bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship of the nursing practice environment with the quality of care and patients’ safety in primary health care
Authors: Lucas Pedro , Jesus Élvio , Almeida Sofia , Araújo Beatriz 
Published: November 2023

Abstract
Background
Nursing practice environment has impact on the quality of nursing care and on patients’ and nurses’ outcomes, namely better performances of these healthcare workers. Improving the nursing practice environment is a low-cost organizational strategy to achieve better patients’ outcomes and retain qualified nurses, thus improving nursing care of units, healthcare organizations and healthcare system. This study aims to analyse the relationship between nursing practice environment and the nurses` perception of quality of care, patient safety, and safety culture in Primary Health Care in Portugal.

Methods
We conducted a descriptive, analytical, and cross-sectional study using data from RN4CAST Portugal. The sample was composed of 1059 nurses from 55 Health Center Groups of the mainland Portugal, 15 Health Centers of the Autonomous Region of Madeira and 6 Health Centers of the Autonomous Region of the Azores. Multivariate analysis and correlation analysis methods were used for data processing.

Results
Nurses consider that, in the Portuguese Primary Health Care, there is a mixed and unfavourable nursing practice environment, with a perception of a good quality of care, and both acceptable patients’ safety and safety culture. The Collegial Nurse-Physician Relations and Nursing Foundations for Quality of Care dimensions to have the best ratings. The perception of Primary Health Care nurses on the dimension Nurse Participation in Organization Affairs was the one that showed the lowest score, followed by Staffing and Resource Adequacy and Nurse Manager Ability, Leadership, and Support of Nurses. Based on perception of nurses, the relationship between the nursing practice environment and the safety culture is higher, followed by the quality of care and patients’ safety.

Conclusions
The perception of Primary Health Care nurses is that there is an unfavourable and mixed nursing practice environment, with good quality of care, and acceptable patient safety and safety culture. The quality of the nursing practice environments is associated to better quality and safety of care. Thus, improving the nursing practice environments in healthcare organizations is a low-cost organizational strategy to achieve greater patients and nurses’ outcomes, improving the quality of nursing care to patients in the Primary Health Care units.
Nanoengineered injectable hydrogels derived from layered double hydroxides and alginate for sustained release of protein therapeutics in tissue engineering applications
Authors: Phan V. H. Giang , Duong Hai-Sang , Le Quynh-Giao Thi , Janarthanan Gopinathan , Vijayavenkataraman Sanjairaj , Nguyen Hoang-Nam Huynh , Nguyen Bich-Phuong Thi , Manivasagan Panchanathan , Jang Eue-Soon , Li Yi , Thambi Thavasyappan 
Published: November 2023

AbstractChronic Kidney Disease (CKD) which involves gradual loss of kidney function is characterized by low levels of a glycoprotein called Erythropoietin (EPO) that leads to red blood cell deficiency and anemia. Recombinant human EPO (rhEPO) injections that are administered intravenously or subcutaneously is the current gold standard for treating CKD. The rhEPO injections have very short half-lives and thus demands frequent administration with a risk of high endogenous EPO levels leading to severe side effects that could prove fatal. To this effect, this work provides a novel approach of using lamellar inorganic solids with a brucite-like structure for controlling the release of protein therapeutics such as rhEPO in injectable hydrogels. The nanoengineered injectable system was formulated by incorporating two-dimensional layered double hydroxide (LDH) clay materials with a high surface area into alginate hydrogels for sustained delivery. The inclusion of LDH in the hydrogel network not only improved the mechanical properties of the hydrogels (5–30 times that of alginate hydrogel) but also exhibited a high binding affinity to proteins without altering their bioactivity and conformation. Furthermore, the nanoengineered injectable hydrogels (INHs) demonstrated quick gelation, injectability, and excellent adhesion properties on human skin. The in vitro release test of EPO from conventional alginate hydrogels (Alg-Gel) showed 86% EPO release within 108 h while INHs showed greater control over the initial burst and released only 24% of EPO in the same incubation time. INH-based ink was successfully used for 3D printing, resulting in scaffolds with good shape fidelity and stability in cell culture media. Controlled release of EPO from INHs facilitated superior angiogenic potential in ovo (chick chorioallantoic membrane) compared to Alg-Gel. When subcutaneously implanted in albino mice, the INHs formed a stable gel in vivo without inducing any adverse effects. The results suggest that the proposed INHs in this study can be utilized as a minimally invasive injectable platform or as 3D printed patches for the delivery of protein therapeutics to facilitate tissue regeneration.
Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development
Authors: Du Yifan , Sun Huimin , Shi Zhiyuan , Sui Xiuyuan , Liu Bin , Zheng Zeyuan , Liu Yankuo , Xuan Zuodong , Zhong Min , Fu Meiling , Bai Yang , Zhang Qian , Shao Chen 
Published: November 2023

