bluuebunny/crossref_metadata_2025 huggingface dataset:
Pelatihan Pengembangan LKPD Menggunakan Aplikasi Wizer. Me Berbasis Model ASSURE untuk Meningkatkan Kemampuan Pemecahan Masalah pada Guru Sekolah Dasar
Authors: Susanti Atika , Yuliantini Nani , Dalifa  , Lorenza Sovia , Kurniasari Herlin , Darmansyah Ady
Published: September 2023

Keterampilan guru dalam mengembangkan Lembar Kerja Peserta Didik (LKPD) untuk meningkatkan kemampuan pemecahan masalah siswa merupakan kompetensi yang penting. Program PPM ini bertujuan untuk melatih guru SDN 41 Kota Bengkulu dalam mengembangkan LKPD menggunakan Aplikasi Wizer.Me berbasis model ASSURE untuk meningkatkan kemampuan pemecahan masalah guru SD. Metode pelatihan dengan model Analisis, Pelatihan, Tindakan, Evaluasi (APTE). Instrumen evaluasi kegiatan ini adalah lembar pretest dan posttest. Pelatihan dilakukan dalam dua tahap, yaitu memberikan pelatihan mengenai konsep pengembangan LKPD dan mempraktikkan pengembangan LKPD menggunakan aplikasi Wizer.Me. Hasil penilaian menunjukkan adanya peningkatan pengetahuan dan keterampilan pengembangan LKPD. Rata-rata nilai pretest untuk 22 guru peserta pelatihan adalah 63.18, sedangkan rata-rata nilai posttest adalah 81.14, menunjukkan peningkatan kemampuan peserta pelatihan setelah mengikuti pelatihan. Hasil uji N-Gain didapatkan nilai rata-rata N-Gain score sebesar 0.49 atau 49%, pada kategori "Sedang". Dengan demikian, pelatihan ini berhasil memberikan dampak positif dan signifikan terhadap pengetahuan para peserta dalam pengembangan LKPD dan penerapan model ASSURE serta kemampuan pemecahan masalah dalam konteks pembelajaran di SD.
Edukasi Pemanfaatan Limbah Bambu Melalui Pembuatan Biochar di Desa Banjarwaru Kecamatan Nusawungu Kabupaten Cilacap
Authors: Utami Sari Widya , Pratiwi Artdhita Fajar , Aji Galih Mustiko
Published: September 2023

Desa Banjarwaru adalah salah satu sentra industri kerajinan anyaman bambu, telah menciptakan berbagai inovasi-inovasi terbaru terhadap kerajinan anyaman bambunya. Namun, Petani tetaplah menjadi mata pencaharian utama penduduk. Meskipun, permasalahan pertanian di desa ini adalah tingkat kesuburan tanah yang rendah (kadar pH rendah), sehingga pemberian pupuk dalam jumah yang tinggi pun tidak mampu memberikan hasil yang baik pada pertumbuhan tanaman. Oleh sebab itu, dibutuhkan bahan pembenah yang mampu memperbaiki kesuburan tanah dengan meningkatkan pH tanah mendekati netral, seperti Biochar. Biochar dapat diperoleh dengan memanfaatkan sisa bambu yang tidak terpakai dalam produksi kerajinan bambu dan tidak dikelola dengan baik akibat kurangnya pengetahuan penduduk. Dalam kegiatan PkM ini, memperkenalkan biochar bambu dan manfaatnya sebagai bahan pembenah tanah, serta pembuatannya menggunakan metode soil-pit. Kegiatan ini telah mendorong masyarakat, untuk mengembangkan nilai lebih dari limbah bambu terutama untuk dimanfaatkan menjadi biochar untuk memperbaiki kualitas tanah pertanian di Desa Banjarwaru.
Edukasi Kebersihan Tangan Kepada Masyarakat Ketika Berkunjung Ke Rumah Sakit
Authors: Kusumawardhani Oktavy Budi , Kismanto Joko , Widyastuti Kristina
Published: September 2023

Menurut WHO, rata-rata 1 dari 10 pasien terkena Healthcare Acquired Infections (HAIs’) atau infeksi nosocomial di dunia. Sebesar 61% tenaga kesehatan ditemukan tidak mematuhi praktik mencuci tangan sesuai yang disarankan WHO. Membuat tenaga kesehatan cukup kesulitan dalam menyampaikan penyuluhan tentang cuci tangan kepada pengunjung rumah sakit (RS). Hal ini membuat pengunjung rumah sakit menjadi enggan melakukan cuci tangan yang membuat resiko infeksi nosocomial terjadi. Tujuan untuk meningkatkan upaya kebersihan tangan kepada masyarakat ketika berkunjung ke RS. Metodeengabdian ini dilakukan secara offline dan sasaran pada pasien serta masyarakat pengguna RS. Hasilsymp. Sign nilai 0,000 lebih kecil dari <0,05 artinya ada perbedaan antara hasil pengetahuan, sikap dan tindakan untuk pre test dan post test. Sehingga dapat disimpulkan pula bahwa ada pengaruh edukasi kebersihan tangan kepada masyarakat ketika berkunjung ke rumah sakit. Kontribusi penelitian dapat meningkatkan kebersihan tangan kepada masyarakat ketika berkunjung ke RS.
ENVIRONMENTAL SECURITY THREATS DUE TO CLIMATE CHANGE FACED BY THE PACIFIC ISLAND FORUM
Authors: Ardita Tazya Nuraini  , M. Syaprin Zahidi
Published: September 2023

