bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biologic switching patterns among children with non-systemic juvenile idiopathic arthritis
Authors: Pedersen Mia Lindegaard , Neve-Græsbøll Amalie , Herlin Troels , Glerup Mia 
Published: September 2023

Abstract
Background
In juvenile idiopathic arthritis (JIA) clinical remission is unattainable in some patients despite modern biologic disease-modifying antirheumatic drugs (bDMARD) therapy and switching bDMARD is required. The best choice of second-line bDMARD remains unclear. This retrospective observational study aims to describe the pattern, timing, frequency, and reasons for bDMARD switching among children diagnosed with non-systemic JIA.

Methods
Patients were identified by combining unique personal identification numbers, the International Code of Diagnosis (ICD10) for JIA and biologic therapy. Clinical characteristics were collected retrospectively from the electronic medical records. Included were 200 children diagnosed with non-systemic JIA initiating their first biologic drug between January 1st, 2012, and March 1st, 2021. We compared characteristics of non-switchers vs switchers and early switchers (≤ 6 months) vs late switchers (> 6 months).

Results
The median age at diagnosis was 7.7 years. We found that 37% switched to a different bDMARD after a median age of 6.3 years after diagnosis. In total, and 17.5% of patients switched at least twice, while 6% switched three or more times. The most common reason for switching was inefficacy (57%) followed by injection/infusion reactions (15%) and uveitis (13%). 77% were late switchers, and switched primarily due to inefficacy. All patients started a tumor necrosis factor inhibitor (TNFi) as initial bDMARD (Etanercept (ETN): 49.5%, other TNFis: 50.5%). The patients who started ETN as first-line bDMARD were more likely to be switchers compared to those who started another TNFi.

Conclusion
During a median 6.3-year follow-up biologic switching was observed in more than one third, primarily due to inefficacy.
LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement
Authors: Zhang Cong , Wang Huixia , Liu Qingwei , Dai Suli , Tian Guo , Wei Xintong , Li Xiaoya , Zhao Lianmei , Shan Baoen 
Published: September 2023

Abstract
Background
Gastric cancer (GC) is one of the most prevalent malignant tumors of the digestive system. As a hallmark of cancer, energy-related metabolic reprogramming is manipulated by multiple factors, including long non-coding RNAs (lncRNAs). Notably, lncRNA CCAT1 has been identified as a crucial regulator in tumor progression. Nevertheless, the precise molecular mechanisms underlying the involvement of CCAT1 in metabolic reprogramming of GC remain unclear.

Methods
Gain- and loss-of-function experiments were performed to evaluate the roles of CCAT1 in tumorigenesis and glycolysis of GC. Bioinformatics analyses and mechanistic experiments, such as mass spectrometry (MS), RNA-pulldown, and RNA immunoprecipitation (RIP), were employed to reveal the potential interacting protein of CCAT1 and elucidate the regulatory mechanism of CCAT1 in GC glycolysis. Moreover, the nude mice xenograft assay was used to evaluate the effect of CCAT1 on GC cells in vivo.

Results
In this study, we identified that CCAT1 expression was significantly elevated in the tissues and plasma exosomes of GC patients, as well as GC cell lines. Functional experiments showed that the knockdown of CCAT1 resulted in a substantial decrease in the proliferation, migration and invasion of GC cells both in vitro and in vivo through decreasing the expression of glycolytic enzymes and glycolytic rate. Conversely, overexpression of CCAT1 exhibited contrasting effects. Mechanistically, CCAT1 interacted with PTBP1 and effectively maintained its stability by inhibiting the ubiquitin-mediated degradation process. As a critical splicing factor, PTBP1 facilitated the transition from PKM1 to PKM2, thereby augmenting the glycolytic activity of GC cells and ultimately fostering the progression of GC.

