bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity Analysis of Urban Rail Transit on Housing with Different Price Levels: A Case Study of Chengdu, China
Authors: Ren Pengyu , Li Zhaoji , Cai Weiguang , Ran Lina , Gan Lei
Published: December 2021

The impact of urban rail transit on housing prices has attracted the extensive attention of scholars, but few studies have explored the heterogeneous impact of rail transit on housing prices with different price levels. To solve this problem, we adopted the hedonic price model based on ordinary least squares regression as a supplementary method of quantile regression to study the heterogeneous impact of the Chengdu Metro system on low-, middle-, and high-priced housing. The result shows that the housing price rises first, then falls with the distance from the housing to the nearest subway station. Besides, the influence of transportation accessibility on low-, middle-, and high-priced housing decreases progressively. This research can provide a reference for the government’s transportation planning and decision-making.
Resource Opportunity in China’s Market Transition and Governance: Time Factor in Urban Housing Inequality
Authors: Zhou Jiawen , Xiong Jing
Published: December 2021

Since China’s reform and opening up, the country’s rapid marketization process has been accompanied by the rapid growth of inequality, which has been significant for all classes of society. In terms of its impact, housing inequality is particularly noticeable. In this paper, we discuss the influence of real-estate purchase time, organization, human capital, and political capital on the value of real estate and the appreciation of real estate in China by using a conditional mean model and a quantile regression model. The differences in the degree of influence of these factors on different quantile levels are also investigated. We found that, after adding the time factor, the prior possession of resources in the early stage of market transformation will benefit the long-term marketization process. Organizations that can penetrate “market-redistribution” and professions that directly participate in the distribution of real-estate resources also have significant advantages in this regard.
Evapotranspiration Measurements and Assessment of Driving Factors: A Comparison of Different Green Roof Systems during Summer in Germany
Authors: Gößner Dominik , Mohri Milena , Krespach Justine Jasmin
Published: December 2021

Green roofs have proven to be a space-saving solution to mitigate peak temperatures and control floods in urban areas through evaporative cooling and storm water retention. To encourage a sustainable city design with large-scale green infrastructure networks, a better differentiation between the diverse existing green roof systems is needed. The aim of this study is to demonstrate differences among green roof systems based on comprehensive microclimatic measurements on four small experimental roofs and to assess differences in evapotranspiration with a partial least square regression. The results show that short-wave solar radiation, relative humidity and water availability are the most important drivers of evapotranspiration. The roof system with permanent water storage maintained significantly higher substrate moisture compared to the other roofs and produced peak evapotranspiration rates of 4.88 mm d−1. The highest total evapo-transpiration of 526 mm from April to September was recorded for the roof system with the thickest substrate layer and grass vegetation. In summer, the shallowest roof showed the highest substrate temperature and air temperature at vegetation level. These findings highlight the importance of specifying the characteristics of the various green roofs in order to turn them into useful planning tools for the design of climate-change-resilient cities.
Description Relationship between Urban Space and Quality of Urban Life. A Geographical Approach
Authors: Petrovič František , Murgaš František
Published: December 2021

The examination of the relationship between the construct of urban space and the construct of the quality of urban life is based on the knowledge that their common element is real physical space, i.e., the place. If the examination of the relationship between the two constructs is to be meaningful, then both must be on the same comparative basis—that means quality. The paper consists of two parts—the first part, which is theoretical, takes the form of conceptualization of urban space and the quality of urban life, including the identification of elements which affect them. The result of conceptualizing urban space into a qualitative form is liveability. The result of conceptualizing the quality of urban life is a holistic quality of life in the city, containing two domains—subjective and objective. The second part of the paper is the application of both constructs in a concrete form, based on measuring the values of these indicators and also the analysis of the results. The measurement takes the form of liveability on the one hand and of satisfaction with the place and/or satisfaction with the quality of urban life on the other hand.
The Role of SARS-CoV-2 Testing on Hospitalizations in California
Authors: Montesinos-López José Cricelio , Daza-Torres Maria L. , García Yury E. , Barboza Luis A. , Sanchez Fabio , Schmidt Alec J. , Pollock Brad H. , Nuño Miriam
Published: December 2021

The rapid spread of the new SARS-CoV-2 virus triggered a global health crisis, disproportionately impacting people with pre-existing health conditions and particular demographic and socioeconomic characteristics. One of the main concerns of governments has been to avoid health systems becoming overwhelmed. For this reason, they have implemented a series of non-pharmaceutical measures to control the spread of the virus, with mass tests being one of the most effective controls. To date, public health officials continue to promote some of these measures, mainly due to delays in mass vaccination and the emergence of new virus strains. In this research, we studied the association between COVID-19 positivity rate and hospitalization rates at the county level in California using a mixed linear model. The analysis was performed in the three waves of confirmed COVID-19 cases registered in the state to September 2021. Our findings suggest that test positivity rate is consistently associated with hospitalization rates at the county level for all study waves. Demographic factors that seem to be related to higher hospitalization rates changed over time, as the profile of the pandemic impacted different fractions of the population in counties across California.
Computational Analysis of a Prebiotic Amino Acid Synthesis with Reference to Extant Codon–Amino Acid Relationships
Authors: Yaman Tolga , Harvey Jeremy N.
Published: December 2021

