bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-Step Targeted Drug Delivery Via Proteinaceous Barnase-Barstar Interface and PLGA-Based Nano-Carrier
Authors: Shipunova Victoria O. , Komedchikova Elena N. , Sogomonyan Anna S. , Kotelnikova Polina A. , Nikitin Maxim P. , Deyev Sergey M. 
Published: November 2021

Abstract
The conventional methods of treating cancer with chemo- and radiotherapy present plenty of serious problems, such as low therapeutic index and high systemic toxicity. The advanced cancer treatment strategies utilize nanoformulations of drugs that can enter a tumor due to the enhanced permeability and retention (EPR) effect. However, EPR fails in the treatment of several human diseases. Mainstream biomedical studies are focused on creating the drugs that would enter the tumor with higher effectiveness and require smaller doses for administration. A two-stage drug delivery system is an encouraging alternative solution. At first, the primary, non-toxic targeting module is delivered to the tumor cells, followed by injection of the second complementary targeting module at a considerably lower dose, thus decreasing systemic toxicity. To meet the challenge, we have developed a two-stage drug delivery system (DDS), mediated by the high-affinity binding of the Barnase*Barstar protein pair. Barnase and Barstar act as lego bricks linking the first and the second modules on the surface of the cancer cell. Barnase (12 kDa) is a natural ribonuclease from Bacillus amyloliquefaciens, while Barstar (10 kDa) is its natural inhibitor. The Barnase*Barstar is one of the strongest known protein*protein complexes with Kaff = 1014 M−1 exhibiting extraordinarily stability in severe conditions. Artificial scaffold polypeptide DARPin9_29 genetically fused with Barstar served is a first module of the developed two-step DDS. DARPin9_29 (14 kDa) specifically recognizes the tumor marker HER2 overexpressed on human breast cancer cells. As a second module, a therapeutic nano-cargo was developed based on fluorescent polymer PLGA nanoparticles loaded with diagnostic Nile Blue dye and the chemotherapeutic drug doxorubicin. This nano-PLGA structure was covalently coupled to Barnase. We showed two-stage efficient labeling of HER2-overexpressing cancer cells using the first non-toxic module DARPin9_29-Barstar and the second toxic nano-module PLGA-Barnase. We demonstrated the doxorubicin-induced cytotoxicity of this two-step DDS based on polymer nanoparticles and proteinaceous Barnase-Barstar interface and showed more than 10-fold therapeutic dose reduction versus free doxorubicin. We believe that the developed two-step DDS based on PLGA nano-cargo and protein interface will promote the creation of new-generation cancer treatment strategies.
Aerobic Exercise Promotes the Expression of ATGL and Attenuates Inflammation to Improve Hepatic Steatosis via lncRNA SRA
Authors: Wu Baoai , Tian Yiming , Xu Chong , Zeng Yu , Yan Feng , Chen AnPing , Zhao Jinfeng , Chen Longchang 
Published: November 2021

Abstract
The role of aerobic exercise in preventing and improving non-alcoholic fatty liver has been widely established. SRA is a long non-coding RNA, which has received increasing attention due to its important role in lipid metabolism. However, it is unclear whether aerobic exercise can prevent and treat hepatic lipid accumulation via SRA. The mice were randomly divided into three groups as follows, normal control group (NC), high-fat diet group (HFD), and high-fat diet plus aerobic exercise (8weeks, 6 days/ week, 18 m/ min for 50 min, 6% slope) group (HAE). After 8 weeks, the mice in the HAE group showed significant improvement in hepatic steatosis. Body weight as well as blood TC, LDL-C, and liver TG levels were significantly lower in the HAE group than in the HFD group. Compared with the HFD group, the expression of SRA was markedly suppressed and the expression of ATGL was significantly increased in the HAE group. Additionally, the JNK/P38 signaling was inhibited, the pro-inflammatory factors were down-regulated, and the anti-inflammatory factor was increased. The results of this study provided new support for aerobic exercise to improve hepatic lipid metabolism via lncRNA.
Poly-γ-Glutamic Acid/Alum Adjuvanted pH1N1 Vaccine-Immunized Aged Mice Exhibit a Significant Increase In Vaccine Efficacy With a Decrease in Age-Associated CD8+ T Cell Proportion in Splenocytes
Authors: Yang Jihyun , Kim Jaemoo , Kwak Chaewon , Poo Haryoung 
Published: November 2021

