bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic investigation of the material basis, effectiveness and safety of Thesium chinense Turcz. and its preparation Bairui Granules against lung inflammation
Authors: Peng Guang-Cheng , Hao Jin-Hua , Guan Yue-Qin , Wang Ying-Yue , Liu Ming-Jie , Li Guo-Hui , Xu Zhen-Peng , Wen Xue-Sen , Shen Tao 
Published: May 2024

Abstract
Background
Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated.

Methods
Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice.

Results
Seven new compounds (1–7) and fifty-six known compounds (8–63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1–2, new fatty acids 4–5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8–11, lignans 46–54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-β). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1β, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic.

Conclusions
The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.
Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives
Authors: Lin Hao , Liu Chaxian , Hu Ankang , Zhang Duanwu , Yang Hui , Mao Ying 
Published: May 2024

AbstractGlioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4–8%) of CD45+ cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.
Fertility-sparing surgery in children and adolescents with borderline ovarian tumors: a retrospective study
Authors: Zhao Jiayuan , Wang Dan , Wang Ruojiao , He Yonglan , Jia Congwei , Pan Lingya , Ma Shuiqing , Wu Ming , Wang Weidi , Cheng Xinghan , Yang Junjun , Xiang Yang 
Published: May 2024

Abstract
Objective
To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients.

Methods
Patients with BOTs younger than 20 years who underwent FSS were included in this study.

Results
A total of 34 patients were included, with a median patient age of 17 (range, 3–19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8–40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10–148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%.

Conclusions
Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.
Approaches and experiences implementing remote, electronic consent at the Leeds Clinical Trials Research Unit
Authors: Cragg William J , Taylor Chris , Moreau Lauren , Collier Howard , Gilberts Rachael , McKigney Niamh , Dennett Joanna , Graca Sandra , Wheeler Ian , Bishop Liam , Barrett Adam , Hartley Suzanne , Greenwood John P , Swoboda Peter P , Farrin Amanda J 
Published: May 2024

Abstract
Background
Use of electronic methods to support informed consent (‘eConsent’) is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK.

Main text
We implemented a remote eConsent process using the REDCap platform. The process can be used in trials of investigational medicinal products and other intervention types or research designs. Our standard eConsent system focuses on documenting informed consent, with other aspects of consent (e.g. providing information to potential participants and a recruiter discussing the study with each potential participant) occurring outside the system, though trial teams can use electronic methods for these activities where they have ethical approval. Our overall process includes a verbal consent step prior to confidential information being entered onto REDCap and an identity verification step in line with regulator guidance. We considered the regulatory requirements around the system’s generation of source documents, how to ensure data protection standards were upheld and how to monitor informed consent within the system.
We present four eConsent case studies from the CTRU: two randomised clinical trials and two other health research studies. These illustrate the ways eConsent can be implemented, and lessons learned, including about differences in uptake.

Conclusions
We successfully implemented a remote eConsent process at the CTRU across multiple studies. Our case studies highlight benefits of study participants being able to give consent without having to be present at the study site. This may better align with patient preferences and trial site needs and therefore improve recruitment and resilience against external shocks (such as pandemics). Variation in uptake of eConsent may be influenced more by site-level factors than patient preferences, which may not align well with the aspiration towards patient-centred research. Our current process has some limitations, including the provision of all consent-related text in more than one language, and scalability of implementing more than one consent form version at a time. We consider how enhancements in CTRU processes, or external developments, might affect our approach.
Insecticidal activity of fluralaner (Exzolt®) administered to Gallus gallus domesticus against triatomines (Hemiptera, Reduviidae, Triatominae)
Authors: Pereira Luanderson Cardoso , Pereira Nathalie de Sena , Barbosa da Silva Andressa Noronha , Bezerra Clarice de Freitas , Sousa Kivia Millana de , Fagundes Neto João Ciro , Sampaio George Harisson Felinto , Brito Carlos Ramon do Nascimento , Souza Rita de Cássia Moreira , Galvão Lúcia Maria da Cunha , Câmara Antônia Claudia Jácome da , Nascimento Manuela Sales Lima , Guedes Paulo Marcos Matta 
Published: May 2024

Abstract
Background
Triatoma infestans, Triatoma brasiliensis, Triatoma pseudomaculata and Rhodnius prolixus are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Chickens serve as an important blood food source for triatomines. This study aimed to assess the insecticidal activity of fluralaner (Exzolt®) administered to chickens against triatomines (R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata).

Methods
Twelve non-breed chickens (Gallus gallus domesticus) were randomized based on weight into three groups: negative control (n = 4); a single dose of 0.5 mg/kg fluralaner (Exzolt®) (n = 4); two doses of 0.5 mg/kg fluralaner (Exzolt®) (n = 4). Nymphs of 3rd, 4th and 5th instars of R. prolixus, T. infestans, T. brasiliensis and T. pseudomaculata (all n = 10) were allowed to feed on chickens before treatment, and at intervals of 1, 7, 14, 21, 28, 35 and 56 days after treatment, with insect mortality determined.