Novel density functional theory calculations are presented regarding a mechanism for prebiotic amino acid synthesis from alpha-keto acids that was suggested to happen via catalysis by dinucleotide species. Our results were analysed with comparison to the original hypothesis (Copley et al., PNAS, 2005, 102, 4442–4447). It was shown that the keto acid–dinucleotide hypothesis for possible prebiotic amino acid synthesis was plausible based on an initial computational analysis, and details of the structures for the intermediates and transition states showed that there was wide scope for interactions between the keto acid and dinucleotide moieties that could affect the free energy profiles and lead to the required proto-metabolic selectivity.
Is There a Role for the Microbiome and Sudden Death? A Systematic Review
Authors: Collados-Ros Aurelia , Pérez-Cárceles María D. , Legaz Isabel
Published: December 2021

Background. Sudden unexpected death (SUD) is one of the most important and worthy investigation case profiles in emergency medicine and forensic pathology. Sudden unexpected deaths in adults (SUDA) are frequently caused by cardiac events, while infections usually cause those in infants younger than one year (SUDI), and to a lesser extent, in children older than one year (SUDC). However, in some instances of children under the age of one dying (SIDS), a cause is not discovered despite a thorough investigation that includes a review of clinical history, examination of the death scene, and a complete autopsy. Several studies demonstrate that the microbiome influences host immunity, alters susceptibility to viral respiratory infections, and has a vital role in various health, disease, and death outcomes. The main objective of this systematic review was to compile and offer a complete vision of the main lines of research on microbiome and sudden death that have emerged in recent years and their relationship with forensic sciences, as well as the possible contributions or limitations in the field of forensic sciences. Methods. Following PRISMA principles, a systematic evaluation of the microbiome and sudden death in forensic science was conducted. In this review, our study classified the sudden deaths as SUDA, SUDI, and SIDS. Results. The role of microbiome research in sudden death is discussed in this review. Various studies have linked the detection of different bacteria or viruses as a probable cause of sudden death. Bacteria analysed differ between studies that used autopsy specimens from deaths classified as SUDA, SUDI, and SIDS, or, except in the case of Staphylococcus aureus and Escherichia coli, which have been analysed in both SUDI and SIDS autopsies. In the case of viruses, only Cytomegalovirus has been analysed in both SIDS and SUDI cases. However, all the viruses studied are respiratory viruses found in samples of nasopharyngeal or lung fluid. Conclusions. Although the application of the microbiome in sudden death and other fields of forensic science is still in its early stages, a role of the microbiome in sudden deaths cannot be ruled out, but we cannot conclude that it is a significant factor either.
Mechanism of Dy3+ and Nd3+ Ions Electrochemical Coreduction with Ni2+, Co2+, and Fe3+ Ions in Chloride Melts
Authors: Kushkhov Khasbi , Ali Zhubagi , Khotov Astemir , Kholkina Anna
Published: December 2021

The present paper is devoted to the study of the processes of the mechanism of electrochemical coreduction of Dy3+ and Nd3+ ions with Ni2+, Co2+, and Fe3+ ions in the equimolar NaCl-KCl melt at 973 K and characterization of the synthesized samples. The performed voltammetry analysis of the electrochemical coreduction processes elucidated a significant difference in the values of the extraction potentials of the studied metals. This melt testifies that intermetallic compounds of Dy and Nd with Ni, Co, and Fe may be synthesized in the kinetic regime. The intermetallic phases of Dy and Nd with Ni, Co, and Fe are found to be formed along with the phases of metallic Ni, Co, and Fe either during electrolysis at the cathode current densities exceeding the limiting diffusion current of Ni2+, Co2+, and Fe3+ ions or in the potentiostatic regime at the potentials of the corresponding voltammetry curves. Therefore, the following interrelated key parameters affecting the electrochemical synthesis of Dy and Nd intermetallic compounds with Ni, Co, and Fe were determined: (i) composition of the electrolyte, i.e., concentrations of FeCl3, CoCl2, NiCl2, DyCl3, and NdCl3; (ii) cathode current density or electrolysis potential and (iii) electrolysis time. The obtained samples were characterized by micro-X-ray diffraction analysis, cyclic voltammetry, and scanning electron microscopy methods.
Continuous Stability TS Fuzzy Systems Novel Frame Controlled by a Discrete Approach and Based on SOS Methodology
Authors: Ellouze Ameni , Kahouli Omar , Ksantini Mohamed , Rebhi Ali , Hnaien Nidhal , Delmotte François
Published: December 2021

