bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of droplet digital PCR to detect human Alu DNA elements in biodistribution assays in pre-clinical studies using rodents
Authors: Kim Jin-Hee , Kim Jin-Hong , Jo Chris H. , Hwang Young-il 
Published: February 2022

Abstract
Biodistribution and engraftment assays for administered human cells in animal organs must be performed to ensure the safety and efficacy of the human cells in preclinical studies. Quantitative real-time polymerase chain reaction (qRT-PCR) is currently the standard method used to detect Alu DNA elements. The recently developed droplet digital PCR (ddPCR) method has been adopted in many biological fields, in which the small quantities of DNA must be detected. In this study, we evaluated whether ddPCR could replace qRT-PCR in biodistribution research. We applied ddPCR to detect human Alu DNA elements using various concentrations of genomic DNA (gDNA) extracted from human mesenchymal stem cells spiked with 100 ng of rat gDNA. We found that ddPCR could specifically detect human DNA and exhibited linearity within a concentration range of 10 ag–100 pg/20 µl. ddPCR was far more sensitive than qRT-PCR in measuring Alu elements, with a reliable lower limit of detection of 100 ag DNA/20 µl reaction. Additionally, the copy numbers of Alu elements were quantified using ddPCR in an ex vivo study examining DNA samples extracted from mouse spleen and lymph nodes that had been spiked with human natural killer cells; no human DNA was detected using qRT-PCR in this assay. Thus, we established a ddPCR method for detecting human gDNA in bio-distribution assays of human cells in rodents in preclinical studies.
Stimulation of dysregulated IFN-β responses by aberrant SARS-CoV-2 small viral RNAs acting as RIG-I agonists
Authors: Watanabe Yohei , Arai Yasuha , Yamanaka Itaru , Okamoto Toru , Isobe Ayana , Nakai Naomi , Kamimura Naoko , Daidoji Tomo , Ono Takao , Nakaya Takaaki , Matsumoto Kazuhiko , Okuzaki Daisuke 
Published: February 2022

Abstract
Patients with severe COVID-19 exhibit a cytokine storm characterized by greatly elevated levels of cytokines during worsening disease1-4. Despite this, the interferon (IFN) response is delayed, contributing to disease progression5. Here, we report that SARS-CoV-2 generates excessive amounts of small viral RNAs (svRNAs) encoding exact 5′ ends of positive sense genes in human cells, whereas significantly fewer similar svRNAs are produced by endemic human coronaviruses (OC43 and 229E). SARS-CoV-2 5′ end svRNAs are potent RIG-I agonists associated with IFN-β expression in later stages of infection. The first 60-nt ends bearing duplex structures and 5′-triphosphates are responsible for immune-stimulation. The 5′ end svRNAs were also produced during infection in vivo. The delta variant retains the robust 5’ end svRNA production of the parental strain, whereas omicron no longer produces these erroneous svRNAs. We propose that RIG-I activation by accumulated 5′ end svRNAs overcomes the initial IFN antagonistic ability of viral proteins and drives late over-exuberant IFN production leading to the development of severe COVID-19 and suggest that evolutionary modification of SARS-CoV-2 5’ end svRNA production may correlate with the reduced disease severity likely seen with omicron.
Holocene sea-level rise evidenced in Hells Bells 234U/238U ratio and geochemical composition
Authors: Schorndorf Nils , Frank Norbert , Ritter Simon , Warken Sophie , Scholz Christian , Keppler Frank , Scholz Denis , Weber Michael , Olguin Jeronimo Aviles , stinnesbeck wolfgang 
Published: February 2022