Conclusions
Our findings demonstrate that CCAT1 plays a significant role in promoting the proliferation, migration, and invasion of GC cells through the PTBP1/PKM2/glycolysis pathway, thus suggesting CCAT1’s potential as a biomarker and therapeutic target for GC.
Histone crotonylation of peripheral blood mononuclear cells is a potential biomarker for diagnosis of colorectal cancer
Authors: Hou Jia-Yi , Li Ning , Wang Jie , Gao Li-Juan , Chang Jia-Song , Cao Ji-Min 
Published: September 2023

AbstractBackgroundBlood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC).ResultsWestern blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins. The correlation of crotonylation with tumor staging and diagnostic efficacy were analyzed. Crotonylation of H2BK12 (H2BK12cr) was identified significantly upregulated in the PBMCs of CRC patients compared to healthy controls, and were closely related to distant metastasis (P = 0.0478) and late TNM stage (P = 0.0201). Receiver operator characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) of H2BK12cr was 0.8488, the sensitivity was 70%, and the specificity was 92.5%. The H2BK12cr parameter significantly increased the diagnostic effectiveness of CRC compared with the commercial carcinoembryonic antigen assays.ConclusionsThe H2BK12cr level in PBMCs of CRC patients has a potential to be a biomarker for distinguishing CRC patients from healthy controls with the advantages of easy operation and high diagnostic efficacy.
Long-term effects of vitamin D supplementation and maintaining sufficient vitamin D on knee osteoarthritis over 5 years
Authors: Wang Zhiqiang , Zhu Zhaohua , Pan Feng , Zheng Shuang , Parameswaran Venkat , Blizzard Leigh , Ding Changhai , Antony Benny 
Published: September 2023

Abstract
Objectives
This study aimed to investigate the long-term effect of vitamin D supplementation compared to placebo over 5 years in participants with knee osteoarthritis (OA). We also aimed to describe the effect of maintaining sufficient serum vitamin D levels over five years in knee OA.

Methods
Participants (n = 173) from the Hobart centre of the Vitamin D Effects on Osteoarthritis (VIDEO) trial were extensively followed up 3 years after the cessation of 2-year investigational treatment. Participants were classified as maintaining sufficient vitamin D (n = 79) and not maintaining sufficient vitamin D (n = 61) groups.

Results
There was no significant difference in change in the knee symptoms, depression, and serum levels of IL6 and hs-CRP between both comparisons after 3 years of cessation of the clinical trial. However, among participants who reported no knee surgery (KS), there was a significant improvement in WOMAC function (β: − 83.7, 95% CI: − 167.3, 0) and depression scores (β: − 1.3, 95% CI: − 2.3, − 0.2) in vitamin D group compared to the placebo group. Similarly, those who maintained adequate vitamin D levels over 5 years had significantly less WOMAC knee pain (β: − 33.9, 95% CI: − 65.7, − 2) and physical dysfunction (β: − 105.5, 95% CI: − 198.2, − 12.8) than participants with vitamin D deficiency over 5 years.

Conclusion
Vitamin D supplementation over 2 years or maintaining vitamin D sufficiency for 5 years was not associated with statistically significant differences in change in knee symptom scores over 5 years. However, among participants who did not report KS, 2-year vitamin D supplementation and maintaining sufficient vitamin D was linked to modest improvements in knee symptoms and depression scores in knee OA.
METTL3 exerts synergistic effects on m6A methylation and histone modification to regulate the function of VGF in lung adenocarcinoma
Authors: Shi Kesong , Sa Rula , Dou Le , Wu Yuan , Dong Zhiqiang , Fu Xinyao , Yu Haiquan 
Published: September 2023

Abstract
Background
Multiple genetic and epigenetic regulatory mechanisms play a vital role in tumorigenesis and development. Understanding the interplay between different epigenetic modifications and its contribution to transcriptional regulation in cancer is essential for precision medicine. Here, we aimed to investigate the interplay between N6-methyladenosine (m6A) modifications and histone modifications in lung adenocarcinoma (LUAD).

