bluuebunny/crossref_metadata_2025_split huggingface dataset:
C5a and C5aR1 are key drivers of microvascular platelet aggregation in clinical entities spanning from aHUS to COVID-19
Authors: Aiello Sistiana , Gastoldi Sara , Galbusera Miriam , Ruggenenti Piero , Portalupi Valentina , Rota Stefano , Rubis Nadia , Liguori Lucia , Conti Sara , Tironi Matteo , Gamba Sara , Santarsiero Donata , Benigni Ariela , Remuzzi Giuseppe , Noris Marina 
Published: December 2021

Abstract
Unrestrained activation of the complement system till the terminal products, C5a and C5b-9, plays a pathogenetic role in acute and chronic inflammatory diseases. In endothelial cells, complement hyperactivation may translate into cell dysfunction, favoring thrombus formation. The aim of this study was to investigate the role of the C5a/C5aR1 axis as opposed to C5b-9 in inducing endothelial dysfunction and loss of antithrombogenic properties. In vitro and ex vivo assays with serum from patients with atypical hemolytic uremic syndrome (aHUS), a prototype rare disease of complement-mediated microvascular thrombosis due to genetically determined alternative pathway dysregulation, and cultured microvascular endothelial cells, demonstrated that the C5a/C5aR1 axis is a key player in endothelial thromboresistance loss. C5a added to normal human serum fully recapitulated the prothrombotic effects of aHUS serum. Mechanistic studies showed that C5a caused RalA-mediated exocytosis of von Willebrand factor (vWF) and P-selectin from Weibel-Palade bodies, which favored further vWF binding on the endothelium and platelet adhesion and aggregation. In patients with severe COVID-19 who suffered from acute activation of complement triggered by severe acute respiratory syndrome coronavirus 2 infection, we found the same C5a-dependent pathogenic mechanisms. These results highlight C5a/C5aR1 as a common prothrombogenic effector spanning from genetic rare diseases to viral infections, and it may have clinical implications. Selective C5a/C5aR1 blockade could have advantages over C5 inhibition because the former preserves the formation of C5b-9, which is critical for controlling bacterial infections that often develop as comorbidities in severely ill patients. The ACCESS trial registered at www.clinicaltrials.gov as #NCT02464891 accounts for the results related to aHUS patients treated with CCX168.
PIAS3 suppresses damage in an Alzheimer’s disease cell model by inducing the STAT3-associated STAT3/Nestin/Nrf2/HO-1 pathway
Authors: Li Chen , Wang Ruili , Zhang Youyou , Hu Chunting , Ma Qiaoya 
Published: November 2021

AbstractBackgroundAlzheimer’s disease (AD), the most common form of dementia, is caused by the degeneration of the central nervous system (CNS). A previous study reported that signal transducer and activator of transcription 3 (STAT3) is activated during AD development; nonetheless, the related mechanism remains unknown. Thus, this study used a cell model to explore whether and how the protein inhibitor of activated STAT3 (PIAS3) is involved in AD development.MethodsCerebrospinal fluid (CSF) specimens of 30 patients with AD and 10 normal participants were included in this study. SH-SY5Y cells were used to constructed AD model. Relevant indices were then detected and analyzed.ResultsThe results showed that compared with the control group, PIAS3 expression was substantially decreased in patients with AD and amyloid beta (Aβ)-treated SH-SY5Y cells. PIAS3 overexpression was able to reverse the detrimental effects of Aβ treatment on cell survival and growth. Further, it could also ameliorate apoptosis and oxidative stress in Aβ-treated SH-SY5Y cells. Additionally, PIAS3 was shown to reduce the activated form of STAT3 and increase the activity of the downstream Nestin/nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway.ConclusionsSTAT3 reactivation by colivelin treatment negated the influence of PIAS3 on the survival, growth, apoptosis, and oxidative stress of Aβ-treated SH-SY5Y cells.
LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway
Authors: Xing Ying , Liu Yang , Qi Zhong , Liu Zhengrong , Wang Xin , Zhang Hongyi 
Published: November 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is now the second leading cause of cancer death worldwide and lacks effectual therapy due to its high rate of tumor recurrence and metastasis. The aim of this study was to investigate the effects of L antigen family member 3 (LAGE3, a member of the LAGE gene family involved in positive transcription) on the progression of HCC.