Abstract
Hells Bells are underwater secondary carbonates discovered in sinkholes (cenotes) southeast of Cancun on the north-eastern Yucatán Peninsula, Mexico. These authigenic calcite precipitates, reaching a length of up to 4 m, most likely grow in the pelagic redoxcline. Here, we report on detailed 230Th/U-dating and in-depth geochemical and stable isotope analyses of specimens from cenotes El Zapote, Maravilla and Tortugas. Hells Bells developed during the end of MIS5b/c (~96–90 thousand years ago) and again since the early Holocene, with active growth until present day. The temporal evolution of the geochemistry and isotope composition of Hells Bells calcites appears closely linked to the mid to late Holocene sea-level rise, which reflects changing hydrological conditions of the aquifer. A stabilization of sea level combined with aquifer occlusion during the past ~8 thousand years probably led to a reduction in hydraulic conductivity and a desalinization of the freshwater layer as indicated by decreasing Sr/Ca values. In addition, initial (234U/238U) activity ratios (δ234U0) in the Bells calcite decrease from 55 to 15‰ as sea level converges toward its present state. We propose that the Holocene sea-level rise drives desalinization and subsequent deceleration of leaching of excess 234U from the previously unsaturated bedrock.
Implantable Polyacrylonitrile-Spermidine Electrospun Nanofibers with Sustainable ROS Scavening Capacity for Osteoarthritis (OA) Therapy
Authors: Gao Shangzhi , Long Bingcai , Lan Ying , Liang Yanling , Li Guanhua , Yang Xin , He Maolin , Zheng Li , Zhong Jingping 
Published: February 2022

Abstract
Osteoarthritis (OA) is a major cause of mobility impairment in the elderly. Scavenging excessive reactive oxygen species (ROS) to inhibit oxidative stress damage is a theraupetic strategy for OA. However, low clearance efficiency, rapid clearance by the joint fliud, poor stability and lack of sustainability challenged most ROS scavengers. Herein, we innovatively synthesized a spermidine (SPD)-acrylonitrile (PAN) copolymer nanofiber membrane using electrostatic spinning technology for effective treatment of OA, wherin SPD that has potent antioxidant ability served as ROS scavenger and PAN as backbone for sustainable release of SPD. Compared with the PAN, the PAN-SPD nanofibers not only greatly improved the mechanical properties, but also exhibited the sustainability and high efficiency to scavenge ROS. Moreover, PAN-SPD nanofibers have good biocompatibility, and can effectively reduce oxidative stress damage in H2O2 induced chondrocytes by down-regulating the expression of pro-inflammatory factors like MMP-13, IL-6 and TNF-α while up-regulating the antioxidant factors such as (SOD, CAT, GSH). There was a dramatic reduction in OA severity after PAN-SPD nanofibrous membrane treatment in OA joints compared to the untreated group after a 8-week therapy. Overall, this study provides effective strategies and new ideas for the future clinical treatment of OA or oxidative stress-related diseases.
Seroprevalence of immunoglobulin G antibodies against SARS-CoV-2 in Cyprus
Authors: Papaneophytou Christos , Nicolaou Andria , Pieri Myrtani , Nicolaidou Vicky , Galatou Eleftheria , Sarigiannis Ioannis , Pantelidou Markella , Panayi Pavlos , Thoma Theklios , Stavraki Antonia , Argyrou Xenia , Kalogiannis Tasos , Yiannoukas Kyriacos , Petrou Christos C. , Felekkis Kyriacos 
Published: February 2022

Abstract
Background: Four vaccines that have been authorized in the European Union offer different levels of protection against SARS-CoV-2 by generating immune responses against the spike receptor-binding domain (RBD) of the virus. Monitoring the levels of IgG antibodies against the SARS-CoV-2 is important during the coronavirus disease 2019 (COVID-19) pandemic to plan an adequate and evidence-based public health response. Methods: We compared the levels of serum IgG antibodies against SARS-CoV-2 spike protein in three groups: i) individuals without evidence of prior infection with SARS-CoV-2 who received one or two doses of either an mRNA-based (Comirnaty BNT162b2/Pfizer-BioNTech or Spikevax mRNA-1273/Moderna) or an adenoviral-based vaccine (Vaxzervia ChAdOx1 nCoV-19 /Oxford-Astra Zeneca) (n=227), ii) unvaccinated individuals with evidence of prior infection with SARS-CoV-2 (n=109), and iii) individuals with evidence of prior infection with SARS-CoV-2 who received at least one dose of a vaccine (n=30). Unvaccinated individuals without evidence of prior infection with SARS-CoV-2 were used as a control group (n=211). Results: The levels of specific SARS-CoV-2 IgG antibodies in all three groups were significantly higher (p<0.001) compared to the control group. The highest levels of virus-specific IgG antibodies were observed in individuals who were infected with SARS-CoV-2 and received at least one dose of a vaccine. Our analyses also revealed that the levels of specific anti- SARS-CoV-2 IgG levels were higher in individuals who received two doses of a licensed vaccine, regardless of the vaccine technology (mRNA-based and adenoviral vector-based). Furthermore, anti- SARS-CoV-2 IgG levels were higher in previously uninfected participants who received at least one dose of a vaccine compared to the unvaccinated individuals with evidence of prior infection. Conclusions: Our results indicate that vaccine-induced responses lead to higher levels of IgG antibodies compared to those produced following infection with the virus. In agreement with previous studies, our results suggest that among individuals previously infected with SARS-CoV-2, even a single dose of a vaccine is adequate to elicit high levels of humoral immunity.
Environmental viromes reveal global virosphere of deep-sea RNA viruses
Authors: Zhang Xiaobo 
Published: February 2022