Climate change has a detrimental impact on living things, including humans. Starting from extreme weather changes, rising sea levels, disasters, and the worst thing is that it can sink the island which is home to several humans and other living things. Climate change is a disaster that should be prevented from getting worse. The Pacific Islands are one of the few areas that are threatened with drowning due to rising sea levels every year. With the various interests held by developed countries, especially in the industrial sector, of course, letting the Pacific Islands sink in without any action for change is a crime.
EXPANSION TREND: INDONESIA'S PALM OIL SECTOR GOVERNMENT PLANTATION HEADING FOR EXTINCTION
Authors: Ovi Vensus Hamubaon Samosir
Published: September 2023

Palm Oil plantations in Indonesia are experiencing a trend of land expansion. The land expansion makes Indonesia, the country with the largest palm oil plantation land in the world, and at the same time the world's largest producer of palm oil. Land expansion is carried out by Government Plantation, Smallholders Plantation, and Private Plantation. However, when observed in more detail, land expansion from Government Plantation has not shown a significant increase and has recently decreased. Seeing the decline in the land area of Government Plantation amid the trend of land expansion of palm oil plantations in Indonesia, this paper argues that liberalization encourages the government to reduce its economic activity in the palm oil plantation sector, and provides opportunities for the market to develop Smallholders Plantation and Private Plantation. Liberalization encouraged the expansion of plantation land nationally, but limited the increase in the land area of Government Plantation.

Keyword: Oil palm plantation, Expansion, Government Plantation, Smallholders Plantation, Private Plantation, Liberalization
TWITAUTOLOGY: NEOLOGISM IN K-POP FANBASE ON TWITTER
Authors: Zayyan Sheilma 'Arivah , Marfu'ah Elsa Lailatul , Samodra Maharani Surya , Salsabilla Hanifah Nur , Amalinda Chika , Istiqomah Diah Ayu
Published: September 2023

Every fandom has a unique pattern of language usage to communicate with one another. Different fandoms, of course, affect their language patterns respectively, because the neologisms that are formed can represent the identity of each fandom. K-Pop fandom itself has a wide community all over the world that is connected through a virtual network. Twitter is a virtual data network platform used by many members of the K-Pop fandom. To find out about at what level neologism in K-Pop fandom on Twitter is formed, the data are collected by sampling tweets of Twitter users who are part of three K-Pop boy group fandom namely Seventeen, Stray Kids and Treasure, who use Vocabulary, Orthography, Grammar and Pragmatic in their tweets using descriptive qualitative methods. The findings reveal that some language aspects in K-Pop fandom share different knowledge from the regular language. The results show that the K-Pop fandom community tend to create neologisms based on the identity of the specific idol they like, not only within the K-Pop fandom itself, which makes it unique. This research provides insight that neologism exists in the K-Pop fandom community on twitter to provide the community members an easier way to communicate without having to explain the context.
GANGSTER, GHOST, AND TRADITION: REPRESENTATION OF MARKET IN THREE INDONESIA FILMS
Authors: Budiman Rido , Puspahaty Novita , Sari Dian Puspita
Published: September 2023

This research aims to determine what kind of market representation is displayed in three Indonesian films namely Di Bawah Lindungan Ka’bah, Gangster, Rumah Hantu Pasar Malam and how the viewers interpret it through various internet platform. The qualitative research design in the field of cultural studies especially the theory of representation and encoding-decoding from Hall is used to analyze data in the present study. By researching the above factors, we aim to provide more information toward the meaning of Indonesian films from the point of view of cultural studies.
A Study on the Distribution of Shear Forces Between Resisting Mechanisms in an RC Element Without Stirrups
Authors: Pérez Caldentey Alejandro
Published: September 2023

This paper explores how the shear force distributes itself among the three main shear resistance mechanisms: shear resistance of the uncracked compressed chord, aggregate interlock, and dowel effect. Today’s dominating shear models, the critical crack theory (Muttoni et al. [1]) and the compression field theory (Collins et al. [2]) maintain that the main shear-resisting mechanism is aggregate interlock, while more recent studies (Marí et al. [3]), maintain that the main resistance mechanism is the shear resistance on the uncracked compression chord.

