bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Stem Cells and Competing Endogenous RNAs
Authors: Aria Hamid , Azizi Mahdieh , Nazem Shima , Bahmanyar Maryam , Moravej Ali , Pourjafarian Mohammad Hosein , Pezeshki Babak , Tavassoli Alireza , Vakil Mohammad Kazem , Mansoori Yaser
Published: July 2022

Cancer stem cells (CSCs) are one of the cell types that account for cancer heterogeneity. They arrest in the G0 phase and generate non-CSC progeny by self-renewing and pluripotency activity, resulting in tumor recurrence, metastasis, and chemoresistance. One CSC can stimulate tumor relapse and can re-grow a metastatic tumor. So, CSC is a promising target for eradicating tumors, and developing an anti-CSC method has become a top priority in cancer therapy. In recent years competing endogenous RNA (ceRNA) have emerged as an important class of post-transcriptional regulators that affect gene expression via competition for microRNA (miRNA) binding. Furthermore, aberrant ceRNA expression is associated with tumor progression. To overcome therapeutic resistance due to CSCs, we need to improve our existing understanding of the mechanisms by which ceRNAs are implicated in CSC-related relapse. Thus, this review was designed in order to discuss the role of ceRNAs in CSCs function. We reviewed the role of ceRNAs in acquiring CSCs characteristics in the form of different pathways including Rho GTPase/F-actin_ Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) (Hippo), Wnt/β-catenin pathway, transforming growth factor (TGF)-b–urothelial carcinoma-associated 1 (UCA1)–Slug pathway, etc. Finally, considering the comprehensive impacts of the ceRNA network on different pathways, a treatment strategy driving the ceRNA network might be effective. Targeting ceRNAs may open the path for new cancer therapeutic targets and can be used in clinical research.
Introducing Non-hierarchical RSM and MIGA for Performance Prediction and Optimization of A Centrifugal Pump under the Nominal Condition
Authors: Wang Wenjie , Sun Ju , Liu Jun , Zhao Jiantao , Pei Ji , Wang Jiabin
Published: July 2022

In order to improve the operation performance of the multi-stage double-suction centrifugal pump and reduce the internal energy loss of the pump, this paper proposes a single-objective optimization design method based on non-hierarchical response surface model (RSM) and the multi-island genetic algorithm (MIGA). Nine parameters, such as the blade outlet width and blade wrap angle, were used as design variables, and the optimization objective was the efficiency under design conditions. In total, 149 sets of valid data were obtained under the latin hypercube sampling method (LHS), the corresponding thresholds were set for efficiency and head, and 99 sets of valid data were obtained. A cross-validation analysis of the sieved data was carried out based on non-hierarchical RSM, global optimization of the efficiency was carried out using MIGA, and numerical verification was carried out via CFD. The research results show that compared with hierarchical RSM, non-hierarchical RSM can approximate the nonlinear relationship between the objective function and the design variables with higher accuracy, and the model fitting R2 value was 0.919. The efficiency was improved by 3.717% after optimization. The overall prewhirl of the impeller inlet after optimization decreased, the internal speed of the volute significantly improved, the large-area vortex at the volute and the outlet pipe was eliminated, the impact loss at the volute separating tongue disappeared, and the overall hydraulic performance of the pump was improved. The total entropy output value of the optimized pump was reduced by 4.79 (W/K), mainly concentrated in the reduction in the entropy output value of the double volute, and the overall energy dissipation of the pump was reduced.
What Determines Muslim-Friendly Tourism in Aceh?
Authors: Musa Armiadi , Halim Hendra , Khalidin Bismi , Ibrahim Azharsyah
Published: July 2022

Aceh is the only province in Indonesia legally allowed to implement sharia law across all sectors, including the tourism industry. This study aims to analyze factors influencing Muslim-Friendly Tourism (MFT) in Aceh. Specifically, it examines the direct and indirect relationship between MFT with travel intention, destination image, and tourist attitude. Data is gathered through a questionnaire survey among 150 respondents that were selected using the convenience sampling method. To explain the tourist’s travel intentions, this study develops and tests a multiple regression analysis using the extended hierarchical linear modeling. Seven hypotheses were proposed regarding the relationships between MFT, tourist attitude, destination image, and travel intention constructs. The empirical results from the structural model suggest that MFT, destination image, and tourist attitude significantly influence travel intention; destination image and tourist attitude are the perfect mediators in influencing the MFT on travel intention to Aceh. These results have the implication in improving the promotions of tourism destinations in Aceh and developing more effective halal tourism positioning strategies for Aceh in particular and Indonesia in general.
A POSSIBLESMILODON(MAMMALIA, FELIDAE) COPROLITE FROM THE PLEISTOCENE OF ARGENTINA
Authors: MORENO RODRÍGUEZ ANA P. , CHIMENTO NICOLÁS R. , AGNOLÍN FEDERICO L. , JOFRÉ GUILLERMO , GENTIL ADRIEL
Published: July 2022

