bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of anti-cardiac fibrosis immune responses by changing M2 macrophages into M1 macrophages
Authors: Chen Shiqi , Wang Kan , Fan Zhengfeng , Zhou Tingwen , Li Rui , Zhang Bingxia , Chen Jie , Chi Jiangyang , Wei Keke , Liu Jincheng , Liu Zongtao , Ma Jingwei , Dong Nianguo , Liu Junwei 
Published: June 2024

Abstract
Background
Macrophages play a crucial role in the development of cardiac fibrosis (CF). Although our previous studies have shown that glycogen metabolism plays an important role in macrophage inflammatory phenotype, the role and mechanism of modifying macrophage phenotype by regulating glycogen metabolism and thereby improving CF have not been reported.

Methods
Here, we took glycogen synthetase kinase 3β (GSK3β) as the target and used its inhibitor NaW to enhance macrophage glycogen metabolism, transform M2 phenotype into anti-fibrotic M1 phenotype, inhibit fibroblast activation into myofibroblasts, and ultimately achieve the purpose of CF treatment.

Results
NaW increases the pH of macrophage lysosome through transmembrane protein 175 (TMEM175) and caused the release of Ca2+ through the lysosomal Ca2+ channel mucolipin-2 (Mcoln2). At the same time, the released Ca2+ activates TFEB, which promotes glucose uptake by M2 and further enhances glycogen metabolism. NaW transforms the M2 phenotype into the anti-fibrotic M1 phenotype, inhibits fibroblasts from activating myofibroblasts, and ultimately achieves the purpose of treating CF.

Conclusion
Our data indicate the possibility of modifying macrophage phenotype by regulating macrophage glycogen metabolism, suggesting a potential macrophage-based immunotherapy against CF.

Graphical Abstract
Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers
Authors: Ghorbani Atefeh , Chatanaka Miyo K. , Avery Lisa M. , Wang Mingyue , Brown Jermaine , Cohen Rachel , Gorham Taron , Misaghian Salvia , Padmanabhan Nikhil , Romero Daniel , Stengelin Martin , Mathew Anu , Sigal George , Wohlstadter Jacob , Horbinski Craig , McCortney Katy , Xu Wei , Zadeh Gelareh , Mansouri Alireza , Yousef George M. , Diamandis Eleftherios P. , Prassas Ioannis 
Published: June 2024

Abstract
Background
Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers – glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) – and compare them with established brain tumor molecular markers and survival.

Methods
Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays.

Results
High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas.

Conclusions
GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.
Explosives leaking from dumped munition contaminate fish from German coastal waters: a reason for chronic effects?
Authors: Kammann Ulrike , Töpker Verena , Schmidt Nicole , Rödiger Marcellus , Aust Marc-Oliver , Gabel Michael , Scharsack Jörn Peter 
Published: June 2024

Abstract
Background
Conventional munition dumped into the North Sea and the Baltic Sea close to the German coastline is corroding. A major concern is that biota, including fish, are negatively affected by toxic explosives leaking into marine environments. With the present study, we investigated fish living in close proximity to munition dumping sites for contamination and for signs of health impairments. The flat fish species common dab (Limanda limanda) was used as a model, since it lives in the vicinity of dumping sites and exhibits minor migratory activity. Since explosives are excreted via the bile, the bile fluids from dab were analysed. Further on we inspected the health status of the fish.

Results
Dab caught in German coastal waters of the Baltic Sea and the North Sea were contaminated with explosives. Probably due to rapid metabolization, concentrations of the explosive 2,4,6-trinitrotoluene (TNT) were always below limit of detection, but its metabolites 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene were detected in bile fluid up to 26.36 ng/ml and 95.91 ng/ml, respectively. Only few fish from the Baltic Sea were positive for the explosive HMX, octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine with a maximum concentration of 0.89 ng/ml. Highest concentrations of TNT metabolites in bile fluid were detected in dab collected near the dumping site “Kolberger Heide” in the bay of Kiel (Baltic Sea). However, also dab from the North Sea were significantly contaminated with TNT metabolites.

