bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a short version of the high-fidelity simulation satisfaction scale in nursing students
Authors: Martínez-Arce Alejandro , Rodríguez-Almagro Julián , Vélez-Vélez Esperanza , Rodríguez-Gómez Paloma , Tovar-Reinoso Alberto , Hernández-Martínez Antonio 
Published: September 2023

Abstract
Background
Clinical simulation provides a practical and effective learning method during the undergraduate education of health professions. Currently there is only one validated scale in Spanish to assess nursing students’ satisfaction with the use of high-fidelity simulation, therefore, our objective is to validate a brief version of this scale in undergraduate nursing students with or without clinical experience.

Method
A cross-sectional descriptive study was performed. Between 2018 and 2020, the students from all academic courses of the Fundación Jiménez Díaz nursing school completed the satisfaction scale at the end of their simulation experiences. To validate this scale, composed of 33 items and eight dimensions, exploratory factor analysis (EFA) of the principal components was performed, the internal consistency was studied using Cronbach’s alpha, and the corrected item-test correlation of each of the items of the total scale was reviewed.

Results
425 students completed the scale, after the exploratory factor analysis, a scale consisting of 25 items distributed into six subscales, each containing between two and six items, explained a variance of 66.5%. The KMO test (Kaiser-Meyer-Olkin) obtained a value of 0.938, Bartlett’s sphericity test was < 0.01 and Goodness of Fit Index (GFI) was 0.991.

Conclusion
The modified ESSAF scale, reduced from 33 to 25 items and divided into six subscales, is as valid and reliable as the original scale for use in nursing students of different levels, with, or without clinical experience.
Economical production of Pichia pastoris single cell protein from methanol at industrial pilot scale
Authors: Meng Jiao , Liu Shufan , Gao Le , Hong Kai , Liu Shuguang , Wu Xin 
Published: September 2023

Abstract
Background
Methanol, synthesized from CO2, is a potentially sustainable one-carbon (C1) resource for biomanufacturing. The use of methanol as a feedstock to produce single cell protein (SCP) has been investigated for decades as an alternative to alleviate the high global demand for animal-derived proteins. The methylotrophic yeast Pichia pastoris is an ideal host for methanol-based SCP synthesis due to its natural methanol assimilation ability. However, improving methanol utilization, tolerance to higher temperature, and the protein content of P. pastoris are also current challenges, which are of great significance to the economical industrial application using methanol as a feedstock for SCP production.

Results
In the present work, adaptive laboratory evolution (ALE) has been employed to overcome the low methanol utilization efficiency and intolerance to a higher temperature of 33 °C in P. pastoris, associated with reduced carbon loss due to the lessened detoxification of intracellular formaldehyde through the dissimilation pathway and cell wall rearrangement to temperature stress resistance following long-term evolution as revealed by transcriptomic and phenotypic analysis. By strengthening nitrogen metabolism and impairing cell wall synthesis, metabolic engineering further increased protein content. Finally, the engineered strain via multi-strategy produced high levels of SCP from methanol in a pilot-scale fed-batch culture at 33 °C with a biomass of 63.37 g DCW/L, methanol conversion rate of 0.43 g DCW/g, and protein content of 0.506 g/g DCW. SCP obtained from P. pastoris contains a higher percentage of protein compared to conventional foods like soy, fish, meat, whole milk, and is a source of essential amino acids, including methionine, lysine, and branched-chain amino acids (BCAAs: valine, isoleucine, leucine).

Conclusions
This study clarified the unique mechanism of P. pastoris for efficient methanol utilization, higher temperature resistance, and high protein synthesis, providing a P. pastoris cell factory for SCP production with environmental, economic, and nutritional benefits.
Cytotoxic effects of halophilic archaea metabolites on ovarian cancer cell lines
Authors: Kowalewicz-Kulbat Magdalena , Krawczyk Krzysztof T. , Szulc-Kielbik Izabela , Rykowski Sebastian , Denel-Bobrowska Marta , Olejniczak Agnieszka B. , Locht Camille , Klink Magdalena 
Published: September 2023

Abstract
Background
Ovarian cancer is one of the most frequent and deadly gynaecological cancers, often resistant to platinum-based chemotherapy, the current standard of care. Halophilic microorganisms have been shown to produce a large variety of metabolites, some of which show toxicity to various cancer cell lines. However, none have yet been shown to be active against ovarian cancer cells. Here, we examined the effects of metabolites secreted by the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae on various cancer cell lines, including ovarian cancer cell lines.

