bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction and validation of common targets in atherosclerosis and non-small cell lung cancer influenced by atorvastatin
Authors: Li Yu-qian , Li Lu-yao , Yang Xue , Lei Qi-qi , Xiang Liu-yan , Wang Yuan-ru , Gu Si-meng , Cao Ya-jun , Pan Yan , Tie Lu , Li Xue-jun 
Published: November 2023

Abstract
Background
Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology.

Methods
The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease–target–component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients.

Results
We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin.

Conclusions
This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.
Perceptions of Nigerian medical students regarding their preparedness for precision medicine: a cross-sectional survey in Lagos, Nigeria
Authors: Ogamba Chibuzor F. , Roberts Alero A. , Ajudua Sharon C. , Akinwale Mosopefoluwa O. , Jeje Fuhad M. , Ibe Festus O. , Afolayan Moses M. , Kuyinu Yetunde A. 
Published: November 2023

Abstract
Background
Advances in precision medicine in Nigeria suggest improving genomics education and competency among healthcare practitioners to facilitate clinical translation. Due to the scarcity of research in this area, this study aimed to assess Nigerian medical students’ perceptions about their preparedness to integrate precision medicine into their future clinical practice.

Methods
This was an institution-based cross-sectional study of medicine and surgery students in their clinical years attending the two fully accredited colleges of medicine in Lagos, Nigeria, between April and October 2022 using an adapted tool administered via Google Forms. The survey assessed their awareness, perceptions about knowledge, ability, and attitudes toward precision medicine, ethical concerns, and perceptions about their education in precision medicine. Multivariate linear regression models were used to assess factors associated with students’ perceptions of their knowledge, ability, and attitudes.

Results
A total of 300 students completed the questionnaires with a response rate of 40%. Awareness of genomic medicine terminology was high (92.0%). Responses to knowledge and ability questions revealed notable gaps, however, respondents had positive attitude scores overall. Higher medical school year was independently associated with lower knowledge (ptrend = 0.003) and ability (ptrend = 0.005) scores, and knowledge score was independently associated with a higher ability score (β: 0.76 95%CI: 0.67, 0.84; p < 0.001). Attitude scores significantly increased with increasing medical school year (ptrend = 0.04). The respondents mostly indicated concerns about government and corporate bodies’ misuse of genomic data (35.7%) and the widening of socioeconomic disparities (34.0%). Although 65.0% of the respondents thought it important to learn about precision medicine, only 11.3% felt that their education had adequately prepared them for precision medicine, knew who to ask questions regarding genomic testing (10.7%), and felt their professors had encouraged the use of precision medicine (10.3%).

Conclusion
Despite high awareness of precision medicine terminology and overall positive attitudes, our findings highlight gaps in knowledge and ability to integrate genomics into the care of patients and a need to improve precision medicine education among Nigerian medical students.
Effectiveness of flipped classroom in pharmacy education – a meta-analysis
Authors: Cui He , Xie Xinyu , Wang Boyang , Zhao Yuan 
Published: November 2023

Abstract
Background
Flipped classroom, blended with online and offline learning, was regarded as an effective learning approach in pharmacy education. This meta-analysis was to comprehensively compare the effectiveness of flipped classroom and traditional lecture-based approaches, attempting to generate a unified and firm conclusion of the effectiveness of flipped classroom in pharmacy education.

Methods
Data were collected from 7 databases, involving Cochrane Library, PubMed, Embase, ScienceDirect, Web of Science, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Service System (SinoMed). The studies were included if they included objective evaluation of students’ performance between groups of flipped classroom and traditional approaches. The standardized mean difference (SMD) with a corresponding 95% confidence interval (95% CI) was used as the outcomes for data pooling.

