bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polo-like Kinase-1, Aurora Kinase A and Wee1 Kinase Are Novel Therapeutic Targets in Chronic Myeloid Leukemia
Authors: Mancini Manuela , De Santis Sara , Monaldi Cecilia , Castagnetti Fausto , Lonetti Annalisa , Bruno Samantha , Dan Elisa , Sinigaglia Barbara , Rosti Gianantonio , Cavo Michele , Gugliotta Gabriele , Soverini Simona 
Published: August 2021

Abstract
BackgroundIn chronic myeloid leukemia (CML), Aurora kinase A and Polo like kinase 1 (Plk1), two serine-threonine kinases involved in the maintenance of a functional G2/M checkpoint, may cooperate with the constitutive tyrosine-kinase (TK) activity of the BCR-ABL1 fusion protein increasing DNA damage, promoting the occurrence of additional genomic alterations ultimately driving resistance to TK inhibitors (TKIs) and progression from chronic phase to blast crisis (BC). MethodsIn this study, we propose a new therapeutic strategy based on the combination of Aurora kinase A or Plk1 inhibition with danusertib or volasertib, respectively, and WEE1 inhibition with AZD1775. Apoptotic cell death was quantified by annexin V/propidium iodide staining and flow cytometry. Cell cycle distribution was assessed by PI staining and flow cytometry. Protein expression and activation was assessed by Western Blotting (WB) and Immunofluorescence. Clonogenic assays were performed to evaluate cells sensitivity to the different drugs.ResultsDanusertib and volasertib used as single drugs induced apoptosis and G2/M-phase arrest, associated with accumulation of phospho-WEE1. Subsequent addition of the WEE1 inhibitor AZD1775 in combination significantly enhanced the induction of apoptotic cell death in TKI-sensitive and -resistant cell lines as compared to both danusertib and volasertib alone and to the simultaneous combination. This schedule indeed induced a significant increase of the DNA double-strand break marker γH2AX, forcing the cells through successive replication cycles ultimately resulting in apoptosis. Finally, combination of danusertib or volasertib+AZD1775 significantly reduced the clonogenic potential of CD34+ CML progenitors. ConclusionsOur results may have implications for the development of innovative therapeutic approaches based on Aurora kinase A or Plk1 inhibition associated with WEE1 blocking, aimed to improve the outcomes of patients with multi-TKI-resistant or BC CML.
Comprehensive Analysis of Lymph Nodes Metastasis Associated Genes in Cervical Cancer and its Significance in Treatment and Prognosis
Authors: Yang Ping , Ruan Youqing , Yan Zhiling , Gao Yang , Yang Hongying , Wang Shaojia 
Published: August 2021

Abstract
Background: Cervical carcinoma is one of the most common malignant tumors of the female reproductive system. Lymph nodes metastasis, the most common metastasis, which can be detected even in small-size tumor patients, results in worse prognosis. Therefore, it is of great significance to explore novel lymph nodes metastasis associated biomarkers, which can predict the prognosis and provide a good reference for clinical decision making in cervical carcinoma patients. However, systematic and comprehensive studies related to the key molecules in lymph node metastasis in cervical carcinoma patients are still absent. Methods: Transcriptome and clinical data of 307 cervical carcinoma patients were obtained from The Cancer Genome Atlas (TCGA). Then, survival of patients with and without lymph node metastasis was analyzed by Kaplan-Meier (K-M) curves. Differential expressed genes (DEGs) were detected between tumor and control samples using limma package and defined as lymph node metastasis related genes. Univariate and multivariate Cox regression analyses were carried out to screen robust prognostic gene signature. The risk score model and nomogram for predicting survival were constructed based on prognostic gene signature. The performance of the risk score model was evaluated by operating characteristic (ROC) curves. Based on risk score, patients were divided into low- and high- risk groups. DEGs, functional enrichment analysis and tumor microenvironment (immune infiltration and expressions of immune checkpoints) were detected in low- and high-risk groups. Results: A total of 103 lymph node metastasis-associated genes were identified. Univariate and multivariate Cox regression analyses identified TEKT2, LPIN2, FABP4 and CXCL2 as prognostic gene signature. The risk score model was constructed and validated in cervical carcinoma patients. 345 DEGs identified between high- and low-risk groups were significantly enriched into immune-related biological processes. Furthermore, we found that the immune infiltration and expressions of immune checkpoints were significantly different between low- and high-risk groups.Conclusion: Our study revealed that lymph node metastasis played an important role in the prognosis of cervical carcinoma patients. Furthermore, we established a risk score model based on lymph node metastasis related genes, which could accurately predict the survival of cervical carcinoma patients. Besides, our findings in tumor microenvironments of low- and high-risk groups improved our understanding of the relationship between lymph node metastasis related genes and cervical carcinoma.
Effects of Long-Term Hydrogen Intervention on Plasma Metabolites and Gut Microbiome of Rats in Health Status
Authors: Xie Fei , Jiang Xue , Yi Yang , Liu Zi-Jia , Ma Chen , He Jin , Xun Zhi-ming , Wang Meng , Liu Meng-yu , Adzavon Yao Mawulikplimi , Zhao Peng-xiang , Ma Xue-mei 
Published: August 2021

