bluuebunny/crossref_metadata_2025 huggingface dataset:
Cricket related hand injury is associated with increased odds of hand pain and osteoarthritis
Authors: Shah Karishma , Furniss Dominic , Collins Gary S. , Peirce Nick , Arden Nigel K. , Filbay Stephanie R.
Published: October 2020

Radiographic osteoarthritis (OA) is most prevalent in the hand. The association of hand injury with pain or OA is unclear. The objective was to describe the relationship between hand injury and ipsilateral pain and OA in cricketers. Data from former and current cricketers aged ≥ 30 years was used. Data included history of cricket-related hand/finger injury leading to > 4 weeks of reduced exercise, hand/finger joint pain on most days of the last month, self-reported history of physician-diagnosed hand/finger OA. Logistic regression assessed the relationship between injury with hand pain (in former cricketers) and with OA (in all cricketers), adjusted for age, seasons played, playing standard. Of 1893 participants (844 former cricketers), 16.9% reported hand pain, 4.3% reported OA. A history of hand injury increased the odds of hand pain (OR (95% CI) 2.2, 1.4 to 3.6). A history of hand injury also had increased odds of hand OA (3.1, 2.1 to 4.7). Cricket-related hand injury was related to an increased odds of hand pain and OA. This highlights the importance of hand injury prevention strategies within cricket. The high prevalence of hand pain is concerning, and further research is needed to determine the impacts of hand pain.
Foxd4l1.1 negatively regulates transcription of neural repressor ventx1.1 during neuroectoderm formation in Xenopus embryos
Authors: Kumar Shiv , Umair Zobia , Kumar Vijay , Kumar Santosh , Lee Unjoo , Kim Jaebong
Published: October 2020

Neuroectoderm formation is the first step in development of a proper nervous system for vertebrates. The developmental decision to form a non-neural ectoderm versus a neural one involves the regulation of BMP signaling, first reported many decades ago. However, the precise regulatory mechanism by which this is accomplished has not been fully elucidated, particularly for transcriptional regulation of certain key transcription factors. BMP4 inhibition is a required step in eliciting neuroectoderm from ectoderm and Foxd4l1.1 is one of the earliest neural genes highly expressed in the neuroectoderm and conserved across vertebrates, including humans. In this work, we focused on how Foxd4l1.1 downregulates the neural repressive pathway. Foxd4l1.1 inhibited BMP4/Smad1 signaling and triggered neuroectoderm formation in animal cap explants of Xenopus embryos. Foxd4l1.1 directly bound within the promoter of endogenous neural repressor ventx1.1 and inhibited ventx1.1 transcription. Foxd4l1.1 also physically interacted with Xbra in the nucleus and inhibited Xbra-induced ventx1.1 transcription. In addition, Foxd4l1.1 also reduced nuclear localization of Smad1 to inhibit Smad1-mediated ventx1.1 transcription. Foxd4l1.1 reduced the direct binding of Xbra and Smad1 on ventx1.1 promoter regions to block Xbra/Smad1-induced synergistic activation of ventx1.1 transcription. Collectively, Foxd4l1.1 negatively regulates transcription of a neural repressor ventx1.1 by multiple mechanisms in its exclusively occupied territory of neuroectoderm, and thus leading to primary neurogenesis. In conjunction with the results of our previous findings that ventx1.1 directly represses foxd4l1.1, the reciprocal repression of ventx1.1 and foxd4l1.1 is significant in at least in part specifying the mechanism for the non-neural versus neural ectoderm fate determination in Xenopus embryos.
Bio fabrication of silver nanoparticles with antibacterial and cytotoxic abilities using lichens
Authors: Alqahtani Mona A. , Al Othman Monerah R. , Mohammed Afrah E.
Published: October 2020

