bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turkish society’s perception of nursing image during the COVID-19 pandemic
Authors: Gündüz Hoşgör Derya , Coşkun Filiz 
Published: February 2024

Abstract
Background
The status of nurses who form the backbone of the health system, and the society’s perspective on nursing has undergone serious transformations during the COVID-19 pandemic. The visibility of nurses, who constantly fought on the front lines in the harsh conditions of the pandemic, increased even more in this period. Thus, this study was aimed at determining Turkish people’s perception of nursing during the COVID-19 pandemic and investigating whether there is a significant relationship between the mean score obtained from the Nursing Image Scale and the descriptive variables.

Method
The sample of this cross-sectional study consisted of 420 Turkish citizens. The “Descriptive Characteristics Form” and “Nursing Image Scale” were used to collect data. In addition to descriptive analysis, the t-test and One-Way ANOVA test were used.

Results
Turkish people’s nursing image during the COVID-19 pandemic was highly positive. Individuals who stated that they had a chronic disease perceived nursing as a professional occupation, which transformed their current nursing image to a more positive image during the COVID-19 pandemic and the mean score they obtained from the Nursing Image Scale was statistically significantly high.

Conclusion
We concluded that Turkish people’s perceptions of nurses changed for the better during the pandemic and their awareness of nursing improved. It is the nurses’ responsibility to improve the nursing image of the society. Therefore, it is critical for nurses to create a modern nurse image picturing them as producers of scientific knowledge and independent leaders.
Is physical restraint unethical and illegal?: a qualitative analysis of Korean written judgments
Authors: Jang Seung Gyeong , Lee Won , Ha Jeongmin , Choi Sungkyoung 
Published: February 2024

Abstract
Background
Physical restraint (PR) is used to ensure the safety of care recipients. However, this causes an ethical dilemma between the autonomy and dignity of the recipients and the provision of effective treatment by health workers. This study aimed to analyze legal and ethical situations related to the use of PR using written judgments.

Methods
This study uses a qualitative retrospective design. Qualitative content analysis was performed on South Korean written judgments. A total of 38 cases from 2015 to 2021 were categorized. The types of court decisions and ethical dilemma situations were examined according to the four principles of bioethics, and the courts’ judgments were compared.

Results
Written judgments related to PR were classified into three types according to the appropriateness of PR use, the presence or absence of duty of care, and legal negligence. Ethical dilemmas were categorized into three situations depending on whether the four principles of bioethics were followed. The courts’ decisions regarding the ethical dilemmas differed depending on the situational factors before and after the use of PR and the conflicting conditions of the ethical principles.

Conclusions
Health workers should consider legal and ethical requirements when determining whether to use PR to provide the care recipient with the necessary treatment.
Stable expression of HIV-1 MPER extended epitope on the surface of the recombinant probiotic bacteria Escherichia Coli Nissle 1917 using CRISPR/Cas9
Authors: Ninyio Nathaniel , Schmitt Katharina , Sergon Gladys , Nilsson Charlotta , Andersson Sören , Scherbak Nikolai 
Published: February 2024

Abstract
Background
Mucosal vaccines have the potential to induce protective immune responses at the sites of infection. Applying CRISPR/Cas9 editing, we aimed to develop a probiotic-based vaccine candidate expressing the HIV-1 envelope membrane-proximal external region (MPER) on the surface of E. coli Nissle 1917.

Results
The HIV-1 MPER epitope was successfully introduced in the porin OmpF of the E. coli Nissle 1917 (EcN-MPER) and the modification was stable over 30 passages of the recombinant bacteria on the DNA and protein level. Furthermore, the introduced epitope was recognized by a human anti-HIV-1 gp41 (2F5) antibody using both live and heat-killed EcN-MPER, and this antigenicity was also retained over 30 passages. Whole-cell dot blot suggested a stronger binding of anti-HIV-1 gp41 (2F5) to heat-killed EcN-MPER than their live counterpart. An outer membrane vesicle (OMV) – rich extract from EcN-MPER culture supernatant was equally antigenic to anti-HIV-1 gp41 antibody which suggests that the MPER antigen could be harboured in EcN-MPER OMVs. Using quantitative ELISA, we determined the amount of MPER produced by the modified EcN to be 14.3 µg/108 cfu.

