bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micro-RNA-125a mediates the effects of hypomethylating agents in chronic myelomonocytic leukemia
Authors: Berg Johannes Lorenz , Perfler Bianca , Hatzl Stefan , Mayer Marie-Christina , Wurm Sonja , Uhl Barbara , Reinisch Andreas , Klymiuk Ingeborg , Tierling Sascha , Pregartner Gudrun , Bachmaier Gerhard , Berghold Andrea , Geissler Klaus , Pichler Martin , Hoefler Gerald , Strobl Herbert , Wölfler Albert , Sill Heinz , Zebisch Armin 
Published: January 2021

Abstract
Background
Chronic myelomonocytic leukemia (CMML) is an aggressive hematopoietic malignancy that arises from hematopoietic stem and progenitor cells (HSPCs). Patients with CMML are frequently treated with epigenetic therapeutic approaches, in particular the hypomethylating agents (HMAs), azacitidine (Aza) and decitabine (Dec). Although HMAs are believed to mediate their efficacy via re-expression of hypermethylated tumor suppressors, knowledge about relevant HMA targets is scarce. As silencing of tumor-suppressive micro-RNAs (miRs) by promoter hypermethylation is a crucial step in malignant transformation, we asked for a role of miRs in HMA efficacy in CMML.

Results
Initially, we performed genome-wide miR-expression profiling in a KrasG12D-induced CMML mouse model. Selected candidates with prominently decreased expression were validated by qPCR in CMML mice and human CMML patients. These experiments revealed the consistent decrease in miR-125a, a miR with previously described tumor-suppressive function in myeloid neoplasias. Furthermore, we show that miR-125a downregulation is caused by hypermethylation of its upstream region and can be reversed by HMA treatment. By employing both lentiviral and CRISPR/Cas9-based miR-125a modification, we demonstrate that HMA-induced miR-125a upregulation indeed contributes to mediating the anti-leukemic effects of these drugs. These data were validated in a clinical context, as miR-125a expression increased after HMA treatment in CMML patients, a phenomenon that was particularly pronounced in cases showing clinical response to these drugs.

Conclusions
Taken together, we report decreased expression of miR-125a in CMML and delineate its relevance as mediator of HMA efficacy within this neoplasia.
RETRACTED ARTICLE: Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction
Authors: Cai Guofeng , Cai Guoliang , Zhou Haichun , Zhuang Zhe , Liu Kai , Pei Siying , Wang Yanan , Wang Hong , Wang Xin , Xu Shengnan , Cui Cheng , Sun Manchao , Guo Sihui , Jia Kunping , Wang Xiuzhen , Zhang Dianquan 
Published: January 2021

AbstractBackgroundCerebral infarction ranks as the second leading cause of disability and death globally, and inflammatory response of glial cells is the main cause of brain damage during cerebral infarction.MethodsStudies have shown that mesenchymal stem cells (MSCs) can secrete exosomes and contribute to cerebral disease. Here, we would explore the function of MSC-derived exosome in cerebral infarction.ResultsMicroarray indicated a decrease of miR-542-3p and an increase of Toll-Like Receptor 4 (TLR4) in middle cerebral artery occlusion (MCAO) mice comparing with sham mice. And luciferase and RIP analysis indicated a binding of miR-542-3p and TLR4. Then, we injected AAV9-miR-542-3p into paracele of sham or MCAO mice. Functional analysis showed that AAV9-miR-542-3p inhibited infarction area and the number of degenerating neurons and suppressed inflammatory factors’ expression and inflammatory cell infiltration. As well, transfection of miR-542-3p mimics into HA1800 cells underwent oxygen and glucose deprivation (OGD). Similarly, overexpression of miR-542-3p alleviated OGD induced cell apoptosis, ROS, and activation of inflammation response. Moreover, miR-542-3p could be packaged into MSCs and secreted into HA1800 cells. The extractive exosome-miR-21-3p treatment relieved MCAO- or OGD-induced cerebral injury and inflammation through targeting TLR4.ConclusionThese results confirmed that MSC-derived exosome miR-542-3p prevented ischemia-induced glial cell inflammatory response via inhibiting TLR4. These results suggest possible therapeutic strategies for using exosome delivery of miR-542-3p to cure cerebral ischemic injury.
Investigation of interleukin-2-mediated changes in blood pressure, fetal growth restriction, and innate immune activation in normal pregnant rats and in a preclinical rat model of preeclampsia
Authors: Cunningham Mark W. , Amaral Lorena M. , Campbell Nathan E. , Cornelius Denise C. , Ibrahim Tarek , Vaka Venkata Ramana , LaMarca Babbette 
Published: January 2021