Pleistocene large carnivores from the Pampean Region have been studied almost always based on bone remains. Here we report the first coprolite of a large carnivore from the Late Pleistocene of the Pampean Region, Argentina. The coprolite was found associated with megafauna bone remains and it shows the typical shape and size of a carnivorous mammal, with a length of 240 mm and a maximum diameter of 39.59 mm. The coprolite contains two bones of the autopodium of an artiodactyl, and numerous dermal ossicles of giant terrestrial sloths. The coprolite's composition, size, and shape allow us to discard ursids, canids, and small felids. Ursid and canid feces contain abundant plant remains, which are absent in the coprolite described here. Feces of extant felids are smaller than the coprolite here as they do not exceed 130 mm in length and 30 mm in diameter. Based on size, shape, and bone inclusions, the discovered coprolite may be attributed to the Machairodontinae saber-toothed felid Smilodon. If correctly identified, this coprolite sheds light on predatory habits of Smilodon.
Integrated Diagenesis Study of Tight Gas Sandstone: The Permian Lower Shihezi Formation, Northern Ordos Basin, China
Authors: Xu Qinghai , Xie Xiangyang , Zhang Changmin , Hai Lianfu , Busbey Arthur
Published: July 2022

Diagenesis varies greatly from basin to basin and has been considered as the key control of the reservoir quality of tight sandstones. In this study, we analyzed the petrographic characteristics, diagenesis, and pore types and characteristics of the Permian Lower Shihezi Formation in the Ordos Basin. Results show that most of sandstones are litharenites with minor sublitharenites and feldspathic litharenites. The tight sandstones have ultralow permeabilities (averaging 0.67 mD) and porosities (averaging 8.35%), with pore-throat sizes ranging from 0.035 to 13.29 μm with 94.12% less than 5 μm. Overall, the tight sandstone reservoirs have undergone complex diagenetic alteration. Compaction and clay mineral cements are the two crucial diagenetic factors that controlled the tightness of the reservoirs. The compaction destroyed most of primary porosity, and the effective pores are mainly dissolved micropores, intragranular dissolved micropores, and micropores in clay minerals and mineral grains. The chlorite coating might have helped preserve a certain amount of porosity, but pore-lining chlorites significantly obstructed pore throats and reduced permeability. Results of the study provide insights and direct implications for the future success of exploration and production of the tight gas sandstone in the Ordos Basin and other similar tight sandstone reservoirs.
Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation
Authors: Oliveira Fábio , Jamur Valderez Ravaglio , Merfort Lismeri Wuicik , Pozzo Aline Rangel , Mai Sabine
Published: July 2022

Background: Telomere dysfunction results in aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells. On the other hand, aurora kinase genes (AURKA and AURKB) play an important role regulating the cell cycle. A correlation between overexpression of aurora kinase genes and clinical aggressiveness has been demonstrated in different types of neoplasias. To better understand cellular and molecular mechanisms of CML evolution, it was examined telomere dysfunction (alterations in the 3D nuclear telomere architecture), and the expression levels of AURKA and AURKB genes in two clinical distinct subgroups of CML samples, from the same patient. Methods: Eighteen CML patients, in total, 36 bone marrow samples (18 patients, chronic vs. accelerated/blast phase) were eligible for 3D telomeric investigations. Quantitative 3D imaging, cytologic diagnosis and cytogenetic determination of additional chromosomal abnormalities were assessed according to standard protocols. Results: Using TeloView software, two CML subgroups were defined based on their 3D telomeric profiles, reflecting the different stages of the disease (chronic vs. accelerated/blast phase). Statistical analyses showed significant differences between the CML subgroups (p<0.001). We also found that AURKA and AURKB mRNA were expressed at significantly higher levels in both CML subgroups, when compared with healthy donors. Our findings suggest that the evolution of CML progresses from a low to a high level of telomere dysfunction, that is, from an early stage to a more aggressive stage, followed by disease transformation, as demonstrated by telomere, additional chromosomal abnormalities, and gene expression profile dynamics. Conclusions: Thus, we demonstrated that 3D telomere organization, in accordance with the genomic instability observed in CML samples were able to distinguish subgroup CML patients. Classifying CML patients based on these characteristics might represent an important strategy to define better therapeutic strategies.
Health Promotion and Empowerment in Collaboration: Theoretical Underpinnings and Methodological Challenges when Creating a Health Equity Program in a Vulnerable Area
Authors: Tengland Per-Anders , Rämgård Margareta
Published: July 2022

In Sweden, as in all other countries, there are inequalities in various areas, such as health and wealth. Research has established a social gradient in health, which means that socio-economic groups differ regarding health status. Furthermore, in many cities today there is segregation and some areas are more “socially vulnerable” than others. Some of these differences between groups and areas can be regarded as unjust and thus constitute inequities.The aim of this paper is to present the creation of a health-promotion innovation program whose purpose is to counteract health inequities in a “vulnerable” urban area in southern Sweden, and to discuss the theoretical and methodological foundations of the program. It does not, then, present any final health outcomes, but rather, gives a description of the, rather complex, initiation and launching of the program, which can in itself be seen as a kind of result.The research carried out in the program is Community-Based Participatory Research (CBPR), grounded in Participatory Action Research (PAR). The paper presents the CBPR program from its start to the present, including its rationale, and sets forth its theoretical underpinnings, i.e., ideas about place, empowerment, health promotion, “human nature,” communication and dialogue, and health equity. It closes by discussing some potential methodological and philosophical problems, namely, issues related to health equity, empowerment as a process, power relations, and community participation in the outcome evaluation.
Statistical Inference of the Mean and Variance of Fuzzy Random Variable: A Parametric Approach
Authors: DAS DHRUBA , Saikia Hemanta , Das Jondeep
Published: July 2022

