bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound targeted microbubble destruction-triggered nitric oxide release via nanoscale ultrasound contrast agent for sensitizing chemoimmunotherapy
Authors: Zhao Yading , Shi Dandan , Guo Lu , Shang Mengmeng , Sun Xiao , Meng Dong , Xiao Shan , Wang Xiaoxuan , Li Jie 
Published: January 2023

AbstractImmunotherapy had demonstrated inspiring effects in tumor treatment, but only a minority of people could benefit owing to the hypoxic and immune-suppressed tumor microenvironment (TME). Therefore, there was an urgent need for a strategy that could relieve hypoxia and increase infiltration of tumor lymphocytes simultaneously. In this study, a novel acidity-responsive nanoscale ultrasound contrast agent (L-Arg@PTX nanodroplets) was constructed to co-deliver paclitaxel (PTX) and L-arginine (L-Arg) using the homogenization/emulsification method. The L-Arg@PTX nanodroplets with uniform size of about 300 nm and high drug loading efficiency displayed good ultrasound diagnostic imaging capability, improved tumor aggregation and achieved ultrasound-triggered drug release, which could prevent the premature leakage of drugs and thus improve biosafety. More critically, L-Arg@PTX nanodroplets in combination with ultrasound targeted microbubble destruction (UTMD) could increase cellular reactive oxygen species (ROS), which exerted an oxidizing effect that converted L-Arg into nitric oxide (NO), thus alleviating hypoxia, sensitizing chemotherapy and increasing the CD8 + cytotoxic T lymphocytes (CTLs) infiltration. Combined with the chemotherapeutic drug PTX-induced immunogenic cell death (ICD), this promising strategy could enhance immunotherapy synergistically and realize powerful tumor treatment effect. Taken together, L-Arg@PTX nanodroplets was a very hopeful vehicle that integrated drug delivery, diagnostic imaging, and chemoimmunotherapy.
Graphical Abstract
Synovial sarcoma with intra-abdominal metastasis causing hemoperitoneum: a case-report
Authors: Thompson Joshua J. , Koch Rachel A. , Keedy Vicki L. , Magge Deepa R. 
Published: January 2023

AbstractSynovial sarcoma is a rare soft tissue sarcoma which frequently involves the upper or lower extremities. Soft tissue sarcomas including synovial sarcoma have a propensity to metastasize to the lungs, and there are very few reports of metastatic lesions in other locations.Here, we report a case of a 49-year-old patient who underwent neoadjuvant chemoradiation for an upper extremity synovial sarcoma and presented approximately 4 years later with abdominal pain and hemoperitoneum and was ultimately found to have metastatic synovial sarcoma involving the greater curvature of the stomach and surrounding peri-gastric soft tissue. We describe the multidisciplinary management of this complex patient presentation and propose that expanded surveillance imaging beyond that of the local tumor resection bed and the chest may be beneficial especially in tumors with high-risk features.
Safety, efficacy and prognosis of anticoagulant therapy for portal vein thrombosis in cirrhosis: a retrospective cohort study
Authors: Zhang Zhiqi , Zhao Ying , Li Dandan , Guo Mingxing , Li Hongyu , Liu Ranjia , Cui Xiangli 
Published: January 2023

Abstract
Background
The role of anticoagulants in the treatment of cirrhotic PVT remains controversial. This study aimed to analyze the safety and efficacy of anticoagulant therapy in patients with cirrhotic portal vein thrombosis (PVT) and its impact on prognosis.

Methods
A retrospective cohort study was conducted for PVT patients with liver cirrhosis in our hospital. The primary outcome of the study was the PVT recanalization rate. Other outcomes included bleeding rate, liver function, and mortality. Cox and Logistic regression were used to explore the risk factors of outcomes.

Results
This study included 77 patients that 27 patients in the anticoagulant group and 50 in the non-anticoagulant group. Anticoagulant therapy was associated with higher rate of PVT recanalization (44.4% vs 20.0%, log-rank P = 0.016) and lower rate of PVT progression (7.4% vs 30.0%, log-rank P = 0.026), and without increasing the rate of total bleeding (14.8% vs 24%, P = 0.343), major bleeding (3.7% vs 6%, P = 0.665) and variceal bleeding (3.7% vs 16%, P = 0.109). The safety and efficacy of different anticoagulants were similar. The Child-Pugh grade of the anticoagulant therapy group was better than that of the non-anticoagulant therapy group (P = 0.030). There was no significant difference in the 2-year survival rate of the two groups.