Recently, increase bacterial resistance to antimicrobial compounds issue constitutes a real threat to human health. One of the useful materials for bacterial control is Silver nanoparticles (AgNPs). Researchers tend to use biogenic agents to synthesize stable and safe AgNPs. The principal aim of this study was to investigate the ability of lichen in AgNPs formation and to find out their suppression ability to MDR bacteria as well as their cytotoxic activity. In the current study, lichens (Xanthoria parietina, Flavopunctelia flaventior) were collected from the south of the Kingdom of Saudi Arabia. Lichens methanolic extracts were used for conversion of Ag ions to AgNPs. Prepared biogenic AgNPs were characterized by Ultraviolet–Visible (UV–Vis) Spectroscopy, Transmission electron microscopy (TEM), Dynamic Light Scattering (DLS) and Zeta potential and Energy-Dispersive X-ray Spectroscopy (EDS). Lichens Secondary metabolites were determined by Fourier-Transform Infrared Spectroscopy (FTIR) and Gas Chromatography–Mass Spectrometry (GC–MS). The antibacterial activity and synergistic effect of AgNPs were evaluated against pathogenic bacteria, including gram-positive; Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), and gram-negative; (Pseudomonas aeruginosa, Escherichia coli) as well as the reference strains (ATCC) using the agar disk diffusion method. Cytotoxic effect of biogenic AgNPs was tested against HCT 116 (Human Colorectal Cancer cell), MDA-MB-231 (Breast cancer cell), and FaDu (Pharynx cancer cell) by MTT test. TEM imaging showed well-dispersed spherical particles of 1–40 nm size as well as zeta size showed 69–145 nm. Furthermore, FTIR and GC–MS identified various lichen chemical molecules. On the other hand, the highest antibacterial activity of AgNPs was noticed against P. aeruginosa, followed by MRSA, VRE, and E. coli. AgNPs influence on gram-negative bacteria was greater than that on gram-positive bacteria and their synergistic effect with some antibiotics was noted against examined microbes. Moreover, higher cytotoxicity for biogenic AgNPs against FaDu and HCT 116 cell line in relation to MDA-MB-231 was noted. Given the current findings, the biogenic AgNPs mediated by lichens had positive antibacterial, synergistic and cytotoxic powers. Therefore, they might be considered as a promising candidate to combat the multi-drug resistance organisms and some cancer cells.
Electronic properties of the Sn1−xPbxO alloy and band alignment of the SnO/PbO system: a DFT study
Authors: Kelaidis N. , Bousiadi S. , Zervos M. , Chroneos A. , Lathiotakis N. N.
Published: October 2020

Tin monoxide (SnO) has attracted attention due to its p-type character and capability of ambipolar conductivity when properly doped, properties that are beneficial for the realization of complementary oxide thin film transistors technology, transparent flexible circuits and optoelectronic applications in general. However, its small fundamental band gap (0.7 eV) limits its applications as a solar energy material, therefore tuning its electronic properties is necessary for optimal performance. In this work, we use density functional theory (DFT) calculations to examine the electronic properties of the Sn1−xPbxO ternary oxide system. Alloying with Pb by element substitution increases the band gap of SnO without inducing defect states in the band gap retaining the anti-bonding character of the valence band maximum which is beneficial for p-type conductivity. We also examine the properties of the SnO/PbO heterojunction system in terms of band alignment and the effect of the most common intrinsic defects. A broken gap band alignment for the SnO/PbO heterojunction is calculated, which can be attractive for energy conversion in solar cells, photocatalysis and hydrogen generation.
Potential utility of reflectance spectroscopy in understanding the paleoecology and depositional history of different fossils
Authors: Chaudhuri Swagata , Guha Arindam , Bhaumik Ajoy K. , Pasricha Komal
Published: October 2020