A parametric method has been developed to estimate the fuzzy mean and variance of fuzzy random variable using Gumbel distribution. It is an extreme value type-I distribution which is a limiting model for the maximum and minimum values of a data set. In order to obtain the fuzzy mean and variance, first, using the method of alpha cut, crisp intervals from each of the fuzzy observation for the same α level are generated. Thereafter, from these crisp intervals for the same α level, the probability distributions of the extreme values and its parameters have been estimated. The interval containing these two parameters as extreme points will represent the estimated crisp interval parameter of the crisp intervals for a certain α level. After estimating all the interval parameters for different levels of alpha cuts, the fuzzy mean and variance of a fuzzy random variable are estimated.
Prognostic value of preoperative lymphocyte-to-C-reactive protein ratio and albumin to alkaline phosphatase ratio in patients with osteosarcoma
Authors: Ji Shu-Yu , Liang Wei-Feng , Huang Xian-Ying
Published: July 2022

Objective: Systemic inflammatory response and nutritional status are not only closely correlated to the occurrence and development of tumors, but also have become recognized indicators of cancer prediction. To explore the impact of lymphocyte-to-C-reactive protein ratio (LCR) and albumin to alkaline phosphatase ratio (AAPR) on the survival of the patients with osteosarcoma, this study was conducted. Methods: This study retrospectively analysed 81 osteosarcoma patients who received surgical treatment in the First Affiliated Hospital of Guangxi Medical University from 2014-2020. Clinical data and auxiliary examination results of enrolled patients were collected. LCR, AAPR, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) are calculated from the preoperative peripheral blood leukocytes, C-reactive protein (CRP), alkaline phosphatase (ALP) and albumin (ALB). The optimal cut-off values of LCR, AAPR, NLR and PLR were determined by receiver operating characteristic curve (ROC), and which were divided into high and low groups according to the truncation values. The Kaplan-Meier method was conducted to plot the survival curve, and the influence of various factors on the prognosis of osteosarcoma was analyzed by univariate and multivariate survival analyses. Results: The optimal cut-off values of LCR, AAPR, NLR and PLR were 0.09, 0.26, 1.23 and 157.03 respectively. The number of patients with preoperative metastasis in the low LCR (LLCR) group was more than that in the high LCR (HLCR) group, while the Enneking stage of the HLCR group was mostly in stage I+II. In the low AAPR (LAAPR) group, most of the patients with mean age ≥17 years, and the number of patients with metastases were more than those in the high AAPR group. In addition, the majority of patients in the LAAPR group underwent tumor resection. In the low PLR (LPLR) group, tumors mostly occurred in the extremities, and most of the patients in the LPLR group did not have tumor metastasis before the operation. Univariate analysis showed that OS was significantly related to Enneking stage, metastasis, preoperative LCR, AAPR, NLR, and PLR (P<0.05). According to the multivariate analysis, preoperative LCR (HR, 0.427; 95% CI, 0.228 to 0.801; P = 0.008), AAPR (HR, 0.464; 95% CI, 0.221 to 0.974; P = 0.042) and Enneking stage (HR, 3.058; 95% CI, 1.209 to 7.737; P = 0.018) was an independent prognostic factor affecting postoperative OS of osteosarcoma. Conclusion: This study provides new proofs that the preoperative LCR, AAPR and Enneking stage could act as vital prognostic parameters in patients with osteosarcoma.
Phenotypic and Genetic trends in Corriedale Sheep under temperate conditions
Authors: Hamadani Ambreen , Ganai N.A. , Nabi Nusrat , Shanaz Syed , Rather Mubashir Ali , Shah Ruksana
Published: July 2022

Sheep constitute an important genetic resource to the J&K, India. Considering its worth, the Corriedale breed was imported for improving the production potential of sheep in J&K, India which has since been maintained at SKUAST K. The current study was undertaken to study the phenotypic, heritability and genetic trends of the Corriedale breed over the years under temperate climatic conditions. Data for Corriedale breed from 1969 to 2016 was collected from Mountain Research Station for Sheep and Goat, SKUAST K for birthweight, weaning weight, 6-month weight, 9-month weight and 12-month weight. Mean phenotypic values, heritability estimates and breeding values using BLUP animal model were used for regression on the birth year to estimate trends over four decades. A decline from 3.81kg to 3.84 kg for birthweight, 16.7 kg to 12.184 kg for weaning weight, 21.03 kg to 15.256 kg for 6-month bodyweight, 24.085 kg to 18.212 kg for 9-month body weight and 28.337 kg to 21.122 kg for 12-month body weight was seen from 1969 to 2017 in Corriedale Sheep. A change in EBV’s for birthweight, weaning weight, 6-month body weight, 9-month body weight and 12-month body weight from 0.00206 ± 0.0067, -0.00114 ± 0.0093, -0.00203 ± 0.0138, 0.00665 ± 0.0130, -0.00061 ± 0.0078 respectively to 0.00103 ± 0.0070, -0.02384 ±0.0159, -0.00918 ± 0.0177, -0.00783 ± 0.0238, -0.01332 ± 0.0171 respectively was seen. Average heritability values for birth weight, weaning weight, 6-month body weight, 9-month body weight and 12-month bodyweight showed a change from 0.1896, 0.1552, 0.2227, 0.2086 and 0.1508 respectively to 0.2754, 0.2768, 0.1961, 0.1892 and 0.1749 respectively. Trends for all the traits were found to be significant except birthweight. Significant heritability trends were found for weaning weight and genetic trends for 6-month body weight. Our study indicates that selection may not have taken place except for 6-month body weight at the farm for the traits under study which is a matter of concern. A robust breeding program for selection of sheep on the basis of economically important traits may be the need of the hour.
Enhancing the economic potential of organic waste by co-composting using optimized mixing ratios toward a circular economy
Authors: Ofei-Quartey Muriel Naa Lamiokor , Appiah-Effah Eugene , Akodwaa-Boadi Kofi , Ampaw Barnabas , Taylor Theodora Sophia , Millogo Zouma Emeline Nadège
Published: July 2022

