bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effect of spermidine and ciprofloxacin against Alzheimer disease in male rat via ferroptosis modulation
Authors: Youssef Menna M , Mohamed Tarek M , Bakry Aza M , El-Keiy Mai M 
Published: August 2023

Abstract
Alzheimer's disease (AD) is a prevalent form of neurodegenerative disease with a complex pathophysiology that remains not fully understood, and the exact mechanism of neurodegeneration is uncertain. Ferroptosis, a programmed cell death mechanism mediated by iron, has been linked to the progression of degenerative diseases observed in clinical AD models. In this study, we aimed to explore the synergistic effects of spermidine and/or ciprofloxacin in combating Alzheimer's disease (AD). We investigated AD-related biomarkers, including neurotoxic Aβ, arginaseI, and serotonin.Spermidine demonstrated an anti-ferroptotic effect in the AD model, evident from the modulation of ferroptosis parameters such as hippocampus iron levels, reduced protein expression of transferrin receptor 1 (TRF1), and arachidonate 15-lipoxygenase (ALOX15). Additionally, the administration of spermidine led to a significant increase in protein expression of phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) and upregulation of Cystine/glutamate transporter (SLC7A11) gene expression. Moreover, spermidine notably decreased p53 protein levels, acrolein, and gene expression of spermidine/spermine N1-acetyltransferase 1 (SAT1). The histopathological examination of hippocampus tissue corroborated these results obtained from molecular biochemical inspection. Overall, our findings suggest that spermidine and/or ciprofloxacin may offer potential benefits against Alzheimer's disease (AD) by modulating ferroptosis. Furthermore, spermidine enhanced the antioxidant efficacy of ciprofloxacin and reduced its toxic effects by increasing antioxidant enzymes, thereby enhancing its potency against oxidative stress.
Innovative Primary Care Clinic for Complex Patients Generates a Financial Benefit for Health System
Authors: Carstarphen Kathy Jo , Shawley Audrey , Li Richard , Hill Sarah , Sharma Sakshi , Wadleigh Marshall , Nehmeh Amal , Denton Gerald D 
Published: August 2023

Abstract
Introduction: The United States ranks far lower than other high-income countries on measures of health care affordability, efficiency, equity, and outcome. A key distinguishing feature of the US from the top-performing countries is the lack of investment in primary care systems that prioritize high quality care delivery to vulnerable populations. Methods: The MedVantage Clinic (MVC) operates within Ochsner Health System, a large academic not-for-profit health system based on a group practice model, located in the New Orleans metropolitan area. We compared cost and utilization for patients enrolled in the MVC vs a comparable control population for one year before and after the index date of program enrollment. Participants include a heterogeneous patient panel of Medicare beneficiaries with multiple comorbid conditions and barriers to care. Results: Our total estimate for the total annual resource benefit generated by the MVC in 2017–2018 is $1,224,648 (n = 189). We estimate this decreased cost of care through 1) improved documentation of hierarchical condition category (HCC) risk adjustment factor (RAF) scores 2) decreased mean per-member-per-month (PMPM) costs 3) decreased inpatient length of stay and 4) decreased mean inpatient utilization Discussion: The MVC model is rooted in providing complex, multi-morbid patients with additional resources and services in order to address intense health needs and decrease costs of care. The MVC case group generated a greater total resource benefit for health systems than the matched control group.
Yinchenhao Decoction mitigates intestinal impairment induced by high carbohydrate diet in largemouth bass: insights from inflammation, apoptosis, oxidative stress, tight junctions, and microbiota homeostasis
Authors: Liang Ji , Zhao Liulan , Cheng Liangshun , Kuang Xu , Hu Yifan , Liu Qiao , Zhang Xin , Wang Hong , Zhu Enpei , Tahir Rabia , Yang Song 
Published: August 2023

