharing data to actively reproduce the sports culture as cultural intermediaries, and trying to project the essence of sports into glocalization advertisements. They also attempted to project the essence of sports into glocalization advertisements. Third, it was noted that study participants felt left out from cultural mediation activities because of their ability to participate as cultural intermediaries was limited by multinational corporations.
KUALITAS LAPORAN KEUANGAN DI INDONESIA: TRANSPARANSI INFORMASI KEUANGAN DAN KARAKATERISTIK PEMERINTAH DAERAH
Authors: Firmansyah Amrie , Yuniar Muhamad Rizal , Arfiansyah Zef
Published: December 2022

Kualitas laporan keuangan mencerminkan kesesuaian informasi keuangan yang disajikan oleh suatu entitas dengan standar akuntansi yang berlaku. Laporan keuangan yang berkualitas baik menunjukkan bahwa informasi yang terkandung di dalamnya dapat digunakan dalam pengambilan keputusan. Penelitian ini bertujuan untuk menginvestigasi pengaruh transparansi informasi keuangan, belanja modal, kesehatan keuangan dan ukuran pemerintah daerah terhadap kualitas laporan keuangan pemerintah daerah. Penelitian ini menggunakan pendekatan metode kuantitatif. Data penelitian diambil dari ikhtisar laporan keuangan pemerintah kabupaten/kota di Indonesia tahun 2016 sampai dengan tahun 2019. Data penelitian ini bersumber dari www.djpk.kemenkeu.go.id, website resmi pemerintah daerah, dan www.bpk.go.id. Berdasarkan purposive sampling, sampel penelitian ini berjumlah 349 observasi. Pengujian hipotesis penelitian ini dilakukan dengan menggunakan analisis regresi logistik. Hasil pengujian menunjukkan bahwa transparansi informasi keuangan dan ukuran pemerintah daerah berpengaruh positif terhadap kualitas laporan keuangan. Penelitian ini juga menyimpulkan bahwa belanja modal dan kesehatan keuangan pemerintah daerah tidak bepengaruh terhadap kualitas laporan keuangan. Penelitian ini dapat digunakan oleh Badan Pemeriksa Keuangan dalam melakukan indikasi awal atas kualitas laporan keuangan pemerintah daerah.
SABERES PROFISSIONAIS DE PROFESSORES NA CONTEMPORANEIDADE: POR UMA EDUCAÇÃO TRANSFORMADORA E SUSTENTÁVEL
Authors: Vieira Cristiane Daniel , Vieira Josimar de Aparecido , Castaman Ana Sara
Published: December 2022

Este estudo busca conhecer saberes profissionais dos professores que são necessários na contemporaneidade a partir da análise das singularidades do mundo contemporâneo, das finalidades da educação escolarizada e das perspectivas para a construção de uma educação transformadora e sustentável. Constituído numa perspectiva qualitativa e dialética, foi produzido por meio de pesquisa bibliográfica, seguindo os tipos de pesquisa descritiva e exploratória, seguindo os movimentos e contradições próprios dos espaços educativos. Como organização, aponta características do mundo contemporâneo, finalidades das instituições escolares, perspectivas para a construção de uma educação transformadora e sustentável e as considerações finais. Esses pontos indicam que alterações advindas do mundo contemporâneo interferem na organização do trabalho educativo, reclamando um processo de formação de professores reflexivo voltado para uma educação transformadora e sustentável.
ONLINE AUTHORSHIP AND TEXT PRODUCTION IN FAN COLLABORATIVE CONTEXT
Authors: Lima Daniella de Jesus , Mercado Luís Paulo Leopoldo , Versuti Andrea Cristina
Published: December 2022

Este artigo tem como objetivos caracterizar o conceito de autoria em rede, descrever os conteúdos disponíveis no site Spirit Fanfics e Histórias, analisar como acontece o processo de construção das estórias e como proporciona aprendizagem aos sujeitos. Foi utilizada a pesquisa netnográfica, por meio da qual analisou-se o site a partir da observação participante para construção dos dados e a metodologia qualitativa quanto aos procedimentos. Foram aplicados questionários aos participantes, a fim de reunir informações acerca da produção de fanfics e da autoria em rede. Como resultados, destacamos que: a autoria em rede e a colaboração presentes na produção de fanfics conduzem os sujeitos ao engajamento; e por meio do engajamento os sujeitos aprendem acerca do conteúdo imerso na narrativa ficcional produzida.
O LETRAMENTO DIGITAL E AS POLÍTICAS DE INCLUSÃO DIGITAL NA FORMAÇÃO INICIAL DE PROFESSORES DE LÍNGUA ESPANHOLA
Authors: Pimentel Yong Lesly Diana , Forneck Kári Lúcia
Published: December 2022