Results
1H NMR analyses of Hrd. rudnickae and Nnm. salaciae culture supernatants contain a complex mixture of metabolites that differ between species, and even between two different strains of the same species, such as Hrd. rudnickae strains 64T and 66. By using the MTT and the xCELLigence RTCA assays, we found that the secreted metabolites of all three halophilic strains expressed cytotoxicity to the ovarian cancer cell lines, especially A2780, as well as its cisplatin-resistant derivative A2780cis, in a dose-dependent manner. The other tested cell lines A549, HepG2, SK-OV-3 and HeLa were only minimally, or not at all affected by the archaeal metabolites, and this was only seen with the MTT assay.

Conclusions
The halophilic archaea Hrd. rudnickae and Nnm. salaciae, isolated from a Polish salt mine and Lake Medee in the Mediterranean Sea, respectively, secrete metabolites that are active against ovarian cancer cells, including those that are resistant to cisplatin. This opens potential new possibilities for the treatment of these frequent and deadly gynaecological cancers.
Targeting MYH9 represses USP14-mediated NAP1L1 deubiquitination and cell proliferation in glioma
Authors: Chen Zigui , Yan Xin , Miao Changfeng , Liu Longyang , Liu Su , Xia Ying , Fang Weiyi , Zheng Dandan , Luo Qisheng 
Published: September 2023

AbstractMyosin heavy chain 9 (MYH9) plays an important role in a number of diseases. Nevertheless, the function of MYH9 in glioma is unclear. The present research aimed to investigate the role of MYH9 in glioma and determine whether MYH9 is involved in the temozolomide chemoresistance of glioma cells. Our results showed that MYH9 increased the proliferation and temozolomide resistance of glioma cells. The mechanistic experiments showed that the binding of MYH9 to NAP1L1, a potential promoter of tumor proliferation, inhibited the ubiquitination and degradation of NAP1L1 by recruiting USP14. Upregulation of NAP1L1 increased its binding with c-Myc and activated c-Myc, which induced the expression of CCND1/CDK4, promoting glioma cell temozolomide resistance and proliferation. Additionally, we found that MYH9 upregulation was strongly related to patient survival and is therefore a negative factor for patients with glioma. Altogether, our results show that MYH9 plays a role in glioma progression by regulating NAP1L1 deubiquitination. Thus, targeting MYH9 is a potential therapeutic strategy for the clinical treatment of glioma in the future.
Epidemiology of malaria in Rohingya refugee camps in Bangladesh within 2017–2020
Authors: Khan Md. Ariful Anwar , Maude Richard James , Musa Sharmin , Khanum Hamida 
Published: September 2023

Abstract
Background
Malaria causes significant morbidity and mortality in tropical and sub-tropical regions, particularly in humanitarian emergencies including refugee camps in malaria endemic areas. An epidemiological investigation was conducted on malaria disease distribution and risk factors in the world’s largest refugee settlement, the Rohingya refugee camps on the south-eastern border area of Bangladesh, within 2017–2020.

Methods
From February 2017 to March 2020, 30,460 febrile patients were tested for malaria using light microscopy and rapid diagnostic tests. Most were self-presenting symptomatic patients and a minority were from door-to-door malaria screening. Diagnostic tests were done by trained medical technologists upon the advice of the concerned physicians in the camps. Test positivity rate (%) and annual parasite incidence were calculated and compared using chi-squared (χ 2) test or odds ratios.

Results
The overall average annual test positivity rate (TPR) was 0.05%. TPR was highest in people who had travelled to the forest in the previous 2 months, at 13.60%. Cases were clustered among male adults aged 15–60 years. There were no cases among children under five years or pregnant women and no deaths from malaria.

Conclusion
This study found very few malaria cases among Rohingya refugees with the majority of cases being imported from hilly forested areas, which were thus assumed to act as the reservoir for transmission.
Novel scaffold platforms for simultaneous induction osteogenesis and angiogenesis in bone tissue engineering: a cutting-edge approach
Authors: Saberi Arezoo , Kouhjani Maryam , Mohammadi Marzieh , Hosta-Rigau Leticia 
Published: September 2023

