bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses
Authors: Chen Sisi , Yang Liu , Ou Xia , Li Jin-Yu , Zi Cheng-Ting , Wang Hao , Hu Jiang-Miao , Liu Ye 
Published: July 2022

Abstract
Background
Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines.

Results
In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites.

Conclusions
PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.
Immune-regulating strategy against rheumatoid arthritis by inducing tolerogenic dendritic cells with modified zinc peroxide nanoparticles
Authors: Qiao Han , Mei Jingtian , Yuan Kai , Zhang Kai , Zhou Feng , Tang Tingting , Zhao Jie 
Published: July 2022

AbstractIn hypoxic dendritic cells (DCs), a low level of Zn2+ can induce the activation of immunogenic DCs (igDCs), thereby triggering an active T-cell response to propel the immune progression of rheumatoid arthritis (RA). This finding indicates the crucial roles of zinc and oxygen homeostasis in DCs during the pathogenesis of RA. However, very few studies have focused on the modulation of zinc and oxygen homeostasis in DCs during RA treatment. Proposed herein is a DC-targeting immune-regulating strategy to induce igDCs into tolerogenic DCs (tDCs) and inhibit subsequent T-cell activation, referred to as ZnO2/Catalase@liposome-Mannose nanoparticles (ZnCM NPs). ZnCM NPs displayed targeted intracellular delivery of Zn2+ and O2 towards igDCs in a pH-responsive manner. After inactivating OTUB1 deubiquitination, the ZnCM NPs promoted CCL5 degradation via NF-κB signalling, thereby inducing the igDC-tDC transition to further inhibit CD4+ T-cell homeostasis. In collagen-induced arthritis (CIA) mice, this nanoimmunoplatform showed significant accumulation in the spleen, where immature DCs (imDCs) differentiated into igDCs. Splenic tDCs were induced to alleviate ankle swelling, improve walking posture and safely inhibit ankle/spleen inflammation. Our work pioneers the combination of DC-targeting nanoplatforms with RA treatments and highlights the significance of zinc and oxygen homeostasis for the immunoregulation of RA by inducing tDCs with modified ZnO2 NPs, which provides novel insight into ion homeostasis regulation for the treatment of immune diseases with a larger variety of distinct metal or nonmetal ions.
Graphical Abstract
Health-related quality of life and influencing factors in drug addicts based on the scale QLICD-DA: a cross-sectional study
Authors: Ma Zilin , Liu Yuxi , Wan Chonghua , Jiang Jianming , Li Xiaomei , Zhang Ying 
Published: July 2022

Abstract
Background
Drug abuse has many negative effects not only on individuals but also on society. Nowadays, researchers pay a lot of attention to quality of life of drug addicts. However, there are few scales available to measure quality of life of drug addicts. The scale QLICD-DA (quality of life instrument for chronic diseases-drug addition) developed by modular approach could be used to measure quality of life of drug addicts with good validity, reliability and sensitivity.

Objective
This study is aimed to understand the quality of life status and influencing factors in drug addicts by suitable sensitively scale, with the hypothesis of the quality of life in drug addicts being different from that of other peoples and possibly being influenced by many factors.

Methods
By cluster random sampling method, 192 drug addicts at Kunming compulsory drug rehabilitation center were recruited to take part in the investigation. All participants completed the general information questionnaire and the scale QLICD-DA. We used a t-test to compare the scores of the quality of life of the participants with the norm (QOL scores from 1953 patients of 10 chronic diseases). A stepwise regression method was applied to explore the influencing factors of the quality of life in drug addicts.

Results
192 participants ranged in age from 19 to 59 with an average age of 34.86. Most of them were male (70.3%), high school education level (67.7%) and of Han nationality (82.8%). The quality of life of drug addicts was lower than the norm in the physical domain, psychological domain, social domain, and general module, and the differences were statistically significant (p < 0.001). Sex and mode of drug abuse were the influencing factors in total score (p = 0.006) and specific module (p = 0.019). Past family atmosphere and the mode of drug abuse were the influencing factors in the general module (p = 0.027, p = 0.037).

Conclusion
The quality of life of drug addicts was worse than that of patients with other chronic diseases, and the influencing factors of the quality of life of drug abusers were sex, mode of drug abuse, and past family atmosphere.
Costing the outpatient rehabilitation services: time-driven activity-based costing approach
Authors: Mohammadpour Farzaneh , Basakha Mehdi , Kamal Seyed Hossein Mohaqeqi , Azari Nadia 
Published: July 2022

Abstract
Background
Considering the importance of healthcare services costing in resource allocation, the aim of this study is to calculate the cost of rehabilitation services in an outpatient rehabilitation clinic in Tehran, Iran.

