bluuebunny/crossref_metadata_2025 huggingface dataset:
Graphite to diamond transition induced by photoelectric absorption of ultraviolet photons
Authors: Gómez de Castro Ana I. , Rheinstädter Maikel , Clancy Patrick , Castilla Maribel , de Isidro Federico , Larruquert Juan I. , de Lis-Sánchez Tomas , Britten James , Cabero Piris Mariona , de Isidro-Gómez Federico P.
Published: January 2021

The phase transition from graphite to diamond is an appealing object of study because of many fundamental and also, practical reasons. The out-of-plane distortions required for the transition are a good tool to understand the collective behaviour of layered materials (graphene, graphite) and the van der Waals forces. As today, two basic processes have been successfully tested to drive this transition: strong shocks and high energy femtolaser excitation. They induce it by increasing either pressure or temperature on graphite. In this work, we report a third method consisting in the irradiation of graphite with ultraviolet photons of energies above 4.4 eV. We show high resolution electron microscopy images of pyrolytic carbon evidencing the dislocation of the superficial graphitic layers after irradiation and the formation of crystallite islands within them. Electron energy loss spectroscopy of the islands show that the sp2 to sp3 hybridation transition is a surface effect. High sensitivity X-ray diffraction experiments and Raman spectroscopy confirm the formation of diamond within the islands.
Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells
Authors: Yang Ming , Darwish Tamana , Larraufie Pierre , Rimmington Debra , Cimino Irene , Goldspink Deborah A. , Jenkins Benjamin , Koulman Albert , Brighton Cheryl A. , Ma Marcella , Lam Brian Y. H. , Coll Anthony P. , O’Rahilly Stephen , Reimann Frank , Gribble Fiona M.
Published: January 2021

Even though metformin is widely used to treat type2 diabetes, reducing glycaemia and body weight, the mechanisms of action are still elusive. Recent studies have identified the gastrointestinal tract as an important site of action. Here we used intestinal organoids to explore the effects of metformin on intestinal cell physiology. Bulk RNA-sequencing analysis identified changes in hexose metabolism pathways, particularly glycolytic genes. Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates. Metformin caused mitochondrial dysfunction and metformin’s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss. Gene expression changes elicited by metformin were replicated in 3D apical-out organoids and distal small intestines of metformin treated mice. We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction. This may explain the effects of metformin on intestinal glucose utilisation and food balance.
A biological Indian Ocean Dipole event in 2019
Authors: Shi Wei , Wang Menghua
Published: January 2021

The 2019 positive Indian Ocean Dipole (IOD) event in the boreal autumn was the most serious IOD event of the century with reports of significant sea surface temperature (SST) changes in the east and west equatorial Indian Ocean. Observations of the Visible Infrared Imaging Radiometer Suite (VIIRS) onboard the Suomi National Polar-orbiting Partnership (SNPP) between 2012 and 2020 are used to study the significant biological dipole response that occurred in the equatorial Indian Ocean following the 2019 positive IOD event. For the first time, we propose, identify, characterize, and quantify the biological IOD. The 2019 positive IOD event led to anomalous biological activity in both the east IOD zone and west IOD zone. The average chlorophyll-a (Chl-a) concentration reached over ~ 0.5 mg m−3 in 2019 in comparison to the climatology Chl-a of ~ 0.3 mg m−3 in the east IOD zone. In the west IOD zone, the biological activity was significantly depressed. The depressed Chl-a lasted until May 2020. The anomalous ocean biological activity in the east IOD zone was attributed to the advection of the higher-nutrient surface water due to enhanced upwelling. On the other hand, the dampened ocean biological activity in the west IOD zone was attributed to the stronger convergence of the surface waters than that in a normal year.
Direct diagnostic testing of SARS-CoV-2 without the need for prior RNA extraction
Authors: Wei Shan , Kohl Esther , Djandji Alexandre , Morgan Stephanie , Whittier Susan , Mansukhani Mahesh , Hod Eldad , D’Alton Mary , Suh Yousin , Williams Zev
Published: January 2021

The COVID-19 pandemic has resulted in an urgent need for a rapid, point of care diagnostic testing that could be rapidly scaled on a worldwide level. We developed and tested a highly sensitive and robust assay based on reverse transcription loop mediated isothermal amplification (RT-LAMP) that uses readily available reagents and a simple heat block using contrived spike-in and actual clinical samples. RT-LAMP testing on RNA-spiked samples showed a limit of detection (LoD) of 2.5 copies/μl of viral transport media. RT-LAMP testing directly on clinical nasopharyngeal swab samples in viral transport media had an 85% positive percentage agreement (PPA) (17/20), and 100% negative percentage agreement (NPV) and delivered results in 30 min. Our optimized RT-LAMP based testing method is a scalable system that is sufficiently sensitive and robust to test for SARS-CoV-2 directly on clinical nasopharyngeal swab samples in viral transport media in 30 min at the point of care without the need for specialized or proprietary equipment or reagents. This cost-effective and efficient one-step testing method can be readily available for COVID-19 testing world-wide, especially in resource poor settings.
Novel gene rearrangement in the mitochondrial genome of Muraenesox cinereus and the phylogenetic relationship of Anguilliformes
Authors: Zhang Kun , Zhu Kehua , Liu Yifan , Zhang Hua , Gong Li , Jiang Lihua , Liu Liqin , Lü Zhenming , Liu Bingjian
Published: January 2021

