bluuebunny/crossref_metadata_2025 huggingface dataset:
Endometrial Factors Causing Subfertility in Cows
Authors: Matsuyama Shuichi , Nakamura Sho , Minabe Shiori , Sakatani Miki , Takenouchi Naoki , Sasaki Takuya , Iwata Hisataka , Kimura Koji
Published: February 2021

An inadequate uterine environment is believed to promote embryonic mortality and to result in reproductive failure. We conducted global endometrial gene expression analyses in fertile and subfertile cows to investigate the cause of reproductive failure. The gene expression pattern differed between fertile and subfertile cows; subfertile cows showed a greater number of highly expressed genes than the fertile cows. In particular, the genes encoding ribosomal proteins and mitochondrial oxidative phosphorylation were found among the more highly expressed genes in subfertile cows. The mitochondrial DNA copy number was significantly higher in the endometrium of subfertile cows, whereas the ATP content did not differ between fertile and subfertile cows. Quantitative RT-PCR analysis demonstrated that the expression of BCL2L13 was significantly lower in subfertile cows than that in fertile cows. These results suggest that cellular senescence occurs in the endometrium and causes poor-quality mitochondria to accumulate there by reducing mitophagy in subfertile cows. Administration of resveratrol into the uteri of subfertile cows partially increased endometrial BCL2L13 mRNA levels, decreased mitochondrial DNA copy numbers, and allowed for conception following embryo transfer. Collectively, these results suggest that decreased mitophagy in the endometrium of subfertile cows may contribute to infertility.
DNA Methylation Signatures Associated With Prognosis of Gastric Cancer
Authors: Dai Jin , Nishi Akihiro , Li Zhe-Xuan , Zhang Yang , Zhou Tong , You Wei-Cheng , Li Wen-Qing , Pan Kai-Feng
Published: February 2021

Background: Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study.Methods: Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n=381), disease-specific survival (DSS, n=372), and progression-free interval (PFI, n=383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n=247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression.Results: We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed. Conclusions: We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.
Persistence and Adherence to Biologic Therapies in Juvenile Idiopathic Arthritis
Authors: Nieto-González Juan Carlos , Trives Laura , Melgarejo-Ortuño Alejandra , Ais Aranzazu , Serrano-Benavente Belen , Sanjurjo María , Álvaro-Gracia José María , Monteagudo-Sáez Indalecio
Published: February 2021

BackgroundJuvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease that often requires the use of biological therapies to control disease activity. Persistence and adherence to treatment are important aspects on which we have scarce information.MethodsWe performed a longitudinal, retrospective, and observational study based on daily clinical management of JIA patients. We calculated the clinical remission status at 6 and 12 months. Persistence of biological therapy was evaluated by Kaplan-Meier curves and adherence by the Medication Possession Ratio (MPR).ResultsWe included 68 patients who received biological therapy. Of these, 11 (16.2%) and 5 (7.4%) required a second and third biological, respectively. Persistence rate of biological therapies at 5 years was 64%, with no differences between the first and second biological line. Adherence was high the first year of treatment (MPR80: 96.3%) as well as the second and third years (MPR80: 85.2% and 91.8% respectively).ConclusionsPersistence and adherence to biological therapies were remarkably high in our JIA cohort. Adherence to biological treatments could be related to a higher probability of accomplishing Wallace remission criteria at 6 months, but it was not confirmed at 12 months.
Enhanced Mutualistic Symbiosis Between Soil Phages and Bacteria With Elevated Chromium-induced Environmental Stress
Authors: Huang Dan , Yu Pingfeng , Ye Mao , Schwarz Cory , Jiang Xin , Alvarez Pedro J.J.
Published: February 2021

Background: Microbe-virus interactions have broad implications on the composition, function, and evolution of microbiomes. Elucidating effects of environmental stresses on these interactions is critical to identify the ecological function of viral communities and understand microbiome environmental adaptation. Heavy metal-contaminated soils represent a relevant ecosystem to study the interplay between microbes, viruses and environmental stressors.Results: Metagenomic analysis revealed that Cr pollution adversely altered the abundance, diversity and composition of viral and bacterial communities. Host-phage linkage based on CRISPR indicated that, in soils with high Cr contamination, the abundance of phages associated with heavy metal tolerant hosts increased, as did the relative abundance of phages with broad host ranges (identified as host-phage linkages across genera), which would facilitate transfection and broader distribution of resistance genes in the bacterial community. Examining variations along the pollutant gradient, phage-bacteria interactions shifted to a more protective mutualistic relationship in the face of greater environmental stresses. Specifically, the fractions of lysogens in bacterial communities (identified by integrase genes within bacterial genomes and prophage induction assay by mitomycin-C) were positively correlated with Cr contamination levels. Furthermore, viral genomic analysis demonstrated that lysogenic phages under higher Cr-induced stresses carried more auxiliary metabolic genes regulating microbial heavy metal detoxification.Conclusion: With the intensification of Cr-induced environmental stresses, the composition, replication strategy, and ecological function of the phage community all evolve alongside the bacterial community to adapt to extreme habitats. This results in a transformation of the phage-bacteria interaction from parasitism to protective mutualism in extreme environments, and underscores the influential role of phages in bacterial adaptation to pollution-related stress and in related biogeochemical processes.
Acute Adverse Effects of Metallic Nanomaterials on Cardiac and Behavioral Changes in Daphnia Magna
Authors: Park Jihoon , Park Chang Gyun , Sung Baeckkyoung , Lee Yong Oh , Ryu Chang Seon , Park Ja Young , Kim Young Jun
Published: February 2021