Results
Based on the data from public databases, including chromatin property data (ATAC-seq, DNase-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), and gene expression data (RNA-seq), a m6A-related differentially expressed gene nerve growth factor inducible (VGF) was identified between LUAD tissues and normal lung tissues. VGF was significantly highly expressed in LUAD tissues and cells, and was associated with a worse prognosis for LUAD, silencing of VGF inhibited the malignant phenotype of LUAD cells by inactivating the PI3K/AKT/mTOR pathway. Through the weighted correlation network analysis (WGCNA) and integration of TCGA-LUAD RNA-seq and m6A methyltransferase METTL3-knockdown RNA-seq data, a significant positive correlation between METTL3 and VGF was observed. By using the MeRIP-qPCR and dual-luciferase reporter assays, we demonstrated that METTL3 knockdown decreased m6A modification level of VGF coding sequences in LUAD cells, the colorimetric m6A quantification assay also showed that METTL3 knockdown significantly decreased global m6A modification level in LUAD cells. Interestingly, we found that METTL3 knockdown also reduced VGF expression by increasing H3K36me3 modification at the VGF promoter. Further research revealed that METTL3 knockdown upregulated the expression of histone methylase SETD2, the major H3K36me3 methyltransferase, by methylating the m6A site in the 3'UTR of SETD2 mRNA in LUAD cells.

Conclusions
Overall, our results reveal that the expression of VGF in LUAD cells is regulated spatio-temporally by METTL3 through both transcriptional (via histone modifications) and post-transcriptional (via m6A modifications) mechanisms. The synergistic effect of these multiple epigenetic mechanisms provides new opportunities for the diagnosis and precision treatment of tumors.
Two cases of successful sirolimus treatment for patients with activated phosphoinositide 3-kinase δ syndrome 1
Authors: Jiang Lu , Hu Xiaohan , Lin Qiang , Chen Ruyue , Shen Yunyan , Zhu Yun , Xu Qinying , Li Xiaozhong 
Published: September 2023

Abstract
Background
Activated phosphoinositide3-kinase (PI3K) δ syndrome 1 (APDS1) is a novel inborn errors of immunity (IEIs) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD). APDS1 has a spectrum of clinical manifestations. Recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, hyper-IgM syndrome and autoimmunity are the common symptoms of this disease.

Case Presentation
Patient 1 presented with recurrent respiratory infections, hepatosplenomegaly and hyper-IgM syndrome. Patient 2 developed early onset systemic lupus erythematosus (SLE)-like disease with resistant thrombocytopenia. c.3061 G > A and c.2314G > A variants in the PIK3CD gene were detected by whole exome sequencing in two patients respectively. c.2314G > A variant in PIK3CD gene of patient 2 is a newly report. After genetic diagnosis, two patients received sirolimus treatment and sirolimus alleviated clinical manifestations, including hepatosplenomegaly in patient 1 and thrombocytopenia in patient 2.

Conclusion
Genetics diagnosis should be considered in patients with complicated clinical manifestations with no or insufficient response to the conventional therapies. If whole exome sequencing suggests a variant in PIK3CD gene, sirolimus may relieve hepatosplenomegaly and resistant thrombocytopenia. This is the first report of c.2314G > A variant in PIK3CD gene.
Effect of once versus twice intracoronary injection of allogeneic-derived mesenchymal stromal cells after acute myocardial infarction: BOOSTER-TAHA7 randomized clinical trial
Authors: Attar Armin , Farjoud Kouhanjani Mohsen , Hessami Kamran , Vosough Massoud , Kojuri Javad , Ramzi Mani , Hosseini Seyed Ali , Faghih Marjan , Monabati Ahmad 
Published: September 2023

Abstract
Background
Mesenchymal stromal cell (MSC) transplantation can improve the left ventricular ejection fraction (LVEF) after an acute myocardial infarction (AMI). Transplanted MSCs exert a paracrine effect, which might be augmented if repeated doses are administered. This study aimed to compare the effects of single versus double transplantation of Wharton’s jelly MSCs (WJ-MSCs) on LVEF post-AMI.

Methods
We conducted a single-blind, randomized, multicenter trial. After 3–7 days of an AMI treated successfully by primary PCI, 70 patients younger than 65 with LVEF < 40% on baseline echocardiography were randomized to receive conventional care, a single intracoronary infusion of WJ-MSCs, or a repeated infusion 10 days later. The primary endpoint was the 6-month LVEF improvement as per cardiac magnetic resonance (CMR) imaging.