In this paper FEM modelling is used to study a test carried out at the Universidad Politécnica de Madrid (UPM) to try to assign the shear force to the different shear mechanisms for different loading steps and elucidate what finally causes the failure of the structure. The results show that as load is increased the relative part of the shear force taken by the uncracked compressed chord increases until finally shear failure is reached when the principal tensile stress in the area located close to the load but towards the support reaches the tensile resistance of concrete, generating a crack that precipitates the failure of the beam.
Energy Flow Considerations for Structural Response under Blast
Authors: Willems K. , Krauthammer Ted , Ohrt Alan
Published: September 2023

Load-impulse (P-I) diagrams are commonly used for structural design and damage assessment. Recently, an energy-based alternative to P-I diagrams, known as Energy vs. Energy Rate (E-R) diagrams, was proposed. E-R diagrams are another tool for structural design and damage assessment from an energy flow perspective. This paper describes a study to assess and compare these two analytical approaches, and to provide examples for illustrating the findings.
Opplevelse av sammenheng i fag- og yrkesopplæring: Et longitudinelt perspektiv
Authors: Hanssen Grete
Published: September 2023

This longitudinal study explores the resources vocational students need to balance stress and develop vocational competence in school- and work-based learning. As a theoretical framework, the concepts of sense of coherence (SOC) and general resistance resources (GRR) are used, as proposed by Antonovsky in his salutogenic theory. SOC consists of three components: comprehensibility, manageability, and meaningfulness. GRR is about how a person, group or community use internal and external resources to promote SOC. Participants are interviewed at the end of their school part of the education and again at the end of the apprenticeship. The two interviews are compared using comparative analysis methods to explore how participants’ GRRs develop. The study shows that comprehensibility increases when practice and theory are integrated into work tasks during the apprenticeship. The manageability component, developed throughout the educational process, helps them master stress and to face unpredictable situations. The GRRs promoting meaningfulness are almost similar in the two interviews and appear to be stable over time and central for participants to engage in learning situations and develop vocational competence.
A brief review on the mechanisms and approaches of silk spinning-inspired biofabrication
Authors: Mu Xuan , Amouzandeh Reza , Vogts Hannah , Luallen Elise , Arzani Milad
Published: September 2023

Silk spinning, observed in spiders and insects, exhibits a remarkable biological source of inspiration for advanced polymer fabrications. Because of the systems design, silk spinning represents a holistic and circular approach to sustainable polymer fabrication, characterized by renewable resources, ambient and aqueous processing conditions, and fully recyclable “wastes.” Also, silk spinning results in structures that are characterized by the combination of monolithic proteinaceous composition and mechanical strength, as well as demonstrate tunable degradation profiles and minimal immunogenicity, thus making it a viable alternative to most synthetic polymers for the development of advanced biomedical devices. However, the fundamental mechanisms of silk spinning remain incompletely understood, thus impeding the efforts to harness the advantageous properties of silk spinning. Here, we present a concise and timely review of several essential features of silk spinning, including the molecular designs of silk proteins and the solvent cues along the spinning apparatus. The solvent cues, including salt ions, pH, and water content, are suggested to direct the hierarchical assembly of silk proteins and thus play a central role in silk spinning. We also discuss several hypotheses on the roles of solvent cues to provide a relatively comprehensive analysis and to identify the current knowledge gap. We then review the state-of-the-art bioinspired fabrications with silk proteins, including fiber spinning and additive approaches/three-dimensional (3D) printing. An emphasis throughout the article is placed on the universal characteristics of silk spinning developed through millions of years of individual evolution pathways in spiders and silkworms. This review serves as a stepping stone for future research endeavors, facilitating the in vitro recapitulation of silk spinning and advancing the field of bioinspired polymer fabrication.
A Rab-bit hole: Rab40 GTPases as new regulators of the actin cytoskeleton and cell migration
Authors: Neumann Andrew J. , Prekeris Rytis
Published: September 2023

The regulation of machinery involved in cell migration is vital to the maintenance of proper organism function. When migration is dysregulated, a variety of phenotypes ranging from developmental disorders to cancer metastasis can occur. One of the primary structures involved in cell migration is the actin cytoskeleton. Actin assembly and disassembly form a variety of dynamic structures which provide the pushing and contractile forces necessary for cells to properly migrate. As such, actin dynamics are tightly regulated. Classically, the Rho family of GTPases are considered the major regulators of the actin cytoskeleton during cell migration. Together, this family establishes polarity in the migrating cell by stimulating the formation of various actin structures in specific cellular locations. However, while the Rho GTPases are acknowledged as the core machinery regulating actin dynamics and cell migration, a variety of other proteins have become established as modulators of actin structures and cell migration. One such group of proteins is the Rab40 family of GTPases, an evolutionarily and functionally unique family of Rabs. Rab40 originated as a single protein in the bilaterians and, through multiple duplication events, expanded to a four-protein family in higher primates. Furthermore, unlike other members of the Rab family, Rab40 proteins contain a C-terminally located suppressor of cytokine signaling (SOCS) box domain. Through the SOCS box, Rab40 proteins interact with Cullin5 to form an E3 ubiquitin ligase complex. As a member of this complex, Rab40 ubiquitinates its effectors, controlling their degradation, localization, and activation. Because substrates of the Rab40/Cullin5 complex can play a role in regulating actin structures and cell migration, the Rab40 family of proteins has recently emerged as unique modulators of cell migration machinery.
Evaluation of selected parameters of inflammation, coagulation system, and formation of extracellular neutrophil traps (NETs) in the perioperative period in patients undergoing endovascular treatment of thoracoabdominal aneurysm with a branched device (t-Branch)
Authors: Michalska Milena , Grochowiecki Tadeusz , Wyczałkowska-Tomasik Aleksandra , Pączek Leszek , Jakimowicz Tomasz , Cacko Andrzej , Jama Katarzyna , Stec Albert , Sikorska Ewa , Nazarewski Sławomir , Gałązka Zbigniew
Published: September 2023

