bluuebunny/crossref_metadata_2025_split huggingface dataset:
PENGARUH KESADARAN PAJAK, TINGKAT PENDIDIKAN, DAN PERSEPSI TENTANG SANKSI PAJAK PENGUSAHA PENYEDIA JASA INTERNET TERHADAP KEPATUHAN FORMAL
Authors: Musrifah Novianti  , Mienati Somya Lasmana  
Published: March 2024

This study aimed to determine the effect of tax awareness, education level, and the perception about tax penalties of entrepreneurs of internet service providers against formal compliance. The approach used is quantitative explanatory that focuses on hypothesis testing through multiple linear regression analysis. This study uses primary data in the form of questionnaires. The sample used in this study were 31 companies from the member Asosiasi Penyedia Jasa Internet Indonesia (APJII) East Java.
The partial t test indicate that tax awareness and education level of entrepreneurs of internet service providers do not significantly influence formal compliance, while the perception about tax penalties of entrepreneurs of internet service providers significantly influence formal compliance.
PERHITUNGAN PELUNASAN BUNGA FLAT ANTARA TEORI DAN PRAKTIK
Authors: Agustin Defi Nurrokhmah  
Published: March 2024

Bunga flat merupakan pembebanan bunga setiap bulan tetap dari jumlah pinjamannya, demikian pula pokok pinjaman setiap bulan juga dibayar sama sehingga cicilan setiap bulan sama sampai kredit tersebut lunas. Bunga flat dapat dilunasi sebelum jatuh tempo waktu kredit. Pelunasan bunga flat dapat dihitung dengan menggunakan rumus dan tabel pelunasan.
Penelitian ini bertujuan untuk mengetahui perbandingan perhitungan pelunasan suku bunga flat yang ada pada teori dan praktik di bank. Penelitian ini merupakan penelitian komparatif yang membandingan satu variabel dengan dua situasi yang berbeda. Jenis data yang digunakan dalam penelitian ini adalah data kuantitatif. Sumber data dalam peneltian ini adalah data sekunder. Data sekunder dalam penelitian ini adalah rumus perhitungan bunga flat menurut teori dan praktik, perhitungan pelunasan bunga flat menurut praktik dan tabel pelunasan. Analisis dilakukan dengan membandingkan perhitungan pelunasan bunga dengan jangka waktu 12 bulan, 18 bulan dan 24 bulan dengan metode bunga flat berdasarkan teori dan praktik.
Hasil penelitian menunjukkan bahwa perhitungan pelunasan perhitungan bunga flat antara teori dan praktik adalah berbeda. Nilai perhitungan pelunasan bunga yang tinggi adalah menurut teori dengan menggunakan tabel pelunasan bunga kredit
PENGARUH INOVASI PRODUK TERHADAP VOLUME PENJUALAN PADA UD ABADI MULYA KEDIRI
Authors: Rike Kusuma Wardhani  
Published: March 2024

Tujuan Penelitian ini adalah untuk mengetahui pengaruh inovasi produk terhadap volume penjualan pada UD Abadi Mulya Kediri. Metode yang digunakan dalam penelitian ini adalah metode deskriptif kuantitatif. Dengan menggunakan metode ini peneliti akan mengetahui tingkat signifikansi antar variabel yang diteliti sehingga dapat ditarik kesimpulan yang jelas mengenai objek yang akan diteliti.
Penelitian ini menggunakan metode deskriptif kuantitatif untuk menguji pengaruh inovasi produk terhadap volume penjualan pada UD Abadi Mulya serta menguji teori dengan pengujian suatu hipotesis apakah diterima atau ditolak.
Data yang terkumpul akan diproses menggunakan SPSS 16.0 dengan uji statistic untuk menentukan sebaran dan pengaruh variabel bebas terhadap variabel terikat. Uji yang digunakan adalah analisis regresi linier sederhana yang menunjukkan hubungan signifikan (r = 0,850) antara inovasi produk terhadap volume penjualan. Diperoleh nilai t sebesar 2.797 lebih besar dari t tabel sebesar 2.7745. Nilai rsquare sebesar 0.723 menunjukkan bahwa 72.3% varibel independen (inovasi produk) yang dapat menjelaskan variabel dependen (volume penjualan). Sedangkan sisanya sebesar 27,7% dipengaruhi atau dijelaskan oleh variabel lain yang tidak dimasukkan dalam penelitian ini.
Hasil analisa data menunjukkan bahwa inovasi produk berpengaruh secara signifikan terhadap volume penjualan. Sehingga peneliti menyarankan untuk selalu menambah variasi/inovasi produk baru untuk meningkatkan volume penjualan.
Licensing effects of inflammatory factors and TLR ligands on the regenerative capacity of adipose-derived mesenchymal stem cells
Authors: Szűcs Diána , Monostori Tamás , Miklós Vanda , Páhi Zoltán G. , Póliska Szilárd , Kemény Lajos , Veréb Zoltán 
Published: March 2024