Abstract
As a major source of energy, carbohydrates have a protein sparing effect. However, excessive consumption of carbohydrates can harm the intestinal barriers of fish, particularly carnivorous fish. The traditional Chinese medicine component, Yinchenhao Decoction (YD), may improve intestinal barriers and microbial community equilibrium in both animals and humans. In the current investigation, a series of NC and HC with graded YD experiments were undertaken, and the results suggest that 2% and 4% YD treatments significantly reduced gut inflammation and mucosal loss caused by HC. Compared to NC, HC significantly decreased the relative expression of intestinal tight junction-related genes (ZO1, claudin1, claudin7, and occludin). However, with the application of YD, the expression of tight junction-related genes (ZO1, claudin1, and claudin7) increased significantly (p < 0.05). Stepwise, administration of YD significantly reduced elevated plasma diamine oxidase (DAO) activity caused by HC (p < 0.05). Additionally, YD significantly downregulated the mRNA expression of endoplasmic reticulum stress-related genes (GRP78, ATF6, CHOPα, IRE1, XBP1, and Eif2α) and pro-apoptosis genes (caspase3, caspase8, and bax) (p < 0.05), while upregulating the anti-apoptosis gene bcl2 (p < 0.05). Moreover, YD significantly increased the mRNA expression of antioxidant genes CAT and the enzyme activities of CAT and GPX, while decreasing keap1 and MDA concentration significantly (p < 0.05). Additionally, YD markedly decreased the expression of pro-inflammatory genes (IL1β, TNFα, IL8, and NF-κB) and the immune enzyme activity (ACP and AKP) (p < 0.05). By upregulating the expression of anti-inflammatory genes (IKB and IL10). I Notably, YD modulated the largemouth bass intestinal microbial community, enhancing the diversity and increasing the abundance of probiotic microorganisms in the intestinal microbiota. The study's results demonstrate that YD supplementation in a high-carbohydrate (HC) diet reduced inflammation, apoptosis, oxidative stress, and tight-junction injury in the intestines. Furthermore, it helped maintain gut microbiota homeostasis, suggesting that YD could be a valuable functional addition in aquaculture practices.
Factors Associated with Surgical Outcomes of Intermittent Exotropia in Children
Authors: Yang Seungahn , Choi Heeyoung , Kim Su-Jin , Lee Ji-Eun 
Published: August 2023

Abstract
Purpose
To evaluate factors associated with surgical outcomes of children with intermittent exotropia (IXT).
Methods
A retrospective study was performed for 125 patients who had undergone intermittent exotropia surgery with at least one year of follow up. Surgical outcomes were grouped as success (esophoria/tropia ≤ 5 prism diopers (PD) to exophoria/tropia ≤ 10 PD), failure (esophoria/tropia > 5PD or exophoria/tropia > 10PD) according to the angle of deviation at postoperative one year. We investigated subjects’ clinical and demographic factors including magnitude of exo-deviation, stereoacuity at near and distance, and response to patching at 3 months after patching. Factors associated with surgical outcomes were then determined through univariate and multivariate analyses.
Results
Of a total of 125 patients, 102 (81.6%) were assigned to the success group and 23 (18.4%) to the failure group. Univariate analysis revealed that absence of anisometropia, smaller preoperative near exodeviation, better stereopsis at near, magnitude of deviation at postoperative day 1, and good response to preoperative patching were significantly associated with surgical success for IXT at postoperative one year. In multivariate analysis, distant esotropic magnitude of deviation at postoperative day 1 was the only factor affecting successful surgical outcome.
Conclusions
Preoperative patching and small distant esotropia at postoperative day 1 are prognostic factors that could be altered in an effort to provide a successful surgical outcome.
Effect of Omega-3 Fatty Acid Diet on Prostate Cancer Progression and Cholesterol Efflux in Tumor Associated Macrophages – Dependence on GPR120
Authors: Aronson William , Liang Pei , Henning Susanne , Grogan Tristan , Elashoff David , Said Jonathan W , Cohen Pinchas 
Published: August 2023