Conclusion
Anticoagulants could increase the PVT recanalization rate and reduce the PVT progression rate without increasing the rate of bleeding. Anticoagulants may be beneficial to improving the liver function of patients with cirrhotic PVT. There was no significant difference in the safety and efficacy of different anticoagulants in the treatment of cirrhotic PVT.
Chronic anti-coagulation therapy reduced mortality in patients with high cardiovascular risk early in COVID-19 pandemic
Authors: Zaghloul Mohamed S. , Jammeh Momodou , Gibson Andrew , Luo Suhong , Chadwick-Mansker Kelley , Liu Qianjin , Yan Yan , Zayed Mohamed A. 
Published: January 2023

Abstract
Background
Coronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviating these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients hospitalized during the early phase of the pandemic in the United States.

Methods
A retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous outpatient therapeutic AC for a least 90 days prior to their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR).

Results
We identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events.

Conclusion
AC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. ﻿However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.
How surface acting affects turnover intention among family doctors in rural China: the mediating role of emotional exhaustion and the moderating role of occupational commitment
Authors: Wang Anqi , Tang Changhai , Zhou Lifang , Lv Haiyuan , Song Jia , Chen Zhongming , Yin Wenqiang 
Published: January 2023

Abstract
Background
Family doctors in rural China are the main force for primary health care, but the workforce has not been well stabilized in recent years. Surface acting is an emotional labor strategy with a disparity between inner feelings and emotional displays, provoking negative effects such as emotional exhaustion, occupational commitment reduction, and, consequently, increasing turnover rate. With the Conservation of Resources theory, this study explores how the surface acting of rural family doctors affects turnover intention through emotional exhaustion and investigates what role occupational commitment plays in this relationship.

Methods
With a valid response rate of 93.89%, 953 valid data were collected by an anonymous self-administered questionnaire survey in December 2021 in Shandong Province, China. Cronbach’s Alpha and confirmatory factor analysis (CFA) were used to estimate reliability and construct validity, respectively. The PROCESS macro in SPSS was performed to analyze the mediating and moderated mediation effects of surface acting, emotional exhaustion, occupational commitment, and turnover intention.

Results
Reliability and validity indicated that the measurement instruments were acceptable. Surface acting had a direct positive effect on turnover intention (β = 0.481, 95% CI [0.420, 0.543]). Emotional exhaustion partially mediated the effect of surface acting on turnover intention (indirect effect: 0.214, 95% CI [0.175, 0.256]). Occupational commitment moderated the effect of emotional exhaustion on turnover intention (β = − 0.065, 95% CI [− 0.111, − 0.019]), and moderated the indirect effect of surface acting on turnover intention via emotional exhaustion (index of moderated mediation: − 0.035).

Conclusions
Emotional exhaustion partially mediates the relationship between surface acting and turnover intention among family doctors in rural China, and occupational commitment moderates the direct effect of emotional exhaustion on turnover intention and further moderates the mediating effect. Policymakers should pay more attention to the effects of emotional labor and emotional resource depletion on the stability of rural health human resources.
Everolimus and temsirolimus are not the same second-line in metastatic renal cell carcinoma: a systematic review and meta-analysis
Authors: Goudarzi Zahra , Mostafavi Mehrdad , Salesi Mahmood , Jafari Mojtaba , Mirian Iman , Hashemi Meshkini Amir , Keshavarz Khosro , Ghasemi Younes 
Published: January 2023

Abstract
Objective
Renal cell carcinoma (RCC) is the most common type of kidney cancer. VEGF inhibitors and mTORs are the most common therapeutic options among the different classes of available treatments. In this study, the effectiveness of Everolimus was compared to Temsirolimus, and Everolimus plusLenvatinib in renal cell carcinoma patients by review of the international clinical evidence.

Materials and methods
A systematic review was conducted and all relevant published clinical studies on the efficacy and cost-effectiveness of Everolimus, Temsirolimus, and Lenvatinib plus Everolimus were searched comprehensively in electronic databases including Pubmed, Scopus, Medline, Cochrane Library, and ISI web of science. The Q score and I2 test checked the Heterogeneity and publication bias test, respectively. Egger’s test and Begg’s test were used to checking publication bias. The hazard ratio (HR) of included studies and subclass analysis were estimated by fixed and random effect models.

Results
Out of 1816 found studies, ultimately, were included considering inclusion and exclusion criteria. None of these studies evaluated all three treatment strategies together and each study was about one strategy. Only one study was found for Everolimus plus Lenvatinib, so it was excluded from meta-analysis. Overall, data from 526 patients on Temsirolimus and 648 patients on Everolimus were included in Meta-Analysis. Accordingly, the efficacy of Everolimus and Temsirolimus was not statistically significant in assessed outcomes (PFS, TTSF, and death). However, Everlimus is superior to Temsirolimus in OS (Q = 3.61, p-value: 0.462, I2 = 0%). No heterogeneity or bias was detected.