AbstractTwo important clinical features of preeclampsia (PE) are hypertension and fetal growth restriction. The reduced uterine perfusion pressure (RUPP) preclinical rat model of PE exhibits both of these features. Moreover, RUPP and PE women have elevated vasoconstrictor peptide endothelin-1 (ET-1) and inflammation. Interleukin-2 (IL-2) is a cytokine that regulates NK cell activity and is elevated in miscarriage, PE, and RUPP rats. The objective of this study was to examine a role for IL-2 in NK cell activation, fetal growth restriction, and hypertension during pregnancy by either infusion of IL-2 or blockade of IL-2 (basiliximab) in normal pregnant (NP) and RUPP rats. On gestational day 14, NP and RUPP rats received low (LD), middle (MD), or high dose (HD) IL-2 (0.05, 0.10, or 0.20 ng/ml) IP or basiliximab (0.07 mg per rat) by IV infusion. On day 19, blood pressure (MAP), pup weights, and blood were collected. Basiliximab had no effect on blood pressure, however, significantly lowered NK cells and may have worsened overall fetal survival in RUPP rats. However, IL-2 LD (102 ± 4 mmHg) and IL-2 HD (105 ± 6 mmHg) significantly lowered blood pressure, ET-1, and activated NK cells compared to control RUPPs (124 ± 3 mmHg,p< 0.05). Importantly, IL-2 in RUPP rats significantly reduced fetal weight and survival. These data indicate that although maternal benefits may have occurred with low dose IL-2 infusion, negative effects were seen in the fetus. Moreover, inhibition of IL-2 signaling did not have favorable outcome for the mother or fetus.
Enzyme additives influence bacterial communities of Medicago sativa silage as determined by Illumina sequencing
Authors: Hu Zongfu , Ma Deying , Niu Huaxin , Chang Jie , Yu Jianhua , Tong Qing , Li Shuguo 
Published: January 2021

AbstractThe goal of the present study was to evaluate the effects of enzymes (cellulase combined with galactosidase) and their combination with Lactobacillus plantarum (LP) on bacterial diversity in alfalfa silages using high-throughput sequencing. Alfalfa forages were treated with or without cellulase + ɑ-galactosidase (CEGA), cellulase + LP (CELP), or ɑ-galactosidase + LP (GALP). After 56 days of ensiling, all treated silages exhibited improved fermentation quality, as reflected by decreased pH, ammonium-N and increased lactic acid levels compared to the control silage (P < 0.05). Enzymatic treatment improved nutrient value by increasing crude protein levels and decreasing neutral detergent fibre (NDF) levels (P < 0.05). Silage treatment significantly altered the bacterial community, as determined by PCoA (P < 0.05). Lactic acid bacteria (LAB) dominated the bacterial community of the treated silage after ensiling. The dominant bacteria changed from Garciella, Enterococcus, Lactobacillus and Pediococcus in the control silage to Lactobacillus and Pediococcus in the CEGA silage and Lactobacillus in the CELP and GALP silages. Collectively, these results suggest that treatment with both enzymes alone and in combination with inoculants greatly increased the abundance of LAB, with Enterococcus, Lactobacillus and Pediococcus observed in the silage treated with enzymes alone (CEGA) and Lactobacillus observed in the silage treated with a combination of enzymes and inoculants (CELP and GALP).
Seed treatment with prodigiosin controls damping-off of cucumber caused by Pythium ultimum
Authors: Roberts Daniel P. , Selmer Kaitlyn , Lupitskyy Robert , Rice Clifford , Buyer Jeffrey S. , Maul Jude E. , Lakshman Dilip K. , DeSouza Jorge 
Published: January 2021

