bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of indicators of longitudinal deformation of the left atrium in patients with chronic heart failure
Authors: Alekhin M. N. , Kalinin A. O.
Published: January 2021

Modern technologies for assessing myocardial strain by means of speckle-tracking echocardiography allow to analyze not only the ventricles of the heart, but also the left atrium (LA). Evaluation of LA strain in patients with chronic heart failure (CHF) can be useful in the terms of diagnostic in patients with first-time symptoms that may indicate the onset of heart failure with a preserved left ventricular ejection fraction. In patients with CHF, LA strain may be important for evaluating the prognosis. Assessment of the dynamics of LA strain in patients with heart failure may indicate the course of CHF and the effectiveness of therapy. The purpose of this article is to analyze the data on the significance of LA longitudinal strain indicators for the diagnosis and management of patients with CHF.
Errors during the exercise test for the diagnosis of Coronary heart disease: negative result in the presence of three-vessel coronary artery disease
Authors: Popova L. A. , Karpina N. L. , Chushkin M. I. , Mandrykin S. Y. , Janus V. M. , Anokhin N. V. , Struchkov P. V.
Published: January 2021

The exercise ECG test is traditionally the first choice in patients with suspected CHD, as the most accessible, despite the fact that its sensitivity and specificity are 68 % and 77 %, respectively. Description of a clinical case of multivessel coronary artery disease in a patient with a negative result of exercise ECG test is presented.
Experiences of social exclusion and inclusion among emerging adult refugees from African Great Lakes Region
Authors: Osezua Victory , Sato Doroty , Harris Lesley M.
Published: January 2021

This study explores and describes social exclusion and inclusion among emerging adult refugees from the African Great Lakes region fleeing the war in the Democratic Republic of Congo. A constructivist grounded theory approach was employed to conduct twelve in-depth interviews with emerging adult refugees aged 18–25 years old. Findings suggest that emerging adult refugees experience discrimination, dehumanization, and loss of identity during pre- and post-migration in the US. In response, social inclusion is promoted through resilience and establishing a community. The findings suggest that young refugees value mentorship to establish social inclusion through community building. This study also suggested that programs and future research build on the existing strengths of young refugees and communities to achieve sustainable refugee programs and initiatives.
Spatial Autocorrelation and the Dynamics of the Mean Center of COVID-19 Infections in Lebanon
Authors: El Deeb Omar
Published: January 2021

In this paper we study the spatial spread of the COVID-19 infection in Lebanon. We inspect the spreading of the daily new infections across the 26 administrative districts of the country, and implement the univariate Moran’sIstatistics in order to analyze the tempo-spatial clustering of the infection in relation to various variables parameterized by adjacency, proximity, population, population density, poverty rate and poverty density. We find out that except for the poverty rate, the spread of the infection is clustered and associated to those parameters with varying magnitude for the time span between July (geographic adjacency and proximity) or August (population, population density and poverty density) through October. We also determine the temporal dynamics of geographic location of the mean center of new and cumulative infections since late March. The understanding of the spatial, demographic and geographic aspects of the disease spread over time allows for regionally and locally adjusted health policies and measures that would provide higher levels of social and health safety in the fight against the pandemic in Lebanon.
Facile Synthesis of Porous ZnO Nanoparticles Efficient for Photocatalytic Degradation of Biomass-Derived Bisphenol A Under Simulated Sunlight Irradiation
Authors: Wang Yujie , Hu Kang , Yang Zhiyu , Ye Chenlu , Li Xin , Yan Kai
Published: January 2021

Bisphenol A (BPA) produced from biomass is a typical endocrine disrupting compound that is carcinogenic and genotoxic and can be accumulated in water due to its extensive use and difficult degradation. In this study, the porous ZnO photocatalyst with core-shell structure and large surface area was successfully developed for the efficient photocatalytic degradation of BPA. The various effects of calcination temperatures, BPA concentrations, ZnO dosages, pH and inorganic ions on the degradation performance were systemically studied. The results showed that 99% degradation of BPA was achieved in 1 h using the porous ZnO calcined at 550°C under the conditions of 30 mg/L BPA, 1 g/L ZnO, and pH of 6.5. Besides, the inhibition effects of anions for the photocatalytic removal of BPA decreased in the order of H2PO4- > HCO3- > SO42- > Cl−, while the cations K+, Ca2+, and Na+ had little effect on the photocatalytic degradation of BPA. The results of scavenging experiments showed that h+, ·O2-, and e− played the key role in the photocatalytic degradation process. Finally, the main pathways of BPA degradation were proposed based on ten intermediates found in the degradation process. This work may provide a good guideline to degrade various endocrine disrupting compounds in wastewater treatment.
Non-viral Gene Therapy for Osteoarthritis
Authors: Uzieliene Ilona , Kalvaityte Ursule , Bernotiene Eiva , Mobasheri Ali
Published: January 2021