Methods
The expression of LAGE3 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, EdU, and cell cycle analysis assay were employed to evaluate the proliferation of HCC cells. Annexin V-FITC/PI and TUNEL assay were used to assess the apoptosis rate of HCC cells. Wound healing and transwell assay were used to investigate the migration and invasion of HCC cells. A xenograft model of HCC was established with 2 × 106 Hep3B or SK-HEP1 cells to investigate the in vivo effects of LAGE3. Then, the protein levels of LAGE3, p-p38, p-38, c-Jun N-terminal kinase (JNK),p-JNK, extracellular signal-regulated kinase (ERK), and p-ERK were detected by western blot.

Results
We found that LAGE3 was upregulated in HCC tissues compared to adjacent tissues, and its high expression was correlated with poor overall survival by bioinformatics analysis. Next, we manually regulated the expression of LAGE3 in HCC cells. The knockdown of LAGE3 inhibited the proliferation of HCC cells by arresting the cell cycle in G1 phase. Also the downregulation of LAGE3 inhibited cell migration and invasion and induced apoptosis of HCC cells, while overexpression of LAGE3 promoted the malignant phenotypes of HCC. These results were further confirmed by the in vivo growth of HCC xenografts and the inhibition of apoptosis of HCC tumor cells. Furthermore, we found that LAGE3 exerted cancer-promoting effects by potentiating the JNK and ERK signaling pathway. An ERK inhibitor (10 μM SCH772984) or JNK inhibitor (25 μM SP600125) repressed the upregulated LAGE3-induced proliferation, migration, and invasion of HCC cells.

Conclusions
LAGE3 enhanced the malignant phenotypes of HCC by promoting the JNK and ERK signaling pathway.
Advances and Challenges of Fluorescent Nanomaterials for Synthesis and Biomedical Applications
Authors: Xiao Deli , Qi Haixiang , Teng Yan , Pierre Dramou , Kutoka Perpetua Takunda , Liu Dong 
Published: November 2021

AbstractWith the rapid development of nanotechnology, new types of fluorescent nanomaterials (FNMs) have been springing up in the past two decades. The nanometer scale endows FNMs with unique optical properties which play a critical role in their applications in bioimaging and fluorescence-dependent detections. However, since low selectivity as well as low photoluminescence efficiency of fluorescent nanomaterials hinders their applications in imaging and detection to some extent, scientists are still in search of synthesizing new FNMs with better properties. In this review, a variety of fluorescent nanoparticles are summarized including semiconductor quantum dots, carbon dots, carbon nanoparticles, carbon nanotubes, graphene-based nanomaterials, noble metal nanoparticles, silica nanoparticles, phosphors and organic frameworks. We highlight the recent advances of the latest developments in the synthesis of FNMs and their applications in the biomedical field in recent years. Furthermore, the main theories, methods, and limitations of the synthesis and applications of FNMs have been reviewed and discussed. In addition, challenges in synthesis and biomedical applications are systematically summarized as well. The future directions and perspectives of FNMs in clinical applications are also presented.
A tool (SPOLERC) to guide the evaluation of phosphorus leaching for agricultural soil by using the change point value in the Xingkai Lake Basin, China
Authors: Xie Zijian , Zhang Fan , Ye Chun , Wang Hao , Wei Weiwei , Li Chunhua , Shi Xiaogang 
Published: November 2021

Abstract
Background
The soil P leaching change point (CP) has been widely used to evaluate soil P leaching risk. However, an automation calculation method for soil P leaching CP value, and an effective risk grading method performed for classifying soil P leaching risk evaluation have not been developed.

Results
This study optimized the calculation process for soil P leaching CP value with two different fitting models. Subsequently, based on the Python programming language, a computation tool named Soil Phosphorus Leaching Risk Calculator (SPOLERC) was developed for soil P leaching risk assessment. SPOLERC not only embedded the calculation process of the soil P leaching CP value, but also introduced the single factor index (SFI) method to grade the soil P leaching risk level. The relationships between the soil Olsen-P and leachable P were fitted by using SPOLERC in paddy soils and arid agricultural soils in the Xingkai Lake Basin, and the results showed that there was a good linear fitting relationship between the soil Olsen-P and leachable P; and the CP values were 59.63 and 35.35 mg Olsen-P kg−1 for paddy soils and arid agricultural soils, respectively. Additionally, 32.7, 21.8, and 3.64% of arid agricultural soil samples were at low risk, medium risk, and high risk of P leaching, and 40.6% of paddy soil samples were at low risk.