Results
A total of 22 studies (28 comparing groups) with 4379 participants were included in the meta-analysis. The risk of bias was relatively high. Results of the analysis revealed that flipped classroom presented significant advantages over traditional approaches in student performance improvement, with no evidence of publication bias. Through subgroup analysis, it showed better outcomes for flipped classrooms over traditional lectures for the other subgroups, including different performance, degree programs.

Conclusions
Current evidence reveals that the flipped classroom approach in pharmacy education yields a statistical improvement in student learning compared with traditional methods. In the future, instructors should introduce more online technology into classroom and construct an interactive learning environment.
First molecular characterization of Dirofilaria Immitis in Cuba
Authors: Roblejo-Arias Lisset , Díaz-Corona Cristian , Piloto-Sardiñas Elianne , Díaz-Sánchez Adrian A. , Zając Zbigniew , Kulisz Joanna , Woźniak Aneta , Moutailler Sara , Obregon Dasiel , Foucault-Simonin Angélique , Corona-González Belkis , Cabezas-Cruz Alejandro 
Published: November 2023

Abstract
Background
Dirofilarioses are widespread diseases caused by mosquito-borne nematodes of the family Onchocercidae, genus Dirofilaria. The major etiologic agent of canine dirofilariosis in the American continent is the zoonotic parasite Dirofilaria immitis. Existing reports of filarioid nematodes in Cuba are based solely on morphological and immunological analysis which do not allow unambiguous identification and/or direct detection of causal agents.

Results
Here we present the molecular characterization of filarioid nematodes found in a dog in Cuba. Based on the molecular and phylogenetic analysis of the 5.8S-ITS2-28S region and cox1 gene fragments, the worms were unambiguously classified as D. immitis. Sequence analysis showed high identity of the gene fragments in this study with others previously obtained from D. immitis found in dogs, wolfs and jackals but also from mosquito vectors of D. immitis.

Conclusions
Further studies are guarantee to better understand the epidemiological impact of canine dirofilariosis in Cuba as well as the competence of different species of culicid mosquitoes as vectors of Dirofilaria in the country.
Spatially distinct molecular patterns of gene expression in idiopathic pulmonary fibrosis
Authors: Blumhagen Rachel Z. , Kurche Jonathan S. , Cool Carlyne D. , Walts Avram D. , Heinz David , Fingerlin Tasha E. , Yang Ivana V. , Schwartz David A. 
Published: November 2023

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease that is pathologically characterized by areas of normal-appearing lung parenchyma, active fibrosis (transition zones including fibroblastic foci) and dense fibrosis. Defining transcriptional differences between these pathologically heterogeneous regions of the IPF lung is critical to understanding the distribution and extent of fibrotic lung disease and identifying potential therapeutic targets. Application of a spatial transcriptomics platform would provide more detailed spatial resolution of transcriptional signals compared to previous single cell or bulk RNA-Seq studies.

Methods
We performed spatial transcriptomics using GeoMx Nanostring Digital Spatial Profiling on formalin-fixed paraffin-embedded (FFPE) tissue from 32 IPF and 12 control subjects and identified 231 regions of interest (ROIs). We compared normal-appearing lung parenchyma and airways between IPF and controls with histologically normal lung tissue, as well as histologically distinct regions within IPF (normal-appearing lung parenchyma, transition zones containing fibroblastic foci, areas of dense fibrosis, and honeycomb epithelium metaplasia).

Results
We identified 254 differentially expressed genes (DEGs) between IPF and controls in histologically normal-appearing regions of lung parenchyma; pathway analysis identified disease processes such as EIF2 signaling (important for cap-dependent mRNA translation), epithelial adherens junction signaling, HIF1α signaling, and integrin signaling. Within IPF, we identified 173 DEGs between transition and normal-appearing lung parenchyma and 198 DEGs between dense fibrosis and normal lung parenchyma; pathways dysregulated in both transition and dense fibrotic areas include EIF2 signaling pathway activation (upstream of endoplasmic reticulum (ER) stress proteins ATF4 and CHOP) and wound healing signaling pathway deactivation. Through cell deconvolution of transcriptome data and immunofluorescence staining, we confirmed loss of alveolar parenchymal signals (AGER, SFTPB, SFTPC), gain of secretory cell markers (SCGB3A2, MUC5B) as well as dysregulation of the upstream regulator ATF4, in histologically normal-appearing tissue in IPF.