Generally, the continuous and discrete TS fuzzy systems’ control is studied independently. Unlike the discrete systems, stability results for the continuous systems suffer from conservatism because it is still quite difficult to apply non-quadratic Lyapunov functions, something which is much easier for the discrete systems. In this paper and in order to obtain new results for the continuous case, we proposed to connect the continuous with the discrete cases and then check the stability of the continuous TS fuzzy systems by means of the discrete design approach. To this end, a novel frame was proposed using the sum of square approach (SOS) to check the stability of the continuous Takagi Sugeno (TS) fuzzy models based on the discrete controller. Indeed, the control of the continuous TS fuzzy models is ensured by the discrete gains obtained from the Euler discrete form and based on the non-quadratic Lyapunov function. The simulation examples applied for various models, by modifying the order of the Euler discrete fuzzy system, are presented to show the effectiveness of the proposed methodology.
Chronic Myeloid Leukemia in a Patient with Previous Idiopathic Thrombocytopenic Purpura: How to Manage Imatinib Together with Eltrombopag
Authors: Autore Francesco , Sora’ Federica , Chiusolo Patrizia , Minnella Gessica , Colangelo Maria , Rossi Elena , Sica Simona
Published: December 2021

The occurrence of chronic myeloid leukemia (CML), or other myeloproliferative diseases, after the development of idiopathic thrombocytopenic purpura (ITP) is very rare in the current medical literature. Considering the advances in ITP management, and the wide use of new drugs for ITP and CML, we report an unusual case with this association. Our case report focused on a 64-year-old man with long-standing ITP treated with eltrombopag, who developed hyperleukocytosis during follow-up; after specific laboratory exams, it was diagnosed as CML and he began treatment with imatinib. The treatment with eltrombopag was balanced with imatinib to stabilize his platelet count. Data on bcr-abl and JAK2 transcripts were collected and revealed an optimal response with the achievement of negativization of both molecular signatures. We could demonstrate that treatment with imatinib and eltrombopag was well tolerated and allowed complete molecular remission of CML to be achieved, as well as of ITP.
Toxocariasis as a Rare Parasitic Complication of a Transthoracic Spine Surgery Procedure
Authors: Soukup Jan , Cerny Jan , Cegan Martin , Kelbich Petr , Novotny Tomas
Published: December 2021

Human toxocariasis is a helminthozoonosis caused by the migration of Toxocara species larvae through an organism. The infection in humans is transmitted either by direct ingestion of the eggs of the parasite, or by consuming undercooked meat infested with Toxocara larvae. This parasitosis can be found worldwide, but there are significant differences in seroprevalence in different areas, depending mainly on hot climate conditions and on low social status. However, the literature estimates of seroprevalence are inconsistent. Infected patients commonly present a range of symptoms, e.g., abdominal pain, decreased appetite, restlessness, fever, and coughing. This manuscript presents a case report of a polytraumatic patient who underwent a two-phase spinal procedure for a thoracolumbar fracture. After the second procedure, which was a vertebral body replacement via thoracotomy, the patient developed a pathologic pleural effusion. A microscopic cytology examination of this effusion revealed the presence of Toxocara species larvae. Although the patient presented no specific clinical symptoms, and the serological exams (Enzyme–linked immunosorbent assay (ELISA), Western blot) were negative, the microscopic evaluation enabled a timely diagnosis. The patient was successfully treated with albendazole, with no permanent sequelae of the infection.
Dynamics of Antibody Response to BNT162b2 mRNA COVID-19 Vaccine: A 7-Month Follow-Up Study
Authors: Olariu Tudor Rares , Ursoniu Sorin , Marincu Iosif , Lupu Maria Alina
Published: December 2021

Background and Objectives: Comprehension regarding immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited, and the durability of immune responses after vaccination is currently unknown. Several studies have reported on the antibody response in fully vaccinated individuals with a limited follow-up of the participants, i.e., below 7 months. Materials and Methods: The antibody response to complete vaccination with the BNT162b2 mRNA COVID-19 vaccine was assessed monthly, for 7 months, in 92 healthcare workers, between February 26 and September 26, 2021. The SARS-CoV-2 anti-spike protein IgG (IgGS) antibody was detected using the SARS-CoV-2 IgG II Quant assay (Abbott, Diagnostics Division, Sligo, Ireland), a chemiluminescent microparticle immunoassay (CMIA) with a sensitivity of 98.1% and specificity of 99.6%. Participants were divided into two groups, one for individuals previously infected with SARS-CoV-2 and the other for individuals without previous infection. Results: The median IgGS titers decreased monthly both in previously infected individuals and in the uninfected group. Previously infected individuals had significantly higher median titers of IgGS compared with previously uninfected subjects at all seven time points after complete vaccination (p < 0.001). Conclusions: Seven months after vaccination, the median IgGS titer had decreased by more than 92% both in individuals previously infected with SARS-CoV-2 and in uninfected individuals. However, IgGS antibodies were still detected in all study participants and persisted throughout the 7 months after the second dose of the vaccine. Further studies should be conducted to monitor the antibody response to the BNT162b2 mRNA vaccine beyond 7 months, to assess the need for a new booster dose in order to extend the duration and amplitude of the specific immune response.
Early Pacemaker Implantation after Transcatheter Aortic Valve Replacement: Impact of PlasmaBlade™ for Prevention of Device-Associated Bleeding Complications
Authors: Lind Alexander , Ahsan Majid , Kaya Elif , Wakili Reza , Rassaf Tienush , Jánosi Rolf Alexander
Published: December 2021