Conclusions
The present study showed for the first time that fish living close to near shore munition dumping sites in the North Sea are contaminated with explosives. Various health indicators (body condition factors, externally visible fish diseases, parasites or liver anomalies) showed differences in health status between fish living in the North Sea and in the Baltic Sea, respectively. However, the health status of fish caught at the most contaminated site in the Baltic Sea was not worse compared to fish living in less contaminated areas. We conclude that fish living in the vicinity of dumping sites in the North Sea and the Baltic Sea can be significantly contaminated with explosives. However, obvious health impairments of the fish were not observed.
Delivery of letrozole-encapsulated niosomes via a 3D bioprinting gelatin–alginate scaffold for potential breast cancer treatment
Authors: Mahdizadeh Neda , Khorshid Shabestari Mahtab , Tafvizi Farzaneh , Khodarahmi Parvin 
Published: June 2024

Abstract3D printing technology is a powerful tool in scaffold engineering for biomedical applications, especially in anticancer activities and drug delivery. The present study developed a 3D-printed gelatin–alginate scaffold incorporating letrozole-loaded niosomes (Let/Nio@Gel-AL-SC) as a more effective drug delivery system. The findings showed that the fabricated niosomes appeared spherical. 3D-printed scaffolds exhibited biodegradability and sustained drug-release properties. The drug release from the scaffold was less prominent under acidic conditions than physiological ones. Cytotoxicity analysis showed that the engineered Let/Nio@Gel-AL-SC scaffold exhibited significant cytotoxicity against MCF-7 cancer cells. Gene expression analysis demonstrated a significant decrease in the expression of BCL2, CCND1, MMP2, and CDK4 genes and a notable increase in the expression of BAX and P53 genes, as well as the activity of Caspase 3/7 enzyme following treatment with Let/Nio@Gel-AL-SC. In addition, flow cytometry analysis revealed that Let/Nio@Gel-AL-SC significantly reduced necrosis and dramatically increased apoptosis. Also, the Let/Nio@Gel-AL-SC formulation exhibited a significantly greater increase in ROS values. The incorporation of letrozole-loaded niosomes into 3D printing gelatin/alginate scaffold has enhanced the efficacy of anticancer therapy. This is demonstrated by the sustained release of drugs, which indicates a promising potential for effective anticancer activity. Consequently, this combination holds promise as a potential future cancer therapy strategy.
Graphical abstract
SpliceAPP: an interactive web server to predict splicing errors arising from human mutations
Authors: Huang Ang-Chu , Su Jia-Ying , Hung Yu-Jen , Chiang Hung-Lun , Chen Yi-Ting , Huang Yen-Tsung , Yu Chen-Hsin Albert , Lin Hsin-Nan , Lin Chien-Ling 
Published: June 2024

Abstract
Background
Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants. Based on the experimental results, we then applied regression-based methods to identify factors determining splicing decisions and their respective weights.

Results
Our statistical modeling is highly sensitive, accurately annotating the splicing defects of near-exon intronic variants, outperforming state-of-the-art predictive tools. We have incorporated the algorithm and branchpoint information into a web-based tool, SpliceAPP, to provide an interactive application. This user-friendly website allows users to upload any genetic variants with genome coordinates (e.g., chr15 74,687,208 A G), and the tool will output predictions for splicing error scores and evaluate the impact on nearby splice sites. Additionally, users can query branch site information within the region of interest.