O artigo traz resultados de uma pesquisa de mestrado que objetivou investigar como as tecnologias digitais são integradas em um Curso de Licenciatura em Letras - Língua e Literatura Portuguesa e Língua e Literatura Espanhola na formação inicial de professores. O estudo foi realizado com docentes e acadêmicos de um Curso de Letras, localizado em região de tríplice fronteira. Os resultados demonstram a relevância de propiciar o letramento digital na formação de professores. Evidenciou-se, também, que a baixa conectividade de internet limita a integração de várias tecnologias digitais na formação inicial. Com a crise sanitária provocada pelo vírus SARS-COV-2, a universidade ofertou políticas de inclusão digital para que os alunos continuem estudando na modalidade do ensino remoto emergencial.
Aumentando as views de Clarice Lispector: intertextualidade, interdiscurso e efeito-leitor em “Sonzers” e “Lispectors”
Authors: Scorsolini-Comin Fabio , Rodrigues Loise Ishikawa , Pacífico Soraya Maria Romano
Published: December 2022

O objetivo deste ensaio é refletir sobre as aproximações intertextuais e interdiscursivas a partir do efeito-leitor produzido entre os aqui denominados “Lispectors” (que leem Clarice Lispector) e “Sonzers” (fandom da cantora Luísa Sonza). Para tanto, será tomado como corpus a veiculação do videoclipe da música Penhasco, os comentários de fãs produzidos a partir do vídeo compartilhado no YouTube, entrevistas com a cantora e com o diretor do videoclipe, bem como a entrevista de Clarice Lispector concedida ao jornalista Julio Lerner em fevereiro de 1977 (TV Cultura). As referências analisadas possuem natureza intertextual, mas também interdiscursiva, apoiadas em um sujeito assujeitado, um sujeito da ideologia, produzindo como efeito de sentido a expressão do mal-estar, da angústia e do esvaziamento. Esse movimento opera proximidades que permitem o efeito-leitor de identificação de “Sonzers” e “Lispectors”.
Can the nucleic acid Ct value of discharged patients infected with SARS-CoV-2 Omicron variant be 35?——A retrospective study on fluctuation of nucleic acid Ct values in SNIEC mobile cabin hospital
Authors: Zhuang Xu , Zheng Yu , Wei Shun , Zhai Wei , Song Qixiang , Chen Min , Xu Qingrong , Fan Yiling , Zheng Junhua
Published: December 2022

Objective

To explore the meaning of cycle threshold (Ct) value fluctuation and the appropriateness of setting the discharge Ct value to 35, which is the current standard in Chinese guidelines.

Method

A retrospective study was conducted on 95 patients with Ct value fluctuation (Ct value below 35 on day 3; group A) and 97 patients with a normal discharge process (control; group B). Their clinical characteristics and follow-up data were collected.

Results

(1) There was no significant difference between the groups in age, gender distribution, number of vaccinations, initial ORF-Ct value, and initial N-Ct value. The proportion of patients complicated with chronic internal disorders, respiratory symptoms, and abnormal chest radiology in group A was significantly higher than that in group B. (2) Between the two groups, there was no significant difference in the ORF-Ct or N-Ct value on day 1, but the ORF-Ct and N-Ct values of group B on days 2 to 4 were significantly higher than those of group A. (3) There was no significant difference between the groups in the ORF-Ct value at discharge, but there was a significant difference in the N-Ct value at discharge. Seven days after discharge, almost 100% of the patients had been cured. The mean negative conversion interval of nucleic acid of the patients in group A was 14.5 ± 4.6 days, which was longer than that of the patients in group B (11.8 ± 4 days). (4) Logistic regression analysis showed that the ORF-Ct value on day 2 was the key factor influencing the Ct value fluctuation.

Conclusion

The fluctuation of Ct value is only a normal phenomenon in the recovery period of the disease, and there is no need for excessive intervention. It is reasonable to set the Ct value of the discharge standard to 35 and retest the nucleic acid on the 10th day after discharge for patients with underlying diseases or symptoms.
The diversity of vaginal microbiome in women infected with single HPV and multiple genotype HPV infections in China
Authors: Liu Shufa , Li Yuanyue , Song Yuzhu , Wu Xiaomei , Baloch Zulqarnain , Xia Xueshan
Published: December 2022

Introduction

The human papillomavirus (HPV) is the leading cause of cervical cancer globally. However, its microbial composition and association with the types of HPV infection remain elusive.

Methods

This study was designed to characterize the vaginal microbiota of 53 HPV-infected and 16 normal women (control group) by using high-throughput sequencing with the Illumina platform.

Results

In this study, the five leading phyla were Firmicutes (73.9%), Actinobacteriota (12.8%), Proteobacteria (6.2%), Fusobacteria (3.5%), and Bacteroidota (3.1%). We found that single HPV genotype–positive women had higher α-microbial diversity compared with HPV-negative and multiple HPV–positive women. In women with a single HPV genotype infection, the HPV-16 infection had significantly higher α-diversity than other genotype infections. In multiple HPV genotype–positive women, the highest α-diversity was found in women positive for HR–HR HPV genotype infection, compared with other infections. Furthermore, in single- and multiple-genotype infections, the abundance of s_unclassified_g_Lactobacillus decreased whereas the abundance of s_Gardnerella_vaginalis increased compared with control. Additionally, s_unclassified_f_Rhizobiaceae and s_sneathia_sanguinegens were only found in HPV-infected women.