The potential of reflectance spectroscopy to infer the paleoecological and depositional evolution of different micro and macro invertebrate fossils has been evaluated by analyzing their reflectance spectra within the spectral domain of 350–2500 nm using the FIELDSPEC3 spectroradiometer. Mineralogical information derived from the rapid and non-destructive spectral analysis has been substantiated using concurrent mineralogical data from conventional geochemical analyses. The diagnostic Fe-crystal field effect induced spectral features are identified on the representative spectra of different benthic foraminifera. These spectral features are resulted due to the incorporation of Fe during the biomineralization process. These features are absent in planktic foraminifera. The encrustation of Fe-oxides is inferred to be responsible for imprinting the Fe-crystal field feature in the spectra of micro and macrofossils at 900–1200 nm. Vibrational spectral features of the Al–OH bond are also identified. Both of these features are an indicator of post-depositional diagenetic history. The presence of Al and Fe in macrofossil shells is also believed to be related to ecological conditions as these elements are biogenically incorporated during shell formation. This study reveals the value of reflectance spectroscopy to infer ecological behavior and post-depositional environment of different organisms.
Coronary micro-computed tomography angiography in mice
Authors: Sawall Stefan , Beckendorf Jan , Amato Carlo , Maier Joscha , Backs Johannes , Vande Velde Greetje , Kachelrieß Marc , Kuntz Jan
Published: October 2020

Coronary computed tomography angiography is an established technique in clinical practice and a valuable tool in the diagnosis of coronary artery disease in humans. Imaging of coronaries in preclinical research, i.e. in small animals, is very difficult due to the high demands on spatial and temporal resolution. Mice exhibit heart rates of up to 600 beats per minute motivating the need for highest detector framerates while the coronaries show diameters below 100 μm indicating the requirement for highest spatial resolution. We herein use a custom built micro–CT equipped with dedicated reconstruction algorithms to illustrate that coronary imaging in mice is possible. The scanner provides a spatial and temporal resolution sufficient for imaging of smallest, moving anatomical structures and the dedicated reconstruction algorithms reduced radiation dose to less than 1 Gy but do not yet allow for longitudinal studies. Imaging studies were performed in ten mice administered with a blood-pool contrast agent. Results show that the course of the left coronary artery can be visualized in all mice and all major branches can be identified for the first time using micro-CT. This reduces the gap in cardiac imaging between clinical practice and preclinical research.
Clinical predictive modelling of post-surgical recovery in individuals with cervical radiculopathy: a machine learning approach
Authors: Liew Bernard X. W. , Peolsson Anneli , Rugamer David , Wibault Johanna , Löfgren Hakan , Dedering Asa , Zsigmond Peter , Falla Deborah
Published: October 2020

Prognostic models play an important role in the clinical management of cervical radiculopathy (CR). No study has compared the performance of modern machine learning techniques, against more traditional stepwise regression techniques, when developing prognostic models in individuals with CR. We analysed a prospective cohort dataset of 201 individuals with CR. Four modelling techniques (stepwise regression, least absolute shrinkage and selection operator [LASSO], boosting, and multivariate adaptive regression splines [MuARS]) were each used to form a prognostic model for each of four outcomes obtained at a 12 month follow-up (disability—neck disability index [NDI]), quality of life (EQ5D), present neck pain intensity, and present arm pain intensity). For all four outcomes, the differences in mean performance between all four models were small (difference of NDI < 1 point; EQ5D < 0.1 point; neck and arm pain < 2 points). Given that the predictive accuracy of all four modelling methods were clinically similar, the optimal modelling method may be selected based on the parsimony of predictors. Some of the most parsimonious models were achieved using MuARS, a non-linear technique. Modern machine learning methods may be used to probe relationships along different regions of the predictor space.
Facial erythema detects diabetic neuropathy using the fusion of machine learning, random matrix theory and self organized criticality
Authors: Nadimi Esmaeil S. , Majtner Tomas , Yderstraede Knud B. , Blanes-Vidal Victoria
Published: October 2020