Results
The mean baseline EF measured by CMR was similar (~ 40%) in all three groups. By the end of the trial, while all patients experienced a rise in EF, the most significant change was seen in the repeated intervention group. Compared to the control group (n = 25), single MSC transplantation (n = 20) improved the EF by 4.54 ± 2%, and repeated intervention (n = 20) did so by 7.45 ± 2% when measured by CMR imaging (P < 0.001); when evaluated by echocardiography, these values were 6.71 ± 2.4 and 10.71 ± 2.5%, respectively (P < 0.001).

Conclusions
Intracoronary transplantation of WJ-MSCs 3–7 days after AMI in selected patients significantly improves LVEF, with the infusion of a booster dose 10 days later augmenting this effect.
Trial registration: Trial registration: Iranian Registry of Clinical Trials, IRCT20201116049408N1. Retrospectively Registered 20 Nov. 2020, https://en.irct.ir/trial/52357
Transcriptomic analysis of stem cells from chorionic villi uncovers the impact of chromosomes 2, 6 and 22 in the clinical manifestations of Down syndrome
Authors: Vaiasicca Salvatore , Melone Gianmarco , James David W. , Quintela Marcos , Preziuso Alessandra , Finnell Richard H. , Conlan Robert Steven , Francis Lewis W. , Corradetti Bruna 
Published: September 2023

Abstract
Background
Down syndrome (DS) clinical multisystem condition is generally considered the result of a genetic imbalance generated by the extra copy of chromosome 21. Recent discoveries, however, demonstrate that the molecular mechanisms activated in DS compared to euploid individuals are more complex than previously thought. Here, we utilize mesenchymal stem cells from chorionic villi (CV) to uncover the role of comprehensive functional genomics-based understanding of DS complexity.

Methods
Next-generation sequencing coupled with bioinformatic analysis was performed on CV obtained from women carrying fetuses with DS (DS-CV) to reveal specific genome-wide transcriptional changes compared to their euploid counterparts. Functional assays were carried out to confirm the biological processes identified as enriched in DS-CV compared to CV (i.e., cell cycle, proliferation features, immunosuppression and ROS production).

Results
Genes located on chromosomes other than the canonical 21 (Ch. 2, 6 and 22) are responsible for the impairment of life-essential pathways, including cell cycle regulation, innate immune response and reaction to external stimuli were found to be differentially expressed in DS-CV. Experimental validation confirmed the key role of the biological pathways regulated by those genes in the etiology of such a multisystem condition.

Conclusions
NGS dataset generated in this study highlights the compromised functionality in the proliferative rate and in the innate response of DS-associated clinical conditions and identifies DS-CV as suitable tools for the development of specifically tailored, personalized intervention modalities.
Mass-Suite: a novel open-source python package for high-resolution mass spectrometry data analysis
Authors: Hu Ximin , Mar Derek , Suzuki Nozomi , Zhang Bowei , Peter Katherine T. , Beck David A. C. , Kolodziej Edward P. 
Published: September 2023

AbstractMass-Suite (MSS) is a Python-based, open-source software package designed to analyze high-resolution mass spectrometry (HRMS)-based non-targeted analysis (NTA) data, particularly for water quality assessment and other environmental applications. MSS provides flexible, user-defined workflows for HRMS data processing and analysis, including both basic functions (e.g., feature extraction, data reduction, feature annotation, data visualization, and statistical analyses) and advanced exploratory data mining and predictive modeling capabilities that are not provided by currently available open-source software (e.g., unsupervised clustering analyses, a machine learning-based source tracking and apportionment tool). As a key advance, most core MSS functions are supported by machine learning algorithms (e.g., clustering algorithms and predictive modeling algorithms) to facilitate function accuracy and/or efficiency. MSS reliability was validated with mixed chemical standards of known composition, with 99.5% feature extraction accuracy and ~ 52% overlap of extracted features relative to other open-source software tools. Example user cases of laboratory data evaluation are provided to illustrate MSS functionalities and demonstrate reliability. MSS expands available HRMS data analysis workflows for water quality evaluation and environmental forensics, and is readily integrated with existing capabilities. As an open-source package, we anticipate further development of improved data analysis capabilities in collaboration with interested users.
Graphical abstract
Iterative machine learning-based chemical similarity search to identify novel chemical inhibitors
Authors: Durai Prasannavenkatesh , Lee Sue Jung , Lee Jae Wook , Pan Cheol-Ho , Park Keunwan 
Published: September 2023