AbstractThe mutation of MET plays a crucial role in the initiation of cancer, while the Hedgehog (Hh) pathway also plays a significant role in cell differentiation and the maintenance of tumor stem cells. Conventional chemotherapy drugs are primarily designed to target the majority of cell populations within tumors rather than tumor stem cells. Consequently, after a brief period of remission, tumors often relapse. Moreover, the exclusive targeting of tumor stemness cell disregards the potential for other tumor cells to regain stemness and acquire drug resistance. As a result, current drugs that solely target the HGF/c-MET axis and the Hh pathway demonstrate only moderate efficacy in specific types of cancer. Mounting evidence indicates that these two pathways not only play important roles in cancer but also exert significant influence on the development of resistance to single-target therapies through the secretion of their own ligands. In this comprehensive review, we analyze and compare the potential impact of the Hh pathway on the tumor microenvironment (TME) in HGF/c-MET-driven tumor models, as well as the interplay between different cell types. Additionally, we further substantiate the potential and necessity of dual-pathway combination therapy as a critical target in MET addicted cancer treatment.
FTO facilitates cancer metastasis by modifying the m6A level of FAP to induce integrin/FAK signaling in non-small cell lung cancer
Authors: Gao Lirong , Wang Anqi , Chen Yuling , Cai Xin , Li Yue , Zhao Jian , Zhang Yang , Zhang Weijie , Zhu Jianjie , Zeng Yuanyuan , Liu Zeyi , Huang Jian-an 
Published: November 2023

Abstract
Background
Emerging evidence suggests the critical roles of N6-methyladenosine (m6A) RNA modification in tumorigenesis and tumor progression. However, the role of m6A in non-small cell lung cancer (NSCLC) is still unclear. This study aimed to explore the role of the m6A demethylase fat mass and obesity-associated protein (FTO) in the tumor metastasis of NSCLC.

Methods
A human m6A epitranscriptomic microarray analysis was used to identify downstream targets of FTO. Quantitative real-time PCR (qRT‒PCR) and western blotting were employed to evaluate the expression levels of FTO and FAP in NSCLC cell lines and tissues. Gain-of-function and loss-of-function assays were conducted in vivo and in vitro to assess the effects of FTO and FAP on NSCLC metastasis. M6A-RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), luciferase reporter assays, and RNA stability assays were used to explore the mechanism of FTO action. Co-immunoprecipitation (co-IP) assays were used to determine the mechanism of FAP in NSCLC metastasis.

Results
FTO was upregulated and predicted poor prognosis in patients with NSCLC. FTO promoted cell migration and invasion in NSCLC, and the FAK inhibitor defactinib (VS6063) suppressed NSCLC metastasis induced by overexpression of FTO. Mechanistically, FTO facilitated NSCLC metastasis by modifying the m6A level of FAP in a YTHDF2-dependent manner. Moreover, FTO-mediated metastasis formation depended on the interactions between FAP and integrin family members, which further activated the FAK signaling.

Conclusion
Our current findings provided valuable insights into the role of FTO-mediated m6A demethylation modification in NSCLC metastasis. FTO was identified as a contributor to NSCLC metastasis through the activation of the FAP/integrin/FAK signaling, which may be a potential therapeutic target for NSCLC.
Comparative metabolomics analysis reveals high-altitude adaptations in a toad-headed viviparous lizard, Phrynocephalus vlangalii
Authors: Zhang Xuejing , Men Shengkang , Jia Lun , Tang Xiaolong , Storey Kenneth B. , Niu Yonggang , Chen Qiang 
Published: November 2023