Introduction: Adipose tissue-derived mesenchymal stem cells are promising contributors to regenerative medicine, exhibiting the ability to regenerate tissues and modulate the immune system, which is particularly beneficial for addressing chronic inflammatory ulcers and wounds. Despite their inherent capabilities, research suggests that pretreatment amplifies therapeutic effectiveness.Methods: Our experimental design exposed adipose-derived mesenchymal stem cells to six inflammatory factors for 24 h. We subsequently evaluated gene expression and proteome profile alterations and observed the wound closure rate post-treatment.Results: Specific pretreatments, such as IL‐1β, notably demonstrated an accelerated wound‐healing process. Analysis of gene and protein expression profiles revealed alterations in pathways associated with tissue regeneration.Discussion: This suggests that licensed cells exhibit potentially higher therapeutic efficiency than untreated cells, shedding light on optimizing regenerative strategies using adipose tissue-derived stem cells.
Unraveling intestinal microbiota’s dominance in polycystic ovary syndrome pathogenesis over vaginal microbiota
Authors: Yu Xia , Li XiaoQin , Yang Hui 
Published: March 2024

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women, intricately linked to hormonal imbalances. The microbiota composition plays a pivotal role in influencing hormonal levels within the body. In this study, we utilized a murine model to investigate how intestinal and vaginal microbiota interact with hormones in the development of PCOS.MethodsTwenty female mice were randomly assigned to the normal group (N) and the model group (P), where the latter received daily subcutaneous injections of 0.1 mL DHEA (6 mg/100 g). Throughout the experiment, we evaluated the PCOS mouse model by estrus cycle, serum total testosterone (T), prolactin (PRL) and luteinizing hormone (LH) levels, and ovarian pathological morphology. The microbial composition in both intestinal content and vaginal microbiota were studied by 16S rRNA gene high-throughput sequencing.ResultsCompared with the N group, the P group showed significant increases in body weight, T, and PRL, with significant decrease in LH. Ovaries exhibited polycystic changes, and the estrous cycle was disrupted. The intestinal microbiota result shows that Chao1, ACE, Shannon and Simpson indexes were decreased, Desulfobacterota and Acidobacteriota were increased, and Muribaculaceae, Limosilactobacillus and Lactobacillus were decreased in the P group. T was significantly positively correlated with Enterorhabdus, and LH was significantly positively correlated with Lactobacillus. The analysis of vaginal microbiota revealed no significant changes in Chao1, ACE, Shannon, and Simpson indices. However, there were increased in Firmicutes, Bacteroidota, Actinobacteriota, Streptococcus, and Muribaculaceae. Particularly, Rodentibacter displayed a robust negative correlation with other components of the vaginal microbiota.ConclusionTherefore, the response of the intestinal microbiota to PCOS is more significant than that of the vaginal microbiota. The intestinal microbiota is likely involved in the development of PCOS through its participation in hormonal regulation.
Acute myocardial infarction complicated by cardiogenic shock in Ukraine: multicentre registry analysis 2021–2022
Authors: Bilchenko Anton O. , Gritsenko Olga V. , Kolisnyk Volodymir O. , Rafalyuk Oleg I. , Pyzhevskii Andrii V. , Myzak Yaroslav V. , Besh Dmytro I. , Salo Victor M. , Chaichuk Sergii O. , Lehoida Mykhailo O. , Danylchuk Ihor V. , Polivenok Ihor V. 
Published: March 2024

