bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of the prevalence of dry mouth and other symptoms using two different versions of the Edmonton Symptom Assessment System on an inpatient palliative care unit
Authors: Monsen Ragnhild Elisabeth , Lerdal Anners , Nordgarden Hilde , Gay Caryl L. , Herlofson Bente Brokstad 
Published: March 2024

Abstract
Background
Symptom assessment is key to effective symptom management and palliative care for patients with advanced cancer. Symptom prevalence and severity estimates vary widely, possibly dependent on the assessment tool used. Are symptoms specifically asked about or must the patients add them as additional symptoms? This study compared the prevalence and severity of patient-reported symptoms in two different versions of a multi-symptom assessment tool. In one version, three symptoms dry mouth, constipation, sleep problems were among those systematically assessed, while in the other, these symptoms had to be added as an “Other problem”.

Methods
This retrospective cross-sectional study included adult patients with advanced cancer at an inpatient palliative care unit. Data were collected from two versions of the Edmonton Symptom Assessment System (ESAS): modified (ESAS-m) listed 11 symptoms and revised (ESAS-r) listed 9 and allowed patients to add one “Other problem”. Seven similar symptoms were listed in both versions.

Results
In 2013, 184 patients completed ESAS-m, and in 2017, 156 completed ESAS-r. Prevalence and severity of symptoms listed in both versions did not differ. In ESAS-m, 83% reported dry mouth, 73% constipation, and 71% sleep problems, but on ESAS-r, these symptoms were reported by only 3%, 15% and < 1%, respectively. Although ESAS-r severity scores for these three symptoms were higher than on ESAS-m, differences did not reach statistical significance.

Conclusion
We identified significant differences in patient symptom reporting based on whether symptoms like dry mouth, obstipation and sleep problems were specifically assessed or had to be added by patients as an “Other problem”.
Clinical virtual simulation: predictors of user acceptance in nursing education
Authors: Padilha José Miguel , Costa Patrício , Sousa Paulino , Ferreira Ana 
Published: March 2024

Abstract
Background
Using virtual patients integrated in simulators expands students’ training opportunities in healthcare. However, little is known about the usability perceived by students and the factors/determinants that predict the acceptance and use of clinical virtual simulation in nursing education.

Objectives
To identify the factors/determinants that predict the acceptance and use of clinical virtual simulation in learning in nursing education.

Methods
Observational, cross-sectional, analytical study of the use of clinical virtual simulation in nursing to answer the research question: What factors/determinants predict the acceptance and use of a clinical virtual simulator in nursing education? We used a non-probabilistic sampling, more specifically a convenience sample of nursing degree students. The data were collected through a questionnaire adapted from the Technology Acceptance Model 3. In technology and education, the Technology Acceptance Model is a theoretical model that predicts the acceptance of the use of technology by users.

Results
The sample comprised 619 nursing students, who revealed mean values of perceived usefulness (M = 5.34; SD = 1.19), ease of use (M = 4.74; SD = 1.07), and intention to use the CVS (M = 5.21; SD = 1.18), in a Likert scale of seven points (1—the worst and 7 the best possible opinion).
This study validated the use of Technology Acceptance Model 3 adapted and tested the related hypotheses, showing that the model explains 62% of perceived utility, 32% of ease of use, and 54% of intention to use the clinical virtual simulation in nursing by nursing students. The adequacy of the model was tested by analysis of the direct effects of the relationships between the internal constructs (PU-BI, β = 0.11, p = 0.012; PEOU-BI, β = -0.11, p = 0.002) and the direct relations between some of the constructs internal to the Technology Acceptance Model 3 and the external determinants Relevance for learning and Enjoyability.
In the proposed model, the external constructs that best predicted perceived usefulness, ease of use, and behaviour intention to use the clinical virtual simulation in nursing were Relevance for learning and Enjoyability.

Conclusions
These study results allowed us to identify relevance for learning and enjoyability as the main factors/determinants that predict the acceptance and use of clinical virtual simulation in learning in nursing.
Equity and unmet need of non-communicable diseases services in Saudi Arabia using a National Household Survey (2019)
Authors: Alattas Maha , Gordon Sarah , Sabin Lora L. , El-jardali Fadi , Wirtz Veronika J. 
Published: March 2024

Abstract
Background
Saudi Arabia is implementing a comprehensive health system transformation in health services provision, governance, and financing. Given the high burden of non-communicable diseases (NCD), a key objective of the transformation is to integrate NCD prevention and treatment into primary care. The study objectives were to assess primary care service use for treatment of NCDs, to quantify existing inequities in preventive services utilization, and to identify regional and sociodemographic factors associated with these inequities.