Conclusions
Our findings demonstrate that histologically normal-appearing regions from the IPF lung are transcriptionally distinct when compared to similar lung tissue from controls with histologically normal lung tissue, and that transition zones and areas of dense fibrosis within the IPF lung demonstrate activation of ER stress and deactivation of wound healing pathways.
Hollow manganese dioxide-chitosan hydrogel for the treatment of atopic dermatitis through inflammation-suppression and ROS scavenging
Authors: Wu Yaguang , Zhou Zihao , Zhang Min , Li Song , Sun Mengyi , Song Zhiqiang 
Published: November 2023

AbstractAtopic dermatitis (AD) is a chronic inflammatory disease associated with immune dysfunction. High levels of reactive oxygen species (ROS) can lead to oxidative stress, release of pro-inflammatory cytokines, and T-cell differentiation, thereby promoting the onset and worsening of AD. In this study, we innovatively used quaternary ammonium chitosan (QCS) and tannic acid (TA) as raw materials to design and prepare a therapeutic hydrogel(H-MnO2-Gel) loaded with hollow manganese dioxide nanoparticles (H-MnO2 NPs). In this system, the hydrogel is mainly cross-linked by dynamic ion and hydrogen bonding between QCS and TA, resulting in excellent moisture retention properties. Moreover, due to the inherent antioxidant properties of QCS/TA, as well as the outstanding H2O2 scavenging ability of H-MnO2 NPs, the hydrogel exhibits significant ROS scavenging capability. In vitro experiments have shown that H-MnO2-Gel exhibits good cellular biocompatibility. Importantly, in an AD-induced mouse model, H-MnO2-Gel significantly enhanced therapeutic effects by reducing epidermal thickness, mast cell number, and IgE antibodies. These findings suggest that H-MnO2-Gel, by effectively clearing ROS and regulating the inflammatory microenvironment, provides a promising approach for the treatment of AD.
Exercise improves cognitive dysfunction and neuroinflammation in mice through Histone H3 lactylation in microglia
Authors: Han Hao , Zhao Yawei , Du Junda , Wang Sushan , Yang Xuehan , Li Weijie , Song Jiayi , Zhang Siwei , Zhang Ziyi , Tan Yongfei , Hatch Grant M. , Zhang Ming , Chen Li 
Published: November 2023

Abstract
Background
Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exercise-induced metabolite, lactate, on the microglia phenotype and its association with learning and memory.

Results
Microglia were hyperactivated in the brains of AlCl3/D-gal-treated mice, which was associated with cognitive decline. Running exercise ameliorated the hyperactivation and increased the anti-inflammatory/reparative phenotype of microglia and improved cognition. Mice were injected intraperitoneally with sodium lactate (NaLA) had similar beneficial effects as that of exercise training. Exogenous NaLA addition to cultured BV2 cells promoted their transition from a pro-inflammatory to a reparative phenotype.

Conclusion
The elevated lactate acted as an “accelerator” of the endogenous “lactate timer” in microglia promoting this transition of microglia polarization balance through lactylation. These findings demonstrate that exercise-induced lactate accelerates the phenotypic transition of microglia, which plays a key role in reducing neuroinflammation and improving cognitive function.
Challenges in substance use treatment as perceived by professionals and Arabic-speaking refugees in Germany
Authors: Saleh Ebtesam A. , Klapprott Felix , Heinz Andreas , Kluge Ulrike 
Published: November 2023

Abstract
Background
Substance use (SU) and substance use disorders (SUDs) have been recently documented among forcibly displaced populations as a coping mechanism to migration and postmigration stressors. Although the literature exploring substance use among refugees has grown recently, little is known about SU among Arabic-speaking refugees and, more specifically, on the challenges and experiences in regards to SU treatment. This study investigates this topic from the perspectives of Arabic-speaking refugees and professionals in Germany.