Background and Objectives: Permanent pacemaker implantation (PPI) is frequently required following transcatheter aortic valve replacement (TAVR). Dual antiplatelet therapy (DAPT) or oral anticoagulation therapy (OAK) is often necessary in these patients since they are at higher risk of thromboembolic events due to TAVR implantation, high incidence of coronary artery diseases (CAD) with the necessity of coronary intervention, and high rate of atrial fibrillation with the need of stroke prevention. We sought to evaluate the safety, efficiency, and clinical outcomes of early PPI following TAVR using the PlasmaBlade™ (Medtronic Inc., Minneapolis, MN, USA) pulsed electron avalanche knife (PEAK) for bleeding control in patients under DAPT or OAK. Materials and Methods: This retrospective single-center study included patients who underwent PPI after transfemoral TAVR (TF) at our center between December 2015 and May 2020. All PPI were performed using the PlasmaBlade™ Device. Results: The overall PPI rate was 14.1% (83 of 587 patients; 82.5 ± 4.6 years; 45.8% male). The PPI procedures were used to treat high-grade atrioventricular block (81.9%), severe sinus node dysfunction (13.3%), and alternating bundle branch block (4.8%). At the time of the procedure, 35 (42.2%) patients received DAPT, and 48 (57.8%) patients received OAK (50% with vitamin K antagonist (VKA) and 50% with novel oral anticoagulants (NOAK)). One device-pocket hematoma treated conservatively occurred in a patient (1.2%) receiving NOAK. Two re-operations were necessary in patients due to immediate lead dislocation (2.4%). Conclusions: The results of this study illustrate that the use of PlasmaBlade™ for PPI in patients after a TAVR who require antithrombotic treatment is feasible and might result into lower rates of severe bleeding complications compared to rates reported in the literature. Use of the PlasmaBlade device may be considered in this specific group of patients because of their high risk of bleeding.
A Novel Method to Predict Mortality and Length of Stay after Transfemoral Transcatheter Aortic Valve Implantation
Authors: Zisiopoulou Maria , Berkowitsch Alexander , Seppelt Philipp , Zeiher Andreas M. , Vasa-Nicotera Mariuca
Published: December 2021

Background and Objectives: We tested if a novel combination of predictors could improve the accuracy of outcome prediction after transfemoral transcatheter aortic valve implantation (TAVI). Materials and Methods: This prospective study recruited 169 participants (49% female; median age 81 years). The primary endpoint was midterm mortality; secondary endpoints were acute Valve Academic Research Consortium (VARC)-3 complication rate and post-TAVI in-hospital length of stay (LoS). EuroSCORE II (ESII), comorbidities (e.g., coronary artery disease), eGFR (estimated glomerular filtration rate; based on cystatin C), hemoglobin, creatinine, N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) levels and patient-reported outcome measures (PROMs, namely EuroQol-5-Dimension-5-Levels, EQ5D5L; Kansas City Cardiomyopathy Questionnaire, KCCQ; clinical frailty scale, CFS) at baseline were tested as predictors. Regression (uni- and multi-variate Cox; linear; binary logistic) and receiver operating characteristic (ROC)-curve analysis were applied. Results: Within a median follow-up of 439 (318–585) days, 12 participants died (7.1%). Independent predictors of mortality using multivariate Cox regression were baseline eGFR (p = 0.001) and KCCQ (p = 0.037). Based on these predictors, a Linear Prediction Score (LPS1) was calculated. The LPS1-area under the curve (AUC)-value (0.761) was significantly higher than the ESII-AUC value (0.597; p = 0.035). Independent predictors for LoS > 6 days (the median LoS) were eGFR (p = 0.028), NTproBNP (p = 0.034), and EQ5D5L values (p = 0.002); a respective calculated LPS2 provided an AUC value of 0.677 (p < 0.001). Eighty participants (47.3%) experienced complications. Male sex predicted complications only in the univariate analysis. Conclusions: The combination of KCCQ and eGFR can better predict midterm mortality than ES II alone. Combining eGFR, NTproBNP, and EQ5D5L can reliably predict LoS after TAVI. This novel method improves personalized TAVI risk stratification and hence may help reduce post-TAVI risk.
Insights into the Neutralization and DNA Binding of Toxin–Antitoxin System ParESO-CopASO by Structure-Function Studies
Authors: Zhou Juan , Du Xue-Jian , Liu Ying , Gao Zeng-Qiang , Geng Zhi , Dong Yu-Hui , Zhang Heng
Published: December 2021