Conclusions
In summary, SpliceAPP represents a pioneering approach to screening pathogenic intronic variants, contributing to the development of precision medicine. It also facilitates the annotation of splicing motifs. SpliceAPP is freely accessible using the link https://bc.imb.sinica.edu.tw/SpliceAPP. Source code can be downloaded at https://github.com/hsinnan75/SpliceAPP.
Identification of key genes for triacylglycerol biosynthesis and storage in herbaceous peony (Paeonia lactifolra Pall.) seeds based on full-length transcriptome
Authors: Xu Huajie , Li Miao , Ma Di , Gao Jiajun , Tao Jun , Meng Jiasong 
Published: June 2024

Abstract
Background
The herbaceous peony (Paeonia lactiflora Pall.) is extensively cultivated in China due to its root being used as a traditional Chinese medicine known as ‘Radix Paeoniae Alba’. In recent years, it has been discovered that its seeds incorporate abundant unsaturated fatty acids, thereby presenting a potential new oilseed plant. Surprisingly, little is known about the full-length transcriptome sequencing of Paeonia lactiflora, limiting research into its gene function and molecular mechanisms.

Results
A total of 484,931 Reads of Inserts (ROI) sequences and 1,455,771 full-Length non-chimeric reads (FLNC) sequences were obtained for CDS prediction, TF analysis, SSR analysis and lncRNA identification. In addition, gene function annotation and gene structure analysis were performed. A total of 4905 transcripts were related to lipid metabolism biosynthesis pathway, belonging to 28 enzymes. We use these data to identify 10 oleosin (OLE) and 5 diacylglycerol acyltransferase (DGAT) gene members after de-redundancy. The analysis of physicochemical properties and secondary structure showed them similarity in gene family respectively. The phylogenetic analysis showed that the distribution of OLE and DGAT family members was roughly the same as that of Arabidopsis. Quantitative real-time polymerase chain reaction (qRT–PCR) analyses revealed expression changes in different seed development stages, and showed a trend of increasing and then decreasing.

Conclusion
In summary, these results provide new insights into the molecular mechanism of triacylglycerol (TAG) biosynthesis and storage during the seedling stage in Paeonia lactiflora. It provides theoretical references for selecting and breeding oil varieties and understanding the functions of oil storage as well as lipid synthesis related genes in Paeonia lactiflora.
Multi-trait association mapping for phosphorous efficiency reveals flexible root architectures in sorghum
Authors: Hufnagel Barbara , Bernardino Karine C. , Malosetti Marcos , Sousa Sylvia M. , Silva Lidianne A. , Guimaraes Claudia Teixeira , Coelho Antônio Marcos , Santos Thiago Teixeira , Viana Joao H. M. , Schaffert Robert E. , Kochian Leon V. , Eeuwijk Fred A. , Magalhaes Jurandir V. 
Published: June 2024

Abstract
Background
On tropical regions, phosphorus (P) fixation onto aluminum and iron oxides in soil clays restricts P diffusion from the soil to the root surface, limiting crop yields. While increased root surface area favors P uptake under low-P availability, the relationship between the three-dimensional arrangement of the root system and P efficiency remains elusive. Here, we simultaneously assessed allelic effects of loci associated with a variety of root and P efficiency traits, in addition to grain yield under low-P availability, using multi-trait genome-wide association. We also set out to establish the relationship between root architectural traits assessed in hydroponics and in a low-P soil. Our goal was to better understand the influence of root morphology and architecture in sorghum performance under low-P availability.

Result
In general, the same alleles of associated SNPs increased root and P efficiency traits including grain yield in a low-P soil. We found that sorghum P efficiency relies on pleiotropic loci affecting root traits, which enhance grain yield under low-P availability. Root systems with enhanced surface area stemming from lateral root proliferation mostly up to 40 cm soil depth are important for sorghum adaptation to low-P soils, indicating that differences in root morphology leading to enhanced P uptake occur exactly in the soil layer where P is found at the highest concentration.