Methods
Using the 2019 Kingdom of Saudi Arabia World Health Survey, multivariable logistic regression models were conducted to identify predictors of utilization of primary care services for NCD prevention and treatment, unmet need among those with a diagnosis of diabetes, hypertension, or dyslipidemia, and unmet need in breast and cervical cancer screening.

Results
Among those with an NCD diagnosis, living in a high-income household was associated with a lower probability of having an unmet need compared to those in low-income households. Furthermore, rural residents were less likely to have an unmet need compared to urban residents (OR 0.58, p=0.029). Individuals without a perceived need for healthcare within the last 12 months had three times the probability of unmet need in comparison to those with such a perceived need (p<0.001). Women in all regions had a lower probability of ever having a mammogram compared to women in the central regions around Riyadh. Women with an education above a secondary level had five times the odds of undergoing cervical cancer screening and three times the likelihood of ever having a mammogram (P=0.012, p=0.02) than other women. Compared to women in low-income households, those in middle (OR 1.99, P=0.026), upper middle (OR 3.47, p<0.001), or high-income households (OR 2.59, p<0.001) had a higher probability of having had cervical cancer screening.

Conclusions
Inequities in NCD treatment and prevention services’ utilization in Saudi Arabia are strongly associated with region of living, population density, wealth, income, education and perceived need for health care. More research is needed to better understand the extent of unmet primary care needs for NCD and how to address the underlying contributing factors to access inequities.
Effect of transporting Oreochromis niloticus in water with and without sodium chloride on skin morphology and some immunity-related genes expression
Authors: Sadek Hana Heba Naeim , Ahmed Abd El Galil Mohamed Abd El Aziz , Allah Mousa Mohamed Abd , El-Lateif Rasha S. B. , Emam Arafah M. 
Published: March 2024

AbstractThe aim of this study was to examine the effects of salt addition on the skin gene expression of Mucin, Antimicrobial peptides, cortisol, and glucose in Oreochromis niloticus after 5-hour transportation in water. Three groups were compared: Control, post-transport without salt (PT-S), and post-transport with 5 g salt-1(PT + S), with a stocking density of 28.6 gL-1, 20 fish for each experimental group. The results showed that the PT-S group had more significant changes in gene expression than the PT + S group, suggesting that salt alleviated the stress and immune responses of O. niloticus. The PT-S group had higher expression of mucin- 2(MUC + 2) (7.58 folds) and mucin-5AC (MUC5-AC) (6.29 folds) than the PT + S group (3.30 folds and 4.16 folds, respectively). The PT-S group also had lower expression of β-defensin-1 (Dβ1) (0.42 folds), β-defensin-2 (Dβ2) (0.29 folds), and Cath1 (0.16 folds) than the PT + S group (0.82 folds, 0.69 folds, and 0.75 folds, respectively). The skin morphology of the PT-S group revealed some white patches with no goblet cell openings, while the PT + S group had better preservation of skin features with some goblet cell openings and slight white patches. This study indicates that O. niloticus can benefit from sodium chloride during transportation, as it helps to reduce stress and inflammation, balance mineral levels, enhance health and immunity, and regulate mucous secretion.
Aptamers as an approach to targeted cancer therapy
Authors: Mahmoudian Fatemeh , Ahmari Azin , Shabani Shiva , Sadeghi Bahman , Fahimirad Shohreh , Fattahi Fahimeh 
Published: March 2024

AbstractConventional cancer treatments can cause serious side effects because they are not specific to cancer cells and can damage healthy cells. Aptamers often are single-stranded oligonucleotides arranged in a unique architecture, allowing them to bind specifically to target sites. This feature makes them an ideal choice for targeted therapeutics. They are typically produced through the systematic evolution of ligands by exponential enrichment (SELEX) and undergo extensive pharmacological revision to modify their affinity, specificity, and therapeutic half-life. Aptamers can act as drugs themselves, directly inhibiting tumor cells. Alternatively, they can be used in targeted drug delivery systems to transport drugs directly to tumor cells, minimizing toxicity to healthy cells. In this review, we will discuss the latest and most advanced approaches to using aptamers for cancer treatment, particularly targeted therapy overcoming resistance to conventional therapies.
The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN
Authors: Jiang Tao , Qi Junwen , Xue Zhenyu , Liu Bowen , Liu Jianquan , Hu Qihang , Li Yuqiu , Ren Jing , Song Hu , Xu Yixin , Xu Teng , Fan Ruizhi , Song Jun 
Published: March 2024

Abstract
Background
Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear.