Abstract
BackgroundHighly contagious respiratory diseases caused by viral infections are a constantly emerging threat, particularly the elderly with the higher risk of developing serious complications. Vaccines are the best strategy for protection against influenza-related diseases. However, the elderly has lower vaccine efficacy and the age-driven decline of the influenza vaccine efficacy remains unresolved. In this study, we investigates the effect of an adjuvant, poly-γ-glutamic acid and alum (PGA/Alum) on vaccine efficacy in aged mice (18-months) and its mechanism is studied using ovalbumin as a model antigen and a commercial pandemic H1N1 flu vaccine. Antigen trafficking, dendritic cell (DC) activation, and the DC-mediated T cell activation were analyzed via in vivo imaging and flow cytometry. Antigen-specific humoral and cellular immune responses were evaluated in sera and splenocytes from the vaccinated mice. Also, we analyzed gene expression profiles of splenocytes of vaccinated mice via single-cell transcriptome sequencing and evaluated the protective efficacy against pH1N1 virus challenge.ResultsAged mice had low antigen trafficking and DC activation than younger mice (6-weeks), which was ameliorated by PGA/Alum with increased antigen uptake and DC activation leading to improved antigen-specific IFN-γ+CD8+ T lymphocyte frequencies higher in the vaccinated aged mice, to a similar extent as PGA/Alum adjuvanted vaccine-immunized young mice. The results of single-cell transcriptome sequencing display that PGA/Alum also reduced the proportion of age-associated CD8+ T cell subsets and gene levels of inhibitory regulators in CD8+ T cells, which may play a role in the recovery of CD8+ T cell activation. Finally, PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice were completely protected (100% survival) compared to aged mice immunized with vaccine only (0% survival) after pH1N1 virus challenge, akin to the efficacy of the vaccinated young mice (100% survival).ConclusionsPGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice showed a significant increase in vaccine efficacy compared to aged mice administered with vaccine only. The enhanced vaccine efficacy by PGA/Alum is associated with significant increases activation of DCs and effector CD8+ T cells and a decrease in age-associated CD8+ T cell proportion of splenocytes. Collectively, PGA/Alum adjuvanted flu vaccine may be a promising vaccine candidate for the elderly.
Analysing The Feature of Meteorological Drought in North East Ethiopia: The Case of Meket and Wadla Districts in North Wello Zone, Amhara Region
Authors: Anteneh Mesfin 
Published: November 2021

Abstract
The study was undertaken to investigate the magnitude, frequency and trends of drought incidence in North Wello Zone, northeast Ethiopia using monthly rainfall record for the period 1987 to 2017 of Meket and Wadla station. Standard precipitation index and Mann–Kendal test were used to analyse drought event and trends of drought occurrences, respectively. Drought Index Calculator used to analyse standard precipitation index. The coefficient variation of the study area for Meket was (21.2%), while for Wadla it was (53%) which showed high inter-annual variability. It was established that both studied stations experienced drought episodes in 1987, 1988, 1991, 1992, 1994, 1998, 1999, 2001, 2006, 2014 and 2015, drought years in the history of Ethiopia. The year 2006 was the most severe and distinct-wide extreme drought episode in both studied stations which standard precipitation index values -2.14 at Wadla and -2.01 at Meket station. The frequency of drought number of years which experienced negative standardize precipitation index values in the total time series of 30 years observed for all time scale at both station is 50 percent and above. The drought magnitude of different time scale varied from slight to extreme severe in the studied stations. The Mann–Kendal trend test shows except two-month timescale at Wadla station, all timescales were not statistically significant (P<0.05). Generally increasing tendencies of drought were observed during main rainy season and decreasing tendencies of drought during short rainy season and annual scale observed in the study area.
Abortion storm of Yili Horses is Associated with Equus Caballus Papillomavirus 2 Variant Infection
Authors: Tong Panpan , Duan Ruli , Song Xiaozhen , Palidan Nuerlan , Deng Haifeng , Duan Liya , Jia Chenyang , Tian Shuyao , Yang Enhui , Ma Wanpeng , Kuang Ling , Wang Jinquan , Xie Jinxin 
Published: November 2021