The structure and gene sequence of the fish mitochondrial genome are generally considered to be conservative. However, two types of gene arrangements are found in the mitochondrial genome of Anguilliformes. In this paper, we report a complete mitogenome of Muraenesox cinereus (Anguilliformes: Muraenesocidae) with rearrangement phenomenon. The total length of the M. cinereus mitogenome was 17,673 bp, and it contained 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNA genes, and two identical control regions (CRs). The mitochondrial genome of M. cinereus was obviously rearranged compared with the mitochondria of typical vertebrates. The genes ND6 and the conjoint trnE were translocated to the location between trnT and trnP, and one of the duplicated CR was translocated to the upstream of the ND6. The tandem duplication and random loss is most suitable for explaining this mitochondrial gene rearrangement. The Anguilliformes phylogenetic tree constructed based on the whole mitochondrial genome well supports Congridae non-monophyly. These results provide a basis for the future Anguilliformes mitochondrial gene arrangement characteristics and further phylogenetic research.
Translational control of enzyme scavenger expression with toxin-induced micro RNA switches
Authors: Pollak Nina M. , Cooper-White Justin J. , Macdonald Joanne
Published: January 2021

Biological computation requires in vivo control of molecular behavior to progress development of autonomous devices. miRNA switches represent excellent, easily engineerable synthetic biology tools to achieve user-defined gene regulation. Here we present the construction of a synthetic network to implement detoxification functionality. We employed a modular design strategy by engineering toxin-induced control of an enzyme scavenger. Our miRNA switch results show moderate synthetic expression control over a biologically active detoxification enzyme molecule, using an established design protocol. However, following a new design approach, we demonstrated an evolutionarily designed miRNA switch to more effectively activate enzyme activity than synthetically designed versions, allowing markedly improved extrinsic user-defined control with a toxin as inducer. Our straightforward new design approach is simple to implement and uses easily accessible web-based databases and prediction tools. The ability to exert control of toxicity demonstrates potential for modular detoxification systems that provide a pathway to new therapeutic and biocomputing applications.
Utilization of the zebrafish model to unravel the harmful effects of biomass burning during Amazonian wildfires
Authors: Babić Sanja , Čižmek Lara , Maršavelski Aleksandra , Malev Olga , Pflieger Maryline , Strunjak-Perović Ivančica , Popović Natalija Topić , Čož-Rakovac Rozelindra , Trebše Polonca
Published: January 2021

Amazonian wildfires in 2019 have raised awareness about rainforest burning due to increased emissions of particulate matter and carbon. In the context of these emissions, by-products of lignin thermal degradation (i.e. methoxyphenols) are often neglected. Methoxyphenols entering the atmosphere may form intermediates with currently unknown reaction mechanisms and toxicity. This study for the first time provides a comprehensive insight into the impact of lignin degradation products [guaiacol, catechol], and their nitrated intermediates [4-nitrocatechol, 4,6-dinitroguaiacol, 5-nitroguaiacol] on zebrafish Danio rerio. Results revealed 4-nitrocatechol and catechol as the most toxic, followed by 4,6DNG > 5NG > GUA. The whole-organism bioassay integrated with molecular modeling emphasized the potential of methoxyphenols to inhibit tyrosinase, lipoxygenase, and carbonic anhydrase, consequently altering embryonic development (i.e. affected sensorial, skeletal, and physiological parameters, pigmentation formation failure, and non-hatching of larvae). The whole-organism bioassay integrated with in silico approach confirmed the harmful effects of lignin degradation products and their intermediates on aquatic organisms, emphasizing the need for their evaluation within ecotoxicity studies focused on aquatic compartments.
Brain-inspired spiking neural networks for decoding and understanding muscle activity and kinematics from electroencephalography signals during hand movements
Authors: Kumarasinghe Kaushalya , Kasabov Nikola , Taylor Denise
Published: January 2021

Compared to the abilities of the animal brain, many Artificial Intelligence systems have limitations which emphasise the need for a Brain-Inspired Artificial Intelligence paradigm. This paper proposes a novel Brain-Inspired Spiking Neural Network (BI-SNN) model for incremental learning of spike sequences. BI-SNN maps spiking activity from input channels into a high dimensional source-space which enhances the evolution of polychronising spiking neural populations. We applied the BI-SNN to predict muscle activity and kinematics from electroencephalography signals during upper limb functional movements. The BI-SNN extends our previously proposed eSPANNet computational model by integrating it with the ‘NeuCube’ brain-inspired SNN architecture. We show that BI-SNN can successfully predict continuous muscle activity and kinematics of upper-limb. The experimental results confirmed that the BI-SNN resulted in strongly correlated population activity and demonstrated the feasibility for real-time prediction. In contrast to the majority of Brain–Computer Interfaces (BCIs) that constitute a ‘black box’, BI-SNN provide quantitative and visual feedback about the related brain activity. This study is one of the first attempts to examine the feasibility of finding neural correlates of muscle activity and kinematics from electroencephalography using a brain-inspired computational paradigm. The findings suggest that BI-SNN is a better neural decoder for non-invasive BCI.
Residual and ecological risk assessment of heavy metals in fly ash from co-combustion of excess sludge and coal
Authors: Tang Yao , Pan Jingshi , Li Biqing , Zhao Suying , Zhang Liguo
Published: January 2021