Nanomaterials are widely believed to induce toxic effects on organisms by evoking oxidative stress. In this study, we evaluated the toxic effects of nanomaterials on cardiac and behavioral changes in Daphnia magna under varying exposure conditions. Titanium dioxide nanoparticles (TiO2 NPs), silver nanoparticles (AgNPs), and silver nitrate (AgNO3) were selected for the acute toxicity tests. The adverse effects of the substances on the neonates including heart rate, swimming speed, and oxidative stress, were measured. The heart rate level decreased as the concentration of NPs and silver ions (Ag+) increased. The average swimming speed was measured to be approximately 15 mm/min for the control group. The swimming speed generally increased for longer exposure to both NPs, although it reached a plateau at the lowest concentration of AgNPs. A similar but less clear trend was observed for Ag+. For all substances, the overall swimming speed exhibited no correlation or weak negative correlations with the exposure concentration. The oxidative stress levels increased after exposure compared to the control group. We conclude that aquatic nanotoxicity tests should consider multilevel physicochemical, physiological, and behavioral parameters for the official guidelines to quantify more robust adverse outcomes.
Contexts and Mechanisms That May Facilitate or Inhibit the Implementation of Assisted Decision-Making Policy With Older People in Acute Care Settings: A Qualitative Analysis of the Experiences of Health and Social Care Professionals, Older People and Family Carers.
Authors: O'Donnell Deirdre , Davies Carmel , Christophers Lauren , Shé Éidín Ní , Donnelly Sarah , Kroll Thilo
Published: February 2021

Background: Assisted Decision-Making (ADM) legislation in Ireland provides a statutory basis for the right of all individuals, including those with a disability, to be supported to participate as fully as possible in all decisions which affect their lives. ADM with older people who have impaired cognition may prove challenging for acute healthcare services. Methods: A qualitative exploration of the experiences of health and social care professionals, older people with and without a diagnosis of dementia and their family carers (N=39) was conducted. A realist programme theory described by Davies et al.(2019) provided an initial coding framework which was adapted through inductive coding of the accounts. Results: Personalisation was established as the core theme, supported by four additional themes reflecting implementation domains: Environment and Resources, Social Restructuring, Education, Training and Enablement and Culture and Leadership.Conclusions: A restructuring of the social and physical infrastructure of acute settings was found to be necessary to maximise insight, ascertain preferences and assist the decision-making of older people. A cultural climate which fosters personalisation is required alongside the cultivation of risk tolerance, collective leadership and inter-professional collaboration. The adapted programme theory described in this article informs policy and practice planning in Ireland. It also contributes to wider debates internationally on the role of socio-cultural and political contexts for ADM implementation.Patient or Public Contribution: A panel of public representatives of older people were consulted in the development of the grant application. A representative from Alzheimer’s Society Ireland and Family Carers Ireland were project steering committee members guiding design and strategy.
Environmental Kuznets Curve Revisit: Role of Economic Diversity in Environmental Degradation
Authors: Ghazal Raza , Karimi Mohammad Sharif , Javaheri Bakhtiar
Published: February 2021

Background: Unlike the classical view, a new path of economic growth and development among the emerging and developing nations seems to have distinct impact on environment. Customary patterns of production and consumption have undergone significant changes and the new “growth with non-smoke-staks” has put the developing economies on a path that can change Environmental Kuznets Curve (EKC) fundamentally. With this view, the current study attempts to examine how these growth patterns among developing world have impacted the degradation of environment. We argue that including income per capita and share of manufacturing would not capture the full growth dynamic of developing and emerging countries and therefore it masks the real impacts on environmental degradation. To this end, we introduce the Economic Complexity Index (ECI) to the model to reflect the full impacts of new growth approaches on CO2 emission levels by using a panel data analyses of 100 emerging and developing countries over 1963-2018 period.Results: The results indicate that complexity of the economies of developing and emerging countries has added to the CO2 emission levels in absolute terms but it has helped to reduce the CO2 intensity. Conclusions: The implications of the findings for developing and developed countries could be quite significant. For advanced economies, a downwardly-shifted Kuznets curve implies that, on one hand, technology transfers have been successful in curbing the environmental degradation of developing economies and, on the other hand, the economic transformation strategies of developing world is working in a sustainable way.
Experimental Analysis of Hydraulic Jump at High Froude Numbers
Authors: Simsek Oguz , Akoz Mevlut Sami , Oksal Nazire Goksu Soydan
Published: February 2021