Conclusion
Integrated QTLs detected in different mapping populations now provide a comprehensive molecular genetic framework for P efficiency studies in sorghum. This indicated extensive conservation of P efficiency QTL across populations and emphasized the terminal portion of chromosome 3 as an important region for P efficiency in sorghum. Increases in root surface area via enhancement of lateral root development is a relevant trait for sorghum low-P soil adaptation, impacting the overall architecture of the sorghum root system. In turn, particularly concerning the critical trait for water and nutrient uptake, root surface area, root system development in deeper soil layers does not occur at the expense of shallow rooting, which may be a key reason leading to the distinctive sorghum adaptation to tropical soils with multiple abiotic stresses including low P availability and drought.
Genome-wide analysis of AP2/ERF transcription factors that regulate fruit development of Chinese prickly ash
Authors: Ma Lei , Shi Qianqian , Ma Qin , Wang Xiaona , Chen Xin , Han Peilin , Luo Yingli , Hu Haichao , Fei Xitong , Wei Anzhi 
Published: June 2024

Abstract
Background
AP2/ERF is a large family of plant transcription factor proteins that play essential roles in signal transduction, plant growth and development, and responses to various stresses. The AP2/ERF family has been identified and verified by functional analysis in various plants, but so far there has been no comprehensive study of these factors in Chinese prickly ash. Phylogenetic, motif, and functional analyses combined with transcriptome analysis of Chinese prickly ash fruits at different developmental stages (30, 60, and 90 days after anthesis) were conducted in this study.

Results
The analysis identified 146 ZbAP2/ERF genes that could be classified into 15 subgroups. The motif analysis revealed the presence of different motifs or elements in each group that may explain the functional differences between the groups. ZbERF13.2, ZbRAP2-12, and ZbERF2.1 showed high levels of expression in the early stages of fruit development. ZbRAP2-4, and ZbERF3.1 were significantly expressed at the fruit coloring stage (R2 and G2). ZbERF16 were significantly expressed at fruit ripening and expression level increased as the fruit continued to develop. Relative gene expression levels of 6 representative ZbAP2/ERFs assessed by RT-qPCR agreed with transcriptome analysis results.

Conclusions
These genes identified by screening can be used as candidate genes that affect fruit development. The results of the analysis can help guide future genetic improvement of Chinese prickly ash and enrich our understanding of AP2/ERF transcription factors and their regulatory functions in plants.
Integrated analysis of transcriptomics and metabolomics of garden asparagus (Asparagus officinalis L.) under drought stress
Authors: Zhang Xuhong , Han Changzhi , Wang Yubo , Liu Tao , Liang Yuqin , Cao Yanpo 
Published: June 2024

Abstract
Background
Drought is a leading environmental factor affecting plant growth. To explore the drought tolerance mechanism of asparagus, this study analyzed the responses of two asparagus varieties, namely, ‘Jilv3’ (drought tolerant) and ‘Pacific Early’ (drought sensitive), to drought stress using metabolomics and transcriptomics.

Results
In total, 2,567 and 7,187 differentially expressed genes (DEGs) were identified in ‘Pacific Early’ and ‘Jilv3’, respectively, by comparing the transcriptome expression patterns between the normal watering treatment and the drought stress treatment. These DEGs were significantly enriched in the amino acid biosynthesis, carbon metabolism, phenylpropanoid biosynthesis, and plant hormone signal transduction pathways. In ‘Jilv3’, DEGs were also enriched in the following energy metabolism-related pathways: citrate cycle (TCA cycle), glycolysis/gluconeogenesis, and pyruvate metabolism. This study also identified 112 and 254 differentially accumulated metabolites (DAMs) in ‘Pacific Early’ and ‘Jilv3’ under drought stress compared with normal watering, respectively. The amino acid, flavonoid, organic acid, and soluble sugar contents were more significantly enhanced in ‘Jilv3’ than in ‘Pacific Early’. According to the metabolome and transcriptome analysis, in ‘Jilv3’, the energy supply of the TCA cycle was improved, and flavonoid biosynthesis increased. As a result, its adaptability to drought stress improved.