Strategies for delivering nucleic acids into damaged and diseased tissues have been divided into two major areas: viral and non-viral gene therapy. In this mini-review article we discuss the application of gene therapy for the treatment of osteoarthritis (OA), one of the most common forms of arthritis. We focus primarily on non-viral gene therapy and cell therapy. We briefly discuss the advantages and disadvantages of viral and non-viral gene therapy and review the nucleic acid transfer systems that have been used for gene delivery into articular chondrocytes in cartilage from the synovial joint. Although viral gene delivery has been more popular due to its reported efficiency, significant effort has gone into enhancing the transfection efficiency of non-viral delivery, making non-viral approaches promising tools for further application in basic, translational and clinical studies on OA. Non-viral gene delivery technologies have the potential to transform the future development of disease-modifying therapeutics for OA and related osteoarticular disorders. However, further research is needed to optimize transfection efficiency, longevity and duration of gene expression.
Perinatal Cells: A Promising COVID-19 Therapy?
Authors: Papait Andrea , Cargnoni Anna , Sheleg Michal , Silini Antonietta R. , Kunis Gilad , Ofir Racheli , Parolini Ornella
Published: January 2021

The COVID-19 pandemic has become a priority in the health systems of all nations worldwide. In fact, there are currently no specific drugs or preventive treatments such as vaccines. The numerous therapies available today aim to counteract the symptoms caused by the viral infection that in some subjects can evolve causing acute respiratory distress syndromes (ARDS) with consequent admission to intensive care unit. The exacerbated response of the immune system, through cytokine storm, causes extensive damage to the lung tissue, with the formation of edema, fibrotic tissues and susceptibility to opportunistic infections. The inflammatory picture is also aggravated by disseminated intravascular coagulation which worsens the damage not only to the respiratory system, but also to other organs. In this context, perinatal cells represent a valid strategy thanks to their strong immunomodulatory potential, their safety profile, the ability to reduce fibrosis and stimulate reparative processes. Furthermore, perinatal cells exert antibacterial and antiviral actions. This review therefore provides an overview of the characteristics of perinatal cells with a particular focus on the beneficial effects that they could have in patients with COVID-19, and more specifically for their potential use in the treatment of ARDS and sepsis.
Different Machine Learning and Deep Learning Methods for the Classification of Colorectal Cancer Lymph Node Metastasis Images
Authors: Li Jin , Wang Peng , Zhou Yang , Liang Hong , Luan Kuan
Published: January 2021

The classification of colorectal cancer (CRC) lymph node metastasis (LNM) is a vital clinical issue related to recurrence and design of treatment plans. However, it remains unclear which method is effective in automatically classifying CRC LNM. Hence, this study compared the performance of existing classification methods, i.e., machine learning, deep learning, and deep transfer learning, to identify the most effective method. A total of 3,364 samples (1,646 positive and 1,718 negative) from Harbin Medical University Cancer Hospital were collected. All patches were manually segmented by experienced radiologists, and the image size was based on the lesion to be intercepted. Two classes of global features and one class of local features were extracted from the patches. These features were used in eight machine learning algorithms, while the other models used raw data. Experiment results showed that deep transfer learning was the most effective method with an accuracy of 0.7583 and an area under the curve of 0.7941. Furthermore, to improve the interpretability of the results from the deep learning and deep transfer learning models, the classification heat-map features were used, which displayed the region of feature extraction by superposing with raw data. The research findings are expected to promote the use of effective methods in CRC LNM detection and hence facilitate the design of proper treatment plans.
Use of Cell Envelope Targeting Antibiotics and Antimicrobial Agents as a Powerful Tool to Select for Lactic Acid Bacteria Strains With Improved Texturizing Ability in Milk Fermentations
Authors: Sørensen Kim I. , Kjærbølling Inge , Neves Ana Rute , Machielsen Ronnie , Johansen Eric
Published: January 2021

Many antibiotics and antimicrobial agents have the bacterial cell envelope as their primary target, interfering with functions such as synthesis of peptidoglycan, membrane stability and permeability, and attachment of surface components. The cell envelope is the outermost barrier of the bacterial cell, conferring protection against environmental stresses, and maintaining structural integrity and stability of the growing cell, while still allowing for required metabolism. In this work, inhibitory concentrations of several different cell envelope targeting antibiotics and antimicrobial agents were used to select for derivatives of lactic acid bacteria (LAB) with improved properties for dairy applications. Interestingly, we observed that for several LAB species a fraction of the isolates had improved milk texturizing capabilities. To further improve our understanding of the mechanisms underlying the improved rheology and to validate the efficacy of this method for strain improvement, genetic and physiological characterization of several improved derivatives was performed. The results showed that the identified genetic changes are diverse and affect also other cellular functions than the targeted cell surface. In short, this study describes a new versatile and powerful toolbox based on targeting of the cell envelope to select for LAB derivatives with improved phenotypic traits for dairy applications.
Transient Diffusion in Bi-Layer Composites With Mass Transfer Resistance: Exact Solution and Time Lag Analysis
Authors: Tran Anh Phong , Meldon Jerry H. , Sontag Eduardo D.
Published: January 2021