Co-combustion of municipal excess sludge (ES) and coal provides an alternative method for disposing ES. The present study aims to investigate the residual and ecological risk of heavy metals in fly ash from co-combustion of ES and coal. The total concentration and speciation distribution of heavy metals, characterization of SEM, EDX, XRD and leaching test were carried out to assess the fly ash in this study. The results showed that the total concentrations of Cu, Zn and Mn were higher than others in fly ash, and most heavy metals were concentrated in fine particles. For Cd, Cr and Pb, the percentages of speciation of F4 and F5 were all over 90%, suggesting the relatively lower leaching toxicity. The leaching percent of all heavy metals was lower than 5% by two diluted HNO3 solutions for fly ash. The potential ecological risks increased with the decrease of particle size of fly ash, and Cd accounted for the main fraction for ecological risk despite of lower concentration in comparison to other measured heavy metals.
The effect of the definition of ‘pandemic’ on quantitative assessments of infectious disease outbreak risk
Authors: Singer Benjamin J. , Thompson Robin N. , Bonsall Michael B.
Published: January 2021

In the early stages of an outbreak, the term ‘pandemic’ can be used to communicate about infectious disease risk, particularly by those who wish to encourage a large-scale public health response. However, the term lacks a widely accepted quantitative definition. We show that, under alternate quantitative definitions of ‘pandemic’, an epidemiological metapopulation model produces different estimates of the probability of a pandemic. Critically, we show that using different definitions alters the projected effects of key parameters—such as inter-regional travel rates, degree of pre-existing immunity, and heterogeneity in transmission rates between regions—on the risk of a pandemic. Our analysis provides a foundation for understanding the scientific importance of precise language when discussing pandemic risk, illustrating how alternative definitions affect the conclusions of modelling studies. This serves to highlight that those working on pandemic preparedness must remain alert to the variability in the use of the term ‘pandemic’, and provide specific quantitative definitions when undertaking one of the types of analysis that we show to be sensitive to the pandemic definition.
Foliar resistance to Rhizoctonia solani in Arabidopsis is compromised by simultaneous loss of ethylene, jasmonate and PEN2 mediated defense pathways
Authors: Kidd Brendan N. , Foley Rhonda , Singh Karam B. , Anderson Jonathan P.
Published: January 2021

Rhizoctonia solani causes damaging yield losses on most major food crops. R. solani isolates belonging to anastomosis group 8 (AG8) are soil-borne, root-infecting pathogens with a broad host range. AG8 isolates can cause disease on wheat, canola and legumes, however Arabidopsis thaliana is heretofore thought to possess non-host resistance as A. thaliana ecotypes, including the reference strain Col-0, are resistant to AG8 infection. Using a mitochondria-targeted redox sensor (mt-roGFP2) and cell death staining, we demonstrate that both AG8 and a host isolate (AG2-1) of R. solani are able to infect A. thaliana roots. Above ground tissue of A. thaliana was found to be resistant to AG8 but not AG2. Genetic analysis revealed that ethylene, jasmonate and PENETRATION2-mediated defense pathways work together to provide resistance to AG8 in the leaves which subsequently enable tolerance of root infections. Overall, we demonstrate a significant difference in defense capabilities of above and below ground tissue in providing resistance to R. solani AG8 in Arabidopsis.
Early stage dental caries detection using near infrared spatial frequency domain imaging
Authors: Bounds Alistair D. , Girkin John M.
Published: January 2021

Early stage dental caries can be remineralized without the need for “drill-and-fill” treatments that are more invasive and less permanent. However, early stage caries lesions typically present as a white spot on a white background, resulting in many lesions only being identified after they have developed beyond the point of remineralization as cavities. We present a spatial frequency domain imaging technique to characterize the optical properties of dental tissue. This technique enables different dental tissue types (healthy enamel, healthy dentin and damaged or demineralized enamel) to be easily distinguished from one another and allows quantification of the reduced scattering coefficients of dental tissue. The use of near-infrared light at 850 nm allows high depth penetration into the tissue and suppression of absorption effects, ensuring only changes in the reduced scattering coefficient that result directly from demineralization of enamel are observed and simplifying the analysis method. This technique provides a tool to both guide the attention of dentists to areas of interest and potential demineralization, and to provide longitudinal quantified assessments to monitor caries lesion behaviour over time.
A new expansion material used for roof-contacted filling based on smelting slag
Authors: Na Hua , Lv Guocheng , Wang Lijuan , Liao Libing , Zhang Dan , Guo Lijie , Li Wenchen
Published: January 2021