AbstractMachine learning-based chemical screening has made substantial progress in recent years. However, these predictions often have low accuracy and high uncertainty when identifying new active chemical scaffolds. Hence, a high proportion of retrieved compounds are not structurally novel. In this study, we proposed a strategy to address this issue by iteratively optimizing an evolutionary chemical binding similarity (ECBS) model using experimental validation data. Various data update and model retraining schemes were tested to efficiently incorporate new experimental data into ECBS models, resulting in a fine-tuned ECBS model with improved accuracy and coverage. To demonstrate the effectiveness of our approach, we identified the novel hit molecules for the mitogen-activated protein kinase kinase 1 (MEK1). These molecules showed sub-micromolar affinity (Kd 0.1–5.3 μM) to MEKs and were distinct from previously-known MEK1 inhibitors. We also determined the binding specificity of different MEK isoforms and proposed potential docking models. Furthermore, using de novo drug design tools, we utilized one of the new MEK inhibitors to generate additional drug-like molecules with improved binding scores. This resulted in the identification of several potential MEK1 inhibitors with better binding affinity scores. Our results demonstrated the potential of this approach for identifying novel hit molecules and optimizing their binding affinities.
Semi-automating abstract screening with a natural language model pretrained on biomedical literature
Authors: Ng Sheryl Hui-Xian , Teow Kiok Liang , Ang Gary Yee , Tan Woan Shin , Hum Allyn 
Published: September 2023

AbstractWe demonstrate the performance and workload impact of incorporating a natural language model, pretrained on citations of biomedical literature, on a workflow of abstract screening for studies on prognostic factors in end-stage lung disease. The model was optimized on one-third of the abstracts, and model performance on the remaining abstracts was reported. Performance of the model, in terms of sensitivity, precision, F1 and inter-rater agreement, was moderate in comparison with other published models. However, incorporating it into the screening workflow, with the second reviewer screening only abstracts with conflicting decisions, translated into a 65% reduction in the number of abstracts screened by the second reviewer. Subsequent work will look at incorporating the pre-trained BERT model into screening workflows for other studies prospectively, as well as improving model performance.
Effect of pH and temperature on the biodegradation of oxytetracycline, streptomycin, and validamycin A in soil
Authors: Kim Seon Hui , Park So Yun , Kim Ga Eun , Jho Eun Hea 
Published: September 2023

AbstractResidual antibiotics in agricultural soils can be of concern due to the development of antibiotic resistant microorganisms. Among various antibiotics, oxytetracycline (OTC), streptomycin (ST), and validamycin A (VA) have been used for agricultural purposes in South Korea; however, studies on the biodegradation of these antibiotics in soil are limited. Therefore, this study investigated the effects of pH (5.5, 6.8, and 7.4) and temperature (1.8, 23.0, and 31.2 °C) conditions on the biodegradation of these antibiotics in soil. The biodegradation tests were carried out in the field soil (FS) and rice paddy soil (RS) for 30 d with OTC and ST and 10 d with VA, and the residual antibiotics concentrations were monitored over the degradation period. Under various conditions, the degradation rates of ST was lower (11–69%) than that of OTC (60–90%) and VA (15–96%). The degradation half-lives of OTC and VA tend to decrease with increasing pH value, while the degradation half-life of ST tend to increase with increasing pH value. But, the effect of soil pH on the antibiotics degradation was not statistically significant, except for ST in the FS and RS and VA in the FS. The degradation of three antibiotics was greater at higher temperatures (23.0 °C and 31.2 °C) than at lower temperature (1.8 °C), and the degradation half-lives decreased with increasing temperature. The different degradation characteristics of different antibiotics in soil can be explained by the different characteristics of the antibiotics (e.g., sorption affinity, chemical forms) and soil (e.g., organic matter content). The results suggest that the degradation characteristics of antibiotics need to be considered in order to properly manage the residual antibiotics in soil.