Exact analytical and closed-form solutions to the transient diffusion in bi-layer composites with external mass transfer resistance are reported. Expressions for the concentrations and the mass permeated are derived in both the Laplace and time domains through the use of the Laplace transform Inversion Theorem. The lead and lag times, which are often of importance in the characterization of membranes and arise from the analysis of the asymptotic behavior of the mass permeated through the bi-layer composite, were also derived. The presented solutions are also compared to previously derived limiting cases of the diffusion in a bi-layer with an impermeable wall and constant concentrations at the upstream and downstream boundaries. Analysis of the time lag shows that this membrane property is independent of the direction of flow. Finally, an outline is provided of how these transient solutions in response to a step function increase in concentration can be used to derive more complex input conditions. The importance of adequately handling boundary layer effects has a wide array of applications such as the study of bi-layers undergoing phenomena of heat convection, gas film resistance, and absorption/desorption.
Chemical Insights Into the Synthetic Chemistry of Quinazolines: Recent Advances
Authors: Faisal Muhammad , Saeed Aamer
Published: January 2021

In medicinal chemistry, one of the most significant heterocyclic compounds are quinazolines, possessing broad range of biological properties such as anti-bacterial, anti-fungal, anti-HIV, anti-cancer, anti-inflammatory, and analgesic potencies. Owing to its numerous potential applications, in the past two decades, there is an increase in the importance of designing novel quinazolines, exploring promising routes to synthesize quinazolines, investigating different properties of quinazolines, and seeking for potential applications of quinazolines. The present review article describes synthesis of quinazolines via eco-friendly, mild, atom-efficient, multi-component synthetic strategies reported in the literature. The discussion is divided into different parts as per the key methods involved in the formation of quinazoline skeletons, aiming to provide readers an effective methodology to a better understanding. Consideration has been taken to cover the most recent references. Expectedly, the review will be advantageous in future research for synthesizing quinazolines and developing more promising synthetic approaches.
Development of a TSR-Based Method for Protein 3-D Structural Comparison With Its Applications to Protein Classification and Motif Discovery
Authors: Kondra Sarika , Sarkar Titli , Raghavan Vijay , Xu Wu
Published: January 2021

Development of protein 3-D structural comparison methods is important in understanding protein functions. At the same time, developing such a method is very challenging. In the last 40 years, ever since the development of the first automated structural method, ~200 papers were published using different representations of structures. The existing methods can be divided into five categories: sequence-, distance-, secondary structure-, geometry-based, and network-based structural comparisons. Each has its uniqueness, but also limitations. We have developed a novel method where the 3-D structure of a protein is modeled using the concept of Triangular Spatial Relationship (TSR), where triangles are constructed with the Cα atoms of a protein as vertices. Every triangle is represented using an integer, which we denote as “key,” A key is computed using the length, angle, and vertex labels based on a rule-based formula, which ensures assignment of the same key to identical TSRs across proteins. A structure is thereby represented by a vector of integers. Our method is able to accurately quantify similarity of structure or substructure by matching numbers of identical keys between two proteins. The uniqueness of our method includes: (i) a unique way to represent structures to avoid performing structural superimposition; (ii) use of triangles to represent substructures as it is the simplest primitive to capture shape; (iii) complex structure comparison is achieved by matching integers corresponding to multiple TSRs. Every substructure of one protein is compared to every other substructure in a different protein. The method is used in the studies of proteases and kinases because they play essential roles in cell signaling, and a majority of these constitute drug targets. The new motifs or substructures we identified specifically for proteases and kinases provide a deeper insight into their structural relations. Furthermore, the method provides a unique way to study protein conformational changes. In addition, the results from CATH and SCOP data sets clearly demonstrate that our method can distinguish alpha helices from beta pleated sheets and vice versa. Our method has the potential to be developed into a powerful tool for efficient structure-BLAST search and comparison, just as BLAST is for sequence search and alignment.
Binding Affinity and Driving Forces for the Interaction of Calixarene-Based Micellar Aggregates With Model Antibiotics in Neutral Aqueous Solution
Authors: Migliore Rossella , Granata Giuseppe , Rivoli Andrea , Consoli Grazia Maria Letizia , Sgarlata Carmelo
Published: January 2021