Abstract
On the earth, the most abundant and diverse life forms are viruses. Both DNA viruses and RNA viruses play important roles in marine ecosystems via regulating biogeochemical cycles. However, the virome of marine RNA viruses has not been explored so far. Here, we established the global virome dataset of deep-sea RNA viruses that were purified from 133 sediment samples collected from typical deep-sea ecosystems (hydrothermal vents, cold seeps, ocean basins and mid-ocean ridges) of the Pacific Ocean, Indian Ocean and Atlantic Ocean. A total of 85,059 viral operational taxonomic units (vOTUs) were identified, of which only 1.72% were hitherto known, indicating that the deep-sea sediment is a repository of novel RNA viruses. The vOTUs were classified into 20 viral families, including prokaryotic (7.09%) and eukaryotic (65.81%) RNA viruses, of which Retroviridae was the most abundant. Furthermore, circular genome analysis revealed 1,463 deep-sea RNA viruses with complete genomes, the majority of which were unclassified. The distribution and differentiation of deep-sea RNA viruses were mainly influenced by the habitat. Taken together, the deep sea is a reservoir of novel RNA viruses, and our study is the first to analyze the composition and diversity of RNA viruses in deep-sea ecosystems.
Identification of a conserved drug binding pocket in TMEM16 proteins
Authors: Cheng Yifan , Feng Shengjie , Puchades Cristina , Ko Juyeon , Figueroa Eric , Chen Yifei , Wu Hao , Gu Shuo , Han Tina , Li Junrui , Ho Brandon , Shoichet Brian , Jan Yuh Nung , Jan Lily 
Published: February 2022

Abstract
The TMEM16 family of calcium-activated membrane proteins includes ten mammalian paralogs (TMEM16A-K) playing distinct physiological roles with some implicated in cancer and airway diseases. Their modulators with therapeutic potential include 1PBC, a potent inhibitor with anti-tumoral properties, and the FDA-approved drug niclosamide that targets TMEM16F to inhibit syncytia formation induced by SARS-CoV-2 infection. Here, we report cryo-EM structures of TMEM16F associated with 1PBC and niclosamide, revealing that both molecules bind the same drug binding pocket. We functionally and computationally validate this binding pocket in TMEM16A as well as TMEM16F, thereby showing that drug modulation also involves residues that are not conserved between TMEM16A and TMEM16F. This study establishes a much-needed structural framework for the development of more potent and more specific drug molecules targeting TMEM16 proteins.
Not enough by half: NFAT5 haploinsufficiency in two patients with Epstein-Barr virus susceptibility
Authors: López-Rivera Daniela Olivia , Castano-Jaramillo Lina Maria , Yamazaki-Nakashimada Marco Antonio , Ramírez-Uribe Rosa María Nideshda , Delgado Celso Tomás Corcuera , Medina-Torres Edgar Alejandro , Berrón-Ruiz Laura , Espinosa-Padilla Sara Elva , Cruz-Munoz Mario Ernesto , Mendoza Selma Cecilia Scheffler , Reyes Saul Oswaldo Lugo 
Published: February 2022

Abstract
INTRODUCTION: The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals. OBJECTIVE: We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology. METHODS: After informed consent, we reviewed their electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and functional assays, including lymphoproliferation, cytotoxicity, and natural killer cells characterization. RESULTS: We describe 2 cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis. DISCUSSION: NFAT5 is an important regulator of the immune response. Haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility is another manifestation in the spectrum of this disease.
Microvascular invasion Risk Scores affect the estimation of early Recurrence after Resection in Patients with Hepatocellular Carcinoma: A Retrospective Study
Authors: Wang Sheng , Zheng Weizhi , Zhang Zhencheng , Zhang Guohua , Huang Danjiang 
Published: February 2022