The improper handling of smelting slag will seriously pollute the environment, and the unfilled roof of the goaf of the mine will threaten the safety of the mine. Expansion materials have attracted more and more attention because of their excellent properties. In this paper, copper-nickel smelting slag that has some active ingredients of gelling is used instead of traditional aggregate and some part of cement in order to reduce its pollution to the environment and its costs. For safety reasons, hydrogen peroxide was chosen as the foaming agent. Sodium silicate and hexadecyl trimethyl ammonium bromide (CTAB) are used as additives. Our results showed that after 28 days of curing, the material has better mechanical properties and the early compressive strength of the material was enhanced by sodium silicate. The efficiency of foaming was improved by CTAB. It also proves that copper–nickel smelting slag can be used in expansion material. At the same time, the utilization rate of the copper–nickel smelting slag of this formula can reach 70%, reduce its pollution to the environment.
Overlooked potential of positrons in cancer therapy
Authors: Hioki Takanori , Gholami Yaser H. , McKelvey Kelly J. , Aslani Alireza , Marquis Harry , Eslick Enid M. , Willowson Kathy P. , Howell Viive M. , Bailey Dale L.
Published: January 2021

Positron (β+) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a β+ emitter fluorine-18 (18F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, 18F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of β+ emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of β+ emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of 18F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for β+ emitters. These results may also have implications for emerging cancer theranostic strategies, where β+ emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.
Fabrication of the magnetic mesoporous silica Fe-MCM-41-A as efficient adsorbent: performance, kinetics and mechanism
Authors: Guo Yige , Chen Bin , Zhao Ying , Yang Tianxue
Published: January 2021

Antibiotics are emerging pollutants and increasingly present in aquaculture and industrial wastewater. Due to their impact on the environment and health, their removal has recently become a significant concern. In this investigation, we synthesized nano zero-valent iron-loaded magnetic mesoporous silica (Fe-MCM-41-A) via precipitation and applied the adsorption of oxytetracycline (OTC) from an aqueous solution. The effects of competing ions such as Na+, Ca2+ and Cu2+ on the adsorption process under different pH conditions were studied in depth to providing a theoretical basis for the application of nanomaterials. The characterization of the obtained material through transmission electron microscopy demonstrates that the adsorbent possesses hexagonal channels, which facilitate mass transfer during adsorption. The loaded zero-valent iron made the magnetic, and was thus separated under an applied magnetic field. The adsorption of OTC onto Fe-MCM-41-A is rapid and obeys the pseudo-second-order kinetic model, and the maximum adsorption capacity of OTC is 625.90 mg g−1. The reaction between OTC and Fe-MCM-41-A was inner complexation and was less affected by the Na+. The effect of Ca2+ on the adsorption was small under acidic and neutral conditions. However, the promotion effect of Ca2+ increased by the increase of pH. Cu2+ decreased the removal efficiencies continuously and the inhibitory effects decrease varied with the increase of pH. We propose that surface complexing, ion-exchange, cationic π-bonding, hydrogen bonding, and hydrophobicity are responsible for the adsorption of OTC onto Fe-MCM-41-A.
Difficult laparoscopic cholecystectomy and preoperative predictive factors
Authors: Di Buono Giuseppe , Romano Giorgio , Galia Massimo , Amato Giuseppe , Maienza Elisa , Vernuccio Federica , Bonventre Giulia , Gulotta Leonardo , Buscemi Salvatore , Agrusa Antonino
Published: January 2021

Laparoscopic cholecystectomy (LC) is the standard technique for treatment of gallbladder disease. In case of acute cholecystitis we can identify preoperative factors associated with an increased risk of conversion and intraoperative complications. The aim of our study was to detect preoperative laboratory and radiological findings predictive of difficult LC with potential advantages for both the surgeons and patients in terms of options for management. We designed a retrospective case–control study to compare preoperative predictive factors of difficult LC in patients treated in emergency setting between January 2015 and December 2019. We included in the difficult LC group the surgeries with operative time > 2 h, need for conversion to open, significant bleeding and/or use of synthetic hemostats, vascular and/or biliary injuries and additional operative procedures. We collected 86 patients with inclusion criteria and difficult LC. In the control group, we selected 86 patients with inclusion criteria, but with no operative signs of difficult LC. The analysis of the collected data showed that there was a statistically significant association between WBC count and fibrinogen level and difficult LC. No association were seen with ALP, ALT and bilirubin values. Regarding radiological findings significant differences were noted among the two groups for irregular or absent wall, pericholecystic fluid, fat hyperdensity, thickening of wall > 4 mm and hydrops. The preoperative identification of difficult laparoscopic cholecystectomy provides an important advantage not only for the surgeon who has to perform the surgery, but also for the organization of the operating block and technical resources. In patients with clinical and laboratory parameters of acute cholecystitis, therefore, it would be advisable to carry out a preoperative abdominal CT scan with evaluation of features that can be easily assessed also by the surgeon.
Comparative models disentangle drivers of fruit production variability of an economically and ecologically important long-lived Amazonian tree
Authors: Staudhammer Christina L. , Wadt Lúcia Helena O. , Kainer Karen A. , da Cunha Thiago Augusto
Published: January 2021