Methods
Design and participants To expand our knowledge on this topic, a qualitative approach was employed by conducting in-depth and semi-structured interviews among 26 participants (13 refugees and 13 professionals) in Germany during 2020–2021. Purposive sampling was used to recruit Arabic-speaking refugees in two rehabilitation centers in Berlin.
Data and analysis Interviews were conducted with 26 participants of which 13 were refugees and 13 professionals. Refugees were interviewed individually in the rehabilitation centers, they ranged from 21 to 52 years of age, and their average time in Germany was 6.3 years. An open-ended survey was conducted among the professionals via the SoSci-survey platform, and they ranged from 22 to 66 years of age, with an average of 5 to 9 years of work experience. Data were analyzed using thematic analysis.

Results
Three themes resulted from the thematic analysis: (1) The treatment is facilitated by institutional and emotional support; (2) The affected refugees struggle with complex contextual barriers to access SUD treatment; and (3) Individual and community preventive strategies are needed.

Conclusions
This study provides insight into the support and challenges of accessing effective SU treatment and prevention among Arabic-speaking refugees in Germany. Collaborative efforts by the community, professionals, and policymakers are needed to facilitate access to effective treatment and implement culturally and linguistically sensitive approaches for the treatment and prevention of SU among refugees.
Is dispatcher-assisted cardiopulmonary resuscitation affected by a bystander’s emotional stress state in out-of-hospital cardiac arrest?
Authors: Tuffley Rebecca Hvidt , Folke Fredrik , Ersbøll Annette Kjær , Blomberg Stig Nikolaj Fasmer , Linderoth Gitte 
Published: November 2023

Abstract
Aim
The study aimed to investigate whether a bystander’s emotional stress state affects dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) in out-of-hospital cardiac arrest (OHCA). The primary outcome was initiation of chest compressions (Yes/No). Secondarily we analysed time until chest compressions were initiated and assessed how dispatchers instructed CPR.

Method
The study was a retrospective, observational study of OHCA emergency calls from the Capital Region of Denmark. Recorded calls were evaluated by five observers using a pre-defined code catalogue regarding the variables wished investigated.

Results
Included were 655 OHCA emergency calls, of which 211 callers were defined as emotionally stressed. When cardiac arrest was recognized, chest compressions were initiated in, respectively, 76.8% of cases with an emotionally stressed caller and 73.9% in cases with a not emotionally stressed caller (2.18 (0.80–7.64)). Cases with an emotionally stressed caller had a longer time until chest compressions were initiated compared to cases with a not emotionally stressed caller, however non-significant (164 s. vs. 146 s.; P = 0.145). The dispatchers were significantly more likely to be encouraging and motivating, and to instruct on speed and depth of chest compressions in cases with an emotionally stressed caller compared to cases with a not emotionally stressed caller (1.64 (1.07–2.56); 1.78 (1.13–2.88)). Barriers to CPR were significantly more often reported in cases with an emotionally stressed caller compared to cases with a not emotionally stressed caller (1.83 (1.32–2.56)).

Conclusion
There was no significant difference in initiation of chest compressions or in time until initiation of chest compressions in the two groups. However, the dispatchers were overall more encouraging and motivating, and likely to instruct on speed and depth of chest compressions when the caller was emotionally stressed. Furthermore, barriers to CPR were more often reported in cases with an emotionally stressed caller compared to cases with a not emotionally stressed caller.