Abstract
Background: Nine different species of Equus caballus papillomavirus (EcPV) and three bovine papillomavirus (BPV) have been reported to infect horses, however, there are so far no describing such infections in China. In January 2021, an abortion storm occurred in Yili horses, as a result of which 50 out of 93 aborted fetus samples were found to be negative for equid herpesvirus (EHV) and equine arteritis virus (EAV).Results: In our pioneer study with Chinese horses, we first found EcPV-2 in the nasal swabs (4/230, 1.7%) of Yili horses, and semen (3/18, 16.7%) of the Thoroughbred horses. This indicated that EcPV can be indeed hosted by horses in China, and that EcPV-2 might be transmitted though breeding. Further detection of EcPVs in the lung tissues of aborted fetus in Yili horses, which were originally negative for equid herpesviruses, established that EcPV-2 was positive in 19 of 50 samples, thereby indicating that EcPV-2 might be a new pathogen causing of abortions. Thereafter, the sequence analyses for L1 genes sequences of 26 China’s EcPV-2 were performed which indicated that EcPV-2, that primarily infected the horses in China, shared 98.3%-99.9% nt identity with the already published sequences for EcPV-2. These observations indicated that EcPV-2 identified in the current study were highly similar variants of the previously identified strains of EcPV-2. Phylogenetic analysis based on L1 genes in GenBank showed that EcPV-2, found in the Chinese horses, was closely related to and clustered together with an already known EcPV-2a lineage. Conclusion: Our study provides the first evidence related to EcPV-2 infection in the Chinese horses, which can serve as a causative agent for Yili horse abortions, and thus can possibly lay the foundation for a systematic and detailed epidemiological study of this infection in the Chinese horses.
Filtering Properties of Hodgkin-Huxley Neuron to Different Time-Scale Signals
Authors: Yu Dong , Wang Guowei , Li Tianyu , Ding Qianming , Jia Ya 
Published: November 2021

Abstract
Neuron can be excited and inhibited by filtered signals. The filtering properties of neural networks have a huge impact on memory, learning, and disease. In this paper, the filtering properties of Hodgkin-Huxley neuron to different time-scale signals are investigated. It is found that the neuronal filtering property depends on the locking relationship between the signal's frequency band and the natural frequency of neuron. The natural firing frequency is a combination of the fundamental component and the various level harmonic components. The response of neuron to the filtered signal is related to the amplitude of the harmonic components. Neuron responds better to the low-frequency signals than the high-frequency signals because of the reduction in the harmonic component amplitude. The filtering ability of neuron can be modulated by the excitation level, and is stronger around the excitation threshold. Our results might provide novel insights into the filtering properties of neural networks and guide the construction of artificial neural networks.
Genomes From Verteba Cave Suggest Diversity Within The Trypillians In Ukraine
Authors: Gelabert Pere , Schmidt Ryan W. , Fernandes Daniel M. , Karsten Jordan K. , Harper Thomas K. , Madden Gwyn D. , Ledogar Sarah H. , Sokhatsky Mykhailo , Oota Hiroki , Kennett Douglas j. , Pinhasi Ron 
Published: November 2021

Abstract
The transition to agriculture occurred relatively late in Eastern Europe, leading researchers to debate whether it was a gradual, interactive process or a colonization event. In the forest and forest-steppe regions of Ukraine, farming appeared during the fifth millennium BCE, associated with the Cucuteni-Trypillian Archaeological Complex (CTCC, 4800-3000 BCE). Across Europe, the Neolithization process was highly variable across space and over time. Here, we investigate the population dynamics of early agriculturalists from the eastern forest-steppe region based on analyses of 20 ancient genomes from the Verteba Cave site (3789-980 BCE). The results reveal that the CTCC individuals’ ancestry is related to both western hunter gatherers and Near Eastern farmers, lacks local ancestry associated with Ukrainian Neolithic hunter gatherers and has steppe ancestry. An Early Bronze Age individual has an ancestry profile related to the Yamnaya expansions but with 20% ancestry related to the other Trypillian individuals, which suggests admixture between the Trypillians and the incoming populations carrying steppe-related ancestry. A Late Bronze Age individual dated to 980-948 BCE has a genetic profile indicating affinity to Beaker-related populations, detected close to 1,000 years after the end of the Bell Beaker phenomenon during the Third millennium BCE.
Soil Chemical Fertility Change Over 4 Decades In The Morvan Mountains And Influence of Tree Species (Burgundy, France)
Authors: Margaux Clesse , Arnaud Legout , Jacques Ranger , Bernd Zeller , Gregory Van Der Heijden 
Published: November 2021