Conclusion

This study showed that the type of HPV infection was associated with the composition of the vaginal microbiota. Further studies on HPV genotypes and vaginal microbiota are necessary to uncover more mysteries of their association and provide a promising therapeutic target as well as low-cost future therapeutic strategies.
Recombinant actin-depolymerizing factor of the apicomplexan Neospora caninum (NcADF) is susceptible to oxidation
Authors: Baroni Luciana , Abreu-Filho Péricles Gama , Pereira Luiz Miguel , Nagl Markus , Yatsuda Ana Patricia
Published: December 2022

Neospora caninum is a member of Apicomplexa Phylum and the causative agent of neosporosis, a disease responsible for abortions in cattle. Apicomplexan parasites have a limited set of actin-binding proteins conducting the regulation of the dynamics of nonconventional actin. The parasite actin-based motility is implicated in the parasite invasion process in the host cell. Once no commercial strategy for the neosporosis control is available, the interference in the parasite actin function may result in novel drug targets. Actin-depolymerization factor (ADF) is a member of the ADF/cofilin family, primarily known for its function in actin severing and depolymerization. ADF/cofilins are versatile proteins modulated by different mechanisms, including reduction and oxidation. In apicomplexan parasites, the mechanisms involved in the modulation of ADF function are barely explored and the effects of oxidation in the protein are unknown so far. In this study, we used the oxidants N-chlorotaurine (NCT) and H2O2 to investigate the susceptibility of the recombinant N. caninum ADF (NcADF) to oxidation. After exposing the protein to either NCT or H2O2, the dimerization status and cysteine residue oxidation were determined. Also, the interference of NcADF oxidation in the interaction with actin was assessed. The treatment of the recombinant protein with oxidants reversibly induced the production of dimers, indicating that disulfide bonds between NcADF cysteine residues were formed. In addition, the exposure of NcADF to NCT resulted in more efficient oxidation of the cysteine residues compared to H2O2. Finally, the oxidation of NcADF by NCT reduced the ability of actin-binding and altered the function of NcADF in actin polymerization. Altogether, our results clearly show that recombinant NcADF is sensitive to redox conditions, indicating that the function of this protein in cellular processes involving actin dynamics may be modulated by oxidation.
Can the utility value of educational sciences be induced based on a reflection example or empirical findings—Or just somehow?
Authors: Rochnia Michael , Gräsel Cornelia
Published: December 2022

Educational sciences are a major component of German teacher education. However, student teachers often do not consider educational sciences in university courses (a profession-specific combination of educational psychology, pedagogy and sociology) as helpful for the practice of teaching. To prepare future teachers for evidence-based practice, this is a disadvantageous motivational starting point, because educational sciences offer a large amount of current and relevant findings that can have a positive impact on educational practice. Thus, it would be beneficial for student teachers to see the utility value of educational sciences. The present study attempts to encourage student teachers to perceive the utility value of educational sciences with a utility value short intervention. Utility value interventions contribute to connecting the learning content with one’s own life to foster the motivation to use scientific knowledge. A 2 × 2 quasi-experiment was conducted. Two of the four groups received a utility value short intervention about educational sciences (Factor 1). In addition, a second factor was analyzed that takes up two patterns of educational reasoning in teacher education (Factor 2): Reasoning was either exemplified with an instruction to reflect on the usefulness of educational sciences (like in reflection-oriented educational reasoning) or with exemplary empirical findings from educational sciences (like in evidence-based educational reasoning). These two kinds of reasoning are objectives of teacher education and therefore could influence the effect of a utility value short intervention. Since epistemic goals influence engagement with educational sciences, they are also taken into account. The results showed that all four variants of the treatment increased the students’ assessment of the utility value of educational sciences; the utility value intervention had no additional effect. This is discussed with recourse to motivational theories and concepts of teacher education.
The attitudes of Jordanian English language and literature undergraduate students toward open-book exams
Authors: Abu-Snoubar Tamador Khalaf , Aldowkat Issam , Al-Shboul Yasser , Atiyat Mona Ahmad , Al-Hyari Hadeel
Published: December 2022

Introduction

The paper aims to investigate the attitudes of English Language and Literature students toward implementing the open-book exam in literature courses.

Methods

The research applied a mixed-method approach. The researchers interviewed five undergraduate students enrolled in the American Literature course for the qualitative part. In contrast, the research includes the results of 62 questionnaires for the quantitative part. Moreover, a survey questionnaire was developed by the researchers to collect data concerning the participants’ attitudes toward OBEs.

Results

The study found a positive attitude toward OBEs. Moreover, the study participants demonstrated that OBEs reduce stress levels that occur during exams in general. A statistical representation of the findings showed that the sample students have a positive attitude in relation to this unconventional assessment protocol.