Extracellular Neutrophils Traps (NETs) and their formation, known as NETosis, have become pivotal in the pathogenesis of aortic aneurysm development. This study investigates the NETosis markers with the assessment of selected parameters of inflammation and coagulation system in patients with thoracoabdominal aortic aneurysms in the pre-and postop period undergoing t-Branch stent-graft implantation. The study included 20 patients with thoracoabdominal aortic aneurysms. Three markers double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and citrullinated H3 histones (Cit-H3) were tested at three-time points from patients’ blood. The parameters of NETosis, inflammation, and coagulation system were examined in the preoperative period (within 24 h before surgery) and in the postoperative period (on the 3rd and 5th postoperative day). Free-circulating DNA (cfDNA) was isolated from the blood using the MagMAXTM Cell-Free DNA Extraction Kit. Double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) were then quantified using the Qubit dsDNA HS Assay Kit and the Qubit ssDNA Assay Kit. Cit-H3 concentration was determined by enzyme immunoassay ELISA (Cayman). The results revealed the significance of NETs secretion in response to the complex processes after stent-graft implantation. All NET markers increased shortly after surgery, with histones being the first to return to preoperative levels. The lack of normalization of dsDNA and ssDNA levels to preoperative levels by the last postoperative blood collection demonstrates NETs reorganization. The increase in the number of neutrophils was not related to the expansion of postoperative NETosis. The study reveals a new marker of NETosis, ssDNA, that has not been studied so far. The implantation of a stent graft in a patient with TAAA triggers an inflammatory response manifested by an increase in inflammatory parameters. One of the hallmarks of inflammation is the activation of neutrophil extracellular traps.
Investigating the role of mitochondrial DNA D-loop variants, haplotypes, and copy number in polycystic ovary syndrome: implications for clinical phenotypes in the Chinese population
Authors: Chen Yang , Wu Wei-jia , Xing Li-wei , Zhang Xiao-juan , Wang Jing , Xia Xiao-yan , Zhao Rui , Zhao Rong
Published: September 2023

Background

The presence of genetic variations in mitochondrial DNA (mtDNA) has been associated with a diverse array of diseases. The objective of this study was to examine the correlations between mtDNA D-loop, its haplotypes, and polycystic ovary syndrome (PCOS) in the Chinese population, and the associations between mtDNA D-loop and symptoms of PCOS. The study also sought to determine whether the mtDNA copy number in Chinese patients with PCOS differed from that of individuals in the control group.

Methods

Infertile individuals who only had tubal or male factor treatment were the focus of research by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). mtDNA haplotypes were categorized using polymorphic D-loop sites. mtDNA D-loop, PCOS features, and mtDNA haplotypes were analyzed using R software to determine the strength of the association between the three. There are certain DNA haplotypes linked to PCOS. Microdroplet digital polymerase chain reaction (PCR) was used to determine the mtDNA copy number in a convenience sample of 168 PCOS patients and 83 controls.

Results

Among the research group, the majority of D-loop mutations were infrequent (frequency< 1%), with only 45 variants displaying a minimum allele frequency (MAF) of 5% or higher. No association was found between polymorphism loci in PCOS patients and body mass index (BMI). Noteworthy, C194T, 1A200G, 523delAC, and C16234T showed positive correlations with elevated LH/FSH levels. Additionally, specific polymorphic loci G207A, 16036GGins, and 16049Gins within the D-loop region of mtDNA potentially exerted a protective role in PCOS development. Conversely, no statistical significance was observed in the expression levels of C16291T and T489C. Chinese women with mtDNA haplotype A15 exhibited a decreased risk of developing PCOS. Moreover, a significant difference in mtDNA copy number was detected, with controls averaging 25.87 (21.84, 34.81), while PCOS patients had a mean of 129.91 (99.38, 168.63).

Conclusion

Certain mtDNA D-loop mutations and haplotypes appear to confer protection against PCOS in Chinese women. In addition, elevated mtDNA copy number may serve as an indicator during early stages of PCOS.
Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children
Authors: Lamichhane Santosh , Sen Partho , Dickens Alex M. , Kråkström Matilda , Ilonen Jorma , Lempainen Johanna , Hyöty Heikki , Lahesmaa Riitta , Veijola Riitta , Toppari Jorma , Hyötyläinen Tuulia , Knip Mikael , Orešič Matej
Published: September 2023

Aims/hypothesis

Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody).

Methods

Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites.

Results

We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP.

Conclusion/interpretation

Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.
The value of total tumor diameter in unilateral multifocal papillary thyroid carcinoma: a propensity score matching analysis
Authors: Wu Zhu-juan , Xia Bao-ying , Chen Zi-wei , Gong Hao , Abuduwaili Munire , Xing Zhi-chao , Su An-ping
Published: September 2023

Background

Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC). However, the maximum tumor diameter (MTD), currently utilized in various staging schemes, might not accurately indicate the level of aggressiveness exhibited by multifocal tumors. We aimed to investigate the relationship between total tumor diameter (TTD) and clinicopathological features of papillary thyroid carcinoma.