BackgroundData on the results and management strategies in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) in the Low and Lower-Middle Income Countries (LLMICs) are limited. This lack of understanding of the situation partially hinders the development of effective cardiogenic shock treatment programs in this part of the world.Materials and methodsThe Ukrainian Multicentre Cardiogenic Shock Registry was analyzed, covering patient data from 2021 to 2022 in 6 major Ukrainian reperfusion centres from different parts of the country. Analysis was focusing on outcomes, therapeutic modalities and mortality predictors in AMI-CS patients.ResultsWe analyzed data from 221 consecutive patients with CS from 6 hospitals across Ukraine. The causes of CS were ST-elevated myocardial infarction (85.1%), non-ST-elevated myocardial infarction (5.9%), decompensated chronic heart failure (7.7%) and arrhythmia (1.3%), with a total in-hospital mortality rate for CS of 57.1%. The prevalence of CS was 6.3% of all AMI with reperfusion rate of 90.5% for AMI-CS. In 23.5% of cases, CS developed in the hospital after admission. Mechanical circulatory support (MCS) utilization was 19.9% using intra-aortic balloon pump alone. Left main stem occlusion, reperfusion deterioration, Charlson Comorbidity Index &gt;4, and cardiac arrest were found to be independent predictors for hospital mortality in AMI-СS.ConclusionsDespite the wide adoption of primary percutaneous coronary intervention as the main reperfusion strategy for AMI, СS remains a significant problem in LLMICs, associated with high in-hospital mortality. There is an unmet need for the development and implementation of a nationwide protocol for CS management and the creation of reference CS centers based on the country-wide reperfusion network, equipped with modern technologies for MCS.
Deciphering the causal association and co-disease mechanisms between psoriasis and breast cancer
Authors: Li Xujia , Huang Lingli , Yan Yue , Rong Yuming , Chen Xuxian , Gao Mengge , Huang Jinsheng 
Published: March 2024

BackgroundPrior research has indicated a link between psoriasis and the susceptibility to breast cancer (BC); however, a definitive causal relationship remains elusive. This study sought to elucidate the causal connection and shared underlying mechanisms between psoriasis and BC through bidirectional Mendelian randomization (MR) and bioinformatic approaches.MethodsWe employed a bidirectional MR approach to examine the potential causal connection between psoriasis and BC. Genetic data pertaining to psoriasis and BC were sourced from extensive published genome-wide association studies. The inverse -variance weighted or wald ratio served as the primary method for estimating causal effects. Sensitivity analysis of the MR results was applied with multiple methods. Leveraged datasets from the Gene Expression Omnibus and the Cancer Genome Atlas repositories to identify common differentially expressed genes, shedding light on the shared mechanisms underlying these two conditions.ResultsThe MR analysis revealed that when considering psoriasis as an exposure factor, the incidences of BC (OR=1.027) and estrogen receptor negative (ER-) BC (OR=1.054) were higher than in the general population. When using Her2+ BC as an exposure factor, the risk of psoriasis was 0.822 times higher (OR=0.822) than in the general population. Sensitivity analysis indicated that the results were robust. Transcriptome analysis showed that CXCL13 and CCL20 were activated in both BC and psoriasis. Both diseases were also linked to neutrophil chemotaxis, the IL-17 pathway, and the chemokine pathway.ConclusionThe results suggest that psoriasis may increase the risk of BC, especially ER- BC, while reverse MR suggests a decreased risk of psoriasis in Her2+ BC. Transcriptome analysis revealed a shared mechanism between psoriasis and BC.
Increased interleukin-9 and Th9 cells in patients with refractory Graves’ disease and interleukin-9 polymorphisms are associated with autoimmune thyroid diseases
Authors: Yao Qiuming , Song Zhenyu , Wang Bin , Du Peng , Qin Qiu , Zhao Jing , Zhang Jin-an 
Published: March 2024

IntroductionAutoimmune thyroid diseases (AITDs) are prevalent disorders, primarily encompassing Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Despite their common occurrence, the etiology of AITDs remains elusive. Th9 cells, a new subset of CD4+T cells with immunomodulatory properties, have been linked to the development of various autoimmune diseases. However, research on the role of Th9 cells in AITDs is limited. MethodsWe investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs.ResultsWe reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P&lt;0.001, OR= 0.05, 95% CI=0.03-0.08).DiscussionOur results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.
Evaluation of tumor response to immune checkpoint inhibitors by a 3D immunotumoroid model
Authors: Pezeshki Abdulmohammad , Cheville John C. , Florio Angela B. , Leibovich Bradley C. , Vasmatzis George 
Published: March 2024