Abstract
Background: Microvascular invasion (MVI) is a histological factor that is closely related to the early recurrence of hepatocellular carcinoma (HCC) after resection. To investigate whether the preoperative risk factors based on MVI status can be used to estimate early recurrence of HCC after resection.Methods: Between January 2018 to March 2021, a total of 108 patients with surgically treated single HCC was retrospectively included in our study. Fifty-one patients were pathologically confirmed with MVI and 57 patients were absent of MVI. Univariate and multivariate logistic regression analysis of preoperative laboratory and magnetic resonance imaging (MRI) features were used to screen noninvasive risk factors in association with MVI in HCC. A risk score based on the odds ratio (OR) values of MVI-related risk factors was calculated to estimate the early recurrence after resection of HCC. Results: In multivariate logistic regression analysis, tumor size>2cm (P=0.024, OR=3.05, 95% CI:1.19-11.13), PIVKA-Ⅱ >32 mAU/ml (P=0.001, OR=4.13, 95% CI:1.23-11.38), irregular tumor margin (P=0.018, OR=3.10, 95% CI:1.16-8.31) and ADC <1007 ×10-3mm2/s (P=0.035, OR=2.27, 95% CI:1.14-7.71) were independent risk factors correlated to MVI in HCC. Risk scores of patients were calculated and were then categorized into high, moderate and low risk levels. In multivariate cox survival analysis, only high risk score of MVI was an independent risk factor of early recurrence (P=0.026, OR=1.86, 95% CI:1.08-3.22), with a sensitivity and specificity of 0.52, 0.88, respectively.Conclusions: A risk score based on MVI status can help stratify patients in high risk of early recurrence after resection of HCC.
Incorporating Social Determinants of Health into the Mathematical Modelling of HIV/AIDS
Authors: de Oliveira Robson Bruniera , Rubio Felipe Alves , Anderle Rodrigo , Sanchez Mauro , de Souza Luis Eugenio , Macinko James , Dourado Ines , Rasella Davide 
Published: February 2022

Abstract
Background
Currently, it is estimated that 37.6 million people are living with the HIV/AIDS virus worldwide, placing HIV/AIDS among the 10 leading causes of death, mostly among low- and lower-middle-income countries. Despite the effective intervention in the prevention and treatment, this reduction did not occur equally among populations, subpopulations and geographic regions. This difference in the occurrence of the disease is associated with the social determinants of health (SDH), which could affect the transmission and maintenance of HIV. With the recognition of the importance of SDH in HIV transmission, the development of mathematical models that incorporate these determinants could increase the accuracy and robustness of the modeling. This article aims to propose a theoretical and conceptual way of including SDH in the mathematical modeling of HIV/AIDS.
Methods
The theoretical mathematical model with the Social Determinants of Health has been developed in stages. For the selection of SDH that were incorporated into the model, a narrative literature review was conducted. Secondly, we proposed an extended model in which the population (N) is divided into Susceptible (S), HIV-positive (I), Individual with AIDS (A) and individual under treatment (T). Each SDH had a different approach to embedding in the model.
Results
A total of 31 SDH were obtained in the review, divided into 4 groups: Individual Factors, Socioeconomic Factors, Social Participation, and Health Services. In the end, 4 determinants were selected for incorporation into the model: Education, Poverty, Use of Drugs and Alcohol abuse, and Condoms Use.
Conclusions
The equations presented with the chosen SDH exemplify some approaches that we can adopt when thinking about modeling social effects on the occurrence of HIV. The recognition of the importance of including the SDH in the modeling and studies on HIV/AIDS is evident, due to its complexity and multicausality. Models that do not take into account in their structure, will probably miss a great part of the real trends, especially in periods, as the current on, of economic crisis and strong socioeconomic changes.
Circular RNA hsa_circ_0023404 promotes the proliferation, migration and invasion in endometrial cancer cells through regulating miR-217/MAPK1 axis
Authors: Chen Zhuoying , Huang Meixiu , You Jiaying , Lin Yanhua , Huang Qiaoyun , He Caiping 
Published: February 2022