Conclusions
The CRISPR/Cas9 technology was an effective method for establishment of recombinant EcN-MPER bacteria that was stable over many passages. The developed EcN-MPER clone was devoid of extraneous plasmids and antibiotic resistance genes which eliminates the risk of plasmid transfer to animal hosts, should this clone be used as a vaccine. Also, the EcN-MPER clone was recognised by anti-HIV-1 gp41 (2F5) both as live and heat-killed bacteria making it suitable for pre-clinical evaluation. Expression of OmpF on bacterial surfaces and released OMVs identifies it as a compelling candidate for recombinant epitope modification, enabling surface epitope presentation on both bacteria and OMVs. By applying the methods described in this study, we present a potential platform for cost-effective and rational vaccine antigen expression and administration, offering promising prospects for further research in the field of vaccine development.
ANGPTL4 regulates ovarian cancer progression by activating the ERK1/2 pathway
Authors: Xu Jiaqi , Wu Fei , Zhu Yue , Wu Tiantian , Cao Tianyue , Gao Wenxin , Liu Meng , Qian Weifeng , Feng Guannan , Xi Xiaoxue , Hou Shunyu 
Published: February 2024

Abstract
Background
Ovarian cancer (OC) has the highest mortality rate among all gynecological malignancies. A hypoxic microenvironment is a common feature of solid tumors, including ovarian cancer, and an important driving factor of tumor cell survival and chemo- and radiotherapy resistance. Previous research identified the hypoxia-associated gene angiopoietin-like 4 (ANGPTL4) as both a pro-angiogenic and pro-metastatic factor in tumors. Hence, this work aimed to further elucidate the contribution of ANGPTL4 to OC progression.

Methods
The expression of hypoxia-associated ANGPTL4 in human ovarian cancer was examined by bioinformatics analysis of TCGA and GEO datasets. The CIBERSORT tool was used to analyze the distribution of tumor-infiltrating immune cells in ovarian cancer cases in TCGA. The effect of ANGPTL4 silencing and overexpression on the proliferation and migration of OVCAR3 and A2780 OC cells was studied in vitro, using CCK-8, colony formation, and Transwell assays, and in vivo, through subcutaneous tumorigenesis assays in nude mice. GO enrichment analysis and WGCNA were performed to explore biological processes and genetic networks associated with ANGPTL4. The results obtained were corroborated in OC cells in vitro by western blotting.

Results
Screening of hypoxia-associated genes in OC-related TCGA and GEO datasets revealed a significant negative association between ANGPTL4 expression and patient survival. Based on CIBERSORT analysis, differential representation of 14 distinct tumor-infiltrating immune cell types was detected between low- and high-risk patient groups. Silencing of ANGPTL4 inhibited OVCAR3 and A2780 cell proliferation and migration in vitro and reduced the growth rate of xenografted OVCAR3 cells in vivo. Based on results from WGCNA and previous studies, western blot assays in cultured OC cells demonstrated that ANGPTL4 activates the Extracellular signal-related kinases 1 and 2 (ERK1/2) pathway and this results in upregulation of c-Myc, Cyclin D1, and MMP2 expression. Suggesting that the above mechanism mediates the pro-oncogenic actions of ANGPTL4T in OC, the pro-survival effects of ANGPTL4 were largely abolished upon inhibition of ERK1/2 signaling with PD98059.