Abstract
Background
Preclinical and clinical translational research supports the role of an ω-3 fatty acid diet for prostate cancer prevention and treatment. The anti-prostate cancer effects of an ω-3 diet require a functional host g-protein coupled receptor (GPR120) but the underlying effects on the immune system in the tumor microenvironment are yet to be elucidated.
Methods
FVB mice received bone marrow from green fluorescent protein (GFP) labeled GPR120 wild-type (WT) or knockout (KO) mice followed by MycCap allograft implantation. Mice were fed an ω-3 diet compared to an ω-6 diet. Tumor associated immune cells were characterized by flow cytometry. Transgenic FVB hi-Myc mice were fed an ω-3 compared to an ω-6 diet for 6 months followed by pathology analysis of prostate lobes.
Results
Through the use of a bone marrow transplantation model, we found that an ω-3 as compared to an ω-6 diet inhibited MycCaP allograft tumor growth in mice receiving GPR120 WT but not GPR120 KO bone marrow. In the ω-3 group, GPR120 WT BMD M2-like macrophages infiltrating the tumor were significantly reduced in number and gene expression of cholesterol transporters Abca1, Abca6, and Abcg1. In addition, feeding an ω-3 as compared to an ω-6 diet slowed the progression to adenocarcinoma in a transgenic hi-Myc prostate cancer mouse model with functional GPR120. M2 macrophages play a critically important role in prostate cancer progression. Herein we report that RAW264.7 cells and BMD macrophages exposed to MycCaP cell conditioned media had increased gene expression of cholesterol transporters, depleted cholesterol levels, and were converted to the M2 phenotype. These effects were inhibited by ω-3 fatty acids through the GPR120 receptor.
Conclusion
Our preclinical findings provide rationale for clinical trials evaluating ω-3 fatty acids as a potential therapy for prostate cancer through inhibition of GPR120 functional M2 macrophages.
Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis
Authors: Sarkar Soumyadeep , Deiter Cailin , Kyle Jennifer E. , Guney Michelle A. , Sarbaugh Dylan , Yin Ruichuan , Li Xiangtang , Cui Yi , Ramos-Rodriguez Mireia , Nicora Carrie D. , Syed Farooq , Juan-Mateu Jonas , Muralidharan Charanya , Pasquali Lorenzo , Evans-Molina Carmella , Eizirik Decio L. , Webb-Robertson Bobbie-Jo M. , Burnum-Johnson Kristin , Orr Galya , Laskin Julia , Metz Thomas O. , Mirmira Raghavendra G. , Sussel Lori , Ansong Charles , Nakayasu Ernesto 
Published: August 2023

Abstract
Background.
Lipids have been implicated as regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death.
Methods.
We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling.
Results.
Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholine with polyunsaturated fatty acids and converting enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of adenosine diphosphate ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-induced degradation of the histone methylation polycomb complex PRC2 component Suz12, releasing the expression of Arh3, which in turn reduces cell apoptosis.
Conclusions.
Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids.
Thrombolytic therapy based on lyophilized platelet-derived nanocarriers for ischemic stroke
Authors: Migliavacca Martina , Correa-Paz Clara , Pérez-Mato María , Bielawski Patrick-Brian , Zhang Issan , Hervella Pablo , Rubio Marina , Maysinger Dusica , Vivien Denis , Pino Pablo del , Pelaz Beatriz , Polo Ester , Campos Francisco 
Published: August 2023

Abstract
Background: Intravenous administration of fibrinolytic drugs, such as recombinant tissue plasminogen activator (rtPA) is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and risk of hemorrhagic transformations. Platelet membrane-based nanocarriers have received increasing attention for ischemic stroke therapies, as they have natural thrombus-targeting activity, can prolong half-life of the fibrinolytic therapy, and reduce side effects. In this study, we have gone further in developing platelet-derived nanocarriers (defined as cellsomes) to encapsulate and protect rtPA from degradation. Following lyophilization and characterization, their formulation properties, biocompatibility, therapeutic effect, and risk of hemorrhages were later investigated in a thromboembolic model of stroke in mice.
Results: Cellsomes of 200 nm size and loaded with rtPA were generated from membrane fragments of human platelets. The lyophilization process did not influence the nanocarrier size distribution, morphology, and colloidal stability conferring particle preservation and long-term storage. Encapsulated rtPA in cellsomes showed to be as effective as free rtPA at equal concentration without increasing the risk of hemorrhagic transformations or altering the immune response.
Conclusions: This study provides evidence for the safe and effective use of lyophilized biomimetic platelet-derived nanomedicine for precise thrombolytic treatment of acute ischemic stroke. We have successfully addressed one of the main barriers to drug application and commercialization, the long-term storage of nanomedicines, overcoming the potential chemical and physical instabilities of nanomedicines when stored in an aqueous buffer.
Prediction of five-year survival of patients with esophageal cancer and the effect of biomarkers on predictive performance using Artificial Intelligence
Authors: Lukomski Leandra , Pisula Juan , Wirsik Naita , Damanakis Alexander , Jung Jin-On , Knipper Karl , Datta Rabi , Schröder Wolfgang , Gebauer Florian , Schmidt Thomas , Quaas Alexander , Bozek Katarzyna , Bruns Christiane , Popp Felix 
Published: August 2023