Rubeosis faciei diabeticorum, caused by microangiopathy and characterized by a chronic facial erythema, is associated with diabetic neuropathy. In clinical practice, facial erythema of patients with diabetes is evaluated based on subjective observations of visible redness, which often goes unnoticed leading to microangiopathic complications. To address this major shortcoming, we designed a contactless, non-invasive diagnostic point-of-care-device (POCD) consisting of a digital camera and a screen. Our solution relies on (1) recording videos of subject’s face (2) applying Eulerian video magnification to videos to reveal important subtle color changes in subject’s skin that fall outside human visual limits (3) obtaining spatio-temporal tensor expression profile of these variations (4) studying empirical spectral density (ESD) function of the largest eigenvalues of the tensors using random matrix theory (5) quantifying ESD functions by modeling the tails and decay rates using power law in systems exhibiting self-organized-criticality and (6) designing an optimal ensemble of learners to classify subjects into those with diabetic neuropathy and those of a control group. By analyzing a short video, we obtained a sensitivity of 100% in detecting subjects diagnosed with diabetic neuropathy. Our POCD paves the way towards the development of an inexpensive home-based solution for early detection of diabetic neuropathy and its associated complications.
Prediction of fall events during admission using eXtreme gradient boosting: a comparative validation study
Authors: Hsu Yin-Chen , Weng Hsu-Huei , Kuo Chiu-Ya , Chu Tsui-Ping , Tsai Yuan-Hsiung
Published: October 2020

As the performance of current fall risk assessment tools is limited, clinicians face significant challenges in identifying patients at risk of falling. This study proposes an automatic fall risk prediction model based on eXtreme gradient boosting (XGB), using a data-driven approach to the standardized medical records. This study analyzed a cohort of 639 participants (297 fall patients and 342 controls) from Chang Gung Memorial Hospital, Chiayi Branch, Taiwan. A derivation cohort of 507 participants (257 fall patients and 250 controls) was collected for constructing the prediction model using the XGB algorithm. A comparative validation of XGB and the Morse Fall Scale (MFS) was conducted with a prospective cohort of 132 participants (40 fall patients and 92 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. This machine learning method provided a higher sensitivity than the standard method for fall risk stratification. In addition, the most important predictors found (Department of Neuro-Rehabilitation, Department of Surgery, cardiovascular medication use, admission from the Emergency Department, and bed rest) provided new information on in-hospital fall event prediction and the identification of patients with a high fall risk.
Thermostability of a recombinant G protein-coupled receptor expressed at high level in mammalian cell culture
Authors: Yeliseev Alexei , van den Berg Arjen , Zoubak Lioudmila , Hines Kirk , Stepnowski Sam , Williston Kyle , Yan Wanhua , Gawrisch Klaus , Zmuda Jonathan
Published: October 2020

Rational design of pharmaceutical drugs targeting integral membrane G protein-coupled receptors (GPCR) requires thorough understanding of ligand binding and mechanism of activation through high resolution structural studies of purified proteins. Due to inherent conformational flexibility of GPCR, stabilization of these proteins solubilized from cell membranes into detergents is a challenging task. Here, we take advantage of naturally occurring post-translational modifications for stabilization of purified GPCR in detergent micelles. The recombinant cannabinoid CB2 receptor was expressed at high yield in Expi293F mammalian cell cultures, solubilized and purified in Façade detergent. We report superior stability of the mammalian cell-expressed receptor compared to its E.coli-expressed counterpart, due to contributions from glycosylation of the N terminus and palmitoylation of the C terminus of CB2. Finally, we demonstrate that the mammalian Expi293F amino acid labelling kit is suitable for preparation of multi-milligram quantities of high quality, selectively stable isotope-labeled GPCR for studies by nuclear magnetic resonance.
Real-time on-machine observations close to interelectrode gap in a tool-based hybrid laser-electrochemical micromachining process
Authors: Saxena Krishna Kumar , Chen Xiaolei , Vetrano Maria Rosaria , Qian Jun , Reynaerts Dominiek
Published: October 2020