Methods

Retrospective data analysis was done on 1936 individuals who underwent complete thyroidectomy for PTC. Patients were classified into subgroups according to unilateral multifocality, central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The relationships of clinicopathological features among these groups were analyzed.

Results

Unilateral multifocality was observed in 117 patients. The clinicopathological features of the unilateral multifocal PTC were similar to the unifocal PTC with approximate TTD. The unilateral multifocality played no independent role in CLNM and LLNM. Moreover, the efficiency of TTD in predicting CLNM and LLNM was significantly higher than that of MTD.

Conclusion

In the case of unilateral multifocal PTC, TTD is a more accurate indicator of the biological characteristics of the tumor than MTD.
Data-driven method of solving computationally expensive combined economic/emission dispatch problems in large-scale power systems: an improved kriging-assisted optimization approach
Authors: Lin Chenhao , Liang Huijun , Pang Aokang , Zhong Jianwei
Published: September 2023

Combined economic/emission dispatch (CEED) is generally studied using analytical objective functions. However, for large-scale, high-dimension power systems, CEED problems are transformed into computationally expensive CEED (CECEED) problems, for which existing approaches are time-consuming and may not obtain satisfactory solutions. To overcome this problem, a novel data-driven surrogate-assisted method is introduced firstly. The fuel cost and emission objective functions are replaced by improved Kriging-based surrogate models. A new infilling sampling strategy for updating Kriging-based surrogate models online is proposed, which improves their fitting accuracy. Through this way, the evaluation time of the objective functions is significantly reduced. Secondly, the optimization of CECEED is executed by an improved non-dominated sorting genetic algorithm-II (NSGA-II). The above infilling sampling strategy is also used to reduce the number of evaluations for original mathematic fitness functions. To improve their local convergence ability and global search abilities, the individuals that exhibit excellent performance in a single objective are cloned and mutated. Finally, information about the Pareto front is used to guide individuals to search for better solutions. The effectiveness of this optimization method is demonstrated through simulations of IEEE 118-bus test system and IEEE 300-bus test system.
Identification of novel TMEM231 gene splice variants and pathological findings in a fetus with Meckel Syndrome
Authors: Zhang Qian , Yang Shuya , Chen Xin , Wang Hongdan , Li Keyan , Zhang Chaonan , Liao Shixiu , Qin Litao , Hou Qiaofang
Published: September 2023

Background: Meckel Syndrome (MKS, OMIM #249000) is a rare and fatal autosomal recessive ciliopathy with high clinical and genetic heterogeneity. MKS shows complex allelism with other related ciliopathies such as Joubert Syndrome (JBTS, OMIM #213300). In MKS, the formation and function of the primary cilium is defective, resulting in a multisystem disorder including occipital encephalocele, polycystic kidneys, postaxial polydactyly, liver fibrosis, central nervous system malformations and genital anomalies. This study aimed to analyze the genotype of MKS patients and investigate the correlation between genotype and phenotype.

Methods: A nonconsanguineous couple who conceived four times with a fetus affected by multiorgan dysfunction and intrauterine fetal death was studied. Whole exome sequencing (WES) was performed in the proband to identify the potentially pathogenic variant. Sanger sequencing was performed in family members. In silico tools were used to analyse the pathogenicity of the identified variants. cDNA TA-cloning sequencing was performed to validate the effects of intronic variants on mRNA splicing. Quantitative real-time PCR was performed to investigate the effect of the variants on gene expression. Immunofluorescence was performed to observe pathological changes of the primary cilium in kidney tissue from the proband.

Results: Two splice site variants of TMEM231 (NM_001077418.2, c.583-1G>C and c.583-2_588delinsTCCTCCC) were identified in the proband, and the two variants have not been previously reported. The parents were confirmed as carriers. The two variants were predicted to be pathogenic by in silico tools and were classified as pathogenic/likely pathogenic variants according to the American College of Medical Genetics and Genomics guideline. cDNA TA cloning analysis showed that both splice site variants caused a deletion of exon 5. RT-PCR revealed that the expression of TMEM231 was significantly decreased and immunofluorescence showed that the primary cilium was almost absent in the proband’s kidney tissue.

Conclusion: We reported the clinical, genetic, molecular and histochemical characterisation of a family affected by MKS. Our findings not only extended the mutation spectrum of the TMEM231 gene, but also revealed for the first time the pathological aetiology of primary cilia in humans and provide a basis for genetic counselling of the parents to their offspring.
TAGAP expression influences CD4+ T cell differentiation, immune infiltration, and cytotoxicity in LUAD through the STAT pathway: implications for immunotherapy
Authors: Xu Zhanyu , Zheng Tiaozhan , Zheng Zhiwen , Jiang Wei , Huang Liuliu , Deng Kun , Yuan Liqiang , Qin Fanglu , Sun Yu , Qin Junqi , Li Shikang
Published: September 2023

Background

T-cell Activation GTPase Activating Protein (TAGAP) plays a role in immune cell regulation. This study aimed to investigate TAGAP’s expression and its potential impact on CD4+ T cell function and prognosis in lung adenocarcinoma (LUAD).