AbstractEthanol extract of cell mass of Serratia marcescens strain N4-5, when applied as a treatment to cucumber seed, has been shown to provide control of the oomycete soil-borne plant pathogen Pythium ultimum equivalent to that provided by a seed-treatment chemical pesticide in some soils. Two dominant compounds in this extract, prodigiosin and the serratamolide serrawetin W1, were identified based on mass and collision induced dissociation mass fragmentation spectra. An additional four compounds with M+H+ masses (487, 541, 543, and 571) consistent with serratamolides reported in the literature were also detected. Several other compounds with M+H+ masses of 488, 536, 684, 834, 906, and 908 m/z were detected in this ethanol extract inconsistently over multiple liquid chromatography coupled with tandem mass spectrometry (LC/MS–MS) runs. A purified preparation of prodigiosin provided control of damping-off of cucumber caused by P. ultimum when applied as a seed treatment while ethanol extract of cell mass of strain Tn246, a transposon-mutant-derivative of strain N4-5, did not. Strain Tn246 contained a mini-Tn5 Km insertion in a prodigiosin biosynthetic gene and was deficient in production of prodigiosin. All other compounds detected in N4-5 extract were detected in the Tn246 extract. This is the first report demonstrating that prodigiosin can control a plant disease. Other compounds in ethanol extract of strain N4-5 may contribute to disease control.
Interleukin-22 and connective tissue diseases: emerging role in pathogenesis and therapy
Authors: Xuan Xiuyun , Zhang Lin , Tian Chunxia , Wu Ting , Ye Haihua , Cao Juanmei , Chen Fangqi , Liang Yan , Yang Huilan , Huang Changzheng 
Published: January 2021

AbstractInterleukin-22 (IL-22), a member of the IL-10 family of cytokines, is produced by a number of immune cells involved in the immune microenvironment of the body. IL-22 plays its pivotal roles by binding to the IL-22 receptor complex (IL-22R) and subsequently activating the IL-22R downstream signalling pathway. It has recently been reported that IL-22 also contributes to the pathogenesis of many connective tissue diseases (CTDs). In this review, we will discuss the role of IL-22 in several CTDs, such as system lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis and dermatomyositis, suggesting that IL-22 may be a potential therapeutic target in CTDs.
Identification of predictors based on drug targets highlights accurate treatment of goserelin in breast and prostate cancer
Authors: Zhao Yue , Sun Huimin , Zheng Jianzhong , Shao Chen , Zhang Dongwei 
Published: January 2021

AbstractGoserelin is an effective alternative to surgery or estrogen therapy in prostate cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. However, not all users of goserelin can benefit from it, or some patients are not sensitive to goserelin. The advent of network pharmacology has highlighted the need for accurate treatment and predictive biomarkers. In this study, we successfully to identify 76 potential targets related to the compound of goserelin through network pharmacology approach. We also identified 18 DEGs in breast cancer tissues and 5 DEGs in cells, and 6 DEGs in prostate cancer tissues and 9 DEGs in cells. CRABP2 is the common DEG both in breast and prostate cancer. The risk prediction models constructed with potential prognostic targets of goserelin can successfully predict the prognosis in breast and prostate cancer, especially for very young breast cancer patients. Moreover, seven subgroups in breast cancer and six subgroups in prostate cancer were respectively identified based on consensus clustering using potential prognostic targets of goserelin that significantly influenced survival. The expression of representative genes including CORO1A and ANXA5 in breast and DPP4 in prostate showed strong correlations with clinic-pathological factors. Taken together, the novel signature can facilitate identification of new biomarkers which sensitive to goserelin, increase the using accuracy of goserelin and clarify the classification of disease molecular subtypes in breast and prostate cancer.
An efficient adaptive grid method for a system of singularly perturbed convection-diffusion problems with Robin boundary conditions
Authors: Liu Li-Bin , Liang Ying , Bao Xiaobing , Fang Honglin 
Published: January 2021

AbstractA system of singularly perturbed convection-diffusion equations with Robin boundary conditions is considered on the interval$[0,1]$[0,1]. It is shown that any solution of such a problem can be expressed to a system of first-order singularly perturbed initial value problem, which is discretized by the backward Euler formula on an arbitrary nonuniform mesh. An a posteriori error estimation in maximum norm is derived to design an adaptive grid generation algorithm. Besides, in order to establish the initial values of the original problems, we construct a nonlinear optimization problem, which is solved by the Nelder–Mead simplex method. Numerical results are given to demonstrate the performance of the presented method.
Systematic review of situational prevention methods for crime against species
Authors: Delpech Dorothea , Borrion Herve , Johnson Shane 
Published: January 2021