The hydraulic jump is a rapid transition state from supercritical to subcritical flow that occurs commonly in rivers, prismatic channels and downstream of spillways. In this study, the characteristics of the hydraulic jump in a stilling basin downstream of the spillway chute channel with the slopes of α = 12o and 30o were investigated experimentally for different Froude numbers of incoming flow, Fr1 = 7, 7.5, 8, 9, 10 and 12, and relative heights of sill in the range of 4 < hs/h1 (S) < 13 (S relative height). In the experiments, in which velocity field measured by laser Doppler Anemometry, it was particularly focused on the effects of both different structural configuration and flow conditions on the hydraulic jump and energy dissipation ratio. Experimental measurements showed that the length of hydraulic jump and the roller zone increases with the decrease of the sill height for α = 12o and 30o. In addition, the length of the hydraulic jump and roller zone increased with decreasing Froude numbers. The turbulence intensity in the jump region was determined to be greater than the turbulence intensity in the region near the bottom of stilling basin. The turbulence intensity, in general, tended to decrease with decreasing Froude number.
A Novel Immune-Related lncRNA Signature predict the Immune Landscape and Prognosis for Head and Neck Squamous Cell Carcinoma
Authors: Cai Zhimou , Chen Lin , Lin Yu , Lei Wenbin
Published: February 2021

Background: The tumor immune microenvironment is known to play an important role in head and neck squamous cell carcinomas (HNSCC). Reliable prognostic signatures that could accurately predict immune landscape and survival in HNSCC patients are vitally needed to promote a better individualized and effective treatment.Methods: HNSCC transcriptome data and clinical data in The Cancer Genome Atlas (TCGA) were embedded in our study. The differentially expressed irlncRNAs were identified by differential co-expression analysis, and recognized differently expressed irlncRNA (DEirlncRNA) pairs using univariate analysis. Cox and lasso regression analysis was used to identify DEirlncRNA pairs related to overall survival (OS) and build the prediction model. Then, we compared the areas under curve (AUC) with other published lncRNA signatures, counted the akaike information criterion (AIC) values of 3-year receiver operating characteristic curve, and identified the cut-off point to set up an optimal model for distinguishing the high- or low- risk groups among patients with HNSCC. Receiver operating characteristic (ROC)curves and Kaplan–Meier plot curves were used to validate the prediction model. Besides, We then reevaluated them from the viewpoints of clinical factor, tumor-infiltrating immune cells, chemotherapeutics efficacy, and immunosuppressed biomarkers.Results: We built a risk score model based on 18 DEirlncRNA pairs. The risk model is closely related to the OS of HNSCC patients. The hazard ratio (HR) is 1.376 [95% CI (confidence interval) 1.302-1.453] and log-rank P-value < 0.0001. Compared with two recently published lncRNA signatures, DEirLncRNA pairs signature has higher AUC score which showed the better prognostic performance. Additionally, the signature score showed a positive correlation with aggressive outcomes of HNSCC, such as low immunity score, significantly reduced CD8+ T cell infiltration and lowly expressed immunosuppressed biomarkers. However, high-risk groups of patients may have high chemotherapeutics sensitivity.Conclusions: The signature established by paring irlncRNA regardless of expression levels showed a promising clinical prediction value and revealed tumor immune microenvironment in HNSCC patients which might help in distinguishing those who could benefit from anti-tumor immunotherapy.
Novel Metabolites Identified From Bacillus Safensis and Their Antifungal Property Against Alternaria Alternata 
Authors: Prakash Jai , Arora Naveen
Published: February 2021

Plant growth promoting rhizobacteria offer an effective and eco-sustainable solution to protect crops against phytopathogens. In the present study, Bacillus safensis STJP (NAIMCC-B-02323) from the rhizospheric soil of Stevia rebaudiana showed strong biocontrol activity against phytopathogen, Alternaria alternata. B. safensis STJP produced antifungal volatile organic compounds (AVOC). In the presence of AVOC, there was no conidia germination, mycelium growth was inhibited, and hyphae ruptured as observed by scanning electron microscopy (SEM). When mycelium of the fungus from bacterial treated plate was transferred into fresh potato dextrose agar plate, A. alternata could not grow. Extracted AVOC from B. safensis STJP were identified by thin-layer chromatography (TLC), fourier-transform-infrared spectroscopy (FT-IR) and gas-chromatography-mass spectrometry (GC-MS). In total 25 antifungal metabolites were identified by GC-MS analysis having alcohol, alkane, phenol, alkyl halide and aromatic compounds. Five compounds (phenol, 2,4-bis (1,1-dimethylethyl)-, 3-hexadecanol, pyrrolo(1,2-a)pyrazine-1,4-dione, 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo(1,2-a:1',2'-d)pyrazine and hexadecanoic acid) completely inhibited the mycelium growth, controlling spore formation and conidia germination of A. alternata. This study concluded that AVOC producing B. safensis can be used as a green-fungicide against A. alternata. Bacterial metabolites could pave the way for the development of next generation biopesticide. This can be a reliable technology to enhance the quality and reliability of biopesticides.
Effect of Dividing the Water Transmission Pipe Line in Modeling Residual Chlorine, Case Study: Isfahan Water Transmission Line
Authors: Frozandeh Yasaman , Dehnavi Ali , Shanehsazzadeh Ahmad
Published: February 2021