Results
Treatment with two doses of fluralaner showed higher insecticidal efficacy against R. prolixus, T. infestans and T. brasiliensis compared to the single-dose treatment. Similar insecticidal efficacy was observed for T. pseudomaculata for one and two doses of fluralaner. Insecticidal activity of fluralaner (Exzolt®) against triatomine bugs was noted up to 21 and 28 days after treatment with one and two doses of fluralaner, respectively.

Conclusions
The results demonstrate that treatment of chickens with fluralaner (Exzolt®) induces insecticidal activity against triatomines for up to 28 days post-treatment, suggesting its potential use as a control strategy for Chagas disease in endemic areas.

Graphical Abstract
miR-449a disturbs atherosclerotic plaque stability in streptozotocin and high-fat diet-induced diabetic mice by targeting CEACAM1
Authors: Yu Jie , Liu Han , Chen Yu , Wang Ling , Chen Peng , Zhao Yue , Ou Chunxia , Chen Wei , Hu Jie , Wang Yu , Wang Yan 
Published: May 2024

Abstract
Background
Emerging evidence indicates carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the development of atherosclerosis (AS). However, the roles and functions of CEACAM1 in AS remain unknown. Therefore, this study aims to investigate the roles and molecular functions of CEACAM1 in AS.

Methods
We constructed a diabetes mellitus (DM) + high-fat diet (HFD) mouse model based on the streptozotocin (STZ)-induced apolipoprotein E-knockdown (ApopE−/−) mouse to investigate the roles and regulatory mechanism of miR-449a/CEACAM1 axis. The mRNA expression and protein levels in this study were examined using quantity PCR, western blot, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. And the lipid deposition and collagen content were detected using Oil Red O and Sirius Red staining. Cell apoptosis, migration, invasion, and tuber formation were detected by Annexin-V FITC/PI, wound healing, transwell, and tuber formation assays, respectively. The relationship between miR-449a and CEACAM1 was determined by a dual-luciferase reporter gene assay.

Results
miR-449a and MMP-9 were upregulated, and CEACAM1 was downregulated in the DM + HFD MOUSE model. Upregulation of CEACAM1 promoted atherosclerotic plaque stability and inhibited inflammation in the DM + HFD mouse model. And miR-449a directly targeted CEACAM1. Besides, miR-449a interacted with CEACAM1 to regulate atherosclerotic plaque stability and inflammation in DM-associated AS mice. In vitro, the rescue experiments showed miR-449a interacted with CEACAM1 to affect apoptosis, migration, invasion, and tuber formation ability in high glucose (HG)-induced HUVECs.

Conclusion
These results demonstrated that miR-449a promoted plaque instability and inflammation in DM and HFD-induced mice by targeting CEACAM1.
Stenting for subclavian steal phenomenon to restore cerebral perfusion due to acute carotid occlusion following carotid endarterectomy: a case report
Authors: Hirota Shin , Yoshimura Masataka , Cho Junshi , Hayashi Toshihiko , Kaneoka Azumi , Ito Kei , Kiyokawa Juri , Yamamoto Shinji 
Published: May 2024

Abstract
Background
Perioperative symptomatic carotid artery occlusion after carotid endarterectomy is a rare complication. In this study, we present a case of symptomatic acute carotid artery occlusion that occurred after carotid endarterectomy in a patient with coexistent subclavian artery steal phenomenon, which was successfully treated with subclavian artery stenting.

Case presentation
A 57-year-old East Asian female presented with stenosis in the left common carotid artery and left subclavian artery along with subclavian steal. The proximal segment of the left anterior cerebral artery was hypoplastic, and the posterior communicating arteries on both sides were well-developed. Left internal carotid artery stenosis progressed during the follow-up examination; therefore, left carotid endarterectomy was performed. On the following day, symptoms of cerebral perfusion deficiency appeared due to occlusion of the left carotid artery. The stenotic origin of the left common carotid artery and the suspected massive thrombus in the left carotid artery posed challenges to carotid revascularization. Therefore, left subclavian artery stenting for the subclavian steal phenomenon was determined to be the best option for restoring cerebral blood flow to the whole brain. Her symptoms improved after the procedure, and the postprocedural workup revealed improved cerebral blood flow.

Conclusion
Subclavian artery stenting is safe and may be helpful in patients with cerebral perfusion deficiency caused by intractable acute carotid occlusion coexisting with the subclavian steal phenomenon. Revascularization of asymptomatic subclavian artery stenosis is generally not recommended. However, cerebral circulatory insufficiency as a comorbidity may be worth considering.
The role of validation in optimization models for forest management
Authors: Janová Jitka , Bödeker Kai , Bingham Logan , Kindu Mengistie , Knoke Thomas 
Published: May 2024

Abstract
Key message
A validation convention can be established for forest management optimization models. It consists of (1) the delivery of face validation, (2) performing at least one other validation technique, and (3) an explicit discussion of how the optimization model fulfills the stated purpose. Validation by potential users or external experts is of high importance.