Conclusion
According to the results of this study, Everolimus could be related to an increase of OS versus Temsirolimus as a second line treatment of ORCC patients.
A prediction model for the impact of environmental and genetic factors on cardiovascular events: development in a salt substitutes population
Authors: Zhao Dan , Sun Hao , Li Huamin , Li Chaoxiu , Zhou Bo 
Published: January 2023

Abstract
Background
Cardiovascular disease (CVD) has evolved into a serious public health issue that demands the use of suitable methods to estimate the risk of the disease. As a result, in a sample of individuals who completed a 3-year low-sodium salt or conventional salt intervention in a hypertensive environment, we constructed a 13-year cardiovascular (CV) event risk prediction model with a 10-year follow-up.

Methods
A Cox proportional hazards model was used to build a prediction model based on data from 306 participants who matched the inclusion criteria. Both the discriminating power and the calibration of the prediction models were assessed. The discriminative power of the prediction model was measured using the area under the curve (AUC). Brier scores and calibration plots were used to assess the prediction model's calibration. The model was internally validated using the tenfold cross-validation method. The nomogram served as a tool for visualising the model.

Results
Among the 306 total individuals, there were 100 cases and 206 control. In the model, there were six predictors including age, smoking, LDL-C (low-density lipoprotein cholesterol), baseline SBP (systolic blood pressure), CVD (cardiovascular history), and CNV (genomic copy number variation) nsv483076. The fitted model has an AUC of 0.788, showing strong model discrimination, and a Brier score of 0.166, indicating that it was well-calibrated. According to the results of internal validation, the prediction model utilised in this study had a good level of repeatability. According to the model integrating the interaction of CNVs and baseline blood pressure, the effect of baseline SBP on CV events may be greater when nsv483076 was normal double copies than when nsv483076 was copy number variation.

Conclusions
The efficacy of risk prediction models for CV events that include environmental and genetic components is excellent, and they may be utilised as risk assessment tools for CV events in specific groups to offer a foundation for tailored intervention strategies.
Characterization of large extracellular vesicles (L-EV) derived from human regulatory macrophages (Mreg): novel mediators in wound healing and angiogenesis?
Authors: Albrecht Martin , Hummitzsch Lars , Rusch Rene , Heß Katharina , Steinfath Markus , Cremer Jochen , Lichte Frank , Fändrich Fred , Berndt Rouven , Zitta Karina 
Published: January 2023

Abstract
Background
Large extracellular vesicles (L-EV) with a diameter between 1 and 10 µm are released by various cell types. L-EV contain and transport active molecules which are crucially involved in cell to cell communication. We have shown that secretory products of human regulatory macrophages (Mreg) bear pro-angiogenic potential in-vitro and our recent findings show that Mreg cultures also contain numerous large vesicular structures similar to L-EV with so far unknown characteristics and function.

Aim of this study
To characterize the nature of Mreg-derived L-EV (L-EVMreg) and to gain insights into their role in wound healing and angiogenesis.

Methods
Mreg were differentiated using blood monocytes from healthy donors (N = 9) and L-EVMreg were isolated from culture supernatants by differential centrifugation. Characterization of L-EVMreg was performed by cell/vesicle analysis, brightfield/transmission electron microscopy (TEM), flow cytometry and proteome profiling arrays. The impact of L-EVMreg on wound healing and angiogenesis was evaluated by means of scratch and in-vitro tube formation assays.

Results
Mreg and L-EVMreg show an average diameter of 13.73 ± 1.33 µm (volume: 1.45 ± 0.44 pl) and 7.47 ± 0.75 µm (volume: 0.22 ± 0.06 pl) respectively. Flow cytometry analyses revealed similarities between Mreg and L-EVMreg regarding their surface marker composition. However, compared to Mreg fewer L-EVMreg were positive for CD31 (P < 0.01), CD206 (P < 0.05), CD103 (P < 0.01) and CD45 (P < 0.05). Proteome profiling suggested that L-EVMreg contain abundant amounts of pro-angiogenic proteins (i.e. interleukin-8, platelet factor 4 and serpin E1). From a functional point of view L-EVMreg positively influenced in-vitro wound healing (P < 0.05) and several pro-angiogenic parameters in tube formation assays (all segment associated parameters, P < 0.05; number of meshes, P < 0.05).