Methods
The data for this study were categorised as financial data and information about the process of rehabilitation services. The first category was extracted from the financial documents and the second was obtained by observation of patient flow and interviews with the clinic staff in 2016. The cost of rehabilitation services has been estimated using the time-driven activity-based costing approach.

Results
The findings show that the cost of physical occupational therapy in the Asma rehabilitation center was $18.79 per unit of service. This amount for speech therapy services was $17.23 to $19.40, taking into account the difference in the quality of the service delivered. The cost of mental health occupational therapy service was between $19.46 and $23.57. Comparing the cost of these services with the government’s tariffs makes it clear that there is a huge gap.

Conclusion
The limited number of patients referred to the center makes the cost of one unit of rehabilitation services much higher than the official tariffs. This is true for almost all similar institutions and makes the profitability of small rehabilitation institutions extremely unstable. Therefore, proper marketing for rehabilitation services by promoting patient referral links with larger healthcare centers and reallocation of resources to the formation of integrated rehabilitation complexes can play a significant role in their profitability.
SENP1 regulates the transformation of lung resident mesenchymal stem cells and is associated with idiopathic pulmonary fibrosis progression
Authors: Sun Wei , Liu Xiaoshu , Yang Xiaoyu , Jing Xiaoyan , Duan Chunyan , Yang Ganghao , Wu Chi , Huang Hui , Luo Qun , Xia Shu , Zhang Qian , Yang Yang , Xu Zuojun 
Published: July 2022

Abstract
Background
Lung resident mesenchymal stem cells (LR-MSCs) play an important role in idiopathic pulmonary fibrosis (IPF) by transforming into myofibroblasts, thereby losing their repair ability. Evidence suggests that key proteins of multiple signaling pathways are involved in myofibroblast differentiation of LR-MSCs, such as β-Catenin and GLI family zinc finger 1 (GLI1). These proteins are regulated by SUMO (small ubiquitin-like modifier) modification, which is a post-translational modification that promotes protein degradation, while Sumo specific protein 1 (SENP1)-mediated deSUMOylation produces the opposite biological effects. Therefore, we speculated that SENP1 might be a potential target for treating pulmonary fibrosis by preventing the myofibroblast differentiation of LR-MSCs.

Methods
LR-MSCs were isolated from mice by using immunomagnetic beads. The extracted LR-MSCs were identified by flow cytometric analysis and multilineage differentiation assays. Lentivirus packaged shRNA silenced the expression of SENP1 in vitro and vivo. The silencing efficacy of SENP1 was verified by real-time quantitative PCR. The effect of down-regulated SENP1 on the myofibroblast differentiation of LR-MSCs was assessed by Immunofluorescence and Western blot. Immunoprecipitation was used to clarify that SENP1 was a key target for regulating the activity of multiple signaling pathways in the direction of LR-MSCs differentiation. LR-MSCs resident in the lung was analyzed with in vivo imaging system. HE and Masson staining was used to evaluate the therapeutic effect of LR-MSCs with SENP1 down-regulation on the lung of BLM mice.

Results
In this study, we found that the myofibroblast differentiation of LR-MSCs in IPF lung tissue was accompanied by enhanced SENP1-mediated deSUMOylation. The expression of SENP1 increased in LR-MSCs transition of bleomycin (BLM)-induced lung fibrosis. Interfering with expression of SENP1 inhibited the transformation of LR-MSCs into myofibroblasts in vitro and in vivo and restored their therapeutic effect in BLM lung fibrosis. In addition, activation of the WNT/β-Catenin and Hedgehog/GLI signaling pathways depends on SENP1-mediated deSUMOylation.

Conclusions
SENP1 might be a potential target to restore the repair function of LR-MSCs and treat pulmonary fibrosis.
Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2
Authors: Li Changzhi , Zhou Hongjuan , Guo Lingling , Xie Dehuan , He Huiping , Zhang Hong , Liu Yixiu , Peng Lixia , Zheng Lisheng , Lu Wenhua , Mei Yan , Liu Zhijie , Huang Jie , Wang Mingdian , Shu Ditian , Ding Liuyan , Lang Yanhong , Luo Feifei , Wang Jing , Huang Bijun , Huang Peng , Gao Song , Chen Jindong , Qian Chao-Nan 
Published: July 2022

Abstract
Background
The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19.