Trees in the upper canopy contribute disproportionately to forest ecosystem productivity. The large, canopy-emergentBertholletia excelsaalso supports a multimillion-dollar commodity crop (Brazil nut), harvested almost exclusively from Amazonian forests.B. excelsafruit production, however is extremely variable within populations and years, destabilizing local harvester livelihoods and the extractive economy. To understand this variability, data were collected in Acre, Brazil over 10 years at two sites with similar climate and forest types, but different fruit production levels, despite their proximity (~ 30 km). One site consistently produced more fruit, showed less individual- and population-level variability, and had significantly higher soil P and K levels. The strongest predictor of fruit production was crown area. Elevation and sapwood area also significantly impacted fruit production, but effects differed by site. While number of wet days and dry season vapor pressure prior to flowering were significant production predictors, no climatic variables completely captured annual observed variation. Trees on the site with higher available P and K produced nearly three times more fruits, and appeared more resilient to prolonged drought and drier atmospheric conditions. Management activities, such as targeted fertilization, may shield income-dependent harvesters from expected climate changes and production swings, ultimately contributing to conservation of old growth forests where this species thrives.
Neuronal delivery of nanoparticles via nerve fibres in the skin
Authors: Katiyar Neeraj , Raju Gayathri , Madhusudanan Pallavi , Gopalakrishnan-Prema Vignesh , Shankarappa Sahadev A.
Published: January 2021

Accessing the peripheral nervous system (PNS) by topically applied nanoparticles is a simple and novel approach with clinical applications in several PNS disorders. Skin is richly innervated by long peripheral axons that arise from cell bodies located distally within ganglia. In this study we attempt to target dorsal root ganglia (DRG) neurons, via their axons by topical application of lectin-functionalized gold nanoparticles (IB4-AuNP). In vitro, 140.2 ± 1.9 nm IB4-AuNP were found to bind both axons and cell bodies of DRG neurons, and AuNP applied at the axonal terminals were found to translocate to the cell bodies. Topical application of IB4-AuNP on rat hind-paw resulted in accumulation of three to fourfold higher AuNP in lumbar DRG than in contralateral control DRGs. Results from this study clearly suggest that topically applied nanoparticles with neurotropic targeting ligands can be utilized for delivering nanoparticles to neuronal cell bodies via axonal transport mechanisms.
Approximate conditional phenotype analysis based on genome wide association summary statistics
Authors: Wu Peitao , Wang Biqi , Lubitz Steven A. , Benjamin Emelia J. , Meigs James B. , Dupuis Josée
Published: January 2021

Because single genetic variants may have pleiotropic effects, one trait can be a confounder in a genome-wide association study (GWAS) that aims to identify loci associated with another trait. A typical approach to address this issue is to perform an additional analysis adjusting for the confounder. However, obtaining conditional results can be time-consuming. We propose an approximate conditional phenotype analysis based on GWAS summary statistics, the covariance between outcome and confounder, and the variant minor allele frequency (MAF). GWAS summary statistics and MAF are taken from GWAS meta-analysis results while the traits covariance may be estimated by two strategies: (i) estimates from a subset of the phenotypic data; or (ii) estimates from published studies. We compare our two strategies with estimates using individual level data from the full GWAS sample (gold standard). A simulation study for both binary and continuous traits demonstrates that our approximate approach is accurate. We apply our method to the Framingham Heart Study (FHS) GWAS and to large-scale cardiometabolic GWAS results. We observed a high consistency of genetic effect size estimates between our method and individual level data analysis. Our approach leads to an efficient way to perform approximate conditional analysis using large-scale GWAS summary statistics.
Risk of coronary heart disease among cancer survivors with different prediagnosis body mass index
Authors: Ko Ahryoung , Kim Kyuwoong , Son Joung Sik , Cho Yu Jin , Park Sang Min , Park Minseon
Published: January 2021