Discussion

OBEs should be allowed more space in academic institutions since today’s world does not depend on the amount of information a job applicant deposits in his memory. What matters is the person possesses enough high-order thinking abilities and skills like problem-solving.
Associations of endogenous androgens and sex hormone-binding globulin with kidney function and chronic kidney disease
Authors: Lau Lina Hui Ying , Nano Jana , Prehn Cornelia , Cecil Alexander , Rathmann Wolfgang , Zeller Tanja , Lechner Andreas , Adamski Jerzy , Peters Annette , Thorand Barbara
Published: December 2022

Introduction

The role of endogenous androgens in kidney function and disease has not been extensively explored in men and women.

Research design and methods

We analyzed data from the observational KORA F4 study and its follow-up examination KORA FF4 (median follow-up time 6.5 years) including 1293 men and 650 peri- and postmenopausal women, not using exogenous sex hormones. We examined the associations between endogenous androgens (testosterone [T], dihydrotestosterone [DHT], free T [fT], free DHT [fDHT], and T/DHT), with estimated glomerular filtration rate (eGFR) at baseline and follow-up, prevalent, and incident chronic kidney disease (CKD) adjusting for common CKD risk factors.

Results

At baseline, 73 men (5.7%) and 54 women (8.4%) had prevalent CKD. Cross-sectionally, no significant associations between androgens and kidney function were observed among men. In women, elevated T (β=-1.305, [95% CI -2.290; -0.320]) and fT (β=-1.423, [95% CI -2.449; -0.397]) were associated with lower eGFR. Prospectively, 81 men (8.8%) and 60 women (15.2%) developed incident CKD. In women, a reverse J-shaped associations was observed between DHT and incident CKD (Pnon-linear=0.029), while higher fDHT was associated with lower incident CKD risk (odds ratio per 1 standard deviation=0.613, [95% CI 0.369; 0.971]. Among men, T/DHT (β=-0.819, [95% CI -1.413; -0.226]) and SHBG (Pnon-linear=0.011) were associated with eGFR at follow-up but not with incident CKD. Some associations appeared to be modified by type 2 diabetes (T2D).

Conclusion

Suggestive associations are observed of androgens and SHBG with kidney impairment among men and women. However, larger well-phenotyped prospective studies are required to further elucidate the potential of androgens, SHBG, and T2D as modifiable risk factors for kidney function and CKD.
Impact of objectively-measured sleep duration on cardiometabolic health: A systematic review of recent evidence
Authors: Dejenie Tadesse Asmamaw , G/Medhin Markeshaw Tiruneh , Admasu Fitalew Tadele , Adella Getachew Asmare , Enyew Engidaw Fentahun , Kifle Zemene Demelash , Seid Mohammed Abdu , Mengstie Misganaw Asmamaw , Abebe Endeshaw Chekol
Published: December 2022

Cardiometabolic disease is a spectrum of diseases including, cardiovascular diseases, and metabolic syndrome. It is the leading cause of morbidity and mortality worldwide, with premature deaths being preventable. Currently, sleep has emerged as a potential target for cardiometabolic disease prevention. Several epidemiological studies have provided ample evidence that objectively measured short sleep duration increases the risk of cardiometabolic disease. However, the findings are inconsistent, and few studies measure sleep duration on cardiometabolic profiles objectively. Therefore, in this review, we focused on the recently published literature that explored the association between objectively measured sleep duration and cardiometabolic profiles (cardiovascular diseases, type 2 diabetes mellitus, and metabolic syndrome), seeking more insights regarding the applicability and, in turn, the impact of objectively measured sleep duration on cardiometabolic health, which is relatively understudied. We retrieved the information manually from PubMed, Google Scholar, HINARI, and the Cochrane Library from 2015 to 2022 using appropriate search terms, we included 49 articles. In this review, we found a strong relationship between objectively measured sleep duration and the risk of cardiometabolic disease, indicating that objectively measured short sleep durations increase cardiometabolic risks. In general, the association between objectively measured sleep duration and increased cardiometabolic risks (CMR) has been well-documented in higher-income countries. Several studies found that longer sleep duration was associated with a more favorable cardiometabolic profile in early adolescence, independent of other risk factors. On the other hand, objectively measured short sleep duration is associated with adverse cardiometabolic health outcomes such as coronary heart disease, hypertension, type 2 diabetes mellitus, and metabolic syndrome.
Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss
Authors: Zhang Peng , Ye Jiekai , Dai Jiale , Wang Ying , Chen Genjun , Hu Jinping , Hu Qimiao , Fei Jun
Published: December 2022

Osteoporosis is a common metabolic bone disease with a rapidly increasing prevalence, characterized by massive bone loss because of excessive osteoclast formation. Gallic acid (GA), a phenolic acid isolated from Cornus officinalis, has anti-inflammatory and anti-oxidant effects, but its effect on osteoclast formation has not been confirmed. In our study, we demonstrated that GA significantly inhibited RANKL‐induced osteoclast formation and function of osteoclast in bone marrow monocytes (BMMs) and RAW264.7 cells in a dose-dependent manner without cytotoxicity. For molecular mechanisms, GA repressed osteoclastogenesis by blocking Akt, ERK, and JNK pathways, and suppressed osteoclastogenesis-related marker expression, including nuclear factor of the activated T-cell cytoplasmic 1 (NFATc1), c‐Fos, and cathepsin K (CTSK). In addition, we further assessed the effect of GA in an ovariectomized mouse model, which indicated that GA has a notable effect on preventing bone loss. In conclusion, GA exerts notable effects in inhibiting osteoclastogenesis and preventing ovariectomy-induced bone loss, suggesting that GA is a potential agent in osteoporosis treatment.
Technical advances and stability analysis in wind-penetrated power generation systems—A review
Authors: Yadav V. Vishnuvardhan , Saravanan B.
Published: December 2022