The search for novel surfactants or drug delivery systems able to improve the performance of old-generation antibiotics is a topic of great interest. Self-assembling amphiphilic calix[4]arene derivatives provide well-defined nanostructured systems that exhibit promising features for antibiotics delivery. In this work, we investigated the capability of two micellar polycationic calix[4]arene derivatives to recognize and host ofloxacin, chloramphenicol, or tetracycline in neutral aqueous solution. The formation of the nanoaggregates and the host–guest equilibria were examined by nano-isothermal titration calorimetry, dynamic light scattering, and mono- and bi-dimensional NMR. The thermodynamic characterization revealed that the calix[4]arene-based micellar aggregates are able to effectively entrap the model antibiotics and enabled the determination of both the species and the driving forces for the molecular recognition process. Indeed, the formation of the chloramphenicol–micelle adduct was found to be enthalpy driven, whereas entropy drives the formation of the adducts with both ofloxacin and tetracycline. NMR spectra corroborated ITC data about the positioning of the antibiotics in the calixarene nanoaggregates.
Thiourea-Grafted Graphite Felts as Positive Electrode for Vanadium Redox Flow Battery
Authors: Wu Shangzhuo , Lv Xin , Ge Zhijun , Wang Ling , Dai Lei , He Zhangxing
Published: January 2021

In this paper, thiourea was successfully grafted onto the surface of acid preprocessed graphite felts [sulfuric acid-treated graphite felt (SA-GFs)] by thiol-carboxylic acid esterification. The thiourea-grafted graphite felts (TG-GFs) were investigated as the positive electrode for vanadium redox flow battery (VRFB). X-ray photoelectron spectroscopy results suggested that thiourea was grafted into the surface of graphite felts. The cyclic voltammetry showed that the peak potential separation decreased by 0.2 V, and peak currents were greatly enhanced on TG-GF electrode compared with SA-GF electrode, implying improved electro-catalytic activity and reversibility of TG-GF electrode toward VO2+/VO2+ redox reaction. The initial capacity of TG-GF-based cell reached 55.6 mA h at 100 mA cm−2, 22.6 mA h larger than that of SA-GF-based cell. The voltage and energy efficiency for TG-GF-based cell increased by 4.9% and 4.4% compared with those of SA-GF-based cell at 100 mA cm−2, respectively.
Leaning Into the Bite: The piRNA Pathway as an Exemplar for the Genetic Engineering Need in Mosquitoes
Authors: Macias Vanessa M. , Palatini Umberto , Bonizzoni Mariangela , Rasgon Jason L.
Published: January 2021

The piRNA pathway is a specialized small RNA interference that in mosquitoes is mechanistically distant from analogous biology in theDrosophilamodel. Current genetic engineering methods, such as targeted genome manipulation, have a high potential to tease out the functional complexity of this intricate molecular pathway. However, progress in utilizing these methods in arthropod vectors has been geared mostly toward the development of new vector control strategies rather than to study cellular functions. Herein we propose that genetic engineering methods will be essential to uncover the full functionality of PIWI/piRNA biology in mosquitoes and that extending the applications of genetic engineering on other aspects of mosquito biology will grant access to a much larger pool of knowledge in disease vectors that is just out of reach. We discuss motivations for and impediments to expanding the utility of genetic engineering to study the underlying biology and disease transmission and describe specific areas where efforts can be placed to achieve the full potential for genetic engineering in basic biology in mosquito vectors. Such efforts will generate a refreshed intellectual source of novel approaches to disease control and strong support for the effective use of approaches currently in development.
Persistence of Intracellular Bacterial Pathogens—With a Focus on the Metabolic Perspective
Authors: Eisenreich Wolfgang , Rudel Thomas , Heesemann Jürgen , Goebel Werner
Published: January 2021

Persistence has evolved as a potent survival strategy to overcome adverse environmental conditions. This capability is common to almost all bacteria, including all human bacterial pathogens and likely connected to chronic infections caused by some of these pathogens. Although the majority of a bacterial cell population will be killed by the particular stressors, like antibiotics, oxygen and nitrogen radicals, nutrient starvation and others, a varying subpopulation (termed persisters) will withstand the stress situation and will be able to revive once the stress is removed. Several factors and pathways have been identified in the past that apparently favor the formation of persistence, such as various toxin/antitoxin modules or stringent response together with the alarmone (p)ppGpp. However, persistence can occur stochastically in few cells even of stress-free bacterial populations. Growth of these cells could then be induced by the stress conditions. In this review, we focus on the persister formation of human intracellular bacterial pathogens, some of which belong to the most successful persister producers but lack some or even all of the assumed persistence-triggering factors and pathways. We propose a mechanism for the persister formation of these bacterial pathogens which is based on their specific intracellular bipartite metabolism. We postulate that this mode of metabolism ultimately leads, under certain starvation conditions, to the stalling of DNA replication initiation which may be causative for the persister state.
Co-designing Indices for Tailored Seasonal Climate Forecasts in Malawi
Authors: Mittal Neha , Pope Edward , Whitfield Stephen , Bacon James , Bruno Soares Marta , Dougill Andrew J. , Homberg Marc van den , Walker Dean P. , Vanya Charles Langton , Tibu Austin , Boyce Clement
Published: January 2021