Association between body mass index (BMI) and coronary heart disease (CHD) in cancer survivors is not clearly established. This study analyzed the prediagnosis BMI-CHD association by examining 13,500 cancer survivors identified from the National Health Insurance Service-Health Screening Cohort from January 1, 2004 to December 31, 2009 including the patients who were free of cardiovascular disease at enrollment. The Cox proportional hazards model (adjusted for socioeconomic, health behavior, health status, and medical characteristics) was used for calculating hazard ratios (HR) and 95% confidence intervals (95% CI) for CHD in each prediagnosis BMI category among cancer survivors. Compared to cancer survivors with a prediagnosis BMI between 18.5 and 22.9 kg/m2, those with a prediagnosis BMI of 23.0–24.9 kg/m2 and ≥ 25.0 kg/m2 had significantly higher CHD risk (HR = 1.51; 95% CI: 1.13–2.01 and HR = 1.38; 95% CI: 1.04–1.84, respectively). Cancer survivors with a low prediagnosis BMI (< 18.5 kg/m2) also had significantly higher CHD risk (HR = 1.97; 95% CI: 1.20–3.24) compared to those with a BMI of 18.5–22.9 kg/m2. Similar associations were found after stratifying analyses based on first cancer site and sociodemographic and medical characteristic subgroups. Our study suggests that prediagnosis underweight among patients with cancer is a predictor of CHD risk.
Water-flooding characteristics of lithologic reservoir in Ordos basin
Authors: He Jie , Liu Xiaodong , Zhu Xinyu , Jiang Tao , He Hui , Zhou Lin , Liu Qinghai , Zhu Yushuang , Liu Linyu
Published: January 2021

Due to the poor situation of water-flooding mechanism research on Chang 4 + 5 reservoir of Ordos basin, the authors quantitatively studied the influence factors of water-flooding characteristics by sedimentology, casting thin sections, constant-speed mercury injection, scanning electron microscope as well as production records. The size and distribution of pore-throat were also found closely related with the water-flooding seepage law. The results show that the microscopic seepage paths of Chang 4 + 5 reservoir include uniform displacement, finger displacement and peak displacement, and their correspondent oil displacement efficiency reduces in turn under the same conditions. Reservoir heterogeneity, reservoir properties, distribution of pore structure and wettability play a decisive role in water-flooding efficiency. Generally, When the intra-layer range is greater than 4.65, the breakthrough coefficient is greater than 3.54, the coefficient of variation is greater than 0.7, the distribution frequency of inter-layer is greater than 0.5 per meter, and the distribution density is greater than 0.435%, the range between layers is greater than 6.86, the breakthrough coefficient is greater than 2.58, the coefficient of variation is greater than 0.51, and the thickness of inter-layer is greater than 7.54 m. the increasing trend of oil displacement efficiency will be obviously weakened.
Oral absorption and drug interaction kinetics of moxifloxacin in an animal model of weightlessness
Authors: Liang Dong , Ma Jing , Wei Bo
Published: January 2021

To investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.
High-throughput measurement of fibroblast rhythms reveals genetic heritability of circadian phenotypes in diversity outbred mice and their founder strains
Authors: Kim Sam-Moon , Vadnie Chelsea A. , Philip Vivek M. , Gagnon Leona H. , Chowdari Kodavali V. , Chesler Elissa J. , McClung Colleen A. , Logan Ryan W.
Published: January 2021

Circadian variability is driven by genetics and Diversity Outbred (DO) mice is a powerful tool for examining the genetics of complex traits because their high genetic and phenotypic diversity compared to conventional mouse crosses. The DO population combines the genetic diversity of eight founder strains including five common inbred and three wild-derived strains. In DO mice and their founders, we established a high-throughput system to measure cellular rhythms using in vitro preparations of skin fibroblasts. Among the founders, we observed strong heritability for rhythm period, robustness, phase and amplitude. We also found significant sex and strain differences for these rhythms. Extreme differences in period for molecular and behavioral rhythms were found between the inbred A/J strain and the wild-derived CAST/EiJ strain, where A/J had the longest period and CAST/EiJ had the shortest. In addition, we measured cellular rhythms in 329 DO mice, which displayed far greater phenotypic variability than the founders—80% of founders compared to only 25% of DO mice had periods of ~ 24 h. Collectively, our findings demonstrate that genetic diversity contributes to phenotypic variability in circadian rhythms, and high-throughput characterization of fibroblast rhythms in DO mice is a tractable system for examining the genetics of circadian traits.
Osteoprotegerin is a marker of cardiovascular mortality in patients with chronic kidney disease stages 3–5
Authors: Marques Gustavo Lenci , Hayashi Shirley , Bjällmark Anna , Larsson Matilda , Riella Miguel , Olandoski Marcia , Lindholm Bengt , Nascimento Marcelo Mazza
Published: January 2021