ParESO-CopASO is a new type II toxin–antitoxin (TA) system in prophage CP4So that plays an essential role in circular CP4So maintenance after the excision in Shewanella oneidensis. The toxin ParESO severely inhibits cell growth, while CopASO functions as an antitoxin to neutralize ParESO toxicity through direct interactions. However, the molecular mechanism of the neutralization and autoregulation of the TA operon transcription remains elusive. In this study, we determined the crystal structure of a ParESO-CopASO complex that adopted an open V-shaped heterotetramer with the organization of ParESO-(CopASO)2-ParESO. The structure showed that upon ParESO binding, the intrinsically disordered C-terminal domain of CopASO was induced to fold into a partially ordered conformation that bound into a positively charged and hydrophobic groove of ParESO. Thermodynamics analysis showed the DNA-binding affinity of CopASO was remarkably higher than that of the purified TA complex, accompanied by the enthalpy change reversion from an exothermic reaction to an endothermic reaction. These results suggested ParESO acts as a de-repressor of the TA operon transcription at the toxin:antitoxin level of 1:1. Site-directed mutagenesis of ParESO identified His91 as the essential residue for its toxicity by cell toxicity assays. Our structure-function studies therefore elucidated the transcriptional regulation mechanism of the ParESO-CopASO pair, and may help to understand the regulation of CP4So maintenance in S. oneidensis.
Single- and Dual-Species Biofilm Formation by Shiga Toxin-Producing Escherichia coli and Salmonella, and Their Susceptibility to an Engineered Peptide WK2
Authors: Ma Zhi , Tang Xia , Stanford Kim , Chen Xiaolong , McAllister Tim A. , Niu Yan D.
Published: December 2021

Shiga toxin-producing Escherichia coli (STEC) and Salmonella enterica are important foodborne pathogens capable of forming both single- and multi-species biofilms. In this study, the mono- and dual-species biofilms were formed by STEC O113:H21 and Salmonella enterica serovar Choleraesuis 10708 on stainless steel in the presence of beef juice over 5 d at 22 °C. The dual-species biofilm mass was substantially (p < 0.05) greater than that produced by STEC O113:H21 or S. Choleraesuis 10708 alone. However, numbers (CFU/mL) of S. Choleraesuis 10708 or STEC O113:H21 cells in the dual-species biofilm were (p < 0.05) lower than their respective counts in single-species biofilms. In multi-species biofilms, the sensitivity of S. Choleraesuis 10708 to the antimicrobial peptide WK2 was reduced, but it was increased for STEC O113:H21. Visualization of the temporal and spatial development of dual-species biofilms using florescent protein labeling confirmed that WK2 reduced cell numbers within biofilms. Collectively, our results highlight the potential risk of cross-contamination by multi-species biofilms to food safety and suggest that WK2 may be developed as a novel antimicrobial or sanitizer for the control of biofilms on stainless steel.
A Structural Approach to Anti-Virulence: A Discovery Pipeline
Authors: McCarthy Michael , Goncalves Monica , Powell Hannah , Morey Blake , Turner Madison , Merrill Allan Rod
Published: December 2021

The anti-virulence strategy is designed to prevent bacterial virulence factors produced by pathogenic bacteria from initiating and sustaining an infection. One family of bacterial virulence factors is the mono-ADP-ribosyltransferase toxins, which are produced by pathogens as tools to compromise the target host cell. These toxins are bacterial enzymes that exploit host cellular NAD+ as the donor substrate to modify an essential macromolecule acceptor target in the host cell. This biochemical reaction modifies the target macromolecule (often protein or DNA) and functions in a binary fashion to turn the target activity on or off by blocking or impairing a critical process or pathway in the host. A structural biology approach to the anti-virulence method to neutralize the cytotoxic effect of these factors requires the search and design of small molecules that bind tightly to the enzyme active site and prevent catalytic function essentially disarming the pathogen. This method requires a high-resolution structure to serve as the model for small molecule inhibitor development, which illuminates the path to drug development. This alternative strategy to antibiotic therapy represents a paradigm shift that may circumvent multi-drug resistance in the offending microbe through anti-virulence therapy. In this report, the rationale for the anti-virulence structural approach will be discussed along with recent efforts to apply this method to treat honey bee diseases using natural products.
A New Method to Analyze the Mine Liquidation Costs in Poland
Authors: Smoliło Janusz , Chmiela Andrzej , Gajdzik Marta , Menéndez Javier , Loredo Jorge , Turek Marian , Bernardo-Sánchez Antonio
Published: December 2021

Coal mine closure processes are being carried out in the European Union due to the current energy transition. The use of coal-fired power plants has been significantly reduced in recent years. Because of the significant financial outlays, processes of rationalization and minimization of the mine liquidation cost should be carried out. In this paper, a statistical analysis of the liquidation processes in hard coal mines in Poland was carried out. A new tool was developed in order to optimize the mine liquidation costs. The mine liquidation process can be divided into ten different processes, which have been analyzed in detail in this research work. The method of the assessment of the amount of estimated liquidation costs described is based on the analysis of the total liquidation cost. The presented method of signaling deviations of the costs of the liquidation of the mining plant from the average value is a useful tool in the process approach to the issues connected with the restructuring of post-industrial property. The presented cost assessment procedure may facilitate the monitoring of conducted activities in terms of rationalization and minimization of the costs incurred. Finally, the proposed method for assessing the cost of mine liquidation is understandable, simple, and easy to use for applications in preliminary design works and on-going engineering works.
Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy
Authors: Liu Wei , Ma Xingqun , Jin Yingying , Zhang Jie , Li Yang , Tang Yuxia , Song Yong , Wang Shouju
Published: December 2021

