bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemopreventive effect of modified zeng-sheng-ping on oral squamous cell carcinoma by regulating tumor associated macrophages through targeting tnf alpha induced protein 6
Authors: Wang Jiaqi , Lin Feiran , Zhou Yongxiang , Cong Yuyi , Yang Sen , Wang Sujuan , Guan Xiaobing 
Published: July 2024

Abstract
Background
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck. Zeng-Sheng-Ping, composed of Sophora tonkinensis Gagnep., Bistorta officinalis Delarbre, Sonchus arvensis L., Prunella vulgaris L., Dioscorea bulbifera L., and Dictamnus dasycarpus Turcz., was regarded as an anti-cancer drug with significant clinical efficacy, but was discontinued due to liver toxicity. Our research group developed a modified Zeng-Sheng-Ping (ZSP-M) based on original Zeng-Sheng-Ping that exhibited high efficiency and low toxicity in preliminary investigations, although its pharmacodynamic mechanism is still unclear. Here, we aimed to elucidate the pharmacodynamic material basis of ZSP-M and investigate its chemopreventive effect on OSCC by modulating tumor associated macrophages (TAMs).

Methods
Components of ZSP-M were characterized using ultra-performance liquid chromatography-mass spectrometry. Chemopreventive effect induced by ZSP-M against experimental oral cancer was investigated using the 4-nitroquinoline N-oxide precancerous lesion mouse model. RNA sequencing analysis was used to gain a global transcriptional view of the effect of ZSP-M treatment. A cell co-culture model was used to study the targeted effect of ZSP-M on TAMs and the biological properties of OSCC cells and to detect changes in TAM phenotypes. The binding of ZSP-M active compounds to TNF alpha induced protein 6 (TNFAIP6) protein was analyzed by molecular docking and dynamic simulation.

Results
Forty main components of ZSP-M were identified, the most abundant of which were flavonoids. ZSP-M inhibited the degree of epithelial dysplasia in precancerous lesions by inhibiting the expression of the TNFAIP6 and CD163 proteins in the precancerous lesions of the tongue. ZSP-M inhibited proliferation, colony formation, migration and invasion of SCC7 cells by targeting TAMs. ZSP-M reduced the expression of CD163+ cells, inhibited the expression of TNFAIP6 protein, Arg1 mRNA and Il10 mRNA in TAMs, and reduced IL-10 cytokine release in the co-culture environment. This effect was maintained after the addition of recombinant TNFAIP6 protein. Computer simulations showed that trifolirhizin and maackiain are well-connected to TNFAIP6.

Conclusions
ZSP-M counteracts the immunosuppressive action of TAMs by specific targeting of TNFAIP6, thereby exerting chemopreventive activity of OSCC.
Ethics, design, and implementation criteria of digital assistive technologies for people with dementia from a multiple stakeholder perspective: a qualitative study
Authors: Köhler Stefanie , Perry Julia , Biernetzky Olga A. , Kirste Thomas , Teipel Stefan J. 
Published: July 2024

Abstract
Background
Dementia impairs the ability of people with dementia to be autonomous and independent. They need support from third parties, who should ideally respect their autonomy and independence as much as possible. Supporting people with dementia can be very burdensome for caregivers and numbers of patients increase while numbers of potential caregivers decline. Digital assistive technologies (DATs) that directly support patients or their caregivers may help bridging the increasing gap between need of support and available resources. DATs have the potential to preserve the autonomy and independence of people with dementia and promote their abilities, if they are properly designed in close interaction with future users. In our study, we focused on ethical concerns, technological requirements, and implementation criteria for DAT in general and specifically to support outdoor mobility of people with dementia.

Methods
We applied a qualitative approach and conducted a World Café (2 tables, n = 7) and an online focus group (n = 6) with people with dementia, relatives, healthcare professionals, scientists, ethics experts, and experts for digitally-assisted medical care. We descriptively analyzed the data using a content analysis approach.