Recently, wind power from renewable energy power generation has been extended quickly to another level. To the grid, most renewable generators synchronize through the power electronic converters controlled flexibly. The high-level wind power penetration into the power generation system affects the dynamic performance of the power system and presents substantial uncertainties in system operation. This study mainly focuses on reviewing the various types of stability analyses in high-level wind penetration of power generation systems. It describes several challenges and simulation analyses related to stability issues. A comparative analysis has also been carried out for the various types of stability related to different research studies. The data show that transient stability has been significantly focused on in most of the studies.
Interplay of four types of RNA modification writers revealed distinct tumor microenvironment and biological characteristics in pancreatic cancer
Authors: Gao Wenzhe , Chen Dongjie , Liu Jixing , Zang Longjun , Xiao Tijun , Zhang Xianlin , Li Zheng , Zhu Hongwei , Yu Xiao
Published: December 2022

Background

Pancreatic cancer (PC) is one of the most lethal malignancies and carries a dismal mortality and morbidity. Four types of RNA modification (namely m6A, m1A, APA and A-to-I) could be catalyzed by distinct enzymatic compounds (“writers”), mediating numerous epigenetic events in carcinogenesis and immunomodulation. We aim to investigate the interplay mechanism of these writers in immunogenomic features and molecular biological characteristics in PC.

Methods

We first accessed the specific expression pattern and transcriptional variation of 26 RNA modification writers in The Cancer Genome Atlas (TCGA) dataset. Unsupervised consensus clustering was performed to divide patients into two RNA modification clusters. Then, based on the differentially expressed genes (DEGs) among two clusters, RNA modification score (WM_Score) model was established to determine RNA modification-based subtypes and was validated in International Cancer Genome Consortium (ICGC) dataset. What’s more, we manifested the unique status of WM_Score in transcriptional and post-transcriptional regulation, molecular biological characteristics, targeted therapies and immunogenomic patterns.

Results

We documented the tight-knit correlations between transcriptional expression and variation of RNA modification writers. We classified patients into two distinct RNA modification patterns (WM_Score_high and _low), The WM_Score_high subgroup was correlated with worse prognosis, Th2/Th17 cell polarization and oncogenic pathways (e.g. EMT, TGF-β, and mTORC1 signaling pathways), whereas the WM_Score_low subgroup associated with favorable survival rate and Th1 cell trend. WM_Score model also proved robust predictive power in interpreting transcriptional and post-transcriptional events. Additionally, the potential targeted compounds with related pathways for the WM_Score model were further identified.

Conclusions

Our research unfolds a novel horizon on the interplay network of four RNA modifications in PC. This WM_Score model demonstrated powerful predictive capacity in epigenetic, immunological and biological landscape, providing a theoretical basis for future clinical judgments of PC.
Appropriate level of cuproptosis may be involved in alleviating pulmonary fibrosis
Authors: Li Guoxing , Peng Lihua , Wu Mingjun , Zhao Yipin , Cheng Zhe , Li Gang
Published: December 2022

Objective

Cuproptosis is a newly discovered form of programmed cell death that has not been studied in pulmonary fibrosis. The purpose of the present study was to explore the relationship between cuproptosis and pulmonary fibrosis.

Methods

Single-cell sequencing (scRNA-seq) data for human and mouse pulmonary fibrosis were obtained online from Gene Expression Omnibus (GEO) database. First, fibroblast lineage was identified and extracted using the Seurat toolkit. The pathway was then evaluated via Gene Set Enrichment Analyses (GSEA), while transcription factor activity was analyzed using DoRothEA. Next, fibroblast differentiation trajectory was inferred via Monocle software and changes in gene expression patterns during fibroblast activation were explored through gene dynamics analysis. The trajectory was then divided into three cell states in pseudotime order and the expression level of genes related to cuproptosis promotion in each cell state was evaluated, in addition to genes related to copper export and buffering and key genes in cellular metabolic pathways.

Results

In the mouse model of pulmonary fibrosis induced by bleomycin, the genes related to cuproptosis promotion, such as Fdx1, Lias, Dld, Pdha1, Pdhb, Dlat, and Lipt1, were gradually down-regulated in the process of fibroblast differentiation from resting fibroblast to myofibroblast. Consistently, the same results were obtained via analysis of scRNA-seq data for human pulmonary fibrosis. In addition, genes related to copper ion export and buffering gradually increased with the activation of fibroblasts. Metabolism reprogramming was also observed, while fibroblast activation and tricarboxylic acid(TCA) cycle and lipid metabolism were gradually down-regulated and mitochondrial metabolism was gradually up-regulated.