Trial registration
We applied for ethical approval from The Danish National Committee on Health Research Ethics, but formal approval was waived. We received permission for storage of data and to use these for research of OHCAs in the Capital Region of Denmark by Danish Data Protection Agency (P-2021-670) and Danish Health Authorities (R-2,005,114). The study is registered at ClinicalTrials (NTC05113706).
Loss of p53-DREAM-mediated repression of cell cycle genes as a driver of lymph node metastasis in head and neck cancer
Authors: Brennan Kevin , Espín-Pérez Almudena , Chang Serena , Bedi Nikita , Saumyaa Saumyaa , Shin June Ho , Plevritis Sylvia K. , Gevaert Olivier , Sunwoo John B. , Gentles Andrew J. 
Published: November 2023

Abstract
Background
The prognosis for patients with head and neck cancer (HNC) is poor and has improved little in recent decades, partially due to lack of therapeutic options. To identify effective therapeutic targets, we sought to identify molecular pathways that drive metastasis and HNC progression, through large-scale systematic analyses of transcriptomic data.

Methods
We performed meta-analysis across 29 gene expression studies including 2074 primary HNC biopsies to identify genes and transcriptional pathways associated with survival and lymph node metastasis (LNM). To understand the biological roles of these genes in HNC, we identified their associated cancer pathways, as well as the cell types that express them within HNC tumor microenvironments, by integrating single-cell RNA-seq and bulk RNA-seq from sorted cell populations.

Results
Patient survival-associated genes were heterogenous and included drivers of diverse tumor biological processes: these included tumor-intrinsic processes such as epithelial dedifferentiation and epithelial to mesenchymal transition, as well as tumor microenvironmental factors such as T cell-mediated immunity and cancer-associated fibroblast activity. Unexpectedly, LNM-associated genes were almost universally associated with epithelial dedifferentiation within malignant cells. Genes negatively associated with LNM consisted of regulators of squamous epithelial differentiation that are expressed within well-differentiated malignant cells, while those positively associated with LNM represented cell cycle regulators that are normally repressed by the p53-DREAM pathway. These pro-LNM genes are overexpressed in proliferating malignant cells of TP53 mutated and HPV + ve HNCs and are strongly associated with stemness, suggesting that they represent markers of pre-metastatic cancer stem-like cells. LNM-associated genes are deregulated in high-grade oral precancerous lesions, and deregulated further in primary HNCs with advancing tumor grade and deregulated further still in lymph node metastases.

Conclusions
In HNC, patient survival is affected by multiple biological processes and is strongly influenced by the tumor immune and stromal microenvironments. In contrast, LNM appears to be driven primarily by malignant cell plasticity, characterized by epithelial dedifferentiation coupled with EMT-independent proliferation and stemness. Our findings postulate that LNM is initially caused by loss of p53-DREAM-mediated repression of cell cycle genes during early tumorigenesis.
The single and interactive effects of aluminium and low pH, or Ca/Al ratios on red pine seedlings
Authors: Shan Yunfeng , Riaz Ammara 
Published: November 2023

AbstractAcid deposition has been one of the major environmental pollution problems for longer than 50 years, since the 1970s. Investigation on the interactive effects of aluminum (Al) and low pH or Ca/Al ratios on red pine (Pinus densiflora Sieb. and Zucc.) has been required but lacking. In the present study, needles of red pine seedlings exposed to Al treatments with solution pH 4.0 and 3.5 exhibited purplish leaf characteristics of Al toxicity. The dry weights of the needle and whole plant, and the current needle elongation were linearly reduced with Al concentrations from 0, 13 to 26 ppm. Results show that red pine is an intermediate species in sensitivity to Al and is insensitive to low pH. However, the synergistic interactions of low pH treatments with the elevated Al were significant. Al toxicity to red pine was significantly enlarged with reduced pH. The root length and whole plant length were significantly decreased at 1:10 of Ca/Al ratios (p < 0.05), but Al phytotoxicity was completely lost when the Ca/Al molar ratio was 10:1. Liming is still an applicable measure to remediate acidification problems by natural or anthropogenic factors such as acid deposition.