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.
Pharmacological Activities and Characterization of Phenolic and Flavonoid Compounds in Methanolic Extract of Euphorbia cuneata Vahl Aerial Parts
Authors: Soliman Mohamed S. M. , Abdella Asmaa , Khidr Yehia A. , Hassan Gamal O. O. , Al-Saman Mahmoud A. , Elsanhoty Rafaat M.
Published: December 2021

Euphorbia cuneata Vahl. (Euphorbiaceae) is a plant used in folk medicine for the treatment of pain and inflammation, although the biological basis for these effects has not been thoroughly investigated. The goal of this study was to investigate the pharmacological properties and characterization of phenolic and flavonoid compounds present in the aerial parts of E. cuneata. E. cuneata aerial parts were tested for antioxidant activity (DPPH), antibacterial activity, cell viability and cytotoxic effects, and anti-inflammatory activity. Phenolic and flavonoid contents (HPLC), and volatile constituents (GC-MS) were also characterized. The methanol extract had the highest antioxidant activity, while the ether extract had the lowest. The antioxidant activity of E. cuneata extract increased from (21.11%) at a concentration of 10 µg/mL to (95.53%) at a concentration of 1280 µg/mL. S. aureus was the most sensitive organism with the highest zone of inhibition and lowest MIC, with acetone extract; whereas C. tropicalis was the most resistant, with the lowest inhibition zone. MTT assay revealed that the methanol extract of E. cuneata had significant cytotoxic effects on the A549, Caco-2, and MDA-MB-231 cell lines, respectively. Lower concentrations of methanolic extract gave anti-inflammatory activity, and those effects were compared with indomethacin as a positive control. Pyrogallol was the most abundant phenolic acid, followed by caffeic, p-coumaric, ferulic, syringic, and gallic acids, respectively. The 7-hydroxyflavone and rutin flavonoids were also found in the extract. GC-mass analysis showed that aerial parts of E. cuneata were rich in methyl 12-hydroxy-9-octadecenoate. The volatile components were also composed of considerable amounts of hexadecanoic acid, methyl ester, (9E,12E)-octadeca-9,12-dienoyl chloride, and methyl octadeca-9,12-dienoate as well as a little amount of hexanal dimethyl acetal. It can be concluded that methanolic extract of E. cuneata could be used as an available source of natural bioactive constituents with consequent health benefits.
Toward a Disease-Modifying Therapy of Alpha-Synucleinopathies: New Molecules and New Approaches Came into the Limelight
Authors: Upcott Matthew , Chaprov Kirill D. , Buchman Vladimir L.
Published: December 2021

The accumulation of the various products of alpha-synuclein aggregation has been associated with the etiology and pathogenesis of several neurodegenerative conditions, including both familial and sporadic forms of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). It is now well established that the aggregation and spread of alpha-synuclein aggregation pathology activate numerous pathogenic mechanisms that contribute to neurodegeneration and, ultimately, to disease progression. Therefore, the development of a safe and effective disease-modifying therapy that limits or prevents the accumulation of the toxic intermediate products of alpha-synuclein aggregation and the spread of alpha-synuclein aggregation pathology could provide significant positive clinical outcomes in PD/DLB cohorts. It has been suggested that this goal can be achieved by reducing the intracellular and/or extracellular levels of monomeric and already aggregated alpha-synuclein. The principal aim of this review is to critically evaluate the potential of therapeutic strategies that target the post-transcriptional steps of alpha-synuclein production and immunotherapy-based approaches to alpha-synuclein degradation in PD/DLB patients. Strategies aimed at the downregulation of alpha-synuclein production are at an early preclinical stage of drug development and, although they have shown promise in animal models of alpha-synuclein aggregation, many limitations need to be resolved before in-human clinical trials can be seriously considered. In contrast, many strategies aimed at the degradation of alpha-synuclein using immunotherapeutic approaches are at a more advanced stage of development, with some in-human Phase II clinical trials currently in progress. Translational barriers for both strategies include the limitations of alpha-synuclein aggregation models, poor understanding of the therapeutic window for the alpha-synuclein knockdown, and variability in alpha-synuclein pathology across patient cohorts. Overcoming such barriers should be the main focus of further studies. However, it is already clear that these strategies do have the potential to achieve a disease-modifying effect in PD and DLB.
Virtual Screening with Gnina 1.0
Authors: Sunseri Jocelyn , Koes David Ryan
Published: December 2021