Conclusion

The present study is the first to reveal a negative correlation between cuproptosis and fibrosis, suggesting that an appropriate cuproptosis level may be involved in inhibiting fibroblast activation. This may provide a new method for the treatment of pulmonary fibrosis.
Aryl hydrocarbon receptor: The master regulator of immune responses in allergic diseases
Authors: Riaz Farooq , Pan Fan , Wei Ping
Published: December 2022

The aryl hydrocarbon receptor (AhR) is a widely studied ligand-activated cytosolic transcriptional factor that has been associated with the initiation and progression of various diseases, including autoimmune diseases, cancers, metabolic syndromes, and allergies. Generally, AhR responds and binds to environmental toxins/ligands, dietary ligands, and allergens to regulate toxicological, biological, cellular responses. In a canonical signaling manner, activation of AhR is responsible for the increase in cytochrome P450 enzymes which help individuals to degrade and metabolize these environmental toxins and ligands. However, canonical signaling cannot be applied to all the effects mediated by AhR. Recent findings indicate that activation of AhR signaling also interacts with some non-canonical factors like Kruppel-like-factor-6 (KLF6) or estrogen-receptor-alpha (Erα) to affect the expression of downstream genes. Meanwhile, enormous research has been conducted to evaluate the effect of AhR signaling on innate and adaptive immunity. It has been shown that AhR exerts numerous effects on mast cells, B cells, macrophages, antigen-presenting cells (APCs), Th1/Th2 cell balance, Th17, and regulatory T cells, thus, playing a significant role in allergens-induced diseases. This review discussed how AhR mediates immune responses in allergic diseases. Meanwhile, we believe that understanding the role of AhR in immune responses will enhance our knowledge of AhR-mediated immune regulation in allergic diseases. Also, it will help researchers to understand the role of AhR in regulating immune responses in autoimmune diseases, cancers, metabolic syndromes, and infectious diseases.
Focusing on NK cells and ADCC: A promising immunotherapy approach in targeted therapy for HER2-positive breast cancer
Authors: Li Feifei , Liu Sheng
Published: December 2022

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer has a high metastatic potential. Monoclonal antibodies (mAbs) that target HER2, such as trastuzumab and pertuzumab, are the cornerstone of adjuvant therapy for HER2-positive breast cancer. A growing body of preclinical and clinical evidence points to the importance of innate immunity mediated by antibody-dependent cellular cytotoxicity (ADCC) in the clinical effect of mAbs on the resulting anti-tumor response. In this review, we provide an overview of the role of natural killer (NK) cells and ADCC in targeted therapy of HER2-positive breast cancer, including the biological functions of NK cells and the role of NK cells and ADCC in anti-HER2 targeted drugs. We then discuss regulatory mechanisms and recent strategies to leverage our knowledge of NK cells and ADCC as an immunotherapy approach for HER2-positive breast cancer.
A practical scoring model to predict the occurrence of critical illness in hospitalized patients with SARS-CoV-2 omicron infection
Authors: Zhang Yao , Han Jiajia , Sun Feng , Guo Yue , Guo Yifei , Zhu Haoxiang , Long Feng , Xia Zhijie , Mao Shanlin , Zhao Hui , Ge Zi , Yu Jie , Zhang Yongmei , Qin Lunxiu , Ma Ke , Mao Richeng , Zhang Jiming
Published: December 2022

Background

The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged repeatedly, especially the Omicron strain which is extremely infectious, so early identification of patients who may develop critical illness will aid in delivering proper treatment and optimizing use of resources. We aimed to develop and validate a practical scoring model at hospital admission for predicting which patients with Omicron infection will develop critical illness.

Methods

A total of 2,459 patients with Omicron infection were enrolled in this retrospective study. Univariate and multivariate logistic regression analysis were performed to evaluate predictors associated with critical illness. Moreover, the area under the receiver operating characteristic curve (AUROC), continuous net reclassification improvement, and integrated discrimination index were assessed.

Results

The derivation cohort included 1721 patients and the validation cohort included 738 patients. A total of 98 patients developed critical illness. Thirteen variables were independent predictive factors and were included in the risk score: age > 65, C-reactive protein > 10 mg/L, lactate dehydrogenase > 250 U/L, lymphocyte < 0.8*10^9/L, white blood cell > 10*10^9/L, Oxygen saturation < 90%, malignancy, chronic kidney disease, chronic cardiac disease, chronic obstructive pulmonary disease, diabetes, cerebrovascular disease, and non-vaccination. AUROC in the derivation cohort and validation cohort were 0.926 (95% CI, 0.903–0.948) and 0.907 (95% CI, 0.860-0.955), respectively. Moreover, the critical illness risk scoring model had the highest AUROC compared with CURB-65, sequential organ failure assessment (SOFA) and 4C mortality scores, and always obtained more net benefit.