In central and southern Malawi, climate variability significantly impacts agricultural production and food availability owing to a high dependence on rain-fed maize production. Seasonal climate forecast information has the potential to inform farmers' agricultural planning, thereby improving preparedness to extreme events. In this paper we describe and evaluate an approach to co-designing and testing agro-climatic indices for use in seasonal forecasts that are tailored to farmer-defined decision-making needs in three districts of central and southern Malawi. Specifically, we aim to (a) identify critical maize specific agro-climatic indices by engaging key stakeholders and farmers; (b) compare and triangulate these indices with the historical climate record in study districts; and (c) analyze empirical relationships between seasonal total rainfall and maize specific indices in order to assess the potential for forecasting them at appropriate seasonal timescales. The identified agro-climatic indices include critical temperature/rainfall thresholds that are directly associated with phenological stages of maize growth with direct implications for maize yield and quality. While there are statistically significant relationships between observed wet season rainfall totals and several agro-climatic indices (e.g., heavy rainfall days and dry spell), the forecast skill of the UK Met Office's coupled initialized global seasonal forecasting system (GloSea5) over Malawi is currently low to provide confident predictions of total wet season rainfall and the agro-climatic indices correlated with it. We reflect on some of the opportunities and challenges associated with integrating farmers' information needs into a seasonal forecast process, through the use of agro-climatic indices.
Scalar Implicature, Hurford's Constraint, Contrastiveness and How They All Come Together
Authors: Tomioka Satoshi
Published: January 2021

Disjunction with two scalar items, such assome or all of the books, has been regarded as evidence for the grammatical theory of scalar implicatures (e.g., Chierchia et al.,2012). Hurford's Constraint (Hurford,1974) provides that disjuncts are banned from having an entailing relation, and to make such a disjunction comply with Hurford's Constraint, the meaning ofsomemust be locally strengthened. Interestingly, however, the order of disjoined scalar items is not free, as noted by Singh (2008). The order in which a weaker scalar item comes first followed by its stronger scalar mate is better than the other order. I present an analysis of this ordering restriction based on the novel observation that the restriction is not only found in disjunction but in contrastive environments in general. I propose that contrasting a linguistic expression requires a “contrast antecedent,” which must elicit a set of mutually exclusive alternatives that includes the meaning of the contrasted expression. It will be demonstrated how the mutual exclusivity requirement presents a principled explanation for the ordering asymmetry as well as Hurford's Constraint itself, which indicates that the root of the constraint is not in disjunction but in contrastiveness. One of the indispensable ingredients in the proposal is the grammatical/conventional generation of scalar implicatures, as the strengthened meaning must be the basis of alternatives. The paper also provides a speculative analysis ofonly, in which I suggest that the process of exhaustification in the grammatical theory of scalar implicatures should not be characterized as the implicitonly, the semantic contributions of which are more different than commonly assumed.
Remagnetization of Permian Emeishan basalts: Constraints on the timing of native copper mineralization in northeast Yunnan Province, China
Authors: Liu Chengying , Paterson Greig A. , Li Shihu , Pan Yongxin , Zhu Rixiang
Published: January 2021

New paleomagnetic results from the Permian Emeishan basalts in the Zhaotong area, NE Yunnan province, China show four natural remanent magnetization components. Detailed stepwise thermal demagnetization of basaltic samples from 16 flows from the Dadi section, which represent basalt units III and IV, isolated two groups of characteristic remanent magnetizations. Samples in unit IV (five flows) record a southwest declination and a moderate downward inclination that is considered to be a partial remagnetized remanence. The bottom flows from unit III (11 flows) record a normal polarity direction, interpreted as a remagnetization, which yields a tilt-corrected mean direction of Ds/Is= 8.8°/31.6° (N = 9, ks= 39.7,α95= 8.3°), with a corresponding paleomagnetic pole at 77.1°N, 240.0°E (K = 49.2, A95= 7.4°). The secondary directions have steeper inclinations than primary ones that have been successfully recovered from other studies in this area of the Emeishan basalts. By comparison with the Phanerozoic paleomagnetic poles of the South China Block, the preferred timing of remagnetization is the Lower-Middle Jurassic. Field relationships suggest that the remagnetization of the Emeishan basalts is coeval with the spatially related, but localized, copper mineralization. Thus the timing of the main copper mineralization hosted in the Emeishan basalts is hypothesized to occur in the Early-Middle Jurassic.
Velocity-Porosity-Mineralogy Model for Unconventional Shale and Its Applications to Digital Rock Physics
Authors: Dvorkin Jack , Walls Joel , Davalos Gabriela
Published: January 2021