Abstract
Background: Intensive silvicultural practices and the planting of monospecific forests of coniferous, more productive compared to hardwoods, may threaten over the mid to long-term the sustainability of soil chemical fertility of forest ecosystems and is a major concern for forest managers and policy.Methods: We investigated the tree species effect (Quercus sessiliflora Smith, Fagus sylvatica L., Picea abies Karst., Pseudotsuga menziesii Mirb. Franco., Abies nordmanniana Spach. and Pinus nigra Arn. ssp laricio Poiret var corsicana) on the change over time of soil chemical properties and nutrient pool sizes in the mineral and organic layers of the soil during the 45 years after the plantation of the Breuil-Chenue common garden experiment (Burgundy, France). The organic and mineral soil layers down to 70 cm depth were sampled in the different monospecific plots in 1974, 2001 and 2019. Results: The Ca and Mg exchangeable pools and soil pH increased over the entire soil profile in most stands. However, the decrease of pH and the increase of exchange acidity in the topsoil layers under conifers and the overall decrease of exchangeable K pools in most stands highlighted that soil acidification is still on-going at this site but the intensity of this process depends on the tree species. Indeed, three groups of species could be distinguished: i) Nordmann fir / Norway spruce where acidolysis and chelation occurred, resulting in the most pronounced pH decrease in the topsoil, ii) Douglas fir / Laricio pine where acidification caused by elevated nitrification rates is probably currently compensated by larger weathering and/or atmospheric depositions fluxes, iii) and oak / beech where soil acidification was less intense. Counterintuitively, soil acidification at this site resulted in an increase in soil CEC which limited the loss of nutrient cations. This change in soil CEC was most likely explained by the precipitation/dissolution dynamics of aluminium (Al) (hydr)oxides in the interfoliar space of phyllosilicates and/or the increase in soil carbon (C) content in the topsoil layers. Conclusion: Tree species greatly and fairly rapidly (<45 years) influence the soil chemical fertility and the pedogenetic processes which in turn may impact forest ecosystem functions and services.
Identification of the Key Serum Biomarkers to Diagnose and Predict Metastasis of Osteosarcoma Based on the Analysis of Immune Cell Infiltration Characteristics
Authors: Chen Zhihao , Li Liubing , Li Ziyuan , Wang Xi , Han Mingxiao , Gao Zongshuai , Wang Min , Hu Gangfeng , Xie Xiaolu , Du Hong , Xie Zonggang , Zhang Haifang 
Published: November 2021

Abstract
Background: The potential functions of circular RNAs (circRNAs) and micro RNAs (miRNAs) in osteosarcoma (OS) have not been fully elucidated. Especially, the behavior and mechanism of immune responses in OS development and progression have not been fully demonstrated. It was reported that circRNAs and miRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of many cancers. This study aimed to identify novel key serum biomarkers to diagnose and predict metastasis of OS based on the analysis of immune cell infiltration characteristics.Methods: The differentially-expressed circRNAs (DEcircRNAs), differentially-expressed miRNAs (DEmiRNAs),and differentially-expressed mRNAs (DEmRNAs) of human OS were investigated based on the microarray data downloaded from Gene Expression Omnibus (GEO) datasets. Then, we analyzed immune characteristics pattern of tumor-infiltrating immune cells in OS. On this basis, we identified statistically-significant transcription factors and performed pathway enrichment analysis. Subsequently, we constructed protein-protein interaction (PPI) and competitive endogenous RNA (ceRNA) networks. Moreover, the biological characteristic of targets in ceRNA networks was proposed. Finally, the expression and diagnostic capability of these potential biomarkers from ceRNA network were confirmed by RT-qPCR in patients’ serum.Results: Seven differentially-expressed circRNAs (DEcircRNAs), 166 differentially-expressed miRNAs (DEmiRNAs) and 175 differentially-expressed mRNAs (DEmRNAs) were identified in total. The highest level of infiltration in OS patients were M0 macrophages, M2 macrophages and CD8+ T cells. Further, M0 macrophages and CD8+ T cells were showed the largest negative correlation coefficients. These significant immune characteristics pattern of tumor-infiltrating immune cells were revealed by the principal component analysis in OS. Moreover, we found 185 statistically-significant transcription factors in which the main significant molecules show the potential in immunotherapy of OS. Hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A from ceRNA networks associated with immune cell infiltration were confirmed as the potential novel biomarkers for OS diagnosis, of which FAM98A could distinguish and predict metastasis. Most importantly, a novel diagnostic model consisting of the four promising biomarkers (hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A) was highlighted with 0.928 AUC value.Conclusions: In summary, the potenial serum biomarkers to diagnose and predict metastasis of OS based on the analysis of immune cell infiltration characteristics were found, and a novel diagnostic model consisting of four promising serum biomarkers was proposed firstly. These results provided a new perspective for the immunotherapy of OS.
Prevalence of Small Intestinal Bacterial Overgrowth (SIBO) In Type 2 Diabetes Mellitus: A Systematic Review
Authors: Tarigan Tri Juli Edi , Caputra Hadyanto , Hasan Irsan , Shatri Hamzah 
Published: November 2021