Conclusion

The risk scoring model based on the characteristics of patients at the time of admission to the hospital may help medical practitioners to identify critically ill patients and take prompt measures.
Degradation of polyethylene plastic bags and bottles using microorganisms isolated from soils of Morogoro, Tanzania
Authors: Nakei Monica D. , Misinzo Gerald , Tindwa Hamisi , Semu Ernest
Published: December 2022

Plastics are of great significance in today’s world due to their extensive use such as packaging food and carrying other goods, which have improved the quality of human life. However, plastics have low biodegradability and are persistent in the environment, becoming a major source of pollution. With regard to the current methods used in the management of plastic wastes, the degradation of plastics using beneficial soil microorganisms has recently gained attention due to their ability to degrade different types of plastics including polyethylene (PE) polymers. The study herein was conducted to isolate and identify microorganisms from agricultural soils capable of degrading plastics. Soil samples were inoculated into nutrient, potato dextrose, and starch-casein agar for the isolation of bacteria, fungi, and actinomycetes, respectively. During isolation, fungi and bacterial plates were incubated for 5 days and for 14 days, respectively. The population of bacteria ranged from 1 × 105 to 1.215 × 105 and that of fungi from 1.604 × 104 to 8.6 × 104 whereby actinomycetes ranged from 1.045 × 105 to 2.995 × 105 CFU/g of soil. However, the tested microorganisms showed significant (p ≤ 0.05) differences in the ability to degrade PE bags and bottles as depicted by the diameters of clear zones around the colonies. The diameters of clear zones ranged from 19.3 to 47.5 mm and 25.9 to 32.2 mm after 17 days for bacteria and actinomycetes, respectively, and those of fungi ranged from 30.0 to 66.3 mm after 13 days. Among the bacteria, actinomycetes, and fungi, unsequenced bacterial and actinomycete isolates B1 and A3 as well as Aspergillus sp. (F7) were the most efficient degraders of PE plastic bags. This retrospective study sheds light on our understanding and the need for the bioprospecting of agricultural soils, water bodies, and landfills containing plastic wastes that could lead to the identification of more efficient microbial species with the ability to degrade plastics.
Elevated VCAM-1, MCP-1 and ADMA serum levels related to pulmonary fibrosis of interstitial lung disease associated with rheumatoid arthritis
Authors: Pulito-Cueto Verónica , Remuzgo-Martínez Sara , Genre Fernanda , Atienza-Mateo Belén , Mora-Cuesta Víctor M. , Iturbe-Fernández David , Lera-Gómez Leticia , Sebastián Mora-Gil María , Prieto-Peña Diana , Portilla Virginia , Blanco Ricardo , Corrales Alfonso , Ocejo-Vinyals J. Gonzalo , Gualillo Oreste , Ferraz-Amaro Iván , Cifrián José M. , López-Mejías Raquel , González-Gay Miguel A.
Published: December 2022

Introduction: Early diagnosis of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA) constitutes a challenge for the clinicians. Pulmonary vasculopathy is relevant in the development of interstitial lung disease. Accordingly, we aimed to explore the role of vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and asymmetric dimethylarginine (ADMA), key molecules in the vasculopathy, as potential biomarkers of pulmonary fibrosis in RA-ILD+.

Methods: We included 21 RA-ILD+ patients and two comparative groups: 25 RA-ILD- patients and 21 idiopathic pulmonary fibrosis (IPF) patients. Serum levels of the molecules were determined by ELISA, and mRNA expression was quantified by qPCR.

Results: VCAM-1, MCP-1 and ADMA serum levels were increased in RA-ILD+ patients in relation to RA-ILD- and IPF patients. Additionally, RA-ILD+ patients exhibited increased CCL2 (gene encoding MCP-1) and decreased PRMT1 (gene related to ADMA synthesis) mRNA expression in relation to RA-ILD- patients. A lower expression of VCAM1, CCL2, and PRMT1 was observed in RA-ILD+ patients when compared with those with IPF. Furthermore, MCP-1 serum levels and PRMT1 mRNA expression were positively correlated with RA duration, and ADMA serum levels were positively associated with C-reactive protein in RA-ILD+ patients.

Conclusion: Our study suggests that VCAM-1, MCP-1 and ADMA could be considered as useful biomarkers to identify ILD in RA patients, as well as to discriminate RA-ILD+ from IPF, contributing to the early diagnosis of RA-ILD+.
Protein sumoylation in normal and cancer stem cells
Authors: Zhu Qiuhong , Liang Panpan , Chu Cuiying , Zhang Aili , Zhou Wenchao
Published: December 2022