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG), known to regulate bone mass by inhibiting osteoclast differentiation and activation, might also play a role in vascular calcification. Increased circulating OPG levels in patients with CKD are associated with aortic calcification and increased mortality. We assessed the predictive role of OPG for all-cause and cardiovascular mortality in patients with CKD stages 3–5 over a 5-year follow-up period. We evaluated the relationship between OPG and all-cause and cardiovascular mortality in 145 CKD patients (stages 3–5) in a prospective observational follow-up study. Inflammation markers, including high-sensitivity C-reactive protein, standard echocardiography, and estimation of intima-media thickness in the common carotid artery, were assessed at baseline, and correlations with OPG levels were determined. The cutoff values for OPG were defined using ROC curves for cardiovascular mortality. Survival was assessed during follow up lasting for up to 5.5 years using Fine and Gray model. A total of 145 (89 men; age 58.9 ± 15.0 years) were followed up. The cutoff value for OPG determined using ROC was 10 pmol/L for general causes mortality and 10.08 pmol/L for CV causes mortality. Patients with higher serum OPG levels presented with higher mortality rates compared to patients with lower levels. Aalen–Johansen cumulative incidence curve analysis demonstrated significantly worse survival rates in individuals with higher baseline OPG levels for all-cause and cardiovascular mortality (p < 0.001). In multivariate analysis, OPG was a marker of general and cardiovascular mortality independent of sex, age, CVD, diabetes, and CRP levels. When CKD stages were included in the multivariate analysis, OPG was an independent marker of all-cause mortality but not cardiovascular mortality. Elevated serum OPG levels were associated with higher all-cause and cardiovascular mortality risk, independent of age, CVD, diabetes, and inflammatory markers, in patients with CKD.
A novel hyperthermophilic methylglyoxal synthase: molecular dynamic analysis on the regional fluctuations
Authors: Seo Gyo-Yeon , Lee Hoe-Suk , Kim Hyeonsoo , Cho Sukhyeong , Na Jeong-Geol , Yeon Young Joo , Lee Jinwon
Published: January 2021

Two putative methylglyoxal synthases, which catalyze the conversion of dihydroxyacetone phosphate to methylglyoxal, from Oceanithermus profundus DSM 14,977 and Clostridium difficile 630 have been characterized for activity and thermal stability. The enzyme from O. profundus was found to be hyperthermophilic, with the optimum activity at 80 °C and the residual activity up to 59% after incubation of 15 min at 95 °C, whereas the enzyme from C. difficile was mesophilic with the optimum activity at 40 °C and the residual activity less than 50% after the incubation at 55 °C or higher temperatures for 15 min. The structural analysis of the enzymes with molecular dynamics simulation indicated that the hyperthermophilic methylglyoxal synthase has a rigid protein structure with a lower overall root-mean-square-deviation value compared with the mesophilic or thermophilic counterparts. In addition, the simulation results identified distinct regions with high fluctuations throughout those of the mesophilic or thermophilic counterparts via root-mean-square-fluctuation analysis. Specific molecular interactions focusing on the hydrogen bonds and salt bridges in the distinct regions were analyzed in terms of interatomic distances and positions of the individual residues with respect to the secondary structures of the enzyme. Key interactions including specific salt bridges and hydrogen bonds between a rigid beta-sheet core and surrounding alpha helices were found to contribute to the stabilisation of the hyperthermophilic enzyme by reducing the regional fluctuations in the protein structure. The structural information and analysis approach in this study can be further exploited for the engineering and industrial application of the enzyme.
Quantum dot and electron acceptor nano-heterojunction for photo-induced capacitive charge-transfer
Authors: Karatum Onuralp , Eren Guncem Ozgun , Melikov Rustamzhon , Onal Asim , Ow-Yang Cleva W. , Sahin Mehmet , Nizamoglu Sedat
Published: January 2021

Capacitive charge transfer at the electrode/electrolyte interface is a biocompatible mechanism for the stimulation of neurons. Although quantum dots showed their potential for photostimulation device architectures, dominant photoelectrochemical charge transfer combined with heavy-metal content in such architectures hinders their safe use. In this study, we demonstrate heavy-metal-free quantum dot-based nano-heterojunction devices that generate capacitive photoresponse. For that, we formed a novel form of nano-heterojunctions using type-II InP/ZnO/ZnS core/shell/shell quantum dot as the donor and a fullerene derivative of PCBM as the electron acceptor. The reduced electron–hole wavefunction overlap of 0.52 due to type-II band alignment of the quantum dot and the passivation of the trap states indicated by the high photoluminescence quantum yield of 70% led to the domination of photoinduced capacitive charge transfer at an optimum donor–acceptor ratio. This study paves the way toward safe and efficient nanoengineered quantum dot-based next-generation photostimulation devices.
The correction of conjunctivochalasis using high-frequency radiowave electrosurgery improves dry eye disease
Authors: Ji Yong Woo , Seong Hyojin , Lee Sujung , Alotaibi Mutlaq Hamad , Kim Tae-im , Lee Hyung Keun , Seo Kyoung Yul
Published: January 2021

We aimed to determine the clinical impact of conjunctivochalasis (CCh) and its correction using high-frequency radiowave electrosurgery (HFR-ES), for signs and symptoms of dry eye disease (DED). Forty patients diagnosed with symptomatic CCh were prospectively enrolled. As a result, patients with CCh had moderate to severe DED and most of them exhibited meibomian gland dysfunction (MGD). Corneo-conjunctival fluorescein staining score (CFS) and all lid-parallel-conjunctival-folds scores (LIPCOFs) were positively correlated. Nasal LIPCOF significantly correlated with symptoms and tear volume. Central, temporal, and total LIPCOF significantly correlated with MG loss, MGD stage, and lipid layer thickness. Independent significant factors associated with total LIPCOF included CFS, tear break-up time, and MGD stage. One month following HFR-ES, CCh was completely resolved in all cases. Patient age and preoperative nasal LIPCOF were determinants of outcomes associated with postoperative improvements in symptoms. Ocular surface parameters significantly improved, but MGD-related signs did not. Collectively, CCh associated with MGD severity deteriorates not only tear film stability and reservoir capacity, leading to DED exacerbation. Therefore, CCh should be corrected in patients with DED and MGD. Younger patients with nasal CCh are likely to experience more symptomatic relief after HFR-ES. Particularly, management for MGD should be maintained after CCh correction.
Safety profiles of terahertz scanning in ophthalmology
Authors: Liu Yu-Chi , Ke Lin , Yang Steve Wu Qing , Nan Zhang , Teo Ericia Pei Wen , Lwin Nyein Chan , Lin Molly Tzu-Yu , Lee Isabelle Xin Yu , Chan Anita Sook-Yee , Schmetterer Leopold , Mehta Jodhbir S.
Published: January 2021