AbstractDespite the recent advances in the development of bone graft substitutes, treatment of critical size bone defects continues to be a significant challenge, especially in the elderly population. A current approach to overcome this challenge involves the creation of bone-mimicking scaffolds that can simultaneously promote osteogenesis and angiogenesis. In this context, incorporating multiple bioactive agents like growth factors, genes, and small molecules into these scaffolds has emerged as a promising strategy. To incorporate such agents, researchers have developed scaffolds incorporating nanoparticles, including nanoparticulate carriers, inorganic nanoparticles, and exosomes. Current paper provides a summary of the latest advancements in using various bioactive agents, drugs, and cells to synergistically promote osteogenesis and angiogenesis in bone-mimetic scaffolds. It also discusses scaffold design properties aimed at maximizing the synergistic effects of osteogenesis and angiogenesis, various innovative fabrication strategies, and ongoing clinical studies.
Graphical Abstract
Natural exosomes-like nanoparticles in mung bean sprouts possesses anti-diabetic effects via activation of PI3K/Akt/GLUT4/GSK-3β signaling pathway
Authors: He Chengxun , Wang Ke , Xia Jun , Qian Die , Guo Juan , Zhong Lian , Tang Dandan , Chen Xiuping , Peng Wei , Chen Yunhui , Tang Yong 
Published: September 2023

Abstract
Background
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and insulin resistance. Mung bean sprouts are traditionally considered a “folk” hypoglycemic food and their pharmacological effects and underlying mechanisms warrant further investigation.

Purpose
This study aimed to investigate the anti-diabetic effects of the exosomes-like nanoparticles in mung bean sprouts (MELNs) and explore the related molecular mechanisms.

Results
MELNs were isolated using a differential centrifugation-polyethylene glycol (PEG) method, and the identification of MELNs were confirmed by PAGE gel electrophoresis, agarose gel electrophoresis, thin-layer chromatography (TLC), and transmission electron microscopy (TEM). In the high-fat diet/streptozotocin (HFD/STZ) mouse model, MELNs ameliorated the progression of T2DM by increasing oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results, decreasing the fasting blood glucose level, and reducing the serum triglycerides (TG) and total cholesterol (TC). Histopathological examinations indicated MELNs diminished inflammatory infiltration of hepatocytes and amplified the area of islet B cells. In addition, MELNs decreased the oxidative stress levels in liver tissue and had good biocompatibility. In vitro experiments verified that MELNs improved the viability of glucosamine (GlcN) induced insulin-resistant hepatocytes. Furthermore, this study also revealed that MELNs upregulated GLUT4 & Nrf2 and down-regulated GSK-3β via activating the PI3K/Akt signaling pathway, promoting the production of antioxidant enzymes, such as HO-1 and SOD, to reduce oxidative stress.

Conclusion
MELNs mitigated the progression of type 2 diabetes in HFD/STZ mouse model. The underlying molecular mechanism is related to PI3K/Akt/GLUT4/GSK-3β signaling pathway.
Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities
Authors: Li Siyi , Sampson Chibuzo , Liu Changhao , Piao Hai-long , Liu Hong-Xu 
Published: September 2023

AbstractIntegrins are transmembrane receptors that possess distinct ligand-binding specificities in the extracellular domain and signaling properties in the cytoplasmic domain. While most integrins have a short cytoplasmic tail, integrin β4 has a long cytoplasmic tail that can indirectly interact with the actin cytoskeleton. Additionally, 'inside-out' signals can induce integrins to adopt a high-affinity extended conformation for their appropriate ligands. These properties enable integrins to transmit bidirectional cellular signals, making it a critical regulator of various biological processes.Integrin expression and function are tightly linked to various aspects of tumor progression, including initiation, angiogenesis, cell motility, invasion, and metastasis. Certain integrins have been shown to drive tumorigenesis or amplify oncogenic signals by interacting with corresponding receptors, while others have marginal or even suppressive effects. Additionally, different α/β subtypes of integrins can exhibit opposite effects. Integrin-mediated signaling pathways including Ras- and Rho-GTPase, TGFβ, Hippo, Wnt, Notch, and sonic hedgehog (Shh) are involved in various stages of tumorigenesis. Therefore, understanding the complex regulatory mechanisms and molecular specificities of integrins are crucial to delaying cancer progression and suppressing tumorigenesis. Furthermore, the development of integrin-based therapeutics for cancer are of great importance.This review provides an overview of integrin-dependent bidirectional signaling mechanisms in cancer that can either support or oppose tumorigenesis by interacting with various signaling pathways. Finally, we focus on the future opportunities for emergent therapeutics based on integrin agonists.
Meta-analysis of senescent cell secretomes to identify common and specific features of the different senescent phenotypes: a tool for developing new senotherapeutics
Authors: Oguma Yo , Alessio Nicola , Aprile Domenico , Dezawa Mari , Peluso Gianfranco , Di Bernardo Giovanni , Galderisi Umberto 
Published: September 2023