In assessing the quality of drinking water in transmission and distribution lines, the study on chlorine reactions is of particular importance. Chlorine decay happens in bulk and wall and it is mainly affected by the water age which depends on the transmission line length. Residual chlorine concentration in Isfahan water transmission line (IWTL) is simulated through three decay models, namely the first order, parallel first order and second order single reactant (SR model) which incorporated in EPANET and EPANET MSX, respectively. The results of the models are compared through two approaches, one is the one-part approach (OPA) whereby chlorine decay simulation is performed taking into account the whole line as one section and the second is multi-part approach (MPA) whereby the line is divided into two sections and decay coefficients of chlorine for each section are separately determined. Results show that in the OPA, the SR model in summer and the parallel model in winter are the best kinetic models. While in the MPA, the results of first order model has the same order of accuracy as the more complex models of parallel and SR models. In general, the simple first order model in the MPA applied by EPANET2.0 s/w provides acceptable level of accuracy in compare to the complex models applied in EPANET MSX s/w. The average RMSE volumes are reduced from 0.078 in OPA to 0.029 in MPA in summer and from 0.059 to 0.015 in winter, indicating that the dividing the line in simulation procedure and considering the individual decay coefficient for each part, considerably improves the results, more effectively than the application of advanced decay models.
Efficient Production of Human Hyaluronidase PH20 in HEK293T Cells Using Site Specific Integration
Authors: Ata-abadi Nafiseh Sanei , Dormiani Kianoush , Varnosfaderani Shiva Rouhollahi , Forouzanfar Mahboube , Pirjamali Leila , Nasr-Esfahani Mohammad Hossein , Hajidavaloo Reza Moradi
Published: February 2021

PH20 is hyaluronidase that hydrolyze the glycosidic bond of hyaluronic acid as a major proteoglycan found in extracellular matrices. PH20 is used in the subcutaneous space to increase the dispersion and absorption of co-administered drugs. PH20 is also injected against solid tumors for to better penetration of anticancer agents into the tumor tissue and inhibiting the tumor cell growth. In the present study, we have developed HEK293T stable cell lines secreting His-tagged human recombinant PH20 (rhPH20) in the culture supernatant through the PhiC31 integrase system. The produced rhPH20 was quantify using ELISA and turbidimetric assay and its activity was assessed through treatment of mouse cumulus-oocyte-complex (COCs). Furthermore, we have characterized genomic integration of PH20-containing vectors in one of the isolated clone with the highest levels of rhPH20 production. Our results demonstrated that the secreted rhPH20 in the culture supernatant contained a specific activity of approximately 3.5 IU/ml and it was properly able to denote all mouse oocytes. Consequently, it was revealed that PH20-expressing vectors integrated site-specifically in the PhiC31 pseudo attP sites in the host genome. Taken together, these results confirmed successful application of PhiC31 integrase as a robust approach for production of soluble, active rhPH20 in HEK293T cells.
Spectral-Domain Optical Coherence Tomography For Evaluating Palisades of Vogt in Ocular Surface Disorders With Limbal Involvement
Authors: Chen Ying-Yi , Sun Yi-Chen , Tsai Chia-Ying , Chu Hsiao-Sang , Wu Jo-Hsuan , Chang Huai-Wen , Chen Wei-Li
Published: February 2021

Spectral-domain optical coherence tomography (SD-OCT) has been used to observe the morphology and epithelial thickness of the palisades of Vogt (POV) with satisfactory resolutions. In this study, we used SD-OCT to examine the microstructure of the POV in ocular surface disorders with limbal involvement and to detect subclinical limbal pathologies based on five parameters. Eighteen eyes of 10 patients (2 men and 8 women; mean age, 48.7 ± 14.0 years) with advancing wavelike epitheliopathy (AWE) and 15 eyes of 9 patients (2 men and 7 women; mean age, 30.3 ± 18.2 years) with phlyctenular keratitis/ocular rosacea were recruited. SD-OCT could detect abnormal changes in the POV in 100% of the lesion sites. In presumed-healthy areas of the diseased eyes diagnosed by slit-lamp biomicroscopy, SD-OCT detected abnormal changes in the POV in 100% of the eyes in both the AWE and phlyctenular keratitis/ocular rosacea groups. In patients with unilateral disease, abnormal changes in the POV were detected by SD-OCT in 50% and 100% of presumed-healthy eyes diagnosed by slit-lamp biomicroscopy in the AWE and the phlyctenular keratitis/ocular rosacea group, respectively. SD-OCT is powerful in detecting POV changes in ocular surface disorders and can provide useful information that cannot be provided by slit-lamp biomicroscopy.
Investigation of Optical Properties for N and F Doped Triangular Shaped Carbon Molecules 
Authors: Xu Shuhong , Tan Linfeng , Liu Fan , Cui Yiping , Wang Chunlei , Zhang Rong
Published: February 2021