AbstractIllegal activities concerning terrestrial species (TS) are responsible for a variety of health, environmental, economic and security issues. The majority of academic research associated with species relates to conservation, with few publications specifically investigating the scale of crimes impacting species or how they can be prevented. This article systematically reviews the available evidence about what works to prevent crime against terrestrial species. Of over 29,000 documents that were returned in the first stage of the review, these were filtered to just over 100. The remaining documents were partially or fully read to identify the most relevant documents to include in the final qualitative synthesis. The review results show there is a significant lack of primary research in this area, as only five articles were found that met the study inclusion criteria. The identified articles focus on the effects of two types of situational crime prevention interventions: community outreach and ranger patrol frequency. Community outreach was shown to have a significant impact on local poaching levels, while for patrolling the evidence suggests a positive impact on the discovery of poachers, animal carcasses and poaching paraphernalia, however, the quality of these studies varied greatly. To prevent the further decline of species numbers internationally, more effort should be invested in publicising existing research into the effectiveness of prevention strategies that have not reached the wider scientific audience, as well as the funding and promotion of research into alternate methods of crime prevention.
Microbial diversity of co-occurring heterotrophs in cultures of marine picocyanobacteria
Authors: Kearney Sean M. , Thomas Elaina , Coe Allison , Chisholm Sallie W. 
Published: January 2021

Abstract
Background
The cyanobacteria Prochlorococcus and Synechococcus are responsible for around 10% of global net primary productivity, serving as part of the foundation of marine food webs. Heterotrophic bacteria are often co-isolated with these picocyanobacteria in seawater enrichment cultures that contain no added organic carbon; heterotrophs grow on organic carbon supplied by the photolithoautotrophs. For examining the selective pressures shaping autotroph/heterotroph interactions, we have made use of unialgal enrichment cultures of Prochlorococcus and Synechococcus maintained for hundreds to thousands of generations in the lab. We examine the diversity of heterotrophs in 74 enrichment cultures of these picocyanobacteria obtained from diverse areas of the global oceans.

Results
Heterotroph community composition differed between clades and ecotypes of the autotrophic ‘hosts’ but there was significant overlap in heterotroph community composition across these cultures. Collectively, the cultures were comprised of many shared taxa, even at the genus level. Yet, observed differences in community composition were associated with time since isolation, location, depth, and methods of isolation. The majority of heterotrophs in the cultures are rare in the global ocean, but enrichment conditions favor the opportunistic outgrowth of these rare bacteria. However, we found a few examples, such as bacteria in the family Rhodobacteraceae, of heterotrophs that were ubiquitous and abundant in cultures and in the global oceans. We found their abundance in the wild is also positively correlated with that of picocyanobacteria.

Conclusions
Particular conditions surrounding isolation have a persistent effect on long-term culture composition, likely from bottlenecking and selection that happen during the early stages of enrichment for the picocyanobacteria. We highlight the potential for examining ecologically relevant relationships by identifying patterns of distribution of culture-enriched organisms in the global oceans.
Continuous glucose monitoring in older people with diabetes receiving home care—a feasibility study
Authors: Larsen Annette Bævre , Hermann Monica , Graue Marit 
Published: January 2021