Conclusions
SPOLERC can accurately fit the split-line model relationship between the soil Olsen-P and leachable P, and greatly improved the calculation efficiency for the soil P leaching CP value. Additionally, the obtained CP value can be used for soil P leaching risk assessment, which could help recognize key area of soil P leaching.
Differences in olfactory habituation between orthonasal and retronasal pathways
Authors: Xiao Wei , Sun Zhifu , Yan Xiaoguang , Gao Xing , Lv Qianwen , Wei Yongxiang 
Published: November 2021

AbstractThe odorant arrives at nasal olfactory epithelium ortho- and retronasally. This experiment aimed to study the potential different olfactory habituation in orthonasal and retronasal pathways. 68 subjects were stimulated by constant airflow with an odor (50% phenethyl alcohol, PEA or 5% n-butyl acetate, BA) presented ortho- or retronasally. Participants rated the perceived odor intensity (0–10 points) per minute until the odor sensation disappeared. We also investigated the cross-habituation: when the subjects achieved full habituation, continue to rate odor intensity in a different pathway after instantly switching the odor stimulation pathway. The olfactory habituation curve was drawn. The differences of ratings between the orthonasal and retronasal olfaction at different time points and between male and female subjects were analyzed. The two odor intensity ratings decreased as the time extended, share the same “fast followed by slow” type. The ratings of orthonasal olfaction decreased faster than that of retronasal. The intensity rating of PEA of male retronasal approach was lower than that of female at the 5th min (p = 0.018). When orthonasal full habituation achieved, there was significant difference between the intensity ratings and the initial ratings of the retronasal stimulation pathway (p < 0.0001), and vice versa. We found obvious habituation as well as cross-habituation in both orthonasal and retronasal olfaction. The habituation of orthonasal olfaction was faster than that of retronasal olfaction. These different habituations were related to the gender.
Synergistic action of curcumin and cisplatin on spinel ferrite/hierarchical MCM-41 nanocomposite against MCF-7, HeLa and HCT 116 cancer cell line
Authors: Jermy B. Rabindran , Almohazey D. , Alamoudi W. A. , Palanivel R. M. , AlSudairi Nora , Dafalla H. , Almofleh A. A. , Alfareed T. M. , Ravinayagam Vijaya 
Published: November 2021

AbstractBackgroundPlatinum-based drugs are widely used in cancer therapy, but are known for toxic side effects and resistance. Combinational drug delivery represents an effective chemotherapeutic strategy, but often leads to an increased toxicity. Aim of this study is to test the co-delivery of cisplatin with natural antioxidants on hierarchial porous large surface area hexagonal nanocarriers for synergistic action.ResultsA series of structured mesoporous materials were impregnated with magnetic spinel ferrite (30% CuFe2O4) and then coated with curcumin (25% wt/wt). Mesosilicalite and MCM-41 with high curcumin release abilities were functionalized with cisplatin (5% wt/wt) for synergistic effect of combinational drugs. The cytotoxic efficiency of our nanocomposites was tested on cell viability of MCF7 (human breast cancer), human cervical cancer (HeLa), colorectal cancer (HCT116), and HFF (human foreskin fibroblasts) cell lines using the MTT cell viability assay. At a concentration of 0.1 mg/ml, CuFe2O4/mesosilicalite/curcumin/cisplatin resulted in 89.53% reduction in viability in MCF7, 94.03% in HeLa, 64% in HCT116 and 87% in HFF; whereas, CuFe2O4/MCM-41/curcumin/cisplatin resulted in 76% reduction in viability in MCF7, 64.46% in HeLa, 64% in HCT116 and 24% in HFF. The EC50for CuFe2O4/mesosilicalite/curcumin/cisplatin was 81.23 µg/ml in MCF7, 47.55 µg/ml in HeLa, 48.96 µg/ml in HCT116 and 76.83 µg/ml in HFF. The EC50for CuFe2O4/MCM-41/curcumin/cisplatin was 72.51 µg/ml in MCF7, 58.6 µg/ml in HeLa, 62.58 µg/ml in HCT116 and 154.2 µg/ml in HFF. Furthermore, cells treated with both nanocomposites had a high number of cleaved Caspase 3-positive cells suggesting that the reduction in cell viability was triggered by activating the apoptotic signaling pathway.ConclusionOur results show that CuFe2O4/MCM-41/curcumin/cisplatin is a better candidate for combinational drug therapy due to its lowest EC50value and the wider difference in EC50(a fold change) between cancerous and non-cancerous cell line.
Predictive modeling of gene expression regulation
Authors: Regondi Chiara , Fratelli Maddalena , Damia Giovanna , Guffanti Federica , Ganzinelli Monica , Matteucci Matteo , Masseroli Marco 
Published: November 2021