Conclusions
Our work suggests that the hypoxia-associated gene ANGPTL4 stimulates OC progression through activation of the ERK1/2 pathway. These findings may offer a new prospect for targeted therapies for the treatment of OC.
Detecting bulbar amyotrophic lateral sclerosis (ALS) using automatic acoustic analysis
Authors: Simmatis Leif E. R. , Robin Jessica , Spilka Michael J. , Yunusova Yana 
Published: February 2024

AbstractAutomatic speech assessments have the potential to dramatically improve ALS clinical practice and facilitate patient stratification for ALS clinical trials. Acoustic speech analysis has demonstrated the ability to capture a variety of relevant speech motor impairments, but implementation has been hindered by both the nature of lab-based assessments (requiring travel and time for patients) and also by the opacity of some acoustic feature analysis methods. These challenges and others have obscured the ability to distinguish different ALS disease stages/severities. Validation of automated acoustic analysis tools could enable detection of early signs of ALS, and these tools could be deployed to screen and monitor patients without requiring clinic visits. Here, we sought to determine whether acoustic features gathered using an automated assessment app could detect ALS as well as different levels of speech impairment severity resulting from ALS. Speech samples (readings of a standardized, 99-word passage) from 119 ALS patients with varying degrees of disease severity as well as 22 neurologically healthy participants were analyzed, and 53 acoustic features were extracted. Patients were stratified into early and late stages of disease (ALS-early/ALS-E and ALS-late/ALS-L) based on the ALS Functional Ratings Scale-Revised bulbar score (FRS-bulb) (median [interquartile range] of FRS-bulbar scores: 11[3]). The data were analyzed using a sparse Bayesian logistic regression classifier. It was determined that the current relatively small set of acoustic features could distinguish between ALS and controls well (area under receiver-operating characteristic curve/AUROC = 0.85), that the ALS-E patients could be separated well from control participants (AUROC = 0.78), and that ALS-E and ALS-L patients could be reasonably separated (AUROC = 0.70). These results highlight the potential for automated acoustic analyses to detect and stratify ALS.
Single-cell transcriptome analysis reveals immunosuppressive landscape in overweight and obese colorectal cancer
Authors: Xiao Guozhong , Zheng Yihui , Chen Huaxian , Luo Minyi , Yang Chaoxin , Ren Donglin , Qin Pengfei , Zhang Heng , Lin Hongcheng 
Published: February 2024

Abstract
Background
Overweight and obesity are established risk factors for various types of cancers including colorectal cancer (CRC). However the underlying molecular mechanisms remain unclear. An in-depth understanding of the oncologic characteristics of overweight and obese CRC at the single-cell level can provide valuable insights for the development of more effective treatment strategies for CRC.

Methods
We conducted single-cell RNA sequencing (scRNA-seq) analysis on tumor and adjacent normal colorectal samples from 15 overweight/obese and 15 normal-weight CRC patients. Immunological and metabolic differences between overweight/obese CRC and non-obese CRC were characterized.

Results
We obtained single-cell transcriptomics data from a total of 192,785 cells across all samples. By evaluating marker gene expression patterns, we annotated nine main cell types in the CRC ecosystem. Specifically, we found that the cytotoxic function of effector T cells and NK cells was impaired in overweight/obese CRC compared with non-obese CRC, relating to its metabolic dysregulation. CD4+T cells in overweight/obese CRC exhibited higher expression of immune checkpoint molecules. The antigen-presenting ability of DCs and B cells is down-regulated in overweight/obese CRC, which may further aggravate the immunosuppression of overweight/obese CRC. Additionally, dysfunctional stromal cells were identified, potentially promoting invasion and metastasis in overweight/obese CRC. Furthermore, we discovered the up-regulated metabolism of glycolysis and lipids of tumor cells in overweight/obese CRC, which may impact the metabolism and function of immune cells. We also identified inhibitory interactions between tumor cells and T cells in overweight/obese CRC.

Conclusions
The study demonstrated that overweight/obese CRC has a more immunosuppressive microenvironment and distinct metabolic reprogramming characterized by increased of glycolysis and lipid metabolism. These findings may have implications for the development of novel therapeutic strategies for overweight/obese CRC patients.
Tumor mutational burden predictability in head and neck squamous cell carcinoma patients treated with immunotherapy: systematic review and meta-analysis
Authors: Rodrigo Juan P. , Sánchez-Canteli Mario , Otero-Rosales María , Martínez-Camblor Pablo , Hermida-Prado Francisco , García-Pedrero Juana M. 
Published: February 2024

Abstract
Background
Tumor mutational burden (TMB) has been demonstrated to predict the response to immune checkpoint inhibitors (ICIs) in various cancers. However, the role of TMB in head and neck squamous cell carcinoma (HNSCC) has not yet been specifically addressed. Since HNSCC patients exhibit a rather limited response to ICIs, there is an unmet need to develop predictive biomarkers to improve patient selection criteria and the clinical benefit of ICI treatment.