Stem cells with the capacity of self-renewal and differentiation play pivotal roles in normal tissues and malignant tumors. Whereas stem cells are supposed to be genetically identical to their non-stem cell counterparts, cell stemness is deliberately regulated by a dynamic network of molecular mechanisms. Reversible post-translational protein modifications (PTMs) are rapid and reversible non-genetic processes that regulate essentially all physiological and pathological process. Numerous studies have reported the involvement of post-translational protein modifications in the acquirement and maintenance of cell stemness. Recent studies underscore the importance of protein sumoylation, i.e., the covalent attachment of the small ubiquitin-like modifiers (SUMO), as a critical post-translational protein modification in the stem cell populations in development and tumorigenesis. In this review, we summarize the functions of protein sumoylation in different kinds of normal and cancer stem cells. In addition, we describe the upstream regulators and the downstream effectors of protein sumoylation associated with cell stemness. We also introduce the translational studies aiming at sumoylation to target stem cells for disease treatment. Finally, we propose future directions for sumoylation studies in stem cells.
Different effects of air microembolism through patent foramen ovale in patients with migraine: A quantitative electroencephalogram case series
Authors: Ornello Raffaele , Spezialetti Matteo , Caponnetto Valeria , Frattale Ilaria , Grappasonni Monica , Pistoia Francesca , Placidi Giuseppe , Sacco Simona
Published: December 2022

Background

Literature suggests an association between patent foramen ovale (PFO) and migraine, mostly migraine with aura (MA). Previous data suggest that air microembolism through PFO can lead to bioelectrical abnormalities detectable at electroencephalogram (EEG) in patients with MA, thus suggesting a pathophysiological mechanism for the MA-PFO association. However, those data lack replication.

Methods

Patients with MA or migraine without aura (MO) and large PFO underwent a 19-channel EEG recording before and after injection of air microbubbles. We compared EEG power before and after microbubble injection for each electrode location, for each frequency band (theta: 5–7 Hz; alpha: 8–12 Hz; beta: 13–30 Hz; lower gamma: 31–45 Hz), and for total global power (the average of EEG power at each location and frequency band).

Results

We included 10 patients, four with MA and six with MO; six patients had medium-to-high migraine frequency (four or more monthly migraine days), while four had low frequency (one monthly migraine day). EEG power changes after air microembolism varied across patients. Considering the overall group, total global EEG power did not change; however, EEG power in the higher frequency ranges (beta and lower gamma) increased in patients with MA.

Conclusions

We did not replicate the effects of air microembolism previously reported in patients with migraine. Aura status, migraine frequency, and medications might influence patients' response to microembolism. More refined EEG measurements are needed to clarify the dynamic role of PFO on migraine occurrence.
Overlapping activation pattern of bitter taste receptors affect sensory adaptation and food perception
Authors: Lang Roman , Lang Tatjana , Dunkel Andreas , Ziegler Florian , Behrens Maik
Published: December 2022

The composition of menus and the sequence of foodstuffs consumed during a meal underlies elaborate rules. However, the molecular foundations for the observed taste- and pleasure-raising effects of complex menus are obscure. The molecular identification and characterization of taste receptors can help to gain insight into the complex interrelationships of food items and beverages during meals. In our study, we quantified important bitter compounds in chicory and chicory-based surrogate coffee and used them to identify responsive bitter taste receptors. The two receptors, TAS2R43 and TAS2R46, are exquisitely sensitive to lactucin, lactucopicrin, and 11β,13-dihydrolactucin. Sensory testing demonstrated a profound influence of the sequence of consumption of chicory, surrogate coffee, and roasted coffee on the perceived bitterness by human volunteers. These findings pave the way for a molecular understanding of some of the mixture effects underlying empirical meal compositions.
A necroptosis-related lncRNA signature was identified to predict the prognosis and immune microenvironment of IDH-wild-type GBM
Authors: Song Chong , Zhu Liwen , Gu Junwei , Wang Tong , Shi Linyong , Li Chiyang , Chen Lei , Xie Sidi , Lu Yuntao
Published: December 2022

Introduction

Necroptosis-related genes are essential for the advancement of IDH-wild-type GBM. However, the putative effects of necroptosis-related lncRNAs (nrlncRNAs) in IDH-wild-type GBM remain unknown.

Methods

By using the TCGA and GTEx databases, a nrlncRNA prognostic signature was created using LASSO Cox regression. The median risk score was used to categorize the patients into low and high-risk groups. To confirm the validity, univariate, multivariate Cox regression and ROC curves were used. Furthermore, by enrichment analysis, immune correlation analysis, and drug sensitivity analysis, the targeted lncRNAs were selected for further verification. As the highest upregulated expression in tumor than peritumor specimens, RP11-131L12.4 was selected for phenotype and functional experiments in primary GBM cells.

Results

Six lncRNAs were proved to be closely related to necroptosis in IDH-1-wild-type GBM, which were used to create a new signature. For 1-, 2-, and 3-year OS, the AUCs were 0.709, 0.645 and 0.694, respectively. Patients in the low-risk group had a better prognosis, stronger immune function activity, and more immune cell infiltration. In contrast, enrichment analysis revealed that the malignant phenotype was more prevalent in the high-risk group. In vitro experiments indicated that RP11-131L12.4 increased the tumor proliferation, migration and invasion, but decreased the necroptosis. Moreover, this nrlncRNA was also proved to be negatively associated with patient prognosis.

Conclusion

The signature of nrlncRNAs may aid in the formulation of tailored and precise treatment for individuals with IDH-wild-type GBM. RP11-131L12.4 may play indispensable role in necroptosis suppression.