Abstract
Background
In-depth analysis of regulation networks of genes aberrantly expressed in cancer is essential for better understanding tumors and identifying key genes that could be therapeutically targeted.

Results
We developed a quantitative analysis approach to investigate the main biological relationships among different regulatory elements and target genes; we applied it to Ovarian Serous Cystadenocarcinoma and 177 target genes belonging to three main pathways (DNA REPAIR, STEM CELLS and GLUCOSE METABOLISM) relevant for this tumor. Combining data from ENCODE and TCGA datasets, we built a predictive linear model for the regulation of each target gene, assessing the relationships between its expression, promoter methylation, expression of genes in the same or in the other pathways and of putative transcription factors. We proved the reliability and significance of our approach in a similar tumor type (basal-like Breast cancer) and using a different existing algorithm (ARACNe), and we obtained experimental confirmations on potentially interesting results.

Conclusions
The analysis of the proposed models allowed disclosing the relations between a gene and its related biological processes, the interconnections between the different gene sets, and the evaluation of the relevant regulatory elements at single gene level. This led to the identification of already known regulators and/or gene correlations and to unveil a set of still unknown and potentially interesting biological relationships for their pharmacological and clinical use.
Clinical characteristics and prognosis in patients with urosepsis from intensive care unit in Shanghai, China: a retrospective bi-centre study
Authors: Sheng Ying , Zheng Wen-long , Shi Qi-fang , Zhang Bing-yu , Yang Guang-yao 
Published: November 2021

Abstract
Background
The purpose of this study was to retrospectively analyze clinical characteristics and prognostic risk factors of urosepsis patients admitted to two intensive care units in Shanghai, China.

Methods
Clinical data from patients diagnosed with urosepsis were retrospectively retrieved and analyzed from ICU in two regional medical centers from January 2015 to December 2019.

Results
Two hundred two patients were included in the subsequent analysis eventually, with an average age of 72.02 ± 9.66 years, 79.21% of the patients were female and the mortality rate of 15.84%.The proportion of patients with chronic underlying diseases such as diabetes and hypertension was relatively high (56.44, 49.50%, respectively), and the incidence of shock was also high (41.58%) correspondingly. The most common pathogen isolated was Escherichia coli (79.20%), of which the extended-spectrumβ-lactamases (ESBLs)(+) accounted for 42.57%. In multivariate analysis, the strongest predictors for death were mechanical ventilation (OR 7.260, 95% CI 2.200–23.963; P = 0.001),chronic kidney disease (CKD) (OR 5.140, 95% CI 1.596–16.550; P = 0.006), APACHE II score (OR 1.321, 95% CI 1.184–1.473; P < 0.001) and lactate (OR 1.258, 95% CI 1.037–1.527; P = 0.020). Both APACHE II score and lactate had the ideal predictive value, with the area under the ROC curve (AUC) of 0.858 and 0.805 respectively.