Optical properties of N and F doping triangular shaped carbon molecules have been investigated in theory and experiment. The theoretical results showed that carbon molecules with impurity F and Cl have the same characters with pure carbon. Doping N into pure carbon molecule would change the optical rotation at 589nm. For doping N replacing hydrogen atom structures (N-doping 1 and N-doping 2 molecules), the absorption spectra of them are similar to pure carbon molecule. However, for molecules with impurity N atom in benzene ring (N-doping 3 and N-doping 4 molecules), the peaks of wavelength of absorption spectra shift to long wavelength compared to that of pure carbon molecule. Moreover, the delocalization of molecular orbital (MO) is different from pure carbon molecule, which is caused by the impurity N changing the electrons distribution of benzene ring. We have calculated 3 without H and 4 without H molecules which are removing hydrogen atom in nitrogen atom from N-doping 3 and 4. 3 without H and 4 without H molecules have similar optical properties with pure carbon molecule. The results testified that the impurity N and F would not change the optical properties of carbon molecule if impurity did not change the delocalization of all benzene rings.
Apolipoprotein M in High Density Lipoprotein Protects Against Astrocyte Apoptosis Induced By Ischemic Insult Via Sphingosine 1-Phosphate Signaling
Authors: Huang Xiaojia , Zhai Zhiqi , Zhou Ting , Sheng Chengju , Zhou Chao , Deng Linhong
Published: February 2021

Apolipoprotein M (ApoM) has been reported to be contained in high density lipoprotein (HDL) and bound with sphingosine-1-phosphate (S1P). ApoM-associated HDL exerts protective effects against cell death. The aims of the study were to evaluate the effects of ApoM-associated HDL on astrocytes following ischemic insult. Primary cultured mouse astrocytes were treated with oxygen-glucose deprivation (OGD) followed by recovery. The astrocytes underwent apoptosis after treatment with OGD for 4 h and recovery for 24 h. The addition of HDL with ApoM attenuated apoptotic cell death, but HDL without ApoM did not show any effect. Free S1P or ApoM-bound S1P promoted cell survival and inhibited apoptosis. Only S1P receptor 1 (S1PR1) expression was upregulated and blockage of S1PR1 with specific inhibitor or genetic knockdown of S1pr1 abolished the protective effects. In addition, administration of ApoM containing HDL or free S1P induced activation of Akt and Erk in the astrocytes, and pharmacological inhibition of Akt and Erk rescued cell death after OGD treatment. Taken together, ApoM is required for the protective effects of HDL, which depends on delivery of S1P to S1PR1 by ApoM in HDL, indicating ApoM may be a neuroprotective constituent in plasma.
Deleterious mutation load in diverse cattle breeds of the world
Authors: Subramanian Sankar
Published: February 2021

Domestication of wild animals results in a reduction in the effective population size and this could affect the deleterious mutation load of domesticated breeds. Furthermore, artificial selection will also contribute to accumulation deleterious mutations due to the increased rate of inbreeding among these animals. The process of domestication, founder population size, and artificial selection differ between cattle breeds, which could lead to a variation in their deleterious mutation loads. We investigated this using the whole genome data from 432 animals belonging to 54 cattle breeds of the world. Our analysis revealed a negative correlation between the genomic heterozygosity and the ratio of amino acid changing diversity to silent diversity. This suggests a proportionally higher amino acid changing Single Nucleotide variants (SNVs) in breeds with low diversity. Our results also showed that breeds with low diversity had more high-frequency (DAF > 0.51) deleterious SNVs than those with high diversity. A reverse trend was observed for the low-frequency (DAF ≤ 0.51) deleterious SNVs. Overall, taurine cattle breeds had more high-frequency deleterious SNVs than indicine (or taurine-indicine hybrid) breeds. However, within taurine breeds European or Northeast Asian taurines had more high-frequency deleterious SNVs than East Asian or African taurine breeds. Similarly, within indicine breeds South Asian indicines had more high-frequency deleterious SNVs than East Asian indicine breeds. All the above observed patterns were reversed for low frequency deleterious SNVs. Some of the variation in the deleterious mutation load observed between different breeds could be attributed to the population sizes of the wild progenitors before domestication. However, the variations observed withing taurine and within indicine breeds could be due to the difference in the extent of inbreeding, strength of artificial selection and/or founding population size. The findings of this study imply that the rate of incidence of genetic diseases might vary between cattle breeds.
Place-based Power Production Deliberations in Saskatchewan: Engaging Future Sustainability 
Authors: Hurlbert Margot
Published: February 2021