This study successfully applied co-composting to municipal organic waste, faecal sludge and chicken manure feedstocks using optimized mixing ratios to yield high-end organic fertilizers. Nine (9) compost piles with different mixing ratios were prepared. Composting was monitored against physicochemical and nutritive parameters for 13 weeks. At curing, pH values and organic matter for piles were 5.5 to 9.0 and 15–45%, respectively. C/N ratio, nitrogen, phosphorus, and potassium levels of piles were satisfactory. Heavy metals Ni, Zn, Cu and Pb, met the EU standards except for Cd whose concentration was 12.9 to 73.2 mg/kg. Self-heating test results were comparable to the ambient temperature, and respiration tests showed values < 2 mg CO2•C/g organic carbon/day, indicating the cured compost is very stable. Although pathogens were present in the compost piles, the piles passed the phytotoxicity test with a minimum of 80.09%. Germination Index values were greater than 80% making the compost mature and phytotoxin-free. The variations between the cured compost piles were statistically significant, with a p-value < 0.05.
The Prevalence of HPV Genotypes Detected by Cobas HPV in Cervical Samples among Unvaccinated Women from Isfahan Province, Iran
Authors: Zafarbakhsh Azam , Behnamfar Fariba , Shariati Matin , Vaezi Atefeh , Seresht Leila Mousavi
Published: July 2022

Purpose: Human papillomavirus is suggested as a well-known risk factor for cervical cancers and nowadays, primary HPV typing is recommended as an alternative test to cervical cytology. Methods: This cross-sectional study evaluated the liquid-based cervical smears of 700 women with no history of HPV vaccination and cervical dysplastic disease from 2017 to 2020 in Isfahan, Iran. Here, we try to compare the prevalence of HPV genotypes using COBAS (@roch) with the results of pap smear cytology in evaluating the most appropriate test for cervical cancer screening, especially in low-resource societies. Results: The prevalence of HPV infection was 23.3%, including 8.7% with HPV 16/18 and 14.6% with other HR (high-risk) HPVs. Considering positive HPV genotypes, the frequency of HR HPV decreases in older age groups; 42.1% compared to 6.8%. In cytology reports, 8 out of 16 individuals with high-risk lesions were negative for any type of HPV; on the other hand, there were 129 HR HPV-positive patients out of 570 negative or low-risk pap smear results.Conclusion: It assumed that there is no superiority for HPV genotyping over cytology or vice versa in detecting high-risk patients for cervical cancer; As only 26.8% of women with HPV show abnormal cytology; and from those with normal cytology, 17.9% were positive for HR HPV. Screening with one method had a rare but high risk of delay in the timely detection of cervical cancer. Above that, the high prevalence of HPV infection in unvaccinated women also reveals the need for studies on the cost-effectiveness of universal vaccination.
Fate and Spatial Distribution of Co, Cr and Ni in the Water Column and in the Surface Sediment of Indonesian Estuary (Citarum River Estuary)
Authors: Fahimah Nurul , Oginawati Katharina , Salami Indah Rachmatiah Siti , Susetyo Septian Hadi , Mubiarto Haryo , Kurnia Asep , Ardiwinata Asep Nugraha , Sukarjo Sukarjo
Published: July 2022

The Citarum River estuary is directly connected to the Java Sea and is characterized by high salinity and turbidity. Estuaries are heavy metal receptors from anthropogenic sources. There is the potential for heavy metals in the sediment to be released back into the water column which can cause secondary contamination in the water column, this is influenced by hydrodynamic conditions and environmental factors. Water samples at 3 depth layers (surface, middle and bottom layer or) and samples from the sediment surface were collected to study this. Heavy metals contained in water and sediment samples were analyzed by Flame AAS variant 240FS. The results of investigation showed that Co and Ni in the water column still comply the river water quality standards, Cr are included in the slightly polluted category. In the sediment, Co is categorized as moderately polluted and Cr and Ni are categorized as unpolluted to lightly polluted. Heavy metal pollution in sediments comes from heavy metals in the water column which undergo adsorption and deposition processes or vice versa. Co, Cr and Ni in the waters of the Citarum River estuary tend to be particulates that are deposited to the bottom of the estuary waters and accumulate in sediments, while only a small part of heavy metals is dissolved in the water column. The distribution of heavy metals in the water column to the sediment and vice versa tends to occur in one layer (monolayer) and describes the process chemisorption. Ni, Co and Cr have a slightly mobile level and have hydrophobic or lipophilic properties There were significant differences between the concentrations of heavy metals, especially Co and Ni (p < 0.05) in several depth layers. Co and Ni in water and sediment were significantly positively correlated (p < 0.01) which indicated that the two metals had the same fate or behavior and came from the same source.
A Novel Defined Pyroptosis-Related Gene Signature for Predicting Prognosis of Acute Myeloid Leukemia
Authors: Wang Fan
Published: July 2022