A tool-based hybrid laser-electrochemical micromachining process involves concurrent application of two process energies i.e. electrochemical and laser in the same machining zone by means of a hybrid tool which serves as an ECM tool as well as a multimode waveguide. It is a relatively novel process finding applications in defect-free machining of difficult-to-cut materials without affecting their microstructure. In order to understand the physical phenomena occurring during this process, in-situ observations are required. Therefore, in this work, a real time observation was carried out of a novel tool-based hybrid laser electrochemical micromachining process. A combination of high-speed imaging and Large Scale Particle Image Velocimetry (LSPIV) was used to visualize the tool-based hybrid laser-ECM process in real time. It also allowed to carry out experimental investigations on the by-products and bubble generation which have a direct effect on process performance in terms of accuracy and efficiency. The real-time on-machine observations are unique of its kind and they will facilitate the understanding of underlying mechanisms governing this hybrid laser-electrochemical micromachining process. This will ultimately help in improving the quality of parts manufactured. This research is also a step forward towards making these physics-based hybrid processes deterministic by employing high-speed imaging in a closed loop control.
Swirlonic state of active matter
Authors: Brilliantov Nikolai V. , Abutuqayqah Hajar , Tyukin Ivan Yu , Matveev Sergey A.
Published: October 2020

We report a novel state of active matter—a swirlonic state. It is comprised of swirlons, formed by groups of active particles orbiting their common center of mass. These quasi-particles demonstrate a surprising behavior: In response to an external load they move with a constant velocity proportional to the applied force, just as objects in viscous media. The swirlons attract each other and coalesce forming a larger, joint swirlon. The coalescence is extremely slow, decelerating process, resulting in a rarified state of immobile quasi-particles. In addition to the swirlonic state, we observe gaseous, liquid and solid states, depending on the inter-particle and self-driving forces. Interestingly, in contrast to molecular systems, liquid and gaseous states of active matter do not coexist. We explain this unusual phenomenon by the lack of fast particles in active matter. We perform extensive numerical simulations and theoretical analysis. The predictions of the theory agree qualitatively and quantitatively with the simulation results.
Effects of seasonality and previous logging on faecal helminth-microbiota associations in wild lemurs
Authors: de Winter I. I. , Umanets A. , Gort G. , Nieuwland W. H. , van Hooft P. , Heitkönig I. M. A. , Kappeler P. M. , Prins H. H. T. , Smidt H.
Published: October 2020

Gastrointestinal helminth-microbiota associations are shaped by various ecological processes. The effect of the ecological context of the host on the bacterial microbiome and gastrointestinal helminth parasites has been tested in a number of ecosystems and experimentally. This study takes the important step to look at these two groups at the same time and to start to examine how these communities interact in a changing host environment. Fresh faecal samples (N = 335) from eight wildEulemurpopulations were collected over 2 years across Madagascar. We used 16S ribosomal RNA gene sequencing to characterise the bacterial microbiota composition, and faecal flotation to isolate and morphologically identify nematode eggs. Infections with nematodes of the generaCallistouraandLemuricolaoccurred in all lemur populations. Seasonality significantly contributed to the observed variation in microbiota composition, especially in the dry deciduous forest. Microbial richness andLemuricolaspp. infection prevalence were highest in a previously intensely logged site, whereasCallistouraspp. showed no such pattern. In addition, we observed significant correlations between gastrointestinal parasites and bacterial microbiota composition in these lemurs, with 0.4–0.7% of the variation in faecal bacterial microbiota composition being explained by helminth infections. With this study, we show effects of environmental conditions on gastrointestinal nematodes and bacterial interactions in wild lemurs and believe it is essential to consider the potential role of microbiome-parasite associations on the hosts’ GI stability, health, and survival.
ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity
Authors: de Moura Ferraz Leslie Raphael , Tabosa Alinne Élida Gonçalves Alves , da Silva Nascimento Débora Dolores Souza , Ferreira Aline Silva , de Albuquerque Wanderley Sales Victor , Silva José Yago Rodrigues , Júnior Severino Alves , Rolim Larissa Araújo , de Souza Pereira Jorge José , Rolim-Neto Pedro José
Published: October 2020