BackgroundOnly 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response.MethodsWe developed an “immunotumoroid” cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange. Immunohistochemistry was used to detect immune and non-immune cells in cryopreserved source tumors and the resulting immunotumoroids. Immunotumoroid response to ICIs (nivolumab, pembrolizumab, and durvalumab) and chemotherapy (cisplatin, gemcitabine, and paclitaxel) was monitored in real-time with Cytotox Red staining in an Incucyte device, and the immunotumoroid response was compared to retrospective clinical drug responses.ResultsSix of the 13 cases tested grew viable immunotumoroid models, with failed cases attributed to extensive tumor tissue necrosis or excess lymphocytes preventing spheroid formation. One successfully cultured case was excluded from the study due to low TIL infiltration (&lt;5%) in the primary tumor sample. The five remaining models contained immune cells (CD4+ and CD8+ T cells, and macrophages), non-immune cells (fibroblasts), and tumor cells. Chemotherapy and ICI drugs were tested in immunotumoroids from 5 cases and compared to clinical outcomes where data was available. Four/five models showed cell killing in response to chemotherapy and two/five showed sensitivity to ICI. In three cases, the immunotumoroid model accurately predicted the patient’s clinical response or non-response to ICIs or chemotherapy.ConclusionOur immunotumoroid model replicated the multicellular nature of the tumor microenvironment sufficiently for preclinical ICI screening. This model could enable valuable insights into the complex interactions between cancer cells, the immune system, and the microenvironment. This is a feasibility study on a small number of cases, and additional studies with larger case numbers are required including correlation with clinical response.
TOB1 modulates neutrophil phenotypes to influence gastric cancer progression and immunotherapy efficacy
Authors: Zhang Jinfeng , Li Yunlong , Chen Jing , Huang Tongtong , Lin Jing , Pi Yilin , Hao Huiting , Wang Dong , Liang Xiao , Fu Songbin , Yu Jingcui 
Published: March 2024

IntroductionThe ErbB-2.1(TOB1) signaling transducer protein is a tumor-suppressive protein that actively suppresses the malignant phenotype of gastric cancer cells. Yet, TOB1 negatively regulates the activation and growth of different immune cells. Understanding the expression and role of TOB1 in the gastric cancer immune environment is crucial to maximize its potential in targeted immunotherapy.MethodsThis study employed multiplex immunofluorescence analysis to precisely delineate and quantify the expression of TOB1 in immune cells within gastric cancer tissue microarrays. Univariate and multivariate Cox analyses were performed to assess the influence of clinical-pathological parameters, immune cells, TOB1, and double-positive cells on the prognosis of gastric cancer patients. Subsequent experiments included co-culture assays of si-TOB1-transfected neutrophils with AGS or HGC-27 cells, along with EdU, invasion, migration assays, and bioinformatics analyses, aimed at elucidating the mechanisms through which TOB1 in neutrophils impacts the prognosis of gastric cancer patients.ResultsWe remarkably revealed that TOB1 exhibits varying expression levels in both the nucleus (nTOB1) and cytoplasm (cTOB1) of diverse immune cell populations, including CD8+ T cells, CD66b+ neutrophils, FOXP3+ Tregs, CD20+ B cells, CD4+ T cells, and CD68+ macrophages within gastric cancer and paracancerous tissues. Significantly, TOB1 was notably concentrated in CD66b+ neutrophils. Survival analysis showed that a higher density of cTOB1/nTOB1+CD66b+ neutrophils was linked to a better prognosis. Subsequent experiments revealed that, following stimulation with the supernatant of tumor tissue culture, the levels of TOB1 protein and mRNA in neutrophils decreased, accompanied by enhanced apoptosis. HL-60 cells were successfully induced to neutrophil-like cells by DMSO. Neutrophils-like cells with attenuated TOB1 gene expression by si-TOB1 demonstrated heightened apoptosis, consequently fostering a malignant phenotype in AGS and HCG-27 cells upon co-cultivation. The subsequent analysis of the datasets from TCGA and TIMER2 revealed that patients with high levels of TOB1 combined neutrophils showed better immunotherapy response.DiscussionThis study significantly advances our comprehension of TOB1’s role within the immune microenvironment of gastric cancer, offering promising therapeutic targets for immunotherapy in this context.
Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study
Authors: Choi Chel Hun , Lee Jeong-Won , Bae Duk-Soo , Kang Eun-Suk , Cho Duck , Kim Yong-Man , Kim Kidong , Kim Jae-Weon , Kim Hee Seung , Kim Young-Tae , Lee Jung-Yun , Lim Myong Cheol , Oh Taegwon , Song Boyeong , Jeon Insu , Park Myunghwan , Kim Wu Hyun , Kang Chang-Yuil , Kim Byoung-Gie 
Published: March 2024

BackgroundBVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or 18–positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.Patients and methodsPatients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsOf the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1–not reported), the median PFS was 5.8 months (95% CI 4.2–10.3), and the median OS was 17.7 months (95% CI 12.0–not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.ConclusionBVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.Clinical trial registrationClinicalTrials.gov, identifier NCT02866006.
Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis
Authors: Wang Lihong , He Wenhui , Wang Xilin , Wang Jianrong , Wei Xiaojuan , Wu Dongzhi , Wu Yundan 
Published: March 2024

BackgroundEvidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear.ObjectiveThis study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets.MethodsWe downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells.ResultsThe WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells.ConclusionWe identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.