This article reports research results from two day deliberative focus groups in three Saskatchewan communities addressing power production planning, in the context of climate change and sustainability. Mixed methods included pre and post-focus group surveys, coding and analysis of discussions, and the creation by each focus group of a strategy for sustainable power production in the future. Results of comparative case study analysis provide strong support for renewables and illustrate place based differences.All communities strongly supported wind, solar and hydroelectricity. Estevan, located in the south of the province in proximity to coal, oil and gas production and coal power generating plants supported coal, and coal with carbon capture and storage (CCS). Saskatoon (situate in the middle of the province) and Regina (the center of government and between the other two) stressed the importance of engaging the public in decision making, education, providing information, and the importance that all costs, risk, benefits across the entire lifespan of the power production source be considered. In contrast, Estevan was concerned about the cost implications of power production source choice across the entire socio-economic system, including the social cost of job loss on the welfare system. Public participation in decision making in Estevan was not a priority. The reflexivity of the focus groups in Estevan brought closer together divergent views and increased support for coal and coal with CCS.
RNA Sensor MDA5 Suppresses LINE-1 Retrotransposition By Regulating The Promoter Activity of LINE-1 5’-UTR
Authors: Yan Jiaxiu , Zhao Yifei , Du Juan , Wang Yu , Wang Shaohua , Wang Qing , Zhao Xu , Xu Wei , Zhao Ke
Published: February 2021

Background: Type 1 long interspersed elements, or LINE-1, are the only active retroelements in human cells. The retrotransposition process of LINE-1 can trigger the activation of the innate immune system and has been proposed to play a role in the development of several autoimmune diseases, including Aicardi-Goutières syndrome (AGS). In contrast, all known AGS-associated proteins, except MDA5, have been reported to affect LINE-1 activity. Thus, MDA5 is likely to also function as a LINE-1 suppressor. Results: MDA5 was found to potently suppress LINE-1 activity in a reporter-based LINE-1 retrotransposition assay. Although MDA5 is an endogenous RNA sensor able to activate the innate immune system, increased interferon (IFN) expression only weakly contributed to MDA5-mediated LINE-1 suppression. Instead, MDA5 effectively reduced the levels of LINE-1 ORF1p and ORF2p, as a result of the MDA5-mediated downregulation of the promoter activity of LINE-1 5’-UTR, and the subsequent generation of LINE-1 RNA. Interestingly, despite MDA5 being a multi-domain protein, the N-terminal 2CARD domain alone is sufficient to inhibit LINE-1 activity. Conclusion: Our data reveal that MDA5 functions as a promoter regulator and suppresses the promoter activity of LINE-1 5’-UTR. Consequently, MDA5 reduces LINE-1 RNA and protein levels, and ultimately inhibits LINE-1 retrotransposition. In contrast, MDA5-induced IFN expression only plays a mild role in MDA5-mediated LINE-1 suppression. In addition, the N-terminal 2CARD domain was found to be a functional region for MDA5 upon inhibition of LINE-1 replication. Thus, our data suggest that besides being an initiator of the innate immune system, MDA5 is also an effector against LINE-1 activity, potentially forming a feedback loop by suppressing LINE-1-induced innate immune activation.
Spatiotemporal change and attribution of potential evapotranspiration over China from 1901 to 2100
Authors: Peng Shouzhang , DING Yongxia
Published: February 2021

Global warming has accelerated surface water loss around the world. This study investigates in detail the change and attribution of potential evapotranspiration (PET) across China from 1901 to 2100 by the Hargreaves model, based on a 1-km temperature dataset downscaled from the low-spatial-resolution datasets using a Delta downscaling framework. Results showed that (1) relative to 1961–1990, PET increased by 0.62% in the historic period (1901–2017) and 6.43–12.89% for the future period (2018–2100), suggesting considerable future drying for China. Moreover, these increments had strong spatial variations and the largest increases were detected in high-elevation regions; (2) PET over entire China demonstrated a nonsignificant upward trend during the historic period and significant upward trends for the future period. For each period and GCM, significant upward PET trends occupied a much larger percent area than significant downward trends; (3) PET variations during the historic period were most sensitive to mean temperature (TMP), while in the future period it was more sensitive to maximum temperature (TMX), suggesting a change in the primary sensitivity factor due to global warming; (4) minimum temperature (TMN) made the largest contribution (45%) to PET variations during the historic period, while TMX had the largest contribution (36–40%) in the future period. Therefore, the primary contributing factor might transform from TMN to TMX under climate change; and (5) PET variations exhibited strong spatial heterogeneity, detected on fine geographic scales, due to the use of downscaled dataset. Overall, the results present a deep insight for planning coping strategies of global warming in China.
Challenges of organizational structure and human resources in pre-hospital emergency medical systems for cardiopulmonary resuscitation: A qualitative study
Authors: Nayeri Nahid Dehghan , Senmar Mojtaba , BahramNezhad Fatemeh , HajiBabaee Fatemeh
Published: February 2021

The authors have requested that this preprint be removed from Research Square.
Multiplicative Gains, Non-ergodic Utility, and the Just One More Paradox (with Supplemental Information)
Authors: Myers John K.
Published: February 2021