Conclusion
The patients with urosepsis were characterized by a higher proportion of female, older age, more percentage of comorbidities in this region, and patients with ESBLs (+) Escherichia coli infection were more prone to shock. Mechanical ventilation, comorbidity with CKD, APACHE II score and lactate were independent risk factors for death in urosepsis patient, but lactate level and APACHE II score had better predictive value for prognosis.
Similarities, reliability and gaps in assessing the quality of conduct of systematic reviews using AMSTAR-2 and ROBIS: systematic survey of nutrition reviews
Authors: Swierz Mateusz J. , Storman Dawid , Zajac Joanna , Koperny Magdalena , Weglarz Paulina , Staskiewicz Wojciech , Gorecka Magdalena , Skuza Anna , Wach Adam , Kaluzinska Klaudia , Bochenek-Cibor Justyna , Johnston Bradley C. , Bala Malgorzata M. 
Published: November 2021

Abstract
Background
AMSTAR-2 (‘A Measurement Tool to Assess Systematic Reviews, version 2’) and ROBIS (‘Risk of Bias in Systematic Reviews’) are independent instruments used to assess the quality of conduct of systematic reviews/meta-analyses (SR/MAs). The degree of overlap in methodological constructs together with the reliability and any methodological gaps have not been systematically assessed and summarized in the field of nutrition.

Methods
We performed a systematic survey of MEDLINE, EMBASE, and the Cochrane Library for SR/MAs published between January 2010 and November 2018 that examined the effects of any nutritional intervention/exposure for cancer prevention. We followed a systematic review approach including two independent reviewers at each step of the process. For AMSTAR-2 (16 items) and ROBIS (21 items), we assessed the similarities, the inter-rater reliability (IRR) and any methodological limitations of the instruments. Our protocol for the survey was registered in PROSPERO (CRD42019121116).

Results
We found 4 similar domain constructs based on 11 comparisons from a total of 12 AMSTAR-2 and 14 ROBIS items. Ten comparisons were considered fully overlapping. Based on Gwet’s agreement coefficients, six comparisons provided almost perfect (> 0.8), three substantial (> 0.6), and one a moderate level of agreement (> 0.4). While there is considerable overlap in constructs, AMSTAR-2 uniquely addresses explaining the selection of study designs for inclusion, reporting on excluded studies with justification, sources of funding of primary studies, and reviewers’ conflict of interest. By contrast, ROBIS uniquely addresses appropriateness and restrictions within eligibility criteria, reducing risk of error in risk of bias (RoB) assessments, completeness of data extracted for analyses, the inclusion of all necessary studies for analyses, and adherence to predefined analysis plan.

Conclusions
Among the questions on AMSTAR-2 and ROBIS, 70.3% (26/37 items) address the same or similar methodological constructs. While the IRR of these constructs was moderate to perfect, there are unique methodological constructs that each instrument independently addresses. Notably, both instruments do not address the reporting of absolute estimates of effect or the overall certainty of the evidence, items that are crucial for users’ wishing to interpret the importance of SR/MA results.
Comparing current and emerging practice models for the extrapolation of survival data: a simulation study and case-study
Authors: Kearns Benjamin , Stevenson Matt D. , Triantafyllopoulos Kostas , Manca Andrea 
Published: November 2021

AbstractBackgroundEstimates of future survival can be a key evidence source when deciding if a medical treatment should be funded. Current practice is to use standard parametric models for generating extrapolations. Several emerging, more flexible, survival models are available which can provide improved within-sample fit. This study aimed to assess if these emerging practice models also provided improved extrapolations.MethodsBoth a simulation study and a case-study were used to assess the goodness of fit of five classes of survival model. These were: current practice models, Royston Parmar models (RPMs), Fractional polynomials (FPs), Generalised additive models (GAMs), and Dynamic survival models (DSMs). The simulation study used a mixture-Weibull model as the data-generating mechanism with varying lengths of follow-up and sample sizes. The case-study was long-term follow-up of a prostate cancer trial. For both studies, models were fit to an early data-cut of the data, and extrapolations compared to the known long-term follow-up.ResultsThe emerging practice models provided better within-sample fit than current practice models. For data-rich simulation scenarios (large sample sizes or long follow-up), the GAMs and DSMs provided improved extrapolations compared with current practice. Extrapolations from FPs were always very poor whilst those from RPMs were similar to current practice. With short follow-up all the models struggled to provide useful extrapolations. In the case-study all the models provided very similar estimates, but extrapolations were all poor as no model was able to capture a turning-point during the extrapolated period.ConclusionsGood within-sample fit does not guarantee good extrapolation performance. Both GAMs and DSMs may be considered as candidate extrapolation models in addition to current practice. Further research into when these flexible models are most useful, and the role of external evidence to improve extrapolations is required.