Virtual screening—predicting which compounds within a specified compound library bind to a target molecule, typically a protein—is a fundamental task in the field of drug discovery. Doing virtual screening well provides tangible practical benefits, including reduced drug development costs, faster time to therapeutic viability, and fewer unforeseen side effects. As with most applied computational tasks, the algorithms currently used to perform virtual screening feature inherent tradeoffs between speed and accuracy. Furthermore, even theoretically rigorous, computationally intensive methods may fail to account for important effects relevant to whether a given compound will ultimately be usable as a drug. Here we investigate the virtual screening performance of the recently released Gnina molecular docking software, which uses deep convolutional networks to score protein-ligand structures. We find, on average, that Gnina outperforms conventional empirical scoring. The default scoring in Gnina outperforms the empirical AutoDock Vina scoring function on 89 of the 117 targets of the DUD-E and LIT-PCBA virtual screening benchmarks with a median 1% early enrichment factor that is more than twice that of Vina. However, we also find that issues of bias linger in these sets, even when not used directly to train models, and this bias obfuscates to what extent machine learning models are achieving their performance through a sophisticated interpretation of molecular interactions versus fitting to non-informative simplistic property distributions.
How a Nutritional Deficiency Became Treated with Fluoride
Authors: Hujoel Philippe P.
Published: December 2021

Ignoring evidence on causes of disease such as smoking can harm public health. This report explores how public health experts started to ignore evidence that pediatric vitamin D deficiencies are associated with dental caries. Historical analyses show that an organization of clinical specialists, the American Dental Association (ADA), initiated this view. The ADA was a world-leading organization and its governing bodies worked through political channels to make fluoride a global standard of care for a disease which at the time was viewed as an indicator of vitamin D deficiencies. The ADA scientific council was enlisted in this endeavor and authorized the statement saying that “claims for vitamin D as a factor in tooth decay are not acceptable”. This statement was ghost-written, the opposite of what the ADA scientific council had endorsed for 15 years, and the opposite of what the National Academy of Sciences concluded. Internal ADA documents are informative on the origin of this scientific conundrum; the ADA scientific council had ignored their scientific rules and was assisting ADA governing bodies in conflicts with the medical profession on advertising policies. The evidence presented here suggests that professional organizations of clinical specialists have the power to create standards of care which ignore key evidence and consequently can harm public health.
Mosquito Communities Vary across Landscape and Vertical Strata in Indian River County, Florida
Authors: Giordano Bryan V. , Cruz Anthony , Pérez-Ramos Daniel W. , Ramos Martina M. , Tavares Yasmin , Caragata Eric P.
Published: December 2021

Mosquito and arbovirus surveillance is essential to the protection of public health. A majority of surveys are undertaken at ground level. However, mosquitoes shelter, breed, and quest for hosts across vertical strata, thus limiting our ability to fully describe mosquito and arboviral communities. To elucidate patterns of mosquito vertical stratification, canopy traps were constructed to sample mosquitoes at heights of 1.5, 5.0, and 8.7 m across three different landscape types in a Florida coastal conservation area. We assessed trapping efforts using individual-based rarefaction and extrapolation. The effects of height, landscape, site location, and sampling date on mosquito community composition were parsed out using permutational ANOVA on a Hellinger-transformed Bray–Curtis dissimilarity abundance matrix. Lastly, a generalized linear mixed effects model (GLMM) was used to explore species-specific vertical patterns. We observed differences in sampling effort and community composition structure across various heights and landscapes. Our GLMM revealed significant effects of trap height for Aedes taeniorhynchus, Anopheles crucians, Anopheles quadrimaculatus, and Culex coronator, but not for Culex nigripalpus, the ultra-dominant species present in this area. Together these data provide evidence that height and landscape significantly affect mosquito community structures and highlight a need to develop sampling regimes to target specific vector and nuisance species at their preferred height and across different landscape types.
MCMV Centrifugal Enhancement: A New Spin on an Old Topic
Authors: Hancock Trevor J. , Hetzel Morgan Lynn , Ramirez Andrea , Sparer Tim E.
Published: December 2021

Human cytomegalovirus (HCMV) is a ubiquitous pathogen infecting a majority of people worldwide, with diseases ranging from mild to life-threatening. Its clinical relevance in immunocompromised people and congenital infections have made treatment and vaccine development a top priority. Because of cytomegaloviruses’ species specificity, murine cytomegalovirus (MCMV) models have historically informed and advanced translational CMV therapies. Using the phenomenon of centrifugal enhancement, we explored differences between MCMVs derived in vitro and in vivo. We found centrifugal enhancement on tissue culture-derived virus (TCV) was ~3× greater compared with salivary gland derived virus (SGV). Using novel “flow virometry”, we found that TCV contained a distinct submicron particle composition compared to SGV. Using an inhibitor of exosome production, we show these submicron particles are not extracellular vesicles that contribute to centrifugal enhancement. We examined how these differences in submicron particles potentially contribute to differing centrifugal enhancement phenotypes, as well as broader in vivo vs. in vitro MCMV differences.
Detection, Transmission, and Characterization of Grapevine Virus H in Croatia
Authors: Jagunić Martin , Lazarević Boris , Nikolić Kristina , Stupić Domagoj , Preiner Darko , Vončina Darko
Published: December 2021