Abstract
Purpose: Gastrointestinal symptoms affect 50-70% of diabetic patients, resulting in a microbiota composition imbalance. Autonomic neuropathy is irreversible, resulting in diabetic enteropathy and sometimes even small intestine bacterial overgrowth (SIBO). SIBO can result in bile acid deconjugation, diarrhea, steatorrhea, vitamin and micronutrient malabsorption, weight loss, mucosal injury, bacterial translocation, and worsened intestinal motility. Carbohydrate malabsorption is related to the pathogenesis of diabetic macrovascular complications. The goal of this study is to find out how prevalent SIBO is in type 2 diabetes patients. Methods: "Small intestinal bacterial overgrowth," "small bowel bacterial overgrowth," “SIBO,” "type 2 diabetes mellitus," and "type 2 DM," are the keywords used. We searched Proquest, CINAHL, SCOPUS, ScienceDirect, PubMed/MEDLINE, and manual searches through world diabetes associations such as ADA, EASD, EFSD, IDF, FASEB, and PERKENI using the keywords. We use the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for bias risk assessment, and for data analysis, we use STATA 16. Results: Six articles covered 1072 type 2 diabetes patients in clinics and hospitals. With a minimum score of 7.42% and a maximum value of 53.85%, 95% CI 9.97-38.86, and an I2 of 97.17%, the pooled prevalence was 24.39% SD 15.31. HbA1c levels were higher (p=0.02) in type 2 DM patients with SIBO, and blood insulin levels were lower (p=0.001) in type 2 DM patients with SIBO. Each study was pretty varied, and there was evidence of publication bias. Assessment of findings based on GRADE is moderate. Conclusion: According to this study, SIBO is present in 24.39% of type 2 diabetes patients. SIBO conditions exacerbate the morbidity of patients with type 2 diabetes, as indicated by lower insulin levels and a higher HbA1c. In type 2 diabetes patients, a hydrogen breath test (HBT) is recommended to be performed regularly, especially in those who have had DM for more than 5 years.
Wavelets Based Feature Extraction With PCA For Predicting Autism In Neonates Using Navïe Bayes Classifier
Authors: Mensah Isabel , Amoako-Yirenkyi Peter , Frempong Nana K , Lamptey George P 
Published: November 2021

Abstract
Background: Current studies show early interventions of autism increase significant long-term positive effects, symptoms and, later skills. Currently, These interventions are based on the use of an early diagnostic test. Existing methods for diagnosing Autism Spectrum Disorders (ASDs) such as cognitive tests, Intelligence Quotient, and standardized tests like the Autism Diagnostic Observation Schedule (ADOS) are functionally limited since they rely on child development for diagnoses. The standard is that a child must be at least three(3) years to undergo these tests. Accurate diagnosis is only possible after this period, and this may contribute to delayed diagnosis with an overall effect on the health system. In this era of increasing genetic data, it is possible to infer the genetic patterns of the disorder. This study introduces a novel and rigorous approach for predicting ASDs in neonates and their subsequent severity by identifying significant genes that contribute to the disorder. Methods: We used a wavelet transform and t-test to identify the significant genes that contribute to the disease. We subsequently employed the Naive Bayes classifier in the prediction of the autistic status of the neonate. Additionally, Principal Component Analysis (PCA) was employed to remove all the dependencies among the genes to enhance classification. Finally, we used the K-means clustering method to predict the severity level of the disease in the neonate. Results: Up to 200 differentially expressed genes were identified and used for predicting the ASD status of the child with a classification accuracy of 95.91%. Also, the results of the K-means demonstrated that the higher the mean of the cluster, the more severe the disease would be among that corresponding group. Optimizing and implementing these models in clinical settings may significantly reduce the health burden of ASDs.