Methods
The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT–PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1.

Results
The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells.

Conclusions
Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.
H2O2 self-supplying and GSH-depleting nanosystem for amplified NIR mediated-chemodynamic therapy of MRSA biofilm-associated infections
Authors: Zhao Yulan , Wu Yang , Xu Quan , Liu Yi , Song Zhiyong , Han Heyou 
Published: March 2024

AbstractReactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H2O2) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO2@Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO2) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H2O2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO2@Dex into biofilms, while CaO2 generated a substantial amount of H2O2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H2O2 into hydroxyl radicals (•OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO2@Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.
Tetrahedral framework nucleic acids for improving wound healing
Authors: Zou Wanqing , Lu Jing , Zhang Luyong , Sun Duanping 
Published: March 2024

AbstractWounds are one of the most common health issues, and the cost of wound care and healing has continued to increase over the past decade. In recent years, there has been growing interest in developing innovative strategies to enhance the efficacy of wound healing. Tetrahedral framework nucleic acids (tFNAs) have emerged as a promising tool for wound healing applications due to their unique structural and functional properties. Therefore, it is of great significance to summarize the applications of tFNAs for wound healing. This review article provides a comprehensive overview of the potential of tFNAs as a novel therapeutic approach for wound healing. In this review, we discuss the possible mechanisms of tFNAs in wound healing and highlight the role of tFNAs in modulating key processes involved in wound healing, such as cell proliferation and migration, angiogenesis, and tissue regeneration. The targeted delivery and controlled release capabilities of tFNAs offer advantages in terms of localized and sustained delivery of therapeutic agents to the wound site. In addition, the latest research progress on tFNAs in wound healing is systematically introduced. We also discuss the biocompatibility and biosafety of tFNAs, along with their potential applications and future directions for research. Finally, the current challenges and prospects of tFNAs are briefly discussed to promote wider applications.
Development of rice bran-derived nanoparticles with excellent anti-cancer activity and their application for peritoneal dissemination
Authors: Sasaki Daisuke , Suzuki Hinako , Kusamori Kosuke , Itakura Shoko , Todo Hiroaki , Nishikawa Makiya 
Published: March 2024

Abstract
Background
Rice bran a by-product of the rice milling process is currently underutilized. Recent studies have shown that plant-derived nanoparticles (pdNPs) can be mass-produced at a low cost and exhibit biological and therapeutic activities. Rice bran contains various anti-cancer compounds, including γ-oryzanol and γ-tocotrienol, and rice bran-derived nanoparticles (rbNPs) can be employed as novel therapeutic agents for cancer treatment.

Results
Koshihikari rice bran was suspended in water, and the suspension was centrifuged and filtered through a 0.45-µm-pore size syringe filter. The filtrate was ultracentrifuged, and the precipitates were suspended to obtain rbNPs. The rbNPs were negatively charged exosome-like nanoparticles with an average diameter of approximately 130 nm. The rbNPs exhibited cytotoxic activities against cancer cells but not against normal cells. The cytotoxic activity of rbNPs to murine colon adenocarcinoma colon26 cells was significantly greater than DOXIL® or other pdNPs. The rbNPs induced cell cycle arrest and apoptosis, and reduced the expression of proliferative proteins, including β-catenin and cyclin D1. Intraperitoneal injections of rbNPs into mice bearing peritoneal dissemination of colon26 cells significantly suppressed tumor growth with no significant adverse effects.