Methods

We analyzed TAGAP expression and its correlation with immune infiltration and clinical data in LUAD patients using multiple datasets, including The Cancer Genome Atlas (TCGA-LUAD), Gene Expression Omnibus (GEO), and scRNA-seq datasets. In vitro and in vivo experiments were conducted to explore the role of TAGAP in CD4+ T cell function, chemotaxis, and cytotoxicity.

Results

TAGAP expression was significantly lower in LUAD tissues compared to normal tissues, and high TAGAP expression correlated with better prognosis in LUAD patients. TAGAP was positively correlated with immune/stromal/ESTIMATE scores and immune cell infiltration in LUAD. Single-cell RNA sequencing revealed that TAGAP was primarily distributed in CD4+/CD8+ T cells. In vitro experiments showed that TAGAP overexpression enhanced CD4+ T cell cytotoxicity, proliferation, and chemotaxis. Gene Set Enrichment Analysis (GSEA) indicated that TAGAP was enriched in the JAK-STAT signaling pathway. In vivo experiments in a xenograft tumor model demonstrated that TAGAP overexpression suppressed tumor growth and promoted CD4+ T cell cytotoxicity.

Conclusions

TAGAP influences CD4+ T cell differentiation and function in LUAD through the STAT pathway, promoting immune infiltration and cytotoxicity. This study provides a scientific basis for developing novel LUAD immunotherapy strategies and exploring new therapeutic targets.
Cytotoxic innate intraepithelial lymphocytes control early stages of Cryptosporidium infection
Authors: Hariss Fatima , Delbeke Marie , Guyot Karine , Zarnitzky Pauline , Ezzedine Mohamad , Certad Gabriela , Meresse Bertrand
Published: September 2023

Background

Intraepithelial lymphocytes (IELs) are the first immune cells to contact and fight intestinal pathogens such as Cryptosporidium, a widespread parasite which infects the gut epithelium. IFN-γ producing CD4+ T IELs provide an efficient and a long-term protection against cryptosporidiosis while intraepithelial type 1 innate lymphoid cells limits pathogen spreading during early stages of infection in immunodeficient individuals. Yet, the role of T-cell like innate IELs, the most frequent subset of innate lymphocytes in the gut, remains unknown.

Methods

To better define functions of innate IELs in cryptosporidiosis, we developed a co-culture model with innate IELs isolated from Rag2-/- mice and 3D intestinal organoids infected with C. parvum using microinjection.

Results

Thanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IELs secrete IFN-γ in response to C. parvum, the cytokine was not sufficient to inhibit parasite proliferation at early stages of the infection. The rapid protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis of the Cryptosporidium-infected organoids revealed that epithelial cells down regulated Serpinb9b, a granzyme inhibitor, which may increase their sensitivity to cytolytic attack by innate IELs.

Conclusion

Based on these data we conclude that innate IELs, most likely T-cell-like innate IELs, provide a rapid protection against C. parvum infection through a perforin/granzymes-dependent mechanism. C. parvum infection. The infection may also increase the sensitivity of intestinal epithelial cells to the innate IEL-mediated cytotoxic attack by decreasing the expression of Serpin genes.
Phenotypic and functional characteristics of murine CD11c+ B cells which is suppressed by metformin
Authors: Ramirez De Oleo Ivan , Kim Vera , Atisha-Fregoso Yemil , Shih Andrew J. , Lee Kyungwoo , Diamond Betty , Kim Sun Jung
Published: September 2023

Since the description of age-associated or autoimmune-associated B cells (ABCs), there has been a growing interest in the role of these cells in autoimmunity. ABCs are differently defined depending on the research group and are heterogenous subsets. Here, we sought to characterize ABCs in Sle1/2/3 triple congenic (TC) mice, which is a well accepted mouse model of lupus. Compared to follicular (FO) B cells, ABCs have many distinct functional properties, including antigen presentation. They express key costimulatory molecules for T cell activation and a distinct profile of cytokines. Moreover, they exhibit an increased capacity for antigen uptake. ABCs were also compared with germinal center (GC) B cells, which are antigen activated B cell population. There are several phenotypic similarities between ABCs and GC B cells, but GC B cells do not produce proinflammatory cytokines or take up antigen. While T cell proliferation and activation is induced by both FO B and ABCs in an antigen-dependent manner, ABCs induce stronger T cell receptor signaling in naïve CD4+ T cells and preferentially induce differentiation of T follicular helper (Tfh) cells. We found that ABCs exhibit a distinct transcriptomic profile which is focused on metabolism, cytokine signaling and antigen uptake and processing. ABCs exhibit an increase in both glycolysis and oxidative phosphorylation compared to FO B cells. Treatment of ABCs with metformin suppresses antigen presentation by decreasing antigen uptake, resulting in decreased Tfh differentiation. Taken together, these findings define a fundamental connection between metabolism and function within ABCs.
Molecular and immunological mechanisms of clonal evolution in multiple myeloma
Authors: Forster Stefan , Radpour Ramin , Ochsenbein Adrian F.
Published: September 2023

Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal plasma cells in the bone marrow (BM). It is known that early genetic mutations in post-germinal center B/plasma cells are the cause of myelomagenesis. The acquisition of additional chromosomal abnormalities and distinct mutations further promote the outgrowth of malignant plasma cell populations that are resistant to conventional treatments, finally resulting in relapsed and therapy-refractory terminal stages of MM. In addition, myeloma cells are supported by autocrine signaling pathways and the tumor microenvironment (TME), which consists of diverse cell types such as stromal cells, immune cells, and components of the extracellular matrix. The TME provides essential signals and stimuli that induce proliferation and/or prevent apoptosis. In particular, the molecular pathways by which MM cells interact with the TME are crucial for the development of MM. To generate successful therapies and prevent MM recurrence, a thorough understanding of the molecular mechanisms that drive MM progression and therapy resistance is essential. In this review, we summarize key mechanisms that promote myelomagenesis and drive the clonal expansion in the course of MM progression such as autocrine signaling cascades, as well as direct and indirect interactions between the TME and malignant plasma cells. In addition, we highlight drug-resistance mechanisms and emerging therapies that are currently tested in clinical trials to overcome therapy-refractory MM stages.
Study of efficacy and antibody duration to fourth-dose booster of Ad5-nCoV or inactivated SARS-CoV-2 vaccine in Chinese adults: a prospective cohort study
Authors: Xu Nani , Xu Yu , Dai Rongrong , Zheng Lin , Qin Pan , Wan Peng , Yang Yejing , Jiang Jianmin , Zhang Hangjie , Hu Xiaowei , Lv Huakun
Published: September 2023

Introduction

China experienced a record surge of coronavirus disease 2019 cases in December 2022, during the pandemic.

Methods

We conducted a randomized, parallel-controlled prospective cohort study to evaluate efficacy and antibody duration after a fourth-dose booster with Ad5-nCoV or inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.

Results

A total of 191 participants aged ≥18 years who had completed a three-dose regimen of the inactivated SARS-CoV-2 vaccine 6 months earlier were recruited to receive the intramuscular Ad5-nCoV booster or the inactivated SARS-CoV-2 vaccine. The Ad5-nCoV group had significantly higher antibody levels compared with the inactivated vaccine group at 6 months after the fourth vaccination dose. After the pandemic, the breakthrough infection rate for the Ad5-nCoV and the inactivated vaccine groups was 77.89% and 78.13%, respectively. Survival curve analysis (p = 0.872) and multivariable logistic regression analysis (p = 0.956) showed no statistically significant differences in breakthrough infection between the two groups.

Discussion

Compared with a homologous fourth dose, a heterologous fourth dose of Ad5-nCoV elicited a higher immunogenic response in healthy adults who had been immunized with three doses of inactivated vaccine. Nevertheless, the efficacy of the two vaccine types was equivalent after the pandemic.
Genetic assessment of the effect of red yeast (Sporidiobolus pararoseus) as a feed additive on mycotoxin toxicity in laying hens
Authors: Hosseini Shahrbanou , Brenig Bertram , Winitchakorn Sunattinee , Kanmanee Chanidapha , Srinual Orranee , Tapingkae Wanaporn , Gatphayak Kesinee
Published: September 2023

Toxic fungal species produce hazardous substances known as mycotoxins. Consumption of mycotoxin contaminated feed and food causes a variety of dangerous diseases and can even lead to death of animals and humans, raising global concerns for adverse health effects. To date, several strategies have been developed to counteract with mycotoxin contamination. Red yeast as a novel biological dietary agent is a promising strategy to eliminate mycotoxicity in living organisms. Poultry are most susceptible animals to mycotoxin contamination, as they are fed a mixture of grains and are at higher risk of co-exposure to multiple toxic fungal substances. Therefore, this study investigated the genetic mechanism underlying long-term feeding with red yeast supplementation in interaction with multiple mycotoxins using transcriptome profiling (RNA_Seq) in the liver of laying hens. The results showed a high number of significantly differentially expressed genes in liver of chicken fed with a diet contaminated with mycotoxins, whereas the number of Significantly expressed genes was considerably reduced when the diet was supplemented with red yeast. The expression of genes involved in the phase I (CYP1A1, CYP1A2) and phase II (GSTA2, GSTA3, MGST1) detoxification process was downregulated in animals fed with mycotoxins contaminated diet, indicating suppression of the detoxification mechanisms. However, genes involved in antioxidant defense (GSTO1), apoptosis process (DUSP8), and tumor suppressor (KIAA1324, FBXO47, NME6) were upregulated in mycotoxins-exposed animals, suggesting activation of the antioxidant defense in response to mycotoxicity. Similarly, none of the detoxification genes were upregulated in hens fed with red yeast supplemented diet. However, neither genes involved in antioxidant defense nor tumor suppressor genes were expressed in the animals exposed to the red yeast supplemented feed, suggesting decreases the adsorption of biologically active mycotoxins in the liver of laying hens. We conclude that red yeast can act as a mycotoxin binder to decrease the adsorption of mycotoxins in the liver of laying hens and can be used as an effective strategy in the poultry feed industry to eliminate the adverse effects of mycotoxins for animals and increase food safety for human consumers.
Velocity range-based reward shaping technique for effective map-less navigation with LiDAR sensor and deep reinforcement learning
Authors: Lee HyeokSoo , Jeong Jongpil
Published: September 2023