Results
The participants reported technological (e.g., lack of Wi-Fi), financial (e.g., expensive devices or lack of budget for DATs), political (e.g., legal hurdles such as the European Medical Device Law or data protection regulations) as well as user-related hurdles (e.g., lack of digital competence) for the implementation of DAT in dementia care. Among the issues discussed were the importance of autonomy, independence, safety, privacy, and questions of decision making capacity in DAT’s use. Participants identified opportunities and benefits in self-learning, situation-aware DATs and wished for dementia-friendly communities. They emphasized the value of personal interaction that should not be replaced, but rather supported by DAT.

Conclusion
The results revealed multiple hurdles and ethical concerns for DAT use and provided recommendations for designing and implementing DATs. Further investigations are needed on the impact of DAT on personal interactions in caregiving and the role of DAT in dementia-friendly communities.
A qualitative study of the barriers and facilitators impacting the implementation of a quality improvement program for emergency departments: SurgeCon
Authors: Anaraki Nahid Rahimipour , Mukhopadhyay Meghraj , Jewer Jennifer , Patey Christopher , Norman Paul , Hurley Oliver , Etchegary Holly , Asghari Shabnam 
Published: July 2024

Abstract
Background
The implementation of intervention programs in Emergency Departments (EDs) is often fraught with complications due to the inherent complexity of the environment. Hence, the exploration and identification of barriers and facilitators prior to an implementation is imperative to formulate context-specific strategies to ensure the tenability of the intervention.

Objectives
In assessing the context of four EDs prior to the implementation of SurgeCon, a quality improvement program for ED efficiency and patient satisfaction, this study identifies and explores the barriers and facilitators to successful implementation from the perspective of the healthcare providers, patients, researchers, and decision-makers involved in the implementation.

Settings
Two rural and two urban Canadian EDs with 24/7 on-site physician support.

Methods
Data were collected prior to the implementation of SurgeCon, by means of qualitative and quantitative methods consisting of semi-structured interviews with 31 clinicians (e.g., physicians, nurses, and managers), telephone surveys with 341 patients, and structured observations from four EDs. The interpretive description approach was utilized to analyze the data gathered from interviews, open-ended questions of the survey, and structured observations.

Results
A set of five facilitator-barrier pairs were extracted. These key facilitator-barrier pairs were: (1) management and leadership, (2) available resources, (3) communications and networks across the organization, (4) previous intervention experiences, and (5) need for change.

Conclusion
Improving our understanding of the barriers and facilitators that may impact the implementation of a healthcare quality improvement intervention is of paramount importance. This study underscores the significance of identifing the barriers and facilitators of implementating an ED quality improvement program and developing strategies to overcome the barriers and enhance the facilitators for a successful implementations. We propose a set of strategies for hospitals when implementing such interventions, these include: staff training, champion selection, communicating the value of the intervention, promoting active engagement of ED staff, assigning data recording responsibilities, and requiring capacity analysis.

Trial registration
ClinicalTrials.gov. NCT04789902. 10/03/2021.
Modulation of the intestinal mucosal and cell-mediated response against natural helminth infection in the African catfish Clarias gariepinus
Authors: Abdel-Hakeem Sara Salah , Fadladdin Yousef Abdal Jalil , Khormi Mohsen A. , Abd-El-Hafeez Hanan H. 
Published: July 2024

AbstractFish gut is a versatile organ serving as the primary pathway for invasion by pathogens, particularly parasites, playing a crucial role in modulating the intestinal adaptive immune response. This study aimed to investigate the cellular-mediated reaction, mucosal acidity, and the expression of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and CD68 in the intestines of catfish, Clarias gariepinus, naturally infected with helminths. Forty catfish were collected from the Nile River and examined for intestinal parasites. The intestinal tissues of the control and infected fish were fixed for histochemical and immunohistochemical studies. Two groups of helminths were found: cestodes Tetracampos ciliotheca and Polyonchobothrium clarias, and nematodes Paracamallanus cyathopharynx, with a prevalence rate of 63.63%, 18.0%, and 18.0%, respectively. Our results showed that the infected fish had a statistically significant rise in the activity of immune cells, including mast cells, eosinophil granular cells, and dendritic cells. This correlated with upregulation in the expressions of PCNA, VEGF, and CD68. Histochemical analyses demonstrated a marked increase in acidic mucus production, Sudan black B, and bromophenol mercury blue. This study enriches our understanding of the evolution of vertebrate immunity in combating intestinal parasitic infections and the host’s adaptive responses.
Uncovering novel mechanisms of chitinase-3-like protein 1 in driving inflammation-associated cancers
Authors: Fan Yan , Meng Yuan , Hu Xingwei , Liu Jianhua , Qin Xiaosong 
Published: July 2024

AbstractChitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that is induced and regulated by multiple factors during inflammation in enteritis, pneumonia, asthma, arthritis, and other diseases. It is associated with the deterioration of the inflammatory environment in tissues with chronic inflammation caused by microbial infection or autoimmune diseases. The expression of CHI3L1 expression is upregulated in several malignant tumors, underscoring the crucial role of chronic inflammation in the initiation and progression of cancer. While the precise mechanism connecting inflammation and cancer is unclear, the involvement of CHI3L1 is involved in chronic inflammation, suggesting its role as a contributing factor to in the link between inflammation and cancer. CHI3L1 can aggravate DNA oxidative damage, induce the cancerous phenotype, promote the development of a tumor inflammatory environment and angiogenesis, inhibit immune cells, and promote cancer cell growth, invasion, and migration. Furthermore, it participates in the initiation of cancer progression and metastasis by binding with transmembrane receptors to mediate intracellular signal transduction. Based on the current research on CHI3L1, we explore introduce the receptors that interact with CHI3L1 along with the signaling pathways that may be triggered during chronic inflammation to enhance tumorigenesis and progression. In the last section of the article, we provide a brief overview of anti-inflammatory therapies that target CHI3L1.
Targeted nanoparticles triggered by plaque microenvironment for atherosclerosis treatment through cascade effects of reactive oxygen species scavenging and anti-inflammation
Authors: Luo Xianghong , Zhang Mengjiao , Dai Waicong , Xiao Xianghao , Li Xinyi , Zhu Yingjian , Shi Xiangyang , Li Zhaojun 
Published: July 2024

AbstractInflammatory factors and reactive oxygen species (ROS) are risk factors for atherosclerosis. Many existing therapies use ROS-sensitive delivery systems to alleviate atherosclerosis, which achieved certain efficacy, but cannot eliminate excessive ROS. Moreover, the potential biological safety concerns of carrier materials through chemical synthesis cannot be ignored. Herein, an amphiphilic low molecular weight heparin- lipoic acid conjugate (LMWH-LA) was used as a ROS-sensitive carrier material, which consisted of injectable drug molecules used clinically, avoiding unknown side effects. LMWH-LA and curcumin (Cur) self-assembled to form LLC nanoparticles (LLC NPs) with LMWH as shell and LA/Cur as core, in which LMWH could target P-selectin on plaque endothelial cells and competitively block the migration of monocytes to endothelial cells to inhibit the origin of ROS and inflammatory factors, and LA could be oxidized to trigger hydrophilic-hydrophobic transformation and accelerate the release of Cur. Cur released within plaques further exerted anti-inflammatory and antioxidant effects, thereby suppressing ROS and inflammatory factors. We used ultrasound imaging, pathology and serum analysis to evaluate the therapeutic effect of nanoparticles on atherosclerotic plaques in apoe−/− mice, and the results showed that LLC showed significant anti-atherosclerotic effects. Our finding provided a promising therapeutic nanomedicine for the treatment of atherosclerosis.
PD-L1 siRNA hitched polyethyleneimine-elastase constituting nanovesicle induces tumor immunogenicity and PD-L1 silencing for synergistic antitumor immunotherapy
Authors: Du Li , Gong Yao , Zhang Xiaoying , Sun Jide , Gao Fengxia , Shen Meiying , Bai Huili , Yang Tiantian , Cheng Xiaoxue , Li Siqiao , Peng Jian , Liu Zhangling , Ding Shijia , Chen Junman , Cheng Wei 
Published: July 2024