AbstractExtreme environmental conditions at high altitude, such as hypobaric hypoxia, low temperature, and strong UV radiation, pose a great challenge to the survival of animals. Although the mechanisms of adaptation to high-altitude environments have attracted much attention for native plateau species, the underlying metabolic regulation remains unclear. Here, we used a multi-platform metabolomic analysis to compare metabolic profiles of liver between high- and low-altitude populations of toad-headed lizards, Phrynocephalus vlangalii, from the Qinghai–Tibet Plateau. A total of 191 differential metabolites were identified, consisting of 108 up-regulated and 83 down-regulated metabolites in high-altitude lizards as compared with values for low-altitude lizards. Pathway analysis revealed that the significantly different metabolites were associated with carbohydrate metabolism, amino acid metabolism, purine metabolism, and glycerolipid metabolism. Most intermediary metabolites of glycolysis and the tricarboxylic acid cycle were not significantly altered between the two altitudes, but most free fatty acids as well as β-hydroxybutyric acid were significantly lower in the high-altitude population. This may suggest that high-altitude lizards rely more on carbohydrates as their main energy fuel rather than lipids. Higher levels of phospholipids occurred in the liver of high-altitude populations, suggesting that membrane lipids may undergo adaptive remodeling in response to low-temperature stress at high altitude. In summary, this study demonstrates that metabolic profiles differ substantially between high- and low-altitude lizard populations, and that these differential metabolites and metabolic pathways can provide new insights to reveal mechanisms of adaptation to extreme environments at high altitude.
A shift in psychiatry through AI? Ethical challenges
Authors: Wilhelmy Saskia , Giupponi Giancarlo , Groß Dominik , Eisendle Klaus , Conca Andreas 
Published: November 2023

AbstractThe digital transformation has made its way into many areas of society, including medicine. While AI-based systems are widespread in medical disciplines, their use in psychiatry is progressing more slowly. However, they promise to revolutionize psychiatric practice in terms of prevention options, diagnostics, or even therapy. Psychiatry is in the midst of this digital transformation, so the question is no longer “whether” to use technology, but “how” we can use it to achieve goals of progress or improvement. The aim of this article is to argue that this revolution brings not only new opportunities but also new ethical challenges for psychiatry, especially with regard to safety, responsibility, autonomy, or transparency. As an example, the relationship between doctor and patient in psychiatry will be addressed, in which digitization is also leading to ethically relevant changes. Ethical reflection on the use of AI systems offers the opportunity to accompany these changes carefully in order to take advantage of the benefits that this change brings. The focus should therefore always be on balancing what is technically possible with what is ethically necessary.
Xinyang tablet ameliorates sepsis-induced myocardial dysfunction by regulating Beclin-1 to mediate macrophage autophagy and M2 polarization through LncSICRNT1 targeting E3 ubiquitin ligase TRAF6
Authors: Luo Yuanyuan , Li Yuanmei , He Liwei , Tu Haitao , Lin Xinfeng , Zhao Fengli , Huang Yusheng , Wen Minyong , Wang Lingjun , Yang Zhongqi 
Published: November 2023

Abstract
Objective
Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD).

Methods
A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin–eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays.

Results
Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression.

Conclusion
The study highlights XYT’s potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement.
The Field’s mass shooting: emergency medical services response
Authors: Hansen Peter Martin , Mikkelsen Søren , Alstrøm Henrik , Damm-Hejmdal Anders , Rehn Marius , Berlac Peter Anthony 
Published: November 2023

Abstract
Background
Major incidents (MI) happen infrequently in Scandinavia and mass shootings are even less frequently occurring. Case reports and research are called for, as literature is scarce. On 3rd July 2022, a mass shooting took place at the shopping mall Field’s in Copenhagen, Denmark. Three people were killed and seven injured by a gunman, firing a rifle inside the mall. A further 21 people suffered minor injuries during the evacuation of the mall. In this case report, we describe the emergency medical services (EMS) incident response and evaluate the EMS´ adherence to the MI management guidelines to identify possible areas of improvement.

Case presentation
Forty-eight EMS units including five Tactical Emergency Medical Service teams were dispatched to the incident. Four critically injured patients were taken to two trauma hospitals. The deceased patients were declared dead at the scene and remained there for the sake of the investigation. A total of 24 patients with less severe and minor injuries were treated at four different hospitals in connection with the attack. The ambulance resources were inherently limited in the initial phase of the MI, mandating improvisation in medical incident command. Though challenged, Command and Control, Safety, Communication, Assessment, Triage, Treatment, Transport (CSCATTT) principles were followed.