Background
Pyroptosis is an inflammatory form of programmed necrotic cell death, but its potential prognostic value in acute myeloid leukemia (AML) still remains unclear. In this study, we aimed to construct a pyroptosis genes related signature that can effectively predict the prognosis of AML patients.
Methods
Based on the available AML data from TCGA and TARGET dabases, a pyroptosis-related prognostic model was constructed by performing a LASSO Cox regression analysis, and the predictive value of the model was validated in a GEO cohort. The impact of pyroptosis on the immune microenvironment of AML was explored as well.
Results
A 10-gene signature model was constructed to effectively predict AML prognosis, which showed that patients with low-risk score had a significantly better prognosis than the high-risk group, and receiver operator characteristic (ROC) analysis proved superior performance of the prognostic model. The model was further verified well in an external GEO cohort. Multivariable Cox regression analysis showed that in addition to age, the risk score was also an independent poor survival factor for AML patients. Moreover, the high-risk group generally had higher activity of cytolytic activity and increased levels of infiltrating immune cells including tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs).
Conclusion
A pyroptosis-related gene signature can independently predict the prognosis of AML patients with sufficient predictive power, and pyroptosis plays an important role in the immune microenvironment of AML, which may be used to develop a new effective immunotherapeutic method for AML in the future.
In silico simulations and functional cell studies evidence similar potency and distinct binding of Pacific and Caribbean ciguatoxins
Authors: Raposo-Garcia Sandra , Castro David , Lence Emilio , Estevez Pablo , Leão José Manuel , Gonzalez-Bello Concepción , Gago-Martínez Ana , Louzao M.Carmen , Vale Carmen , Botana Luis M
Published: July 2022

Ciguatoxins (CTX) cause ciguatera fish poisoning, which is the most common reported hu-man food poisoning related to natural marine toxins. Pacific ciguatoxins are the most abundant and studied CTX analogues, however, the growing distribution of Caribbean analogues and the limited data available on their biological effects makes necessary to re-evaluate their relative potency. For decades, the guidelines established by regulatory agencies have assumed that the potency of the Caribbean CTXs were 10-fold lower than the Pacific CTXs. We present here an integrated study involving Neuro-2a MTT and electrophysiological assays and in silico simulations that evidence the similar cytotoxicity of both toxins and the asymmetry binding of CTXs with sodium channels. The simulation studies explain their distinct impact on the activation potential of the channel as experimentally observed and provided a detailed picture of the effects caused by these toxins on an atomic scale.
Direct antagonistic effect of entomopathogenic nematodes and their symbiotic bacteria on root knot nematodes migration toward tomato roots
Authors: Li Jingjing , Li Yang , Wei Xianqin , Cui Yonghe , Gu Xinhu , Li Xingyue , Yoshiga Toyoshi , Abd-Elgawad Mahfouz M. , Shapiro-Ilan David , Ruan Weibin , Rasmann Sergio
Published: July 2022

Aims Negative interactions in the rhizosphere between entomopathogenic nematodes (EPNs) and plant-parasitic nematodes, such as root-knot nematodes (RKNs), have been documented over the past two decades but the mechanisms and dynamics of such interactions remain largely elusive. Methods Here, we evaluated the effect of inoculation position of two EPN species, Steinernema feltiae and Heterorhabditis bacteriophora, as well as different facets of the EPN-bacterial symbiont complex on the migration of RKNs toward tomato roots, both in sand and in Pluronic gel conditions. Results When EPNs were placed between the position of the RKNs and the roots, the movement of RKNs toward the roots was inhibited. We observed this same pattern both in sand and in Pluronic F-127 (PF-127) gel and for two species of EPNs. We also observed that different components of the EPNs/bacterial symbiont complex (bacteria separate from the nematodes vs. the nematode-bacterium complex), and particularly the cell-free supernatant produced by the bacterial culture, displayed inhibitory effects on RKNs.Conclusions Therefore, the EPNs/bacterial complex, by slowing down the movement of RKNs toward the host plant roots, can function as an effective biocontrol strategy. By screening for the most repulsive strains of EPNs that are also effective against insect pests, such combined target suppression should alleviate EPNs application costs in integrated pest management practices.
The Screening of Major Hepatotoxic Components of Tripterygium wilfordii Hook. F. Based on Hepatotoxic Injury Patterns
Authors: Li Meng , Luo Qiong , Chen Xi , Qiu Furong , Tao Yanyan , Sun Xin , Liu Chenghai
Published: July 2022