In recent years, sensor components similar to human sensory functions have been rapidly developed in the hardware field, enabling the acquisition of information at a level beyond that of humans, and in the software field, artificial intelligence technology has been utilized to enable cognitive abilities and decision-making such as prediction, analysis, and judgment. These changes are being utilized in various industries and fields. In particular, new hardware and software technologies are being rapidly applied to robotics products, showing a level of performance and completeness that was previously unimaginable. In this paper, we researched the topic of establishing an optimal path plan for autonomous driving using LiDAR sensors and deep reinforcement learning in a workplace without map and grid coordinates for mobile robots, which are widely used in logistics and manufacturing sites. For this purpose, we reviewed the hardware configuration of mobile robots capable of autonomous driving, checked the characteristics of the main core sensors, and investigated the core technologies of autonomous driving. In addition, we reviewed the appropriate deep reinforcement learning algorithm to realize the autonomous driving of mobile robots, defined a deep neural network for autonomous driving data conversion, and defined a reward function for path planning. The contents investigated in this paper were built into a simulation environment to verify the autonomous path planning through experiment, and an additional reward technique “Velocity Range-based Evaluation Method” was proposed for further improvement of performance indicators required in the real field, and the effectiveness was verified. The simulation environment and detailed results of experiments are described in this paper, and it is expected as guidance and reference research for applying these technologies in the field.
Treatment of multisegmental vertebral compression, burst fractures, and sandwich vertebra with severe osteoporosis using the PKP technique: a case report and literature review
Authors: Han Bo , Pang Daming , Hai Yong , Yang Jincai , Fan Zhexuan , Gao Haifeng , Yin Peng
Published: September 2023

This study aimed to present a special case of treatment of a patient with multisegmental vertebral compression fracture, burst fracture, and sandwich vertebra and to review the literature on this condition. An 85 year-old female presented with severe low back pain but no radiating pain in the lower extremities. The patient was diagnosed with T12 and L5 vertebral compression fractures, fresh vertebral burst fractures in L2 and L3, and osteoporosis. The focus was on formulating a surgical treatment strategy. At the 12 month follow-up, no neurological deficits were observed, and the chosen surgical treatment approach yielded favorable clinical outcomes. A comprehensive literature review indicates that percutaneous kyphoplasty (PKP) can effectively alleviate pain and ensure safety in managing osteoporotic vertebral burst fractures. While complications remain a theoretical risk, they can be mitigated through meticulous assessment, careful surgical procedures, and appropriate preventive measures. PKP is an effective and safe treatment modality for osteoporotic vertebral burst fractures. Conservative management of sandwich vertebrae can yield positive clinical outcomes, but regular anti-osteoporosis treatment is necessary.
Comparison of the safety and efficacy of radiofrequency thermocoagulation with percutaneous balloon compression for treating trigeminal neuralgia: a systematic review and meta-analysis
Authors: Wu Zeyu , Zhao Yongming , Liu Jiang , Fan Yiyue , Yang Ying
Published: September 2023

Objective

This study aimed to systematically assess the efficacy and complications of radiofrequency thermocoagulation (RFT) and percutaneous balloon compression (PBC) for treating trigeminal neuralgia (TN).

Methods

Chinese and English studies on RFT and PBC in the treatment of TN were systematically searched using CNKI, Wanfang Data, VIP, PubMed, EMBASE, Cochrane Library, and until December 31, 2022. Further, the literature was strictly screened using specific inclusion and exclusion criteria. The RevMan 5.4 software was used for data processing and meta-analysis.

Results

Overall, 16 studies with 3,326 patients were included. The results of meta-analysis revealed that no significant difference was present between the two groups in terms of the rate of efficacy immediately after surgery, 1 month after surgery, and 3 months after surgery (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.35–1.54, p = 0.41; OR = 0.41, 95% CI 0.13–1.32, p = 0.13; OR = 0.40, 95% CI 0.10–1.60, p = 0.20); however, at 12 months after surgery, the difference was statistically significant (OR = 0.27, 95% CI 0.10–0.75, p = 0.01). Notably, there was no significant difference in the postoperative sleep quality index between the two groups immediately after surgery and 1 month after surgery (SMD = −0.01, 95% CI −2.47 to 2.44, p = 0.99; SMD = 0.14, 95% CI −3.95 to 4.22, p = 0.95). Further, statistically significant differences were observed between the two groups in the incidence of postoperative masticatory muscle strength decline and oral herpes (OR = 0.37; 95% CI 0.21–0.63, p = 0.0003; OR = 0.25, 95% CI 0.10–0.61, p = 0.003). In addition, a statistically significant difference was found in the recurrence rate at 1-year follow-up (OR = 2.23, 95% CI 1.03–4.81, p = 0.04); however, no statistically significant differences were found in the recurrence rate at the 2-year follow-up (OR = 1.95, 95% CI 0.33–11.59, p = 0.46).

Conclusion

In the treatment of TN, both RFT and PBC can achieve good short-term efficacy, and no significant differences were noted between the outcomes of the two approaches. Compared with RFT, PBC may result in a lower pain score and recurrence rate in the medium and long terms, but it is a higher incidence of cold sores, and the decrease of masticatory muscle strength is more obvious.