AbstractBackgroundHypoglycemic incidents in older people can cause severe health problems, enhance general age-related disabilities, and cause frailty. Little is known about incidences of hypoglycemia in older home-dwelling people with diabetes. Thus, the aim of this study was to examine the feasibility of capturing hypoglycemia and issues associated with increased risk of hypoglycemia by use of continuous glucose monitoring (CGM) and standardized questionnaires among older home-dwelling individuals with diabetes type 2 receiving home care.MethodsCGM with the Ipro2-blinded monitoring system were performed for 5 days in six home-dwelling individuals ≥ 75 years diagnosed with diabetes and receiving home care. Demographic (age, gender, living arrangements) and clinical data (diabetes diagnoses and duration, diabetes medication, documented treatment goal, available glycosylated hemoglobin (HbA1c)) were collected from electronic patient records in home care services. Feasibility (ease of use, quality of data, time spent) of standardized questionnaires to identify the risk of hypoglycemia (the McKellar Risk Assessment Tool), risk of malnutrition (the Mini Nutritional Assessment (MNA)), functional status (the Individual-based Statistics for Nursing and Care Services (IPLOS)), and cognitive status (the Mini Mental Status Exam (MMSE)) was also assessed. Questionnaire data was collected by a study nurse in the individuals’ home.ResultsThe practical use of CGM was satisfactory, with no major remarks about discomfort or technical errors, except for one participant with skin reaction (redness). Collecting data with the McKellar Risk Assessment Tool, MNA and IPLOS worked well according to quality of data, time spent, and ease of use. The MMSE survey required extensive training of personnel to be conducted.ConclusionThe feasibility study informs an upcoming study on the incidence and risk factors of hypoglycemia in home-dwelling older individuals. We will ascertain that personnel who will use the MMSE questionnaire to collect cognitive status and skills are familiar with the tool and adequately educated and trained before study start. The use of blinded CGM in this population was well tolerated and can be used “as is” for future studies.
Safety assessment of oral administration of ethanol extract of Justicia carnea leaf in healthy wistar rats: hematology, antioxidative and histology studies
Authors: Akintimehin Emmanuel Sina , Karigidi Kayode Olayele , Omogunwa Tope Samuel , Adetuyi Foluso Olutope 
Published: January 2021

Abstract
Background
Consumption of medicinal plants has diverse therapeutic benefits and could also have toxic effect. Justicia carnea is a medicinal plant that is used conventionally as blood tonic from time immemorial in Nigeria. The aim of this study is to evaluate the safety of ethanol extract of J. carnea leaf assessing the hematology indices, organ antioxidant system and histology in healthy male wistar rats.

Methods
Powdered sample was extracted using absolute ethanol and concentrated to obtain a slurry paste of J. carnea ethanol extracts. Acute toxicity was determined in two phases using Lorke method. In subacute study, rats were randomized into six groups of five rats per group: Group 1 (control) received distilled water, group 2, 3, 4, 5, 6 received 50, 100, 500, 800 and 1200 mg/kg body weight of J. carnea ethanol extract once daily using oral gavage. At the end of 14th day of administration, rats were allowed to fast overnight, sacrificed to collect samples for biochemical analysis and histopathological examination.

Results
The LD50 of extract was greater than 5000 mg/kg body weight. Higher doses (> 500 mg/kg) of extract significantly (p < 0.05) increased RBC, hemoglobin and platelet compared to the control. Liver superoxide dismutase (SOD) activity was significantly (p < 0.05) increased at 1200 mg/kg while other tested doses caused no detrimental effect on glutathione, catalase, SOD and malondialdehyde level in liver and kidney. Histopathological examination of liver and kidney showed mild to severe pathological lesion in a dose dependent manner.

Conclusions
The results of this study suggests that ethanol extract of J. carnea leaf is relatively safe, could be beneficial in alleviating hematology related abnormalities without causing adverse effects on endogenous antioxidant system. However, caution should be taken as higher dose at 1200 mg/kg could cause noticeable tissue injury.
Forecasting and trading cryptocurrencies with machine learning under changing market conditions
Authors: Sebastião Helder , Godinho Pedro 
Published: January 2021

AbstractThis study examines the predictability of three major cryptocurrencies—bitcoin, ethereum, and litecoin—and the profitability of trading strategies devised upon machine learning techniques (e.g., linear models, random forests, and support vector machines). The models are validated in a period characterized by unprecedented turmoil and tested in a period of bear markets, allowing the assessment of whether the predictions are good even when the market direction changes between the validation and test periods. The classification and regression methods use attributes from trading and network activity for the period from August 15, 2015 to March 03, 2019, with the test sample beginning on April 13, 2018. For the test period, five out of 18 individual models have success rates of less than 50%. The trading strategies are built on model assembling. The ensemble assuming that five models produce identical signals (Ensemble 5) achieves the best performance for ethereum and litecoin, with annualized Sharpe ratios of 80.17% and 91.35% and annualized returns (after proportional round-trip trading costs of 0.5%) of 9.62% and 5.73%, respectively. These positive results support the claim that machine learning provides robust techniques for exploring the predictability of cryptocurrencies and for devising profitable trading strategies in these markets, even under adverse market conditions.