Conclusion
These results indicated that rbNPs are promising nanoparticles, hold significant potential for anti-cancer applications, and are expected to play a vital role in cancer treatment.
Anti-inflammatory and anti-oxidative electrospun nanofiber membrane promotes diabetic wound healing via macrophage modulation
Authors: He Jibing , Zhou Shasha , Wang Jiaxing , Sun Binbin , Ni Dalong , Wu Jinglei , Peng Xiaochun 
Published: March 2024

Abstract
Background
In the inflammatory milieu of diabetic chronic wounds, macrophages undergo substantial metabolic reprogramming and play a pivotal role in orchestrating immune responses. Itaconic acid, primarily synthesized by inflammatory macrophages as a byproduct in the tricarboxylic acid cycle, has recently gained increasing attention as an immunomodulator. This study aims to assess the immunomodulatory capacity of an itaconic acid derivative, 4-Octyl itaconate (OI), which was covalently conjugated to electrospun nanofibers and investigated through in vitro studies and a full-thickness wound model of diabetic mice.

Results
OI was feasibly conjugated onto chitosan (CS), which was then grafted to electrospun polycaprolactone/gelatin (PG) nanofibers to obtain P/G-CS-OI membranes. The P/G-CS-OI membrane exhibited good mechanical strength, compliance, and biocompatibility. In addition, the sustained OI release endowed the nanofiber membrane with great antioxidative and anti-inflammatory activities as revealed in in vitro and in vivo studies. Specifically, the P/G-CS-OI membrane activated nuclear factor-erythroid-2-related factor 2 (NRF2) by alkylating Kelch-like ECH-associated protein 1 (KEAP1). This antioxidative response modulates macrophage polarization, leading to mitigated inflammatory responses, enhanced angiogenesis, and recovered re-epithelization, finally contributing to improved healing of mouse diabetic wounds.

Conclusions
The P/G-CS-OI nanofiber membrane shows good capacity in macrophage modulation and might be promising for diabetic chronic wound treatment.
Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer
Authors: Han Fushi , Chen Shuzhen , Zhang Kangwei , Zhang Kunming , Wang Meng , Wang Peijun 
Published: March 2024

Abstract
Objective
Non-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway.

Methods
The study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models.

Results
Fifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway.

Conclusion
High expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway.
Predictive biomarkers for anti-TNF alpha therapy in IBD patients
Authors: Kumar Manoj , Murugesan Selvasankar , Ibrahim Nazira , Elawad Mamoun , Al Khodor Souhaila 
Published: March 2024

AbstractInflammatory bowel disease (IBD) is a chronic gastrointestinal condition characterized by severe gut inflammation, commonly presenting as Crohn’s disease, ulcerative colitis or categorized as IBD- unclassified. While various treatments have demonstrated efficacy in adult IBD patients, the advent of anti-TNF therapies has significantly revolutionized treatment outcomes and clinical management. These therapies have played a pivotal role in achieving clinical and endoscopic remission, promoting mucosal healing, averting disease progression, and diminishing the necessity for surgery. Nevertheless, not all patients exhibit positive responses to these therapies, and some may experience a loss of responsiveness over time. This review aims to present a comprehensive examination of predictive biomarkers for monitoring the therapeutic response to anti-TNF therapy in IBD patients. It will explore their limitations and clinical utilities, paving the way for a more personalized and effective therapeutic approach.
Redox proteomics of PANC-1 cells reveals the significance of HIF-1 signaling protein oxidation in pancreatic ductal adenocarcinoma pathogenesis
Authors: Tan Chaochao , Chen Lichun , Guan Xiaoyu , Huang Wenyi , Feng Yinhong , Li Ziyi , Wu Ling , Huang Xiangping , Ouyang Qianhui , Liu Sixiang , Huang Ying , Hu Jiliang 
Published: March 2024

Abstract
Background
Protein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood.

Methods and results
In this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins in HPDE6c7 and PANC-1 cells. Among them, 1715 cysteine residues were shown to be differentially oxidized between HPDE6c7 and PANC-1 cells. Also, charged amino acids including aspartate, glutamate and lysine were significantly overrepresented in flanking sequences of oxidized cysteines. Differentially oxidized proteins in PANC-1 cells were enriched in multiple cancer-related biological processes and signaling pathways. Specifically, the HIF-1 signaling proteins exhibited significant oxidation alterations in PANC-1 cells, and the reduced PHD2 oxidation in human PDAC tissues was correlated with lower survival time in pancreatic cancer patients.

Conclusion
These investigations provided new insights into protein oxidation-regulated signaling and biological processes during PDAC pathogenesis, which might be further explored for pancreatic cancer diagnosis and treatment.