Interest in multiplicative vs. additive returns on bets has been revived by Peters, who proposes ergodicity and added noise are useful in understanding utility preferences. Peters requires a Monte Carlo simulation to demonstrate empirically a supposed paradox that arithmetic expectation is inappropriate for multiplicative gain distribution forecasting. Here I formalize the r operator notation, which significantly simplifies multiplicative problems, as an extension of the arithmetic group's Δ/d discrete and continuous operators into the multiplicative semigroup. I show how the annihilating (absorbing) element of the multiplicative semigroup at 0, not +/-∞, may be used to conveniently represent nonlinear sequence occurrences, such as running out of money, without the need for special computer rules outside the mathematics. I use this to solve Peters' expected-value paradox elegantly, without ergodicities nor noise. But Peters misses the real paradox, called “Just One More”: the outcome of an advantageous additive gamble is identical to the outcome of a similar disadvantageous multiplicative gamble, after one trial; hence, by induction, an agent will keep playing. I propose games “Hero or Heroin” and “American Roulette” to highlight this paradox. This may help in explaining addiction. The Supplement contains further visualizations and arguments against the need and applicability of ergodics for utility. The results contribute to the understanding of repeated multiplicative gambles with annihilating states, and their utility.
Current Status on Training and Education on Public and Healthcare Workers towards Tuberculosis Elimination: Case in South Korea
Authors: Kang Taeuk , Park Seungkyu , Ryoo Sungweon
Published: February 2021

Tuberculosis, despite global effort to eliminate tuberculosis, still remains as a high burden to global public health. For tuberculosis elimination to be achieved, trainings and educations play pivotal role, tuberculosis control and prevention in particular. Internationally, several organizations are in charge of tuberculosis training and education program design, especially in its preparation and dissemination. In case of Korea, TB prevalence remains high, 59.0 per 100,000 in 2019. To overcome TB, institutes from both governmental and public sectors are organizing and providing tuberculosis-related training and education programs however, only few investigations on tuberculosis training in Korea was carried out, indicating difficulty lies in understanding and analyzing current TB training and education landscape. Hence, in this study, we have reviewed each institute and their roles in terms TB training and educational aspects as well as current tuberculosis status and strategies employed in Korea. Also, there are limitation lies in tuberculosis training and education thus, the call for global cooperation is necessary to response regional consideration against tuberculosis.
Deep learning analysis of drug-induced ECG changes to inform arrhythmia risk and improve diagnosis of congenital long QT syndrome
Authors: Prifti Edi , Fall Ahmad , Davogustto Giovanni , Pulini Alfredo , Denjoy Isabelle , Funck-Brentano Christian , Khan Yasmin , Durand-Salmon Alexandre , Wells Quinn , Leenhardt Antoine , Zucker Jean-Daniel , Roden Dan , Extramiana Fabrice , SALEM Joe-Elie
Published: February 2021

Congenital or drug-induced long-QT syndromes can cause Torsade-de-Pointes (TdP), a life-threatening ventricular arrhythmia. The current strategy to identify individuals at high risk of TdP consists on measuring the QT duration on the electrocardiogram (ECG), shown to provide limited information. We propose an original method, including training deep neural networks to recognize ECG alterations induced by QT-prolonging drugs, as a comprehensive evaluation of TdP risk. These models accurately detected patients taking QT prolonging drugs during ECGs, while discriminating for the presence and type of congenital long-QT. Moreover, they enhanced prediction of drug-induced TdP events in addition to QT measurement. Analyses of these models revealed footprints of the torsadogenic risk and clinically relevant patient stratification.
Global Stability and Sensitivity Assessment of COVID-19 with Timely and Delayed Diagnosis in Ghana
Authors: Moore Stephen E. , Bamen Hetsron L. Nyandjo , Asamoah Joshua Kiddy K. , Menoukeu-Pamen Olivier , Jin Zhen
Published: February 2021

In this paper, we present the dynamical effects of timely and delayed diagnosis on the spread of COVID-19 in Ghana, using reported data from March 12 to June 19, 2020. The estimated basic reproduction number, R_0, for the proposed model is 1.04. One of the main focus of this study is stability results and senesitity assessment of the parameters. We show both theoretically and numerically that, the disease can be eliminated when the basic reproduction number is less or equal to a unity. Furthermore, we show that the disease persist whenever R_0>1 or whenever there is a delay in the diagnoses of infected individuals in the community. To assess the most influential parameters in the basic reproduction number, we carried out global sensitivity analysis. The scatter plots and the partial rank correlation coefficient reveal that, the most positive sensitive parameter is the recruitment rate, followed by the relative transmissibility of exposed individuals; and that the most negative sensitive parameters are the proportion of the infectious with timely diagnosis, and the transition rate of self-quarantined individuals to the susceptible population. For public health benefit, our analysis suggests that, a reduction in the inflow of new individuals into the country or a reduction in the inter community inflow of individuals will reduce the basic reproduction number and thereby reduce the number of secondary infections (multiple peaks of the infection).
 A Simplified Model of Low Reynolds Number, immiscible, Gas-Liquid Flow and Heat Transfer in Porous Media (Numerical Solution with Experimental Validation)
Authors: Abdelaziz Gamal B. , Abdelgaleel M. , Omara Z.M. , Abdullah A. S. , El-Said Emad M.S. , Sharshir Swellam W. , Elsaid Ashraf Mimi
Published: February 2021