A survey of recently discovered vitiviruses was performed on 113 Croatian autochthonous grapevine cultivars from the national collection “Jazbina” using one-step RT-PCR. The presence of grapevine virus H (GVH) was confirmed in nine (7.9%) cultivars and grapevine virus G in eight (7.1%), while the presence of grapevine viruses I and J were not detected. GVH was transmitted by the vine mealybug (Planococcus ficus) from a source plant to grapevine seedlings with a 10.5% transmission rate using a combination of 10 first and second instars per plant with 48 and 72 h of acquisition and inoculation access period, respectively. Transmission correlated with the presence of grapevine leafroll-associated virus 3 (GLRaV-3) in the GVH-source plant and recipient seedlings. No alternative GVH host was identified. A comparison of 356 nt fragments of the RdRP and CP coding regions showed nucleotide identity between the Croatian GVH isolates in the range of 95.5–99.2% and 97.5–99.4% and amino acid identity between 95.8 and 100% and between 98.3 and 100%, respectively. Comparison with foreign isolates revealed nucleotide sequence similarity in the RdRP and CP between 94 and 100% and between 97.7–100%, respectively. To the best of our knowledge, this is the first report of GVH in Croatia and the first identification of the vine mealybug as a vector of GVH.
Host Range, Biology, and Species Specificity of Seven-Segmented Influenza Viruses—A Comparative Review on Influenza C and D
Authors: Sreenivasan Chithra C. , Sheng Zizhang , Wang Dan , Li Feng
Published: December 2021

Other than genome structure, influenza C (ICV), and D (IDV) viruses with seven-segmented genomes are biologically different from the eight-segmented influenza A (IAV), and B (IBV) viruses concerning the presence of hemagglutinin–esterase fusion protein, which combines the function of hemagglutinin and neuraminidase responsible for receptor-binding, fusion, and receptor-destroying enzymatic activities, respectively. Whereas ICV with humans as primary hosts emerged nearly 74 years ago, IDV, a distant relative of ICV, was isolated in 2011, with bovines as the primary host. Despite its initial emergence in swine, IDV has turned out to be a transboundary bovine pathogen and a broader host range, similar to influenza A viruses (IAV). The receptor specificities of ICV and IDV determine the host range and the species specificity. The recent findings of the presence of the IDV genome in the human respiratory sample, and high traffic human environments indicate its public health significance. Conversely, the presence of ICV in pigs and cattle also raises the possibility of gene segment interactions/virus reassortment between ICV and IDV where these viruses co-exist. This review is a holistic approach to discuss the ecology of seven-segmented influenza viruses by focusing on what is known so far on the host range, seroepidemiology, biology, receptor, phylodynamics, species specificity, and cross-species transmission of the ICV and IDV.
Surface Coatings and Treatments for Controlled Hydrate Formation: A Mini Review
Authors: Altamash Tausif , Esperança José M. S. S. , Tariq Mohammad
Published: December 2021

Gas hydrates (GHs) are known to pose serious flow assurance challenges for the oil and gas industry. Neverthless, over the last few decades, gas hydrates-based technology has been explored for various energy- and environmentally related applications. For both applications, a controlled formation of GHs is desired. Management of hydrate formation by allowing them to form within the pipelines in a controlled form over their complete mitigation is preferred. Moreover, environmental, benign, non-chemical methods to accelerate the rate of hydrate formation are in demand. This review focused on the progress made in the last decade on the use of various surface coatings and treatments to control the hydrate formation at atmospheric pressure and in realistic conditions of high pressure. It can be inferred that both surface chemistry (hydrophobicity/hydrophilicity) and surface morphology play a significant role in deciding the hydrate adhesion on a given surface.
Solar Radiation Flux Provides a Method of Quantifying Weed-Crop Balance in Present and Future Climates
Authors: Squire Geoffrey R. , Young Mark W. , Hawes Cathy
Published: December 2021

A systematic approach to quantifying the weed–crop balance through the flux of solar radiation was developed and tested on commercial fields in a long-established Atlantic zone cropland. Measuring and modelling solar energy flux in crop stands has become standard practice in analysis and comparison of crop growth and yield across regions, species and years. In a similar manner, the partitioning of incoming radiation between crops and the in-field plant community may provide ‘common currencies’ through which to quantify positive and negative effects of weeds in relation to global change. Here, possibilities were explored for converting simple ground-cover measures in commercial fields of winter and spring oilseed rape in eastern Scotland, UK to metrics of solar flux. Solar radiation intercepted by the crops ranged with season and sowing delay from 129 to 1975 MJ m−2 (15-fold). Radiation transmitted through the crop, together with local weed management, resulted in a 70-fold range of weed intercepted radiation (14.2 to 963 MJ m−2), which in turn explained 93% of the corresponding between-site variation in weed dry mass (6.36 to 459 g m−2). Transmitted radiation explained almost 90% of the variation in number of weed species per field (12 to 40). The conversion of intercepted radiation to weed dry matter was far less variable at a mean of 0.74 g MJ−1 at both winter and spring sites. The primary cause of variation was an interaction between the temperature at sowing and the annual wave of incoming solar radiation. The high degree of explanatory power in solar flux indicates its potential use as an initial predictor and subsequent monitoring tool in the face of future change in climate and cropping intensity.