Abstract
The potential for preventive and therapeutic applications of H2 have now been confirmed in various disease. However, the effects of H2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.
Transplantation of Wnt4-modified Neural Stem Cells Mediate M2 Polarization to Promote Spinal Cord Injury Repair
Authors: Li Xiang , Long Lingli , Hu Yue , Zhang Wenwu , Zhong Fangling , Tuo Ying , Cheng Xing , Wan Yong 
Published: August 2021

Abstract
Background: Neural stem cells (NSCs) transplantation has been considered as a potential strategy to reconnect the neural circuit after spinal cord injury (SCI) but the therapeutic effect was still unsatisfied because of the poor inflammatory microenvironment. Wnt4 has been considered to be neurogenesis and anti-inflammatory so that it would be an essential assistant agent for NSCs transplantation. To explore interaction between Wnt4-modified NSCs and macrophages; and the effect of Wnt4-modified NSCs on the inflammatory microenvironment of SCI is relevant for targeted and effective treatments that promote injured spinal cord repair. Methods: In vitro NSCs-macrophages co-cultured system was established to unravel the interaction and involved mechanism between Wnt4-modified NSCs and macrophages. Wnt4-modified NSCs were transplanted into SCI model to confirm the effect of Wnt4-modified NSCs on modulation of inflammatory microenvironment of SCI and the therapeutic effect of Wnt4-modified NSCs on SCI. Results: Wnt4-modified NSCs induce M2 polarization and inhibit M1 polarization of macrophages through suppress TLR4/NF-κB signal pathway; furthermore, M2 cells promote neuronal differentiation of NSCs through MAPK/JNK signal pathway. In vivo, transplantation of Wnt4-modified NSCs improve inflammatory microenvironment through induce M2 polarization and inhibit M1 polarization of macrophages to promote axonal regeneration and tissue repair.Conclusions: Transplantation of Wnt4-modified NSCs effectively improve the inflammatory microenvironment through inducing M2 polarization and suppressing M1 polarization of macrophages after SCI. Considering these positive therapeutic effects, Wnt4 may have remarkable potential to be optimal assistant agent in NSCs transplantation for SCI.
The Use of the Direct Test on Substrate in the Assessment of Phytotoxicity of Foundry Waste
Authors: Bożym Marta 
Published: August 2021

Abstract
The article presents the results of phytotoxicity tests on foundry dust and landfilled waste. Currently, all of this waste is being reused. The results supplement the previous study on the phytotoxicity of waste leachate. The research has focused on phytotoxicity tests performed directly on the waste. Watercress (Lepidium sativum L.) was used as the test plant. The germination test (GI) and the accumulation test were used to assess phytotoxicity. The results show that the dust from electric furnaces, classified as hazardous waste, was the most phytotoxic. Most of the dust samples inhibited germination and root growth. A possible cause of this phytotoxicity was the high content of heavy metals and low pH. The phytotoxicity were different from previous studies on waste leachate. A lower phytotoxicity effect was found for those waste leachates. The differences could have been caused by the higher concentration of toxic substances available to plants in the direct test. Moreover, the direct contact of sprouts and roots of L. sativum could have contributed to the higher phytotoxicity of the wastes than the leachate. Therefore, it seems appropriate to use both tests simultaneously to assess the phytotoxicity of waste.
COL11A1 is the Key Target Gene of MIST1 on Tumor Progression of Pancreatic Cancer
Authors: Li Yang , Liu Zhiqiang , Sun Ying , Ren Dianyun , Li Yongfeng , Gou Shanmiao 
Published: August 2021