This study investigates the thermal-hydraulic characteristics of immiscible two-phase flow (gas/liquid) and heat transfer through porous media. This research topic is interested among others in trickle bed reactors, the reservoirs production of oil, and the science of the earth. Characteristics of two-phase concurrent flow with heat transfer through a vertical, cylindrical, and homogeneous porous medium were investigated both numerically and experimentally. A generalized Darcy model for each phase is applied to derive the momentum equations of a two-phase mixture by appending some constitutive relations. Gravity force is considered through investigation. To promote the system energy equation, the energy equation of solid matrix for each phase are deemed. The test section is exposed to a constant wall temperature after filled with spherical beads. Numerical solution of the model is achieved by the finite volume method. The numerical procedure is generalized such that it can be reduced and applied to single phase flow model. The numerical results are acquired according to, air/water downward flow, spherical beads, ratio of particle diameter to pipe radius D=0.412, porosity φ=0.396, 0.01≤Re≤500, water to air volume ratio 0≤W/A≤∞, and saturation ratio 0≤S1≤1. To validate this model an experimental test rig is designed and constructed, and the corresponding numerical results are compared with its results. Also, the numerical results were compared with other available numerical results. The comparisons show good agreement and validate the numerical model. One of the important results reveals that the heat transfer is influenced by two main parameters; saturation ratios of the two fluids; S1 and S2, and the mixture Reynolds number Re. The thermal entry length is directly dependent on Re, S1, and the thermofluid properties of the fluids. A modified empirical correlation for the entrance length; Xe =0.1 Re.Pr.Rm is predicted, where Rm =Rm(S1, S2, ρ1, ρ2, c1, c2). The predicted correlation is verified by comparing with the supposed correlation of Poulikakos and Ranken (1987) and El-Kady (1997) for a single-phase flow; Xe/Pr=0.1 Re.
COVID-19 Positive Woman Presented with Preterm Labor: Case Report
Authors: Abdelazim Ibrahim A. , AbuFaza Mohannad , Al-Munaifi Sulaiman
Published: February 2021

The novel coronavirus disease-19 (COVID-19) considered a global health problem. Pregnant women are considered a COVID-19 high-risk group. A 26-years old woman, G2 P1+0, previous cesarean section, 31 weeks`+4 days, admitted with preterm labor, without fever, cough, and/or respiratory symptoms on admission. She presented to the emergency department with fever, and cough, 27 days before the current admission, she was referred to the Ministry of Health, and her COVID-19 PCR swab at Ministry of Health was positive. She delivered by cesarean section, and the PCR swab of the studied woman taken on admission came positive for COVID-19. The delivered girl was admitted to the neonatal intensive care unit for 16 days. The PCR swab of the delivered girl came negative for COVID-19. This report highlights that the COVID-19 infection during pregnancy may increase the rates of preterm labor and cesarean section. There is no strong evidence of vertical COVID-19 transmission when the infection manifests during the 3rd trimester of pregnancy.
Prace konserwatorskie przy kamiennej rzeźbie Matki Boskiej autorstwa Andrzeja Pruszyńskiego z elewacji kościoła pw. Matki Bożej Pocieszenia w Żyrardowie – wybrane zagadnienia historyczne i technologiczne
Authors: Owczarek Piotr
Published: February 2021

SUMMARY

The stone sculpture of the Virgin Mary from the facade of the church Our Lady of Consolation in Żyrardów is one of the numerous sculptural implementations of Andrzej Pruszyński workshop. In 2018 the monument was under conservation and restoration works. Preliminary macroscopic examination of the monument showed that under the numerous secondary layers of paint on the stone sculpture there is a dark green, multi-deck colour layer that could imitate a statue had made in bronze casting technique. As a result samples were taken and subjected to laboratory analysis. The research carried out allowed us to conclude that the described layer is kind of a secondary nature and is a testimony to the restoration of the monument probably after the end of World War I. It was decided not to remove the patina and to fill in the gaps in the course of the ongoing restoration and conservation works. This layer had historical and documentary value and was a testimony to the popular in the 19th century and probably known at the beginning of the 20th century practice of patinating sculptures made in less noble and less durable material than bronze. Moreover, in the course of conservation works later layers of paint and cement repairs were removed. Then the structure of weakened limestone rock was strengthened and numerous small losses of stone were filled in. As a witness the defect on the left knee of the figure was left without filling in. It is a trace of the bullet that was probably created during World War I. Moreover, the missing figure’s right hand was reconstructed. A reconstruction of the gilded halo was also made. The design of the conservation work programme is always a very complex process as it requires the simultaneous consideration of many factors. The aesthetic and historical interpretation of the work is important, the understanding of the author’s concept and the essence of the destructive processes. In the case of the described sculpture from Żyrardów it was also necessary to take into account the technical possibilities, take into account the expectations of the owner and users, or customers in general, as well as the conservation community. Preservation and restoration solutions adopted in the work programme, including hand reconstruction and unveiling of the following items and the restoration of a painting layer imitating a green patina, restored historical artistic values to the monument. The aesthetic effect achieved this way brings a new quality to work that can be the object of criticism but by restoring the sculpture’s lost aesthetic values it is possible to continue to function as an object of religious worship.