AbstractDNA damage resulting from genotoxic injury can initiate cellular senescence, a state characterized by alterations in cellular metabolism, lysosomal activity, and the secretion of factors collectively known as the senescence-associated secretory phenotype (SASP). Senescence can have beneficial effects on our bodies, such as anti-cancer properties, wound healing, and tissue development, which are attributed to the SASP produced by senescent cells in their intermediate stages. However, senescence can also promote cancer and aging, primarily due to the pro-inflammatory activity of SASP.Studying senescence is complex due to various factors involved. Genotoxic stimuli cause random damage to cellular macromolecules, leading to variations in the senescent phenotype from cell to cell, despite a shared program. Furthermore, senescence is a dynamic process that cannot be analyzed as a static endpoint, adding further complexity.Investigating SASP is particularly intriguing as it reveals how a senescence process triggered in a few cells can spread to many others, resulting in either positive or negative consequences for health. In our study, we conducted a meta-analysis of the protein content of SASP obtained from different research groups, including our own. We categorized the collected omic data based on: i) cell type, ii) harmful agent, and iii) senescence stage (early and late senescence).By employing Gene Ontology and Network analysis on the omic data, we identified common and specific features of different senescent phenotypes. This research has the potential to pave the way for the development of new senotherapeutic drugs aimed at combating the negative consequences associated with the senescence process.
Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population
Authors: Wu Xiaodong , Liu Zhijuan , Hao Doudou , Zhao Qin , Li Wanjing , Xie Maodi , Feng Xia , Liao Xia , Chen Siyuan , Wang Siyu , Zhou Chaohua , Long Wenchun , Zhong Yajun , Li Shen , Cao Ye , Wang Hong , Wang Aiping , Xu Yuehong , Huang Min , Liu Jiaxin , Zhong Rui , Wu Yunhong , He Zeng 
Published: September 2023

AbstractDue to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body’s oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.
B7H3-targeting chimeric antigen receptor modification enhances antitumor effect of Vγ9Vδ2 T cells in glioblastoma
Authors: Wang Yi , Ji Nan , Zhang Yang , Chu Junsheng , Pan Changcun , Zhang Peng , Ma Weiwei , Zhang Xueguang , Xi Jianzhong Jeff , Chen Mingze , Zhang Yonghui , Zhang Liwei , Sun Tao 
Published: September 2023

AbstractBackgroundGlioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. This study investigates the therapeutic potential of human Vγ9Vδ2 T cells in GBM treatment. The sensitivity of different glioma specimens to Vγ9Vδ2 T cell-mediated cytotoxicity is assessed using a patient-derived tumor cell clusters (PTCs) model.MethodsThe study evaluates the anti-tumor effect of Vγ9Vδ2 T cells in 26 glioma cases through the PTCs model. Protein expression of BTN2A1 and BTN3A1, along with gene expression related to lipid metabolism and glioma inflammatory response pathways, is analyzed in matched tumor tissue samples. Additionally, the study explores two strategies to re-sensitize tumors in the weak anti-tumor effect (WAT) group: utilizing a BTN3A1 agonistic antibody or employing bisphosphonates to inhibit farnesyl diphosphate synthase (FPPS). Furthermore, the study investigates the efficacy of genetically engineered Vγ9Vδ2 T cells expressing Car-B7H3 in targeting diverse GBM specimens.ResultsThe results demonstrate that Vγ9Vδ2 T cells display a stronger anti-tumor effect (SAT) in six glioma cases, while showing a weaker effect (WAT) in twenty cases. The SAT group exhibits elevated protein expression of BTN2A1 and BTN3A1, accompanied by differential gene expression related to lipid metabolism and glioma inflammatory response pathways. Importantly, the study reveals that the WAT group GBM can enhance Vγ9Vδ2 T cell-mediated killing sensitivity by incorporating either a BTN3A1 agonistic antibody or bisphosphonates. Both approaches support TCR-BTN mediated tumor recognition, which is distinct from the conventional MHC-peptide recognition by αβ T cells. Furthermore, the study explores an alternative strategy by genetically engineering Vγ9Vδ2 T cells with Car-B7H3, and both non-engineered and Car-B7H3 Vγ9Vδ2 T cells demonstrate promising efficacy in vivo, underscoring the versatile potential of Vγ9Vδ2 T cells for GBM treatment.ConclusionsVγ9Vδ2 T cells demonstrate a robust anti-tumor effect in some glioma cases, while weaker in others. Elevated BTN2A1 and BTN3A1 expression correlates with improved response. WAT group tumors can be sensitized using a BTN3A1 agonistic antibody or bisphosphonates. Genetically engineered Vγ9Vδ2 T cells, i.e., Car-B7H3, show promising efficacy. These results together highlight the versatility of Vγ9Vδ2 T cells for GBM treatment.