Methods
We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds.

Results
We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2.

Conclusion
This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.
SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer
Authors: Luo Cong , Liu Zhi , Gan Yu , Gao Xiaomei , Zu Xiongbing , Zhang Ye , Ye Wenrui , Cai Yi 
Published: July 2022

Abstract
Background
Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately.

Methods
We screened HRD-related genes based on the HRD scores and constructed an HRD cluster system to explore different clinicopathological, genomic, and immunogenomic patterns among the clusters. A risk signature, HRDscore, was established and evaluated by multivariate Cox regression analysis. We noticed that SLC26A4, a model gene, demonstrated unique potential to predict prognosis and HRD in PCa. Multi-omics analysis was conducted to explore its role in PCa, and the results were validated by qRT-PCR and immunohistochemistry.

Results
Three HRD clusters were identified with significant differences in patient prognosis, clinicopathological characteristics, biological pathways, immune infiltration characteristics, and regulation of immunomodulators. Further analyses revealed that the constructed HRDscore system was an independent prognostic factor of PCa patients with good stability. Finally, we identified a single gene, SLC26A4, which significantly correlated with prognosis in three independent cohorts. Importantly, SLC26A4 was confirmed to distinguish PCa (AUC for mRNA 0.845; AUC for immunohistochemistry score 0.769) and HRD (AUC for mRNA 0.911; AUC for immunohistochemistry score 0.689) at both RNA and protein levels in our cohort.

Conclusion
This study introduces HRDscore to quantify the HRD pattern of individual PCa patients. Meanwhile, SLC26A4 is a novel biomarker and can reasonably predict the prognosis and HRD in PCa.
Application of a virtual reality tracker-based system to measure seated postural stability in stroke patients
Authors: Liang Huey-Wen , Tai Tzu-Ling , Li Yue-Hua , Chen Ying-Chun 
Published: July 2022

AbstractBackgroundPostural stability while sitting is an important indicator of balance and an early predictor for future functional improvement in neurorehabilitation, but the evaluation is usually dependent on clinical balance function measures. Meanwhile, instrumental posturography has been used widely to obtain quantitative data and characterize balance abilities and underlying control mechanisms, but not as often for sitting balance. Moreover, traditional kinetic methods using a force platform to test sitting stability often require modification and are costly. We proposed a tracker-based posturography with a commercial virtual reality system, the VIVE Pro system (HTC, Inc. Taiwan), to record the trunk displacement (TD) path with a lumbar tracker for evaluation of sitting stability. The goals were to test the reliability and validity of the TD parameters among stroke patients.MethodsTwenty-one stroke individuals and 21 healthy adults had their postural sway measured with this system under four sitting conditions, i.e., sitting on a solid surface or a soft surface, with eyes open or closed. The test–retest reliability of the TD parameters was evaluated with intraclass correlation coefficients in 22 participants. We also tested the discriminative validity of these parameters to discriminate between stroke and healthy controls, and among four sitting conditions. Furthermore, the TD parameters were correlated with the three balance function tests: the Berg Balance Scale (BBS), the Postural Assessment Scale for Stroke Patients (PASS) and the Function in Sitting Test (FIST).ResultsThe results indicated that the TD parameters obtained by tracker-based posturography had mostly moderate to good reliability across the four conditions, with a few exceptions in the solid surface and eyes open tasks. The TD parameters could discriminate the postural stability between sitting on solid and soft surfaces. The stroke group had more seated postural sway than the control group, especially while sitting on a soft surface. In addition, velocity measures in the sagittal and frontal planes had moderate to high correlations with the PASS and BBS scores.ConclusionsThis tracker-based system is a cost-effective option for the clinical assessment of body stability for stroke patients in a seated position and shows acceptable reliability and validity.
Hypertension and incident cardiovascular events after next-generation BTKi therapy initiation
Authors: Chen Sunnia T. , Azali Leylah , Rosen Lindsay , Zhao Qiuhong , Wiczer Tracy , Palettas Marilly , Gambril John , Kola-Kehinde Onaopepo , Ruz Patrick , Kalathoor Sujay , Rogers Kerry , Kittai Adam , Grever Michael , Awan Farrukh , Byrd John C. , Woyach Jennifer , Bhat Seema A. , Addison Daniel 
Published: July 2022

Abstract
Background
Post-market analyses revealed unanticipated links between first-generation Bruton’s tyrosine kinase inhibitor (BTKi) therapy, ibrutinib, and profound early hypertension. Yet, whether this is seen with novel selective second (next)-generation BTKi therapy, acalabrutinib, is unknown.