Conclusions
These findings help to better reveal the molecular mechanism underlying how asparagus responds to drought stress and improve researchers’ ability to screen drought-tolerant asparagus varieties as well as breed new varieties.
Sampling weighting strategies in causal mediation analysis
Authors: Coffman Donna L. , Zhou Haoyu , Castellano Katherine E. , Schuler Megan S. , McCaffrey Daniel F. 
Published: June 2024

Abstract
Background
Causal mediation analysis plays a crucial role in examining causal effects and causal mechanisms. Yet, limited work has taken into consideration the use of sampling weights in causal mediation analysis. In this study, we compared different strategies of incorporating sampling weights into causal mediation analysis.

Methods
We conducted a simulation study to assess 4 different sampling weighting strategies-1) not using sampling weights, 2) incorporating sampling weights into mediation “cross-world” weights, 3) using sampling weights when estimating the outcome model, and 4) using sampling weights in both stages. We generated 8 simulated population scenarios comprising an exposure (A), an outcome (Y), a mediator (M), and six covariates (C), all of which were binary. The data were generated so that the true model of A given C and the true model of A given M and C were both logit models. We crossed these 8 population scenarios with 4 different sampling methods to obtain 32 total simulation conditions. For each simulation condition, we assessed the performance of 4 sampling weighting strategies when calculating sample-based estimates of the total, direct, and indirect effects. We also applied the four sampling weighting strategies to a case study using data from the National Survey on Drug Use and Health (NSDUH).

Results
Using sampling weights in both stages (mediation weight estimation and outcome models) had the lowest bias under most simulation conditions examined. Using sampling weights in only one stage led to greater bias for multiple simulation conditions.

Discussion
Using sampling weights in both stages is an effective approach to reduce bias in causal mediation analyses under a variety of conditions regarding the structure of the population data and sampling methods.
Clinicians’ experiences implementing an advance care planning pathway in two Canadian provinces: a qualitative study
Authors: Stevens Julie , Elston Dawn , Tan Amy , Barwich Doris , Carter Rachel Zoe , Cochrane Diana , Frenette Nicole , Howard Michelle 
Published: June 2024

Abstract
Background
Advance care planning (ACP) is a process which enables patients to communicate wishes, values, fears, and preferences for future medical care. Despite patient interest in ACP, the frequency of discussions remains low. Barriers to ACP may be mitigated by involving non-physician clinic staff, preparing patients ahead of visits, and using tools to structure visits. An ACP care pathway incorporating these principles was implemented in longitudinal generalist outpatient care, including primary care/family medicine and general internal medicine, in two Canadian provinces. This study aims to understand clinician experiences implementing the pathway.

Methods
The pathway was implemented in one family practice in Alberta, two family practices in British Columbia (BC), and one BC internal medicine outpatient clinic. Physicians and allied health professionals delivered structured pathway visits based on the Serious Illness Conversation Guide. Twelve physicians and one social worker participated in interviews or focus groups at the end of the study period. Qualitative data were coded inductively using an iterative approach, with regular meetings between coders.

Results
Clinicians described experiences with the ACP care pathway, impact at the clinician level, and impact at the patient level. Within each domain, clinicians described barriers and facilitators experienced during implementation. Clinicians also reflected candidly about potential for future implementation and the sustainability of the pathway.

Conclusions
While the pathway was implemented slightly differently between provinces, core experiences were that implementation of the pathway, and integration with current practice, were feasible. Across settings, similar themes recurred regarding usefulness of the pathway structure and its tools, impact on clinician confidence and interactions with patients, teamwork and task delegation, compatibility with existing workflow, and patient preparation and readiness. Clinicians were supportive of ACP and of the pathway.

Trial registration
The study was prospectively registered with clinicaltrials.gov (NCT03508557). Registered April 25, 2018. https://classic.clinicaltrials.gov/ct2/show/NCT03508557.