Abstract
Background: MIST1, a component of BHLH transcription factors, has been documented to be an important factor in tumor progression of pancreatic cancer, but the molecular mechanism is still unknown.Methods: COL11A1 was screened as a candidate key target gene of MIST1 in pancreatic cancer by ChIP -seq assay and verified by RT-PCR and Western Blotting on MIST1-overexpression pancreatic cancer cells. ChIP and dual-luciferase assays were performed to study the binding domain of MIST1 and COL11A1. Transwell invasion, wound healing, MTT, colony formation assays and animal experiments were performed to investigate the roles of COL11A1 expression on pancreatic cancer cells. Clinical data and TCGA datasets were used to evaluate the role of COL11A1 expression on prognosis for patients with pancreatic cancer.Results: MIST1 could bind to the promoter of COL11A1 as a negative transcription factor in pancreatic cancer. Overexpression of COL11A1 promotes pancreatic cancer cell growth, migration and invasion in vitro and in vivo. Expression of COL11A1 was upregulated in pancreatic cancer and positively correlated with a worse prognosis for patients with pancreatic cancer. Conclusions: These results demonstrated COL11A1 as a carcinogen in pancreatic cancer, and it acts as the key target gene of MIST1 on tumor progression of pancreatic cancer. COL11A1 can act as a potential therapeutic target of pancreatic cancer which is superior to MIST1.
The Influence of Competition Trait-Mediated Effects on Intra-Guild Predation System
Authors: Rong Zhang , Shuai Zhou , Wenjun Zhu , Xiaomei Zhou 
Published: August 2021

Abstract
Parasitism can affect the population dynamics in many ways, and its indirect effect is easy to be ignored, that is, it can weaken the host's behavior, physiology and psychology to affect the whole population. In this paper, we build a differential equation model by adding four parameters to study the influence of multiple competitive relationships on the predator-prey system, It includes the enhancement effect g of intraspecific competition and the enhancement effect h of interspecific competition between susceptible population and infected population, the weakening effect m of intraspecific competition and the weakening effect n of interspecific competition between susceptible population and infected population. Through the analysis, it can be concluded that a single g or m can promote the symbiosis of predator and prey, a single h has little effect on the population dynamics, and a single n is not conducive to the symbiosis; The fusion of g and h promotes coexistence, but the fusion of m and n is on the contrary; Interestingly, the combination of multiple regulatory parameters has a chemical effect on the survival of species, but the combination of g, m and h can inhibit coexistence, while the combination of g, m and n can promote coexistence. The reason is that the combination of parameters is not a simple addition of effects, but a prerequisite for mutual influence. To sum up, the research content provides a reference for considering the role of multiple factors, and provides theoretical guidance for explaining ecological phenomena and proving ecological conclusions.
Attitude and Behaviour For Preventing COVID-19 Disease Infections in Mali: An Analysis Based On COVID-19 Panel Phone Survey
Authors: GUETS Wilfried , Behera Deepak Kumar 
Published: August 2021

Abstract
Background

COVID-19 outbreak has been declared as an emerging and conflict situation by the World Health Organization (WHO) due to the multiple nature of infection through international spread that poses a serious threat to populations’ health and socio-economic conditions household in general.
Objective

This study aims to analyse the behaviour adopted by households’ heads for preventing COVID-19 infection in Mali.
Methods

We collected data from the COVID-19 Panel Households survey collected in Mali by the National Statistical Office, Institut National de la Statistique (INSTAT), in collaboration with the World Bank in October 2020. We used a multivariate logistic regression model.
Results

A total of 1,514 households heads were included. The age between 20 and 90 years old. The poor households represented 27%. Being a household with a low-income reduced the probability of using masks (p < 0.1). Being poor increased the probability to agree with vaccination (p < 0.01). The health services utilisation increased the probability of wear masks (p < 0.01), getting tested (p < 0.01), and agree with the vaccine (p < 0.01). People with a high occupation volume were more likely to wear protective masks (p < 0.1).
Conclusion