By examining wireline data from Woodford and Wolfcamp gas shale, we find that the primary controls on the elastic-wave velocity are the total porosity, kerogen content, and mineralogy. At a fixed porosity, bothVpandVsstrongly depend on the clay content, as well as on the kerogen content. Both velocities are also strong functions of the sum of the above two components. Even better discrimination of the elastic properties at a fixed porosity is attained if we use the elastic-wave velocity of the solid matrix (including kerogen) of rock as the third variable. This finding, fairly obvious in retrospect, helps combine all mineralogical factors into only two variables,VpandVsof the solid phase. The constant-cement rock physics model, whose mathematical form is the modified lower Hashin-Shtrikman elastic bound, accurately describes the data. The inputs to this model include the elastic moduli and density of the solid component (minerals plus kerogen), those of the formation fluid, the differential pressure, and the critical porosity and coordination number (the average number of grain-to-grain contacts at the critical porosity). We show how this rock physics model can be used to predict the elastic properties from digital images of core, as well as 2D scanning electron microscope images of very small rock fragments.
Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes
Authors: Crouse Andrew B. , Grimes Tiffany , Li Peng , Might Matthew , Ovalle Fernando , Shalev Anath
Published: January 2021

Background

Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking.

Methods

We conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19-positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression.

Results

The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans (OR 2.6; 95% CI 2.19–3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95% CI 1.64–2.28; p<0.0001), hypertension (OR 2.46; 95% CI 2.07–2.93; p<0.0001), and diabetes (OR 2.11; 95% CI 1.78–2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95% CI 2.11–6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity, and hypertension. Interestingly, we found that metformin treatment prior to diagnosis of COVID-19 was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95% CI 0.13–0.84; p=0.0210).

Conclusion

Thus, these results suggest that while diabetes is an independent risk factor for COVID-19-related mortality, this risk is dramatically reduced in subjects taking metformin prior to diagnosis of COVID-19, raising the possibility that metformin may provide a protective approach in this high risk population.
Immune System Effects of Insulin-Like Peptide 5 in a Mouse Model
Authors: Vahkal Brett , Yegorov Sergey , Onyilagha Chukwunonso , Donner Jacqueline , Reddick Dean , Shrivastav Anuraag , Uzonna Jude , Good Sara V.
Published: January 2021

Introduction

Insulin-like peptide 5 (INSL5) is a peptide hormone with proposed actions in glucose homeostasis and appetite regulation via its cognate receptor, relaxin family peptide receptor 4 (RXFP4). Here, we look for evidence for their involvement in the immune system using a mouse model.

Methods

In silico analyses: we queried public databases for evidence of expression of INSL5-RXFP4 in immune system tissues/cells (NCBI’s SRA and GeoProfiles) and disorders (EMBO-EBI) and performed phylogenetic footprinting to look for evidence that they are regulated by immune-associated transcription factors (TFs). Experimental analyses: We characterized the expression and correlation of INSL5/RXFP4 and other immune system markers in central and peripheral immune organs from C57/bl6 mice in seven cohorts. We tested whether fluctuations in circulating INSL5 induce an immune response, by injecting mice with 30 μg/kg of INSL5 peptide in the peritoneum, and examining levels of immune markers and metabolic peptides in plasma. Lastly, we quantified the expression of Rxfp4 in T-cells, dendritic cells and cell lines derived from human and mouse and tested the hypothesis that co-incubation of ANA-1 cells in INSL5 and LPS alters cytokine expression.

Results

We find Insl5 expression only in thymus (in addition to colon) where its expression was highly correlated with Il-7, a marker of thymocyte development. This result is consistent with our in silico findings that Insl5 is highly expressed in thymic DP, DN thymocytes and cortical TEC’s, and with evidence that it is regulated by thymocyte-associated TF’s. We find Rxfp4 expression in all immune organs, and moderately high levels in DCs, particularly splenic DCs, and evidence that it is regulated by immune-associated TF’s, such as STAT’s and GATA. Systemic effects: We observed significantly elevated concentrations of blood GLP-1, GIP, GCG and PYY following intraperitoneal injection of INSL5, and significantly altered expression of cytokines IL-5, IL-7, M-CSF, IL-15, IL-27 and MIP-2. Immune cell effects: Incubation of ANA-1 cells with INSL5 impeded cell growth and led to a transient elevation of IL-15 and sustained reduction in IL-1β, IL-6 and TNFα.