Methods
We conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. HNSCC cohort studies were selected when TMB prior to ICI treatment was evaluated, TMB cutoff value was available, and the prognostic value of TMB was evaluated by time-to-event survival analysis. A total of 11 out of 1960 articles were analyzed, including 1200 HNSCC patients.

Results
The results showed that those patients harboring high TMB exhibited a significantly superior overall response rate (OR = 2.62; 95% CI 1.74–3.94; p < 0.0001) and a survival advantage (HR = 0.53; 95% CI 0.39–0.71; p < 0.0001) after ICI treatment.

Conclusion
This is the first meta-analysis to demonstrate a higher response and clinical benefit from ICI therapy in HNSCC patients with high TMB.

Graphical Abstract
Fractalkine isoforms differentially regulate microglia-mediated inflammation and enhance visual function in the diabetic retina
Authors: Rodriguez Derek , Church Kaira A. , Pietramale Alicia N. , Cardona Sandra M. , Vanegas Difernando , Rorex Colin , Leary Micah C. , Muzzio Isabel A. , Nash Kevin R. , Cardona Astrid E. 
Published: February 2024

AbstractDiabetic retinopathy (DR) affects about 200 million people worldwide, causing leakage of blood components into retinal tissues, leading to activation of microglia, the resident phagocytes of the retina, promoting neuronal and vascular damage. The microglial receptor, CX3CR1, binds to fractalkine (FKN), an anti-inflammatory chemokine that is expressed on neuronal membranes (mFKN), and undergoes constitutive cleavage to release a soluble domain (sFKN). Deficiencies in CX3CR1 or FKN showed increased microglial activation, inflammation, vascular damage, and neuronal loss in experimental mouse models. To understand the mechanism that regulates microglia function, recombinant adeno-associated viral vectors (rAAV) expressing mFKN or sFKN were delivered to intact retinas prior to diabetes. High-resolution confocal imaging and mRNA-seq were used to analyze microglia morphology and markers of expression, neuronal and vascular health, and inflammatory mediators. We confirmed that prophylactic intra-vitreal administration of rAAV expressing sFKN (rAAV–sFKN), but not mFKN (rAAV–mFKN), in FKNKO retinas provided vasculo- and neuro-protection, reduced microgliosis, mitigated inflammation, improved overall optic nerve health by regulating microglia-mediated inflammation, and prevented fibrin(ogen) leakage at 4 weeks and 10 weeks of diabetes induction. Moreover, administration of sFKN improved visual acuity. Our results elucidated a novel intervention via sFKN gene therapy that provides an alternative pathway to implement translational and therapeutic approaches, preventing diabetes-associated blindness.
Transforming modeling in neurorehabilitation: clinical insights for personalized rehabilitation
Authors: Lin David J. , Backus Deborah , Chakraborty Stuti , Liew Sook-Lei , Valero-Cuevas Francisco J. , Patten Carolynn , Cotton R James 
Published: February 2024