Behaviour and attitude prevention varied according to households characteristics. Local government and policymakers should continue to provide more economic, medical and social assistance to protect the population, which would reduce the spread of the disease, particularly to households living in vulnerable regions of the country most affected by conflict and food insecurity.
In Vivo Visualization of Collagen Transdermal Absorption by a Combined Second-harmonic Generation and Two-photon Excited Fluorescence Method
Authors: Sun yanan , Ma Shuhua , He Gaiying , Yang Weifeng , Wang Yi 
Published: August 2021

Abstract
The transdermal administration of collagen is an important method used for wound healing and skin regeneration. However, due to the limitations of previous approaches, the process and degree of collagen transdermal absorption could only be quantitatively and qualitatively assessed in vitro. In the present study, we introduced a novel approach combining second-harmonic generation with two-photon excited fluorescence to visualize the dynamics of collagen transdermal absorption in vivo. The high resolution images showed that the exogenous recombinant human collagen permeated through the epidermis, reached the dermis and formed reticular structures in real time. We also validated these findings through traditional in vitro skin scanning and histological examination. Thus, our approach provides a reliable method of measurement for the real-time evaluation of collagen absorption and treatment effects.
Experimental Studies on Frozen Soil
Authors: Gaur Kshitij , Sahu Anil Kumar 
Published: August 2021

Abstract
Various studies have been carried out for soils at normal room temperature but the studies on frozen soils are meagre. For every construction, soil investigation is the most important and the primary step for a site. For constructions at normal room temperature, there is plenty of experimentation and research data on soil is available. But lack of research data for colder regions, where the ambient temperature is below zero degrees Celsius for most of the time. It is therefore the need to study soil under the iced condition to get a better idea about the behaviour of frozen soils. There is little research on the construction and mechanical behaviour of frozen soil but no study on the very basic parameters like void ratio, bulk density, porosity, and the degree of freezing and how these parameters change as the soil temperature changes from normal room temperature to negative values. The main emphasis is on the study and experimentation of frozen soil and the formulation of different relationships between individual soil parameters at various temperatures. The methodology used is to model the soil surface (open grounds in colder regions) by taking sand as the soil after sieving. The model samples are taken into beakers with different bulk densities to replicate real site conditions in the freezer. Then by calculating factors like density, porosity, void ratio, etc at negative temperature (-5, -10, -15, -20 degree Celsius) and forming a relationship with the same parameters as that on room temperature. The experimental data obtained is used in “Eureqa software” that will utilize the input so provided and will find mathematical relations that exist in the soil parameters.
A Prospective, Single-Arm, Phase II Trial of Apatinib Combined With Nab-Paclitaxel and Carboplatin for The Neoadjuvant Treatment of Triple-Negative Breast Cancer
Authors: Zeng Tianyu , Wang Jue , Li Wei , Yang Yiqi , Yang Fan , Yang Mengzhu , Sun Chunxiao , Huang Xiang , Liang Yan , Fu Ziyi , Zha Xiaoming , Yin Yongmei , Li Jun 
Published: August 2021

Abstract
Background: Pathological complete response (pCR) is essential for improvements of prognosis in triple-negative breast cancer (TNBC). We evaluated the efficacy of apatinib combined with nab-paclitaxel and carboplatin in patients in this phase II clinical trial.Methods: Women with hormone receptor- and human epidermal growth factor receptor 2 (HER2)- negative, stage II/III breast cancer received six cycles of 75 mg/m2 docetaxel, carboplatin (AUC = 5) and 15 mg/kg bevacizumab every 21 days. The primary end point was pathological complete response (pCR) in the primary breast and axillary lymph nodes (ALN).Results: Thirty-two patients were recruited into the clinical trial, the vast majority of the patients had stage III tumors (65.6%) and the median longest tumor size was 3.5 cm. The pCR rate was 43.8% (n = 14); clinical response rate 93.8% (n = 30); complete response rate 21.9% (n = 7); partial response rate 71.9% (n = 23); stable disease 6.2% (n = 2). After surgery, 7 (63.6%) of the 11 patients without axillary lymph node metastasis achieved a pCR. The median target lesions in breast reduced to 1.2 cm after the third cycle treatment and 0.9cm after the last cycle. Most frequent grade 3/4 adverse events were thrombopenia (40.6%, n = 13) and neutropenia (25%, n = 8). Conclusions: Neoadjuvant apatinib, combined with albumin paclitaxel and carboplatin resulted in an encouraging pCR rate in locally advanced breast cancer and no major safety concerns during the therapy.Clinical trial registration: NCT03650738
An Initial Evaluation of Human Plasma cMLC-1 as a Potential Protein Biomarker for Trastuzumab-Induced Cardiotoxicity, Breast Cancer Screening and Progression
Authors: Yu Ling , Allen Read , Jia Lin , Sun Ting , Isakoff Steve J. , Scherrer-Crosbie Marielle , Zheng Hui , Walmsley Charlotte S. , Hesler Katherine , Varasteh Ava N. , Pinto Christopher J. , McLoughlin Daniel E. , Wu Wenjin , Wang Xinhui 
Published: August 2021