Methods
Leveraging a large cohort of consecutive B cell cancer patients treated with acalabrutinib from 2014 to 2020, we assessed the incidence and ramifications of new or worsened hypertension [systolic blood pressure (SBP) ≥ 130 mmHg] after acalabrutinib initiation. Secondary endpoints were major cardiovascular events (MACE: arrhythmias, myocardial infarction, stroke, heart failure, cardiac death) and disease progression. Observed incident hypertension rates were compared to Framingham heart-predicted and ibrutinib-related rates. Multivariable regression and survival analysis were used to define factors associated with new/worsened hypertension and MACE, and the relationship between early SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of acalabrutinib-related hypertension was assessed.

Results
Overall, from 280 acalabrutinib-treated patients, 48.9% developed new/worsened hypertension over a median of 41 months. The cumulative incidence of new hypertension by 1 year was 53.9%, including 1.7% with high-grade (≥ 3) hypertension. Applying the JNC 8 cutoff BP of ≥ 140/90 mmHg, the observed new hypertension rate was 20.5% at 1 year, > eightfold higher than the Framingham-predicted rate of 2.4% (RR 8.5, P < 0.001), yet 34.1% lower than ibrutinib (12.9 observed-to-expected ratio, P < 0.001). In multivariable regression, prior arrhythmias and Black ancestry were associated with new hypertension (HR 1.63, HR 4.35, P < 0.05). The degree of SBP rise within 1 year of treatment initiation predicted MACE risk (42% HR increase for each + 5 mmHg SBP rise, P < 0.001). No single antihypertensive class prevented worsened acalabrutinib-related hypertension.

Conclusions
Collectively, these data suggest that hypertension may be a class effect of BTKi therapies and precedes major cardiotoxic events.
Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction
Authors: Mir Shakeel , Ormsbee Golden Briana D. , Griess Brandon J. , Vengoji Raghupathy , Tom Eric , Kosmacek Elizabeth A. , Oberley-Deegan Rebecca E. , Talmon Geoffrey A. , Band Vimla , Teoh-Fitzgerald Melissa LT. 
Published: July 2022

Abstract
Background
A pro-oxidant enzyme, NADPH oxidase 4 (Nox4) has been reported to be a critical downstream effector of TGFβ-induced myofibroblast transformation during fibrosis. While there are a small number of studies suggesting an oncogenic role of Nox4 derived from activated fibroblasts, direct evidence linking this pro-oxidant to the tumor-supporting CAF phenotype and the mechanisms involved are lacking, particularly in breast cancer.

Methods
We targeted Nox4 in breast patient-derived CAFs via siRNA-mediated knockdown or administration of a pharmaceutical inhibitor (GKT137831). We also determine primary tumor growth and metastasis of implanted tumor cells using a stable Nox4-/- syngeneic mouse model. Autophagic flux of CAFs was assessed using a tandem fluorescent-tagged ptfl-LC3 plasmid via confocal microscopy analysis and determination of the expression level of autophagy markers (beclin-1 and LC3B). Nox4 overexpressing CAFs depend on the Nrf2 (nuclear factor-erythroid factor 2-related factor 2) pathway for survival. We then determined the dependency of Nox4-overexpressing CAFs on the Nrf2-mediated adaptive stress response pathway for survival. Furthermore, we investigated the involvement of Birc5 on CAF phenotype (viability and collagen contraction activity) as well as the expression level of CAF markers, FAP and αSMA.

Conclusions
We found that deletion of stroma Nox4 and pharmaceutically targeting its activity with GKT137831 significantly inhibited orthotopic tumor growth and metastasis of implanted E0771 and 4T1 murine mammary carcinoma cell lines in mice. More importantly, we found a significant upregulation of Nox4 expression in CAFs isolated from human breast tumors versus normal mammary fibroblasts (RMFs). Our in situ RNA hybridization analysis for Nox4 transcription on a human breast tumor microarray further support a role of this pro-oxidant in the stroma of breast carcinomas. In addition, we found that Nox4 promotes autophagy in CAFs. Moreover, we found that Nox4 promoted survival of CAFs via activation of Nrf2, a master regulator of oxidative stress response. We have further shown Birc5 is involved as a downstream modulator of Nrf2-mediated pro-survival phenotype. Together these studies indicate a role of redox signaling via the Nox4-Nrf2 pathway in tumorigenesis and metastasis of breast cancer cells by promoting autophagy and survival of CAFs.