Background: Tripterygium wilfordii Hook. F. (TwHF), a traditional Chinese medicine, is widely used in treatment of rheumatoid arthritis (RA), etc.. Due to multiorgan toxicity, particularly hepatotoxicity, the application of TwHF is restricted. In order to clarify the hepatotoxic substances, zebrafishes, hepatocytes and macrophages were used for screening based on hepatotoxic injury patterns. It provided a basis for further hepatotoxic mechanism of TwHF. Methods: First, 12 compounds were selected according to the chemical categories of TwHF. The fluorescence area and fluorescence intensity of zebrafishes liver were observed and calculated. The viability of two hepatocyte lines were detected by CCK8. TNF-α and IL-1β mRNA expression of BMDM was used to evaluate macrophage activation, a factor of potential indirect hepatotoxicity. Finally, hepatotoxic characteristics of 4 representative components were verified by mice in vivo. Results: Parthenolide, Triptolide, Triptonide, Triptobenzene H, Celastrol, Demethylzeylasteral, Wilforlide A, Triptotriterpenic acid A and Regelidine can significantly reduce the fluorescence area and fluorescence intensity of zebrafish liver. The viability of L-02 or AML-12 was significantly inhibited by Parthenolide, Triptolide, Triptonide, Celatrol, Demethylzeylasteral, Triptotriterpenic acid A. Parthenolide, Triptolide, Triptonide, Celatrol, Demethylzeylasteral and Triptobenzene H significantly increased TNF-α and IL-1β mRNA levels of BMDM, while Triptophenolide, Hypodiolide and Wilforine significantly reduced. Triptotriterpenic acid A, Celastrol and Triptobenzene H at dose of 10 mg/kg significantly increased the levels of mice serum ALT and AST, and aggravated liver inflammation. Conclusions: Parthenolide, Triptolide, Triptonide, Celatrol, Demethylzeylasteral, Triptotriterpenic acid A and Triptobenzene H might be main hepatotoxic components of TwFH. Among them, Triptotriterpenic acid A only presented a direct hepatotoxicity. Triptobenzene H showed indirect liver damage by activating macrophages. Parthenolide, Triptolide, Triptonide, Celatrol, Demethylzeylasteral could directly and indirectly cause liver injury.
Which type of fear of cancer progression contributes to the quality of life of Romanian cancer patients during the COVID-19 pandemic?
Authors: Kállay Éva , Medrea Flavia , Müller-Fábián Andrea , Dégi Csaba László
Published: July 2022

Purpose: Fear of cancer progression (FoP) is one of the most frequently reported unmet needs invoked by the majority of cancer patients, which may significantly impair the quality of life (QoL) of patients. The major objective of the present study was to investigate the specificities of the relationship between different dimensions and intensity of FoP and different aspects of patients’ QoL during the COVID-19 pandemic in Romania. Methods: A nationwide sample of 330 participants completed a survey, including measures of demographic characteristics, medical variables, QoL, and FoP. Multivariate General Linear and Hierarchical Regression Models were conducted in order to assess the relationship between variables. Results: Our results indicate that less than a quarter of the sample experienced low, between 63%-70% moderate, and 15% high levels of FoP. Our results also indicate that anxiety/worry related to the possibility of progression of the disease, and loss of independence produced significant differences with large effect sizes in all the dimensions of QoL. Conclusions: Our results indicate that besides affective reactions, the fear of cancer survivors to lose independence, not being able to attend to their own lives, seems to be a considerable threat, especially in the context of Romanian health system which has difficulties in offering qualitative psychosocial care for cancer patients. The idea that patients will have to rely on others and may not function well independently, not being able to attend to their own lives, seems to be a considerable threat, next to the experienced affective reactions per se.
MoIsw2; the missing link between adaptation and mutation instrumental for natural adaptation-directed fast evolution (NADFE) of Magnaporthe oryzae
Authors: Pei Mengtian , Abubakar Yakubu , Ali Hina , Dou Xianying , Lu Guo-dong , Wang Zonghua , Li Ya , Olsson Stefan
Published: July 2022

Isw2 binds DNA using a Myb-type DNA binding domain, interacts with histones (especially His4) in the closest nucleosome, and regulates gene access by the nucleosome limited-sliding mechanism resulting in lower access to DNA close to the binding site and better access in the immediate surroundings. We had previously made a GFP complementation of the potential MoIsw2 and first confirmed that MoISW2 is co-regulated with MoHIS4. ChIP-seq found DNA binding sites, and a common palindromic motif was identified in about 200 sequences that, in addition, were in retrotransposon sequences where most avirulence genes are. These were downregulated in the background strain compared to DMoisw2, while further away from the binding site, the absolute difference in regulation was higher and varied in a wave-like pattern as expected for the limited sliding-type mechanism. The avirulence genes downregulation in two M. oryzae isolates were compared and confirmed. Finally, we found that most genes differentially upregulated in the DMoisw2 mutant regulate biomass growth. In contrast, the ones downregulated have to do with mainly niche adaptations and niche fitness. MoIsw2 retrotransposon binding and actions lay a possible mechanistic ground for a natural adaptation-directed fast evolution (NADFE) of M. oryzae, a new concept for Eukaryotes.
Atrophy and hypometabolism patterns in Niemann-Pick type C: A cross-sectional and longitudinal study
Authors: Silva-Rodríguez Jesús , Castro Cristina , Cortés Julia , Arias Manuel , Pubul Virginia , Moscoso Alexis , Rouco Idoia , Gascón Jordi , Sobrido María Jesús , Aguiar Pablo
Published: July 2022