AbstractPracticing clinicians in neurorehabilitation continue to lack a systematic evidence base to personalize rehabilitation therapies to individual patients and thereby maximize outcomes. Computational modeling— collecting, analyzing, and modeling neurorehabilitation data— holds great promise. A key question is how can computational modeling contribute to the evidence base for personalized rehabilitation? As representatives of the clinicians and clinician-scientists who attended the 2023 NSF DARE conference at USC, here we offer our perspectives and discussion on this topic. Our overarching thesis is that clinical insight should inform all steps of modeling, from construction to output, in neurorehabilitation and that this process requires close collaboration between researchers and the clinical community. We start with two clinical case examples focused on motor rehabilitation after stroke which provide context to the heterogeneity of neurologic injury, the complexity of post-acute neurologic care, the neuroscience of recovery, and the current state of outcome assessment in rehabilitation clinical care. Do we provide different therapies to these two different patients to maximize outcomes? Asking this question leads to a corollary: how do we build the evidence base to support the use of different therapies for individual patients? We discuss seven points critical to clinical translation of computational modeling research in neurorehabilitation— (i) clinical endpoints, (ii) hypothesis- versus data-driven models, (iii) biological processes, (iv) contextualizing outcome measures, (v) clinical collaboration for device translation, (vi) modeling in the real world and (vii) clinical touchpoints across all stages of research. We conclude with our views on key avenues for future investment (clinical-research collaboration, new educational pathways, interdisciplinary engagement) to enable maximal translational value of computational modeling research in neurorehabilitation.
The in vitro gastrointestinal digestion-associated protein corona of polystyrene nano- and microplastics increases their uptake by human THP-1-derived macrophages
Authors: Brouwer Hugo , Porbahaie Mojtaba , Boeren Sjef , Busch Mathias , Bouwmeester Hans 
Published: February 2024

Abstract
Background
Micro- and nanoplastics (MNPs) represent one of the most widespread environmental pollutants of the twenty-first century to which all humans are orally exposed. Upon ingestion, MNPs pass harsh biochemical conditions within the gastrointestinal tract, causing a unique protein corona on the MNP surface. Little is known about the digestion-associated protein corona and its impact on the cellular uptake of MNPs. Here, we systematically studied the influence of gastrointestinal digestion on the cellular uptake of neutral and charged polystyrene MNPs using THP-1-derived macrophages.

Results
The protein corona composition was quantified using LC‒MS–MS-based proteomics, and the cellular uptake of MNPs was determined using flow cytometry and confocal microscopy. Gastrointestinal digestion resulted in a distinct protein corona on MNPs that was retained in serum-containing cell culture medium. Digestion increased the uptake of uncharged MNPs below 500 nm by 4.0–6.1-fold but did not affect the uptake of larger sized or charged MNPs. Forty proteins showed a good correlation between protein abundance and MNP uptake, including coagulation factors, apolipoproteins and vitronectin.

Conclusion
This study provides quantitative data on the presence of gastrointestinal proteins on MNPs and relates this to cellular uptake, underpinning the need to include the protein corona in hazard assessment of MNPs.

Graphical abstract
Small- and medium-sized rice fields identification in hilly areas using all available sentinel-1/2 images
Authors: Wang Lihua , Ma Hao , Gao Yanghua , Chen Shengbo , Yang Songling , Lu Peng , Fan Li , Wang Yumiao 
Published: February 2024

AbstractBackgroundMastering the spatial distribution and planting area of paddy can provide a scientific basis for monitoring rice production, and planning grain production layout. Previous remote sensing studies on paddy concentrated in the plain areas with large-sized fields, ignored the fact that rice is also widely planted in vast hilly regions. In addition, the land cover types here are diverse, rice fields are characterized by a scattered and fragmented distribution with small- or medium-sized, which pose difficulties for high-precision rice recognition.MethodsIn the paper, we proposed a solution based on Sentinel-1 SAR, Sentinel-2 MSI, DEM, and rice calendar data to focus on the rice fields identification in hilly areas. This solution mainly included the construction of rice feature dataset at four crucial phenological periods, the generation of rice standard spectral curve, and the proposal of spectral similarity algorithm for rice identification.ResultsThe solution, integrating topographical and rice phenological characteristics, manifested its effectiveness with overall accuracy exceeding 0.85. Comparing the results with UAV, it presented that rice fields with an area exceeding 400 m2(equivalent to 4 pixels) exhibited a recognition success rate of over 79%, which reached to 89% for fields exceeding 800 m2.ConclusionsThe study illustrated that the proposed solution, integrating topographical and rice phenological characteristics, has the capability for charting various rice field sizes with fragmented and dispersed distribution. It also revealed that the synergy of Sentinel-1 SAR and Sentinel-2 MSI data significantly enhanced the recognition ability of rice paddy fields ranging from 400 m2to 2000 m2.