Abstract
Background
PD-1/PD-L1 blockade has become a powerful method to treat malignant tumors. However, a large proportion of patients still do not benefit from this treatment, due to low tumor immunogenicity and low tumor penetration of the agents. Recently, neutrophil elastase has been shown to induce robust tumor immunogenicity, while the insufficient enzyme activity at the tumor site restricted its anti-tumor application. Here, we designed polyethyleneimine-modified neutrophil elastase (PEI-elastase) loaded with PD-L1small interfering RNA (PD-L1 siRNA) for improving enzymatic activity and delivering siRNA to tumor, which was expected to solve the above-mentioned problems.

Results
We first demonstrated that PEI-elastase possessed high enzymatic activity, which was also identified as an excellent gene-delivery material. Then, we synthesized anti-tumor lipopolymer (P-E/S Lip) by encapsulating PEI-elastase and PD-L1siRNA with pH-responsive anionic liposomes. The P-E/S Lip could be rapidly cleaved in tumor acidic environment, leading to exposure of the PEI-elastase/PD-L1 siRNA. Consequently, PEI-elastase induced powerful tumor immunogenicity upon direct tumor killing with minimal toxicity to normal cells. In parallel, PEI-elastase delivered PD-L1siRNA into the tumor and reduced PD-L1 expression. Orthotopic tumor administration of P-E/S Lip not only attenuated primary tumor growth, but also produced systemic anti-tumor immune response to inhibit growth of distant tumors and metastasis. Moreover, intravenous administration of P-E/S Lip into mice bearing subcutaneous tumors leaded to an effective inhibition of established B16-F10 tumor and 4T1 tumor, with histological analyses indicating an absence of detectable toxicity.

Conclusions
In our study, a protease-based nanoplatform was used to cooperatively provoke robust tumor immunogenicity and down-regulate PD-L1 expression, which exhibited great potential as a combination therapy for precisely treating solid tumors.

Graphical Abstract
Repolarizing neutrophils via MnO2 nanoparticle-activated STING pathway enhances Salmonella-mediated tumor immunotherapy
Authors: Lu Shan , Mi Ze , Liu Peng , Ding Jinsong , Ma Yiran , Yang Jieru , Rong Pengfei , Zhou Wenhu 
Published: July 2024

AbstractEngineered Salmonella has emerged as a promising microbial immunotherapy against tumors; however, its clinical effectiveness has encountered limitations. In our investigation, we unveil a non-dose-dependent type of behavior regarding Salmonella’s therapeutic impact and reveal the regulatory role of neutrophils in diminishing the efficacy of this. While Salmonella colonization within tumors recruits a substantial neutrophil population, these neutrophils predominantly polarize into the pro-tumor N2 phenotype, elevating PD-L1 expression and fostering an immunosuppressive milieu within the tumor microenvironment. In order to bypass this challenge, we introduce MnO2 nanoparticles engineered to activate the STING pathway. Harnessing the STING pathway to stimulate IFN-β secretion prompts a shift in neutrophil polarization from the N2 to the N1 phenotype. This strategic repolarization remodels the tumor immune microenvironment, making the infiltration and activation of CD8+ T cells possible. Through these orchestrated mechanisms, the combined employment of Salmonella and MnO2 attains the synergistic enhancement of anti-tumor efficacy, achieving the complete inhibition of tumor growth within 20 days and an impressive 80% survival rate within 40 days, with no discernible signs of significant adverse effects. Our study not only unveils the crucial in vivo constraints obstructing microbial immune therapy but also sets out an innovative strategy to augment its efficacy. These findings pave the way for advancements in cell-based immunotherapy centered on leveraging the potential of neutrophils.
Graphical Abstract
HiViPore: a highly viable in-flow compression for a one-step cell mechanoporation in microfluidics to induce a free delivery of nano- macro-cargoes
Authors: Maremonti Maria Isabella , Panzetta Valeria , Netti Paolo Antonio , Causa Filippo 
Published: July 2024

Abstract
Background
Among mechanoporation techniques for intracellular delivery, microfluidic approaches succeed in high delivery efficiency and throughput. However, especially the entry of large cargoes (e.g. DNA origami, mRNAs, organic/inorganic nanoparticles) is currently impaired since it requires large cell membrane pores with the need to apply multi-step processes and high forces, dramatically reducing cell viability.