Abstract
Background

Trastuzumab is a targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, trastuzumab-induced cardiotoxicity (TIC) has been reported as a single agent or combined with anthracycline. Methods such as biomarkers for early TIC detection is not available. Blood-based protein biomarker prostate-specific antigen (PSA) for diagnosis, screening, prediction of response to therapy, and disease progression has revolutionized management and outcome of prostate cancer. Nevertheless, no blood biomarkers exist for breast cancer diagnosis or screening.
Methods

We evaluated for the first time the potentials of cardiac myosin light chain 1(cMLC-1) as a biomarker to predict TIC, screen breast cancer and monitor breast cancer progression. Plasma cMCL-1 was measured quantitatively using enzyme-linked immunosorbent assays (ELISA). Archived paired plasma samples collected before and after trastuzumab treatment from 15 HER2 + patients with or without cardiotoxicity, recently collected unpaired plasma samples from 79 breast cancer patients (40 HER2+, 39 HER2- ) and 46 healthy donors were tested for cMLC-1 levels.
Results

We found that elevated plasma level of cMLC-1 is associated with cardiotoxicity in 43% of trastuzumab-treated patients. In addition, we demonstrated that elevated plasma cMCL-1 is associated with breast cancer. The cutoff cMLC-1 concentration is estimated to be 44.99 ng/mL with a sensitivity of 59.49% (95%CI: 48.47%-69.63%) and specificity of 71.74% (95%CI: 57.45% -82.68%). We also found that plasma cMCL-1 is more elevated in HER2- than in HER2 + breast cancer patients. As a result, improved sensitivity of 79.49% (95%CI: 64.47%-89.22%) with the specificity of 63.04% (95%CI:48.60%-75.48%) were obtained for cMLC-1 to predict HER2- breast cancer with the cutoff at 37.17 ng/mL. Moreover, we determined that cMLC-1 level was significantly higher in patients with metastatic breast cancer than in patients with non-metastatic breast cancer.
Conclusions

Here we report the first exploratory human study on the potential of cMLC-1 as a blood protein biomarker for predicting TIC. Additionally, we show our findings which shed light on and filled, to some extent, the gap of knowledge of the potential of cMLC-1 as a blood protein biomarker for screening breast cancer, especially for HER2- breast cancer, and disease progression of breast cancer.
Inflammation and obstruction of the small intestine due to phytobezoar
Authors: Hoang Van Trung , Hoang The Huan , Pham Ngoc Trinh Thi , Chansomphou Vichit , Hoang Duc Thanh 
Published: August 2021

Abstract
Background: Bezoar bowel obstruction is a rare entity and remains difficult to detect on imaging studies. Recognition of its characteristic imaging pattern will be useful for diagnosis and management in the setting of intestinal obstruction.Case presentation: We report a 68-year-old female patient who was admitted to the hospital with signs of intestinal obstruction including abdominal pain, nausea, vomiting, and abdominal distention. She was diagnosed with phytobezoar small bowel obstruction on computed tomography (CT) imaging. The patient underwent surgery to confirm the diagnosis and subsequently recovered well.Conclusions: Bezoar is indicated by the sign of floating fat-density debris sign on CT images. It needs to be differentiated from small-bowel feces sign in intestinal obstruction.