Context
Optimization modeling has long assisted the management of forest ecosystems, but the credibility of these models has always been debated with criticisms concerning data quality, failures to include relevant processes in the scope of models, and the inclusion of unrealistic assumptions. Validation is widely considered to be crucial to establishing the credibility of models in general, but how to validate optimization models in particular represents a permanent question generally in operations research.

Aims
We aim to synthesize practical recommendations for the development of validation frameworks in the optimization modeling for forest management.

Methods
We selected a sample of 46 studies devoted to optimization models to be applied in practice, analysed the contents with respect to validation, and provided a critical review.

Results
We (1) clarified the meaning and usage of different validation-related terms that are commonly encountered in the literature, (2) identified and categorised the various methods and frameworks that are used to demonstrate model credibility, and (3) derived organizing principles that helped to suggest improvements in validation frameworks.

Conclusions
A practical validation convention can be established and we suggest the convention to consist of three stages. By providing structured and consistent information about validation processes, researchers in forest management optimization can better demonstrate the credibility of their work to readers and potential users.
Dual-polarized IRS-assisted wireless network: relative phase modulation
Authors: Munawar Muteen , Lee Kyungchun 
Published: May 2024

AbstractThe metasurface is a promising technology that can help next-generation wireless communication systems not only improve the signal-to-noise ratio (SNR), but also increase security and mitigate interference. Further, introducing dual polarization (DP) in a metasurface can enhance its capabilities with polarization diversity, polarization multiplexing, and polarization-switched modulation. In this paper, we study a DP-metasurface-assisted single-user wireless communication system and propose a novel scheme that can improve the spectral efficiency (SE) and bit-error-rate (BER) performance compared to those of conventional schemes by exploiting the orthogonal property of dual-polarized waves. We employ the DP metasurface to increase the SNR at the receiver and create a specific phase difference between the polarized signals by controlling the transmit precoder and the phases of the metasurface reflecting elements representing some modulated bits. At the receiver, we use the recovered phase information to realign the modulated symbols in both polarizations, which are then added coherently. The simulation results demonstrate that the proposed scheme achieves significantly higher SE and BER performance than those of some closely related works.
Characterization of zinc finger protein 536, a neuroendocrine regulator, using pan-cancer analysis
Authors: Zeng Longjin , Zhang Longyao , Yin Chenrui , Chen Xu , Chen Xiewan , Sun Lingyou , Sun Jianguo 
Published: May 2024

Abstract
Background
Previous studies suggested that zinc finger protein 536 (ZNF536) was abundant in the central brain and regulated neuronal differentiation. However, the role of ZNF536 in cancer has remained unclear.

Methods
ZNF536 mutation, copy number alteration, DNA methylation, and RNA expression were explored using public portals. Data from The Cancer Genome Atlas (TCGA) were utilized to analyze pathways and tumor microenvironment (TME), with a focus on prognosis in both TCGA and immunotherapy pan-cancer cohorts. Methylated ZNF536 from small cell lung cancer (SCLC) cell lines were utilized to train with probes for conducting enrichment analysis. Single-cell RNA profile demonstrated the sublocalization and co-expression of ZNF536, and validated its targets by qPCR.

Results
Genetic alterations in ZNF536 were found to be high-frequency and a single sample could harbor different variations. ZNF536 at chromosome 19q12 exerted a bypass effect on CCNE1, supported by CRISPR data. For lung cancer, ZNF536 mutation was associated with longer survival in primary lung adenocarcinoma (LUAD), but its prognosis was poor in metastatic LUAD and SCLC. Importantly, ZNF536 mutation and amplification had opposite prognoses in Stand Up To Cancer-Mark Foundation (SU2C-MARK) LUAD cohort. ZNF536 mutation altered the patterns of genomic alterations in tumors, and had distinct impacts on the signaling pathways and TME compared to ZNF536 amplification. Additionally, ZNF536 expression was predominantly in endocrine tumors and brain tissues. High-dimensional analysis supported this finding and further revealed regulators of ZNF536. Considering that the methylation of ZNF536 was involved in the synaptic pathway associated with neuroendocrine neoplasms, demonstrating both diagnostic and prognostic value. Moreover, we experimentally verified ZNF536 upregulated neuroendocrine markers.

Conclusions
Our results showed that ZNF536 alterations in cancer, including variations in copy number, mutation, and methylation. We proved the involvement of ZNF536 in neuroendocrine regulation, and identified highly altered ZNF536 as a potential biomarker for immunotherapy.
Human pan-cancer analysis of the predictive biomarker for the CDKN3
Authors: Chen Yingjun , Li Dai , Sha Kaihui , Zhang Xuezhong , Liu Tonggang 
Published: May 2024

Abstract
Background
Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3.

Methods
Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways.

Results
CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance.

Conclusion
Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.