Abstract
Aim: Studies indicated that Circular RNA hsa_circ_0023404 play a critical role in cancer progression. The aim of our research is to investigate the functions of hsa_circ_0023404 in endometrial cancer （EC） and the potential molecular mechanism.Methods: We used RT-qPCR and Western blot approach to detect the expressed levels of related genes in EC cell lines. Transfected siRNAs were applied to knockdown the level of related mRNA in cells. Cell proliferation by CCK-8 assay and colony formation assay were applied to detect cell proliferation. Transwell migration and invasion assay was for detecting the migration and invasion of the cells. Results: RT-qPCR showed that the level of hsa_circ_0023404 and MARK1 mRNA were upregulated but mirR-217 was decreased in three endometrial cancer cell lines. Knockdown of hsa_circ_0023404 by siRNA markedly increased the level of miR-217 and reduced the proliferation of the Ishikawa cells。 It also inhibited the cell migration and invasion. Anti-miR-217 can reverse the promoted proliferation, migrations and invasion of Ishikawa cells mediated by si-circ_0023404. si-MARK1 restored the inhibited cell proliferation, migration and invasion of the co-transfected Ishikawa cells with si- circ_0023404 and anti-miR-217.Conclusion: hsa_circ_0023404 exerts a tumor-promoting role in endometrial cancer by regulating miR-217/MARK1 axis. hsa_circ_0023404 inhibit miR-217 as sponge which inhibit endometrial cancer cell growth and metastasis. MARK1 is downstream target of miR217 and upregulated by hsa_circ_0023404/miR-217 axis and involved in the endometrial cancer progression.
Optimal flood susceptibility model based on performance comparisons of LR, EGB, and RF algorithms
Authors: Youssef Ahmed M. , Mahdi Ali M. , Pourghasemi Hamid Reza 
Published: February 2022

Abstract
The Wadi El-Matulla, located in the eastern desert of Egypt, is the most important water basin. The Qift - Qusayr highway (west-east direction) and the Cairo - Aswan eastern desert highway (north-south) pass through the basin. Many urban areas (villages and industrial areas) and agricultural lands are located at the outlet of these basins. In addition, the basin has a promising potential for future economic and urban development as it is located within the Golden Triangle (governmental megaproject). The current study investigates flood hazard modeling and its impact on the area. To determine the optimal algorithm for flood susceptibility mapping, performance comparisons of three techniques were conducted: logistic regression (LR), extreme gradient boosting (EGB), and random forest (RF). Remote sensing, topographic, geologic, and meteorological data were used with the help of field visits to provide spatial database and inventory datasets required by the models. The models’ performances were assessed using five statistical indices, ROC, overall accuracy (OAC), kappa index (Ka), RMSE, and mean absolute error (MAE). Our findings indicate that RF is the optimal algorithm for flood susceptibility mapping, followed by EGB and LR. RF provides high performance with high values of ROC (93%), OAC (88%), and Kappa index (0.85) and the lowest values of RMSE (0.34) and MAE (0.12). Finally, the RF model was verified using sentinel-1 images for real floods in 2016 and 2021, and it provides good agreement. The optimal model could help the decision makers and planners to protect the existing facilities and plan the future projects in non-flood prone areas.
Study on kinetics, thermodynamics and co-pyrolysis studies of sugarcane bagasse and expanded polystyrene
Authors: Mohapatra Sowhm Swain , Gouda Narayan , Mohapatra Soumya Sanjeeb , Singh Raghubansh Kumar 
Published: February 2022

Abstract
The kinetic studies on co-pyrolysis of sugarcane bagasse, and expanded polystyrene (waste thermocol) was performed using a thermogravimetric analyzer to decipher the mechanism of co-pyrolysis at 5, 10, 15, and 20°C min−1 and to estimate the kinetic triplet and thermodynamics of the co-pyrolysis process. The kinetic parameter values were estimated using Maples first order fitting process.. The co-pyrolysis experiments was performed in a semi-batch reactor at 10°C min−1 in an inert nitrogen atmosphere, from ambient temperatures upto 700°C. The outcome revealed that the optimum temperature and blending ratio was 550°C and 1:3 blending ratio of (sugarcane bagasse:thermocol waste) for the optimum bio-oil yield of 66.75 wt. %. The characterization of the co-pyrolysis bio-oil using FT-IR revealed the presence of more amount of aromatic compounds and hydrocarbons. The increase in aromatic compounds was mostly due to the addition of thermocol waste, which is an aromatic polymer.