Conclusion

We propose that INSL5-RXFP4 play a novel role in both central and peripheral immune cell signaling.
Soil Mesofauna Community Changes in Response to the Environmental Gradients of Urbanization in Guangzhou City
Authors: Yu Shiqin , Qiu Junliang , Chen Xiaohua , Luo Xiaofeng , Yang Xiankun , Wang Faming , Xu Guoliang
Published: January 2021

There has been a recent increase in interest on how urbanization affects soil fauna communities. However, previous studies primarily focused on some limited land use types or line transects of urban-rural gradients. At family and higher taxonomic levels, we investigated the changes of soil mesofauna communities (abundance, species richness, and community structure) with urbanization intensity along different disturbance features in 47 sites evenly located in downtown Guangzhou and adjacent regions. The 47 research sites were classified into four ecosystem types mainly according to the location (rural/urban), vegetation cover, and management intensity. In turn, the four types with increasing urbanization intensity were rural forest, urban forest, urban woodland, and urban park. Firstly, the role of urban soil property (soil physicochemical characteristic and soil heavy metal content) in regulating soil mesofauna community was investigated. The results showed that soil mesofauna abundance and diversity decreased with increasing soil pH, total nitrogen content (TN), and heavy metal comprehensive index (CPI). Soil Pb decreased soil mesofauna species richness (taxa number) and regulated soil mesofauna community structure. Secondly, we examined the effects of landscape changes on the soil mesofauna community. We found impervious surface (IS) ratio did not predict changes in soil mesofauna abundance, species richness, or community structure. Instead, IS ratio was positively correlated with soil pH, soil TN, and CPI. After excluding sites that belonged to rural forests and urban parks, site area was positively correlated with soil mesofauna abundance. Thirdly, our results revealed significant differences in soil property, landscape trait, and soil mesofauna community among the four ecosystem types. Interestingly, urban forest, the one lightly disturbed by urbanization, but not rural forest, had the highest soil mesofauna abundance. Soil mesofauna abundance in urban woodlands was similar to that in urban parks, which was about half of that in urban forests. Species richness in urban parks was 21% lower than that in rural forests. Our results also showed that urban woodland and urban parks had distinct mesofauna community structures compared to those in rural forests and urban forests. In conclusion, the present study suggested that (1) soil property changes due to urbanization, such as increased pH and heavy metal enrichment in urban soil, decreased soil mesofauna abundance and species richness, changed community structure, and mediated the effect of landscape change on soil mesofauna community; (2) however, soil and landscape changes could not explain the increase of abundance in urban forests, which supported the intermediate disturbance hypothesis.
Novel Insights to Be Gained From Applying Metacommunity Theory to Long-Term, Spatially Replicated Biodiversity Data
Authors: Record Sydne , Voelker Nicole M. , Zarnetske Phoebe L. , Wisnoski Nathan I. , Tonkin Jonathan D. , Swan Christopher , Marazzi Luca , Lany Nina , Lamy Thomas , Compagnoni Aldo , Castorani Max C. N. , Andrade Riley , Sokol Eric R.
Published: January 2021

Global loss of biodiversity and its associated ecosystem services is occurring at an alarming rate and is predicted to accelerate in the future. Metacommunity theory provides a framework to investigate multi-scale processes that drive change in biodiversity across space and time. Short-term ecological studies across space have progressed our understanding of biodiversity through a metacommunity lens, however, such snapshots in time have been limited in their ability to explain which processes, at which scales, generate observed spatial patterns. Temporal dynamics of metacommunities have been understudied, and large gaps in theory and empirical data have hindered progress in our understanding of underlying metacommunity processes that give rise to biodiversity patterns. Fortunately, we are at an important point in the history of ecology, where long-term studies with cross-scale spatial replication provide a means to gain a deeper understanding of the multiscale processes driving biodiversity patterns in time and space to inform metacommunity theory. The maturation of coordinated research and observation networks, such as the United States Long Term Ecological Research (LTER) program, provides an opportunity to advance explanation and prediction of biodiversity change with observational and experimental data at spatial and temporal scales greater than any single research group could accomplish. Synthesis of LTER network community datasets illustrates that long-term studies with spatial replication present an under-utilized resource for advancing spatio-temporal metacommunity research. We identify challenges towards synthesizing these data and present recommendations for addressing these challenges. We conclude with insights about how future monitoring efforts by coordinated research and observation networks could further the development of metacommunity theory and its applications aimed at improving conservation efforts.
Evolution, Expression Profile, Regulatory Mechanism, and Functional Verification of EBP-Like Gene in Cholesterol Biosynthetic Process in Chickens (Gallus Gallus)
Authors: Jiang Keren , Ma Zheng , Wang Zhang , Li Hong , Wang Yanbin , Tian Yadong , Li Donghua , Liu Xiaojun
Published: January 2021