Results
Here, HiViPore presents as a microfluidic viscoelastic contactless compression for one-step cell mechanoporation to produce large pores while preserving high cell viability. Inducing an increase of curvature at the equatorial region of cells, formation of a pore with a size of ~ 1 μm is obtained. The poration is coupled to an increase of membrane tension, measured as a raised fluorescence lifetime of 12% of a planarizable push-pull fluorescent probe (Flipper-TR) labelling the cell plasma membrane. Importantly, the local disruptions of cell membrane are transient and non-invasive, with a complete recovery of cell integrity and functions in ~ 10 min. As result, HiViPore guarantees cell viability as high as ~ 90%. In such conditions, an endocytic-free diffusion of large nanoparticles is obtained with typical size up to 500 nm and with a delivery efficiency up to 12 times higher than not-treated cells.

Conclusions
The proposed one-step contactless mechanoporation results in an efficient and safe approach for advancing intracellular delivery strategies. In detail, HiViPore solves the issues of low cell viability when multiple steps of poration are required to obtain large pores across the cell plasma membrane. Moreover, the compression uses a versatile, low-cost, biocompatible viscoelastic fluid, thus also optimizing the operational costs. With HiViPore, we aim to propose an easy-to-use microfluidic device to a wide range of users, involved in biomedical research, imaging techniques and nanotechnology for intracellular delivery applications in cell engineering.
Health and disability – a multi-group latent class analysis of the World Health Organization Disability Assessment Schedule 2.0 among those with mental and physical health conditions
Authors: Seet Vanessa , Abdin Edimansyah , Jeyagurunathan Anitha , Chik Tan Sing , Kit Lum Joon , Sing Lee Eng , Verma Swapna , Ker-Chiah Wei , Ng Pamela , Subramaniam Mythily 
Published: July 2024

Abstract
Background
This study aims to identify disability classes among people with schizophrenia spectrum disorder, depression, anxiety or diabetes via the WHODAS 2.0; investigate the invariance of disability patterns among the four diagnostic groups; and examine associations between disability classes and sociodemographic variables.

Methods
Patients seeking treatment for schizophrenia spectrum disorder, depression, anxiety or diabetes (n=1076) were recruited. Latent class analysis was used to identify disability classes based on WHODAS 2.0 responses. Measurement invariance was tested using multi-group latent class analysis. Associations between classes and sociodemographic variables were tested via multinomial logistic regression.

Results
A five-class solution was identified; examination of model invariance showed that the partially constrained five-class model was most appropriate, suggesting that class structure was consistent while class membership differed across diagnostic groups. Finally, significant associations were found between class membership and ethnicity, education level, and employment status.

Conclusions
The results show the feasibility of using the WHODAS 2.0 to identify and compare different disability classes among people with mental or physical conditions and their sociodemographic correlates. Establishing a typology of different disability profiles will help guide research and treatment plans that tackle not just clinical but also functional aspects of living with either a chronic psychiatric or physical condition.
Nomograms to predict tumor regression grade (TRG) and ypTNM staging in patients with locally advanced esophageal cancer receiving neoadjuvant therapy
Authors: Qiu Jianhao , Zhang Zhan , Liu Junjie , Zhao Yue , Li Yongmeng , Tang Zhanpeng , Li Lin , Tian Yu , Tian Hui 
Published: July 2024

Abstract
Background
Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult.

Methods
A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors.

Results
A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility.

Conclusion
The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.