Terahertz (THz) technology has emerged recently as a potential novel imaging modality in biomedical fields, including ophthalmology. However, the ocular biological responses after THz electromagnetic exposure have not been investigated. We conducted a rabbit study to evaluate the safety profiles of THz scanning on eyes, at a tissue, cellular, structural and functional level. Eight animals (16 eyes) were analysed after excessive THz exposure (control, 1 h, 4 h, and 1 week after continuous 4-h exposure; THz frequency = 0.3 THz with continuous pulse generated at 40 µW). We found that at all the time points, the corneas and lens remained clear with no corneal haze or lens opacity formation clinically and histopathologically. No thermal effect, assessed by thermographer, was observed. The rod and cone cell-mediated electroretinography responses were not significantly altered, and the corneal keratocytes activity as well as endothelial viability, assessed by in-vivo confocal microscopy, was not affected. Post-exposed corneas, lens and retinas exhibited no significant changes in the mRNA expression of heat shock protein (HSP)90AB1), DNA damage inducible transcript 3 (DDIT3), and early growth response (EGR)1. These tissues were also negative for the inflammatory (CD11b), fibrotic (fibronectin and α-smooth muscle actin), stress (HSP-47) and apoptotic (TUNEL assay) responses on the immunohistochemical analyses. The optical transmittance of corneas did not change significantly, and the inter-fibrillar distances of the corneal stroma evaluated with transmission electron microscopy were not significantly altered after THz exposure. These results provide the basis for future research work on the development of THz imaging system for its application in ophthalmology.
Virtual reality video game improves high-fidelity memory in older adults
Authors: Wais Peter E. , Arioli Melissa , Anguera-Singla Roger , Gazzaley Adam
Published: January 2021

Therapeutic interventions have not yet been shown to demonstrate restorative effects for declining long-term memory (LTM) that affects many healthy older adults. We developed a virtual reality (VR) spatial wayfinding game (Labyrinth-VR) as a cognitive intervention with the hypothesis that it could improve detailed, high-fidelity LTM capability. Spatial navigation tasks have been used as a means to achieve environmental enrichment via exposure to and learning about novel and complex information. Engagement has been shown to enhance learning and has been linked to the vitality of the LTM system in the brain. In the current study, 48 older adults (mean age 68.7 ± 6.4 years) with average cognitive abilities for their age were randomly assigned to 12 h of computer game play over four weeks in either the Labyrinth-VR or placebo control game arms. Promptly before and after each participant’s treatment regimen, high-fidelity LTM outcome measures were tested to assess mnemonic discrimination and other memory measures. The results showed a post-treatment gain in high-fidelity LTM capability for the Labyrinth-VR arm, relative to placebo, which reached the levels attained by younger adults in another experiment. This novel finding demonstrates generalization of benefits from the VR wayfinding game to important, and untrained, LTM capabilities. These cognitive results are discussed in the light of relevant research for hippocampal-dependent memory functions.
Titi monkey neophobia and visual abilities allow for fast responses to novel stimuli
Authors: Lau Allison R. , Grote Mark N. , Dufek Madison E. , Franzetti Tristan J. , Bales Karen L. , Isbell Lynne A.
Published: January 2021

The Snake Detection Theory implicates constricting snakes in the origin of primates, and venomous snakes for differences between catarrhine and platyrrhine primate visual systems. Although many studies using different methods have found very rapid snake detection in catarrhines, including humans, to date no studies have examined how quickly platyrrhine primates can detect snakes. We therefore tested in captive coppery titi monkeys (Plecturocebus cupreus) the latency to detect a small portion of visible snake skin. Because titi monkeys are neophobic, we designed a crossover experiment to compare theirlatency to lookand theirduration of lookingat a snake skin and synthetic feather of two lengths (2.5 cm and uncovered). To test our predictions that thelatency to lookwould be shorter and theduration of lookingwould be longer for the snake skin, we used survival/event time models forlatency to lookand negative binomial mixed models forduration of looking. While titi monkeys looked more quickly and for longer at both the snake skin and feather compared to a control, they also looked more quickly and for longer at larger compared to smaller stimuli. This suggests titi monkeys’ neophobia may augment their visual abilities to help them avoid dangerous stimuli.