Chagas disease (CD), caused by the flagellate protozoan Trypanosoma cruzi, is one of the major public health problems in developing countries. Benznidazole (BNZ) is the only drug available for CD treatment in most countries, however, it presents high toxicity and low bioavailability. To address these problems this study used Zeolitic Imidazolate Framework-8 (ZIF-8), which has garnered considerable attention due to its potential applications, enabling the controlled delivery of drugs. The present work developed and characterized a BNZ@ZIF-8 system, and the modulation of BNZ release from the ZIF-8 framework was evaluated through the in vitro dialysis release method under sink conditions at different pH values. Moreover, the in vitro evaluation of cell viability and cytotoxicity by MTT assay were also performed. The dissolution studies corroborated that a pH sensitive Drug Delivery System capable of vectorizing the release of BNZ was developed, may leading to the improvement in the bioavailability of BNZ. The MTT assay showed that no statistically significant toxic effects occurred in the developed system, nor significant effects on cell viability.
The rapid CD4 + T-lymphocyte decline and human immunodeficiency virus progression in females compared to males
Authors: Parsa Nader , Zaheri Pari Mahlagha , Hewitt Ross G. , Karimi Akhormeh Ali , Taravatmanesh Samira , Wallin Lisa
Published: October 2020

CD4 + T-lymphocyte counts are used to assess CD4 + decline and the stage of human immunodeficiency virus (HIV) progression in HIV-infected patients. Clinical observation suggests that HIV progress more rapid in females than males. Of the original 5000 HIV-infected population of Western New York HIV/AIDS, Referral Center at Erie County Medical Center (ECMC), 1422 participated in the cohort study. We identified 333 HIV-infected patients with CD4 + T-cell-counts ≥ 500/µƖ, among them 178 met the inclusion criteria for the 10-year study. Females had higher mode (600 vs. 540) and mean (741.9 vs. 712.2) CD4 + counts than males at baseline. However, CD4 + declined faster among females in a shorter time than males (234.5 vs. 158.6, P < 0.004), with rapid HIV progression. Univariate analyses determined that females had a 40% higher risk for CD4 + decline than males. The bivariate analyses specified CD4 + decline remained greater in females than males. Multivariate analyses which employed Cox’s proportional Hazard-Model to adjust for numerous variables simultaneously identified women had almost twice the risk for CD4 + decline and rapid HIV progression than males (RR = 1.93; 95%CI 1.24, 2.99). Although the biological mechanism remains unknown, findings suggest gender differences in CD4 + decline, with a higher risk of rapid HIV progression and shorter longevity in females.
Disease progression modeling of Alzheimer’s disease according to education level
Authors: Kim Ko Woon , Woo Sook Young , Kim Seonwoo , Jang Hyemin , Kim Yeshin , Cho Soo Hyun , Kim Si Eun , Kim Seung Joo , Shin Byoung-Soo , Kim Hee Jin , Na Duk L. , Seo Sang Won
Published: October 2020

To develop a disease progression model of Alzheimer’s disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to the end stage of AD dementia (ADD) and to investigate the effect of education level on the whole disease spectrum, we enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB). Three cohorts, SCI (n = 85), amnestic mild cognitive impairment (AMCI, n = 240), and ADD (n = 240), were overlapped in two consecutive cohorts (SCI and AMCI, AMCI and ADD) to construct a model of disease course, and a model with multiple single-cohorts was estimated using a mixed-effect model. To examine the effect of education level on disease progression, the disease progression model was developed with data from lower (≤ 12) and higher (> 12) education groups. Disease progression takes 274.3 months (22.9 years) to advance