Abstract
AIM
We use Artificial Intelligence (AI) to predict the long-term survival of patients with resectable esophageal cancer (EC). We test whether AI can predict survival with all available data, with data at the time of primary staging (PS) and if biomarker analysis is equivalent to the Tumor, Node, Metastasis (TNM) classification in survival predictions.
METHODS
This retrospective study included 1002 patients with EC, 55 patient characteristics, and 55 biomarkers after surgical treatment between 1996 and 2021. The dataset was divided into short-term survival (overall survival, OS: > 90 days but < 5 years + recorded death) and long-term survival (OS: ≥ 5 years). AI methods (Random Forest RF, XG Boost XG, Artificial neural network ANN, TabNet TN) and logistic regression (LR) were used for predictions on an independent hold-out set. Models were further trained only with data available at PS combined with all biomarkers from tissue microarrays but not TNM (PS dataset). Feature selection was applied with permutation feature importance (PFI) to create reduced datasets with only important variables for predictions.
RESULTS
AI methods predicted the five-year survival status with a comparable accuracy when trained with the whole dataset (Accuracy: 0.77/0.76/0.76/0.74/0.69 RF/XG/ANN/TN/LR, respectively). When trained without the biomarkers but with complete patient characteristics, including TNM, model predictions did not deteriorate. LR showed the least accurate prediction in any conducted computational experiment. In contrast, models trained only with collected data until PS with biomarkers showed better predictive power compared to excluded biomarkers (whole PS dataset vs. PS dataset without biomarkers; Accuracy: 0.77 vs. 0.70/ 0.79 vs. 0.73/0.75 vs. 0.71/0.72 vs.0.69/0.66 vs. 0.63 RF/XG/ANN/TN/LR). Model predictions with selected features via PFI showed similar results compared to when trained with all features. Important feature overlap of AI methods, when trained with all features, was: pN status, pT status, p16 deletion, and Her2/neu amplification. Feature overlap when trained with the PS dataset was: patient age at the time of surgery, TP-53 mutation, Mesothelin expression, TYMP expression, NANOG expression, IDO expressed on tumor-infiltrating lymphocytes, tumor-infiltrating mast- and NK-cells.
CONCLUSION
AI can predict the long-term survival of patients with EC. Survival status can be predicted at the time of PS if additional information on the tumor tissue is available. This suggests that individual predictions are possible early in cancer treatment with biomarkers and do not rely on the pathological TNM status after surgery.
Genome-wide identification of thaumatin-like protein family genes in Panax notoginseng and analysis of their responses to Fusarium solani infection
Authors: yun yang , Guan Huilin , Wei Fugang , Li Zecheng , Yang Shaozhou , Huang Jingxin 
Published: August 2023

Abstract
Panax notoginseng is the most widely used Chinese medicinal herb, and one main challenge to the successful cultivation is root rot, which significantly reduces its yield and quality. Thaumatin-like proteins (TLPs) are a large and complex proteins of pathogenesis-related family 5 (PR-5), which play a important role in plant host defense and other physiological processes. The objective of this study is to identify the TLP gene family in P. notoginseng on a genome-wide scale and explore their response to Fusarium solani infection. In this study, a total of twenty PnTLP genes were identified in P. notoginseng genome and divided into ten subfamilies (Group I–X) by the phylogenetic analysis. Subcellular localization prediction showed that most of the PnTLP proteins were located in the extracellular, and few were distributed in chloroplast. Meanwhile, the gene structure and protein conserved domain were established by MEME Suite. Duplication analysis showed that segmental duplication, rather than tandem duplications promoting the expansion of the PnTLPs gene family. The analysis of collinear relationships reflected that there were 36 homologous genes between P. notoginseng and Arabidopsis and 9 between P. notoginseng and rice. Moreover, cis-acting elements of PnTLP gene promoters were predicted which indicated that PnTLPs are involved in biotic, abiotic stress, and hormone induction. Expression profile analysis revealed the possible roles of TLPs in plant development and fungal stress response. Furthermore, qRT-PCR analyses revealed that the PnTLP members were up-regulated or down-regulated in response to F. solani stress. The results of this study provide insight into the PnTLP gene family, and their potential biological functions in plants’ defenses against pathogenic fungi, which would provide candidate genes for future studies of their roles in disease resistance.
Development of a Ferroptosis-based Molecular Markers for Predicting RFS in Prostate Cancer Patients
Authors: Chen Jinquan , Zhang Longbin , Luo Yiling , Tan Chao , Hu Huang , Jiang Yuling , Xi Na , Zeng Qinghai , Peng H 
Published: August 2023

Abstract
The goal of this study was to develop a ferroptosis-based molecular signature that can predict recurrence-free survival (RFS) in patients with prostate cancer (PCa). In this study, we obtained ferroptosis-related genes (FRGs) in FerrDb database and clinical transcriptome data in TCGA database and GEO database. Consensus cluster analysis was used to identify three molecular markers of ferroptosis in PCa with differential expression of 40 FRGs, including PD-L1 expression levels.We conducted a new ferroptosis- related signature for PCa RFS using four FRGs identified through univariate and multivariate Cox regression analyses. The signature was validated in the training, testing, and validation cohorts, and it demonstrated remarkable results in the area under the time-dependent receiver operating characteristic (ROC) curve of 0.757, 0.715, and 0.732, respectively. Additionally, we observed that younger patients, those with stage T III and stage T IV, stage N0, cluster 1, and cluster 2 PCa were most accurately predicted by the signature as independent predictors of RFS.DU-145 and RWPE-1 cells were successfully analyzed by qRT-PCR and Western blot for ASNS, GPT2, RRM2, and NFE2L2. We conducted a new ferroptosis-based signature for PCa RFS using four FRGs identified through univariate and multivariate Cox regression analyses. The signature was validated in training, testing, and validating cohorts, with an excellent performance based on the ROC curves respectively of 0.757, 0.715, and 0.732. Furthermore, we found that younger patients or those with stage T III and stage T IV, stage N0, cluster 1and cluster 2 were best predicted by the signature as independent predictors of RFS. DU-145 and RWPE-1 cell lines were successfully analyzed by qRT-PCR and Western blot for ASNS, GPT2, RRM2, and NFE2L2.
Dachsous cadherin related 1 (DCHS1) is a novel biomarker for immune infiltration and epithelial- mesenchymal transition in endometrial cancer via pan-cancer analysis
Authors: Meijuan Cai , Fang Min , qian Wang 
Published: August 2023

Abstract

Background
Dachsous cadherin related 1 (DCHS1) is one of calcium-dependent adhesion membrane proteins and is mainly involved in the development of mammalian tissues. There is a lack of more detailed research on the biological function of DCHS1 in pan-cancer.
Materials and methods
We evaluated the expression, the prognostic value, the diagnostic value and genomic alterations of DCHS1 by using the databases, including TCGA, UALCAN, HPA, GEPIA2.0 and GSCA. We employed the databases of UCSC, TIMER2.0, TISIDB, GSCA to analyze the association between DCHS1 expression and the immune microenvironment, stemness, TMB, MSI and anticancer drug sensitivity. BioGRID, STRING and GEPIA2.0 were used to perform protein interaction and functional enrichment analysis. Real-time quantitative PCR, CCK8, Transwell assay and WB were performed to determine the function of DCHS1 in UCEC.
Results
DCHS1 is differentially expressed in many cancers and its expression is significantly associated with tumor prognosis and diagnosis. DCHS1 expression was significantly correlated with the infiltration of cancer-associated fibroblasts (CAFs) and Endothelial cell (ECs), and Hematopoietic stem cell in most cancers. In addition, DCHS1 was significantly associated with sensitivity to many antitumor drugs. Functional enrichment analysis revealed that DCHS1-related proteins were involved in Focal adhesion, Endometrial cancer and Wnt signaling pathway. GSEA results showed that DCHS1 is related to epithelial-mesenchymal transition (EMT) in many cancers. In vitro experiments in UCEC showed that silencing of DCHS1 blocked cell proliferation, migration and EMT.
Conclusions
Our findings indicated that DCHS1 might be a novel prognostic and diagnostic biomarker and immunotherapy target, and plays an important role in the proliferation, migration and EMT in UCEC.