Purpose
We present a cross-sectional study comparing hypometabolism and atrophy patterns in Niemann–Pick disease type C (NP-C). We also present a longitudinal analysis of NP-C [18F]FDG-PET data.
Methods
22 patients NP-C patients underwent MRI and [18F]FDG-PET imaging at baseline, and a subset of 12 patients were able to complete at least one follow-up PET imaging acquisition. Visual assessment and group-level voxel- and region-based analyses of the baseline MRI and PET images were performed by comparing our NP-C cohort to PET and MRI healthy volunteer cohorts. Per cent changes in metabolism (%/year/region) were calculated for longitudinal analysis.
Results
Significant atrophy was present in the cerebellum (p < 0.0001), thalamus (p < 0.001), and frontal and hippocampal regions (p < 0.01). The most common hypometabolism pattern included severe cerebellum, thalamus and cingulate hypometabolism (p < 0.0001), together with mild involvement of cortical areas. [18F]FDG PET provided stronger effect sizes and was able to show significant hypometabolism even in areas without atrophy. [18F]FDG uptake annual changes (p < 0.01) were found mainly in the cerebellum (-11%/year) and different frontal and temporal cortical regions (<-2%/year).
Conclusions
Our results add evidence to support the addition of [18F]FDG PET as a tool for the assessment of cross-sectional and longitudinal neurodegeneration in NP-C.
Exosomes derived from colon cancer cells promote tumour progression by affecting the tumour microenvironment
Authors: Kim Minsung , Son Il Tae , Noh Gyoung Tae , Woo So-Youn , Lee Ryung-Ah , Oh Bo Young
Published: July 2022

Cancer cell-derived exosomes deliver oncogenic factors to other cells and their tumour microenvironment. We aimed to investigate the role of cancer cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines HT-29, SW480, and LoVo. Subsequently, HT-29 cells were treated with these exosomes to evaluate the effect of exosomes on cancer progression. MTT and wound-healing assays were performed to evaluate the effect of exosomes on cellular viability and migration. Moreover, we obtained cancer-associated fibroblasts (CAFs) from patients with colorectal cancer to analyse the effects of cancer cell-derived exosomes on the tumour microenvironment. We performed RNA sequencing to evaluate changes in the mRNA components of the CAFs after exosome treatment. Compared with control cells, exosome-treated cells showed significantly increased proliferation. Regarding western blotting for epithelial-mesenchymal transition markers, exosome-treated cells showed N-cadherin upregulation followed by E-cadherin downregulation. In the wound-healing assay, exosome-treated cells exhibited increased mobile properties. Additionally, exosome-treated CAFs showed increased downregulated genes. In the functional enrichment analysis, exosomes derived from each cell affected different gene regulation pathways. Our findings suggest that cancer cell-derived exosomes are crucially involved in tumour progression and metastasis by affecting the tumour microenvironment.
Validation study of the Functional Assessment of Cancer Therapy - Cognitive Function – Version 3 for the Portuguese population
Authors: Oliveira Ana F. , Torres Ana , Fernandes Sofia , Bem-Haja Pedro , Santos Isabel M.
Published: July 2022

Purpose: The purpose of this study was to evaluate the psychometric properties of the Functional Assessment of Cancer Therapy-Cognitive Function–Version 3 (FACT-Cog-v3) among non-central nervous system (CNS) cancer patients in Portugal. Methods: The validation study was conducted based on a convenience sample of 281 non-CNS cancer patients, aged between 18 and 65 years, recruited online. A confirmatory factor analysis (CFA) was used to test the factor structure of the Portuguese FACT-Cog-v3 version; internal consistency analysis was also conducted. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30–version 3) and the Hospital Anxiety and Depression Scale (HADS) were also used to test the concurrent, convergent, and discriminant validity of the scale.Results: CFA supported a four-factor model with good fix indexes and internal consistencies: perceived cognitive impairments (α=0.97), comments from others (α=0.92), perceived cognitive abilities (α=0.93), and impact on quality of life (α=0.92). Concurrent, convergent, and discriminant validities were confirmed. Moderate and strong correlations were found between the FACT-Cog-v3 subscales and the QLQ-C30 cognitive functioning subscale. Good convergent validity, with moderate correlations, was found between the FACT-Cog-v3 subscales and the HADS-A, HADS-D, and QLQ-C30 fatigue, sleep disturbance, and global health status subscales. There was acceptable discriminant validity, with weak and moderate correlations, between the FACT-Cog-v3 subscales and the QLQ-C30 pain and nausea/vomiting subscales.Conclusion: The Portuguese FACT-Cog-v3 version can be considered a reliable and valid measure to assess cognitive concerns of non-CNS cancer patients, with relevance for research and clinical practice.
Favorable Locoregional Control in Clinically Node- Negative Hormone-receptor Positive Breast Cancer With Low 21-gene Recurrence Scores: a Single Institutional Study With 10-year Follow-up
Authors: Uras Cihan , Cabioglu Neslihan , Tokat Fatma , Er Ozlem , Kara Halil , Korkmaz Taner , Bese Nuran , Ince Umit
Published: July 2022