Conclusions
The EMS response generally adhered to national guidelines for MI. The activation of EMS and the hospital preparedness program was relevant. Important findings were communication shortcomings; inherent lack of readily available ambulance resources in the initial critical phase; uncertainty regarding the number of perpetrators; uncertainty regarding number of casualties and social media rumors that unnecessarily hampered and prolonged the response. The incident command had to use non-standard measures to mitigate potential challenges.
CCN3/NOV serum levels in coronary artery disease (CAD) patients and its correlation with TNF-α and IL-6
Authors: Fadhil Jaafar Alaa , Afrisham Reza , Fadaei Reza , Farrokhi Vida , Moradi Nariman , Abbasi Ali , Einollahi Nahid 
Published: November 2023

Abstract
Introduction
Dysregulation in the secretion of adipokines or adipocytokines plays a significant role in triggering a pro-inflammatory state, leading to endothelial dysfunction and insulin resistance, and ultimately elevating the risk of atherosclerosis and coronary artery disease (CAD). Previous studies have shown a link between NOV/CCN3 (an adipokine) and obesity, insulin resistance, and inflammation. However, no research has explored the relationship between CCN3 serum levels and CAD. Therefore, we conducted the first investigation to examine the correlation between CCN3 and CAD risk factors in patients.

Methods
In a case-control study, we measured the serum levels of CCN3, IL-6, adiponectin, and TNF-α in 88 angiography-confirmed CAD patients and 88 control individuals using ELISA kits. Additionally, we used an auto analyzer and commercial kits to measure the biochemical parameters.

Results
In patients with CAD, the serum levels of CCN3, TNF-α, and IL-6 were significantly higher compared to the control group, whereas lower levels of adiponectin were observed in the CAD group (P < 0.0001). A positive correlation was found between CCN3 and IL-6 and TNF-α in the CAD group ([r = 0.38, P < 0.0001], [r = 0.39, P < 0.0001], respectively). A binary logistic regression analysis showed the risk of CAD in the model adjusted (OR [95% CI] = 1.29 [1.19 − 1.41]), (P < 0.0001). We determined a cut-off value of CCN3 (3169.6 pg/mL) to distinguish CAD patients from the control group, with good sensitivity and specificity obtained for this finding (83.8% and 87.5%, respectively).

Conclusion
This study provides evidence of a positive association between CCN3 serum levels and CAD, as well as inflammation markers such as IL-6 and TNF-α. These findings suggest that CCN3 may serve as a potential biomarker for CAD, and further investigations are necessary to validate this association and explore its potential use in clinical settings.
Sex matters for the enhancement of cognitive training with transcranial direct current stimulation (tDCS)
Authors: Weller Simone , Derntl Birgit , Plewnia Christian 
Published: November 2023

AbstractBackgroundTranscranial direct current stimulation (tDCS) can influence brain network activity and associated cognitive and behavioural functions. In addition to the extensive variety in stimulation parameters, numerous biological factors drive these effects, however these are yet poorly understood. Here, we investigate one of the major biological factors by focusing on sex-dependent effects of tDCS on a challenging cognitive control task (adaptive paced auditory serial addition task[PASAT]) in healthy humans.MethodsThis sex-specific re-analysis was performed on data of 163 subjects who underwent a 2-week cognitive control training (6 sessions in total). Subjects received either verum (anodal/cathodal) or sham tDCS. Electrodes were placed over the left or right dorsolateral prefrontal cortex and the respective contralateral deltoid muscle. Cognitive control was measured as performance in the PASAT and was analysed in respect to stimulation conditions (sham, anodal, cathodal) and sex.ResultsRegardless of stimulation condition, performance gains between the sexes were higher in females compared to males (p = 0.0038). Female’s performance during anodal tDCS exceeded male’s (p = 0.0070), yet no effects were found for cathodal or sham tDCS. Moreover, in females we found a superior effect for anodal tDCS over sham stimulation (fanodal:p = 0.0354; fcathodal:p = 0.6181), but no such effect in males (manodal:p = 0.6882; mcathodal:p = 0.4822).ConclusionsThis study highlights the relevance of biological sex for the effects of tDCS on cognitive training. Thus, an increased attention to biological sex is advisable in future brain stimulation research to highlight and in consequence better understand potentially underlying sex-specific mechanisms. Considering biological sex will further advance customisation and individualisation of tDCS interventions.Trial registrationClinicalTrials.gov, NCT04108663.