The emopamil binding protein (EBP) is an important enzyme participating in the final steps of cholesterol biosynthesis in mammals. A predictive geneEBP-like, which encodes the protein with a high identity to human EBP, was found in chicken genome. No regulatory mechanisms and biological functions ofEBP-likehave been characterized in chickens. In the present study, the coding sequence ofEBP-likewas cloned, the phylogenetic trees of EBP/EBP-like were constructed and the genomic synteny ofEBP-likewas analyzed. The regulatory mechanism ofEBP-likewere explored within vivoandin vitroexperiments. The biological functions ofEBP-likein liver cholesterol biosynthetic were examined by using gain- or loss-of-function strategies. The results showed that chickenEBP-likegene was originated from a common ancestral with Japanese quailEBPgene, and was relatively conservative withEBPgene among different species. TheEBP-likegene was highly expressed in liver, its expression level was significantly increased in peak-laying stage, and was upregulated by estrogen. Inhibition of theEBP-likemRNA expression could restrain the expressions ofEBP-likedownstream genes (SC5D,DHCR24, andDHCR7) in the cholesterol synthetic pathway, therefore downregulate the liver intracellular T-CHO level. In conclusion, as substitute ofEBPgene in chickens,EBP-likeplays a vital role in the process of chicken liver cholesterol synthesis. This research provides a basis for revealing the molecular regulatory mechanism of cholesterol synthesis in birds, contributes insights into the improvement of the growth and development, laying performance and egg quality in poultry.
Sequencing of Transcriptome and Small RNA Revealed the Xenobiotic Metabolism-Related Genes and Potential Regulatory miRNA in Asian Tramp Snail
Authors: Yang Qun , Yang Wanjun , Shang Feng , Ding Biyue , Niu Jinzhi , Wang Jinjun
Published: January 2021

The Asian tramp snail, Bradybaena similaris (Ferusssac), is an invasive land snail species and has been a rising agricultural pest in south of China. As a pest, it also plays a role in transmission of Angiostrongylus cantonensis. However, present studies on this species are rare and the molecular information is limited. For this purpose, we sequenced the transcriptome and small RNA of B. similaris collected from citrus orchards. In total, 89,747 unigenes with an N50 size of 1287 bp and an average length of 817 bp were generated from ∼8.9 Gb transcriptome and 31 Mb clean reads were generated from ∼36 Mb small RNA library. To demonstrate the usefulness of these two datasets, we analyzed a series of genes associated with xenobiotic metabolism and core RNAi machinery. Analysis of the transcripts resulted in annotation of 126 putative genes encoding cytochrome P450 monooxygenases (CYP, 45), carboxyl/cholinesterases (CCE, 13), glutathione-S-transferases (GST, 24), and ATP-binding cassette transporters (ABC, 44). Analysis of the small RNA detected 42 miRNAs. In addition, four genes involved in small RNA pathways (miRNA, piRNA, and siRNA) were identified, and a total of 430 genes that can be targeted by miRNAs were predicted. Moreover, we found that a few miRNAs could target certain genes involved in xenobiotic metabolism. Therefore, we believe that these two datasets and the characterization of the identified/predicted genes will facilitate the molecular study of this species as well as other land snails with agricultural importance.
Re-analysis of a Genome-Wide Gene-By-Environment Interaction Study of Case Parent Trios, Adjusted for Population Stratification
Authors: Ratnasekera Pulindu , McNeney Brad
Published: January 2021

We investigate the impact of confounding on the results of a genome-wide association analysis by Beaty et al., which identified multiple single nucleotide polymorphisms that appeared to modify the effect of maternal smoking, alcohol consumption, or multivitamin supplementation on risk of cleft palate. The study sample of case-parent trios was primarily of European and East Asian ancestry, and the distribution of all three exposures differed by ancestral group. Such differences raise the possibility that confounders, rather than the exposures, are the risk modifiers and hence that the inference of gene-environment (G×E) interaction may be spurious. Our analyses generally confirmed the result of Beaty et al. and suggest the interaction G×E is driven by the European trios, whereas the East Asian trios were less informative.
Genetic Markers for Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in the Asian Indian Population: Implications on Prevention
Authors: Shanbhag Swapna S. , Koduri Madhuri A. , Kannabiran Chitra , Donthineni Pragnya R. , Singh Vivek , Basu Sayan
Published: January 2021

This review attempts to collate all the studies performed in India or comprising a population originating from India and to find out if there is an association between the HLA (human leucocyte antigen) type of individual and development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) subsequent to medication use. The authors performed a PubMed search of all articles published in English from 2009 to 2019 for articles that studied HLA type in patients who developed SJS/TEN after intake of a specific drug in the Asian Indian population or in individuals of Asian Indian origin. The selection criteria were satisfied by a total of 11 studies that reported HLA associations with specific drugs, which induced SJS/TEN, mainly anti-epileptic drugs, and cold medicine/non-steroidal anti-inflammatory drugs. These studies involved a small number of patients, and hence, there is limited evidence to conclude if these associations can be extrapolated to a larger population of the same ethnicity. Similar multi-center studies need to be conducted with a larger sample size to confirm these associations. This would have implications in policy making and for understanding the potential of using genetic markers as a screening tool before prescribing a drug to a patient, which might make them susceptible to developing a potentially life-threatening disease such as SJS/TEN. This is possibly the only mode of primary prevention for this potentially fatal severe cutaneous adverse drug reaction.