Background: Recent studies have shown a lower likelihood of locoregional recurrences in patients with low 21-gene recurrence score (RS). In this single institutional study, we investigated any associations between different cut-off values of 21-gene RS and histopathological factors and outcome in patients with long-term follow-up. Methods: Between February 2010 to February 2013, 61 patients with early stage clinically node-negative hormone receptor-positive and HER2-negative breast cancer tested for the 21-gene RS assay, were included into the study. Demographic, clinicopathological, treatment and outcome characteristics were analyzed.Results: Median age was 48 (range, 29-72). Of those, 53 patients were diagnosed with Stage 1 (86.9%) and 8 patients were Stage 2 (13.1%) following surgery. Patients with high histologic grade (HG), or with Ki-67>25%were more likely to have intermediate/high RS based on RS >11 and >18. Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed local recurrences (4.9%) treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n=42), the clinicopathological characteristics including age <40, age <50, high histologic or nuclear grade, high Ki67-scores (>20%, >25%, >30%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS>18 or RS>11 were not significantly found to be associated with 10-year locoregional recurrence free survival (LRRFS). However, patients with a RS >16 have significantly shown a poorer 10-year LRRFS compared to those with RS <16 (RS <16; 100% vs RS>16; 75%, p=0.039). Conclusions: These results suggest that Oncotpe DX assay may be of little value in patients with high histologic grade or high Ki67 scores (>25%) as treatment decision criteria to determine any benefit from chemotherapy. Furthermore, patients with a RS >16 are more likely to benefit from adjuvant chemotherapies, whereas those with a RS <16 have an excellent outcome and local control on long term follow-up with endocrine treatment alone.
Identification and functional exploration of Ferroptosis and Immune Related Long Non-Coding RNA in Inflammatory bowel disease
Authors: Hu Yunhong , Sun Shaopeng , Li Heng
Published: July 2022

Background：Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease involving ileum, rectum and colon, including ulcerative colitis (UC) and Crohn's disease (CD).The etiology is complex, and immune dysfunction is considered to be the final pathological result. Methods：We constructed a lncRNA-mRNA regulatory network based on ferroptosis-related and immnue-related differentially expressed lncRNAs in IBD. Results: We identified 6 differently expressed lncRNAs associated with of ferroptosis and immune in IBD. We further constructed lncRNA-mRNA regulatory network and found potential miRNAs and transcription factors (TF) based on trans and ceRNAs mechanisms.Conclusion：Ferroptosis and immune related lncRNA participate in the regulation of abnormal immune response in IBD
Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei
Authors: Waithaka Albina , Clayton Christine
Published: July 2022

Objective
The cleavage and polyadenylation endonuclease CPSF73 is thought to be the target of the anti-trypanosomal benzoxaboroles AN7973, acoziborole and AN11736. We previously showed that AN7973 inhibits mRNA processing. We here investigated whether the drug candidates acoziborole (for human sleeping sickness) and AN11736 (for nagana in cattle) have same effect. We also affinity purified tagged CPSF73 from parasites without, or after, AN7973 treatment, and analysed differentially co-purified proteins my mass spectrometry.
Results
AN11736 and acoziborole both inhibited mRNA processing, as demonstrated by decreased levels of spliced mRNAs and accumulation of di- and tri-cistronic mRNAs from the alpha-beta tubulin locus. Treating the cells with AN7973 did not significantly affect the proteins that copurified with CPSF73.
Detection of second primary lymphoma in late diffuse large B-cell lymphoma recurrences
Authors: Berendsen Madeleine , Bladel Diede van , Hesius Eva , de Groot Fleur , Kroeze Leonie , Rijntjes Jos , Luijks Jeroen , Hoevenaars Brigiet , Halilovic Altuna , Nooijen Peet , Spek Ellen van der , Vermaat Joost , Hess Corine , Hebeda Konnie , Stevens Wendy , Krieken J. Han van , Brand Michiel van den , Groenen Patricia , Scheijen Blanca
Published: July 2022

Approximately one-third of diffuse large B-cell lymphoma (DLBCL) patients relapse, who often require salvage chemotherapy followed by autologous stem cell transplantation. In most cases, the clonal relationship between the first diagnosis and subsequent relapse is not assessed, thereby missing the identification of second primary lymphoma. Here, the clonal relationship of 59 paired DLBCL diagnosis and recurrences was established by next-generation sequencing (NGS)-based detection of immunoglobulin gene rearrangements. In 50 cases with interpretable results, 43 DLBCL patients (86%) developed clonally related lymphoma and relapsed disease. In total, 100% of early recurrences (< 2 year), 80% of the recurrences with an interval between 2 and 5 years, and 73% of late recurrences (≥ 5 year) were clonally related. In contrast, 7 out of 50 patients (14%) showed distinct dominant clonotypes in primary DLBCL and its recurrences, suggesting the occurrence of second primary DLBCL, which all occurred at least 4 years after primary diagnosis. Moreover, 43% of clonally unrelated cases were Epstein-Barr virus-positive, while this was 3% in relapsed DLBCL. In conclusion, NGS-based clonality testing in late recurrences should be considered in routine diagnostics to distinguish relapse from second primary lymphoma, as this latter group of DLBCL patients may benefit from less intensified treatment strategies.
Microglia Sirt6 modulates transcriptional activity of NRF2 to defend high fat diet-induced obesity
Authors: Xiao Xiaoxia , Hu Huiling , Zhong Yadi , Chen Yingjian , Tang Kaijia , Pan Zhisen , Huang Jiawen , Yang Xiaoying , Wang Qi , Gao Yong
Published: July 2022

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