Conclusion
L-EVMreg with regenerative and pro-angiogenic potential can be reproducibly isolated from in-vitro cultured human regulatory macrophages. We propose that L-EVMreg could represent a putative therapeutic option for the treatment of chronic wounds and ischemia-associated diseases.
Inhibition of 2-arachidonoylglycerol degradation enhances glial immunity by single-cell transcriptomic analysis
Authors: Zhu Dexiao , Zhang Jian , Hashem Jack , Gao Fei , Chen Chu 
Published: January 2023

AbstractBackground2-Arachidonoylglycerol (2-AG) is the most abundant endogenous cannabinoid. Inhibition of 2-AG metabolism by inactivation of monoacylglycerol lipase (MAGL), the primary enzyme that degrades 2-AG in the brain, produces anti-inflammatory and neuroprotective effects in neurodegenerative diseases. However, the molecular mechanisms underlying these beneficial effects are largely unclear.MethodsHippocampal and cortical cells were isolated from cell type-specific MAGL knockout (KO) mice. Single-cell RNA sequencing was performed by 10 × Genomics platform. Cell Ranger, Seurat (v3.2) and CellChat (1.1.3) packages were used to carry out data analysis.ResultsUsing single-cell RNA sequencing analysis, we show here that cell type-specific MAGL KO mice display distinct gene expression profiles in the brain. Inactivation of MAGL results in robust changes in expression of immune- and inflammation-related genes in microglia and astrocytes. Remarkably, upregulated expression of chemokines in microglia is more pronounced in mice lacking MAGL in astrocytes. In addition, expression of genes that regulate other cellular functions and Wnt signaling in astrocytes is altered in MAGL KO mice.ConclusionsOur results provide transcriptomic evidence that cell type-specific inactivation of MAGL induces differential expression of immune-related genes and other fundamental cellular pathways in microglia and astrocytes. Upregulation of the immune/inflammatory genes suggests that tonic levels of immune/inflammatory vigilance are enhanced in microglia and astrocytes, particularly in microglia, by inhibition of 2-AG metabolism, which likely contribute to anti-inflammatory and neuroprotective effects produced by inactivation of MAGL in neurodegenerative diseases.
Patchouli alcohol attenuates the cognitive deficits in a transgenic mouse model of Alzheimer’s disease via modulating neuropathology and gut microbiota through suppressing C/EBPβ/AEP pathway
Authors: Xu Qing-Qing , Su Zi-Ren , Yang Wen , Zhong Mei , Xian Yan-Fang , Lin Zhi-Xiu 
Published: January 2023

Abstract
Background
Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive dysfunctions and behavioral impairments. Patchouli alcohol (PA), isolated from Pogostemonis Herba, exhibits multiple pharmacological properties, including neuroprotective effects. This study aimed to investigate the therapeutic effects of PA against AD using the TgCRND8 transgenic AD mouse model, and to explore the underlying mechanisms targeting CCAAT/enhancer-binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling pathway.

Methods
After genotyping to confirm the transgenicity, drug treatments were administered intragastrically once daily to 3-month-old TgCRND8 mice for 4 consecutive months. Several behavioral tests were applied to assess different aspects of neurological functions. Then the brain and colon tissues were harvested for in-depth mechanistic studies. To further verify whether PA exerts anti-AD effects via modulating C/EBPβ/AEP signaling pathway in TgCRND8 mice, adeno-associated virus (AAV) vectors encoding CEBP/β were bilaterally injected into the hippocampal CA1 region in TgCRND8 mice to overexpress C/EBPβ. Additionally, the fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of gut microbiota on the anti-AD effects of PA.

Results
Our results showed that PA treatment significantly improved activities of daily living (ADL), ameliorated the anxiety-related behavioral deficits and cognitive impairments in TgCRND8 mice. PA modulated the amyloid precursor protein (APP) processing. PA also markedly reduced the levels of beta-amyloid (Aβ) 40 and Aβ42, suppressed Aβ plaque burdens, inhibited tau protein hyperphosphorylation at several sites and relieved neuroinflammation in the brains of TgCRND8 mice. Moreover, PA restored gut dysbiosis and inhibited the activation of the C/EBPβ/AEP signaling pathway in the brain and colon tissues of TgCRND8 mice. Interestingly, PA strikingly alleviated the AD-like pathologies induced by the overexpression of C/EBPβ in TgCRND8 mice. Additionally, the FMT of fecal microbiota from the PA-treated TgCRND8 mice significantly alleviated the cognitive impairments and AD-like pathologies in the germ-free TgCRND8 mice.

Conclusion
All these findings amply demonstrated that PA could ameliorate the cognitive deficits in TgCRND8 mice via suppressing Aβ plaques deposition, hyperphosphorylation of tau protein, neuroinflammation and gut dysbiosis through inhibiting the activation of C/EBPβ/AEP pathway, suggesting that PA is a promising naturally occurring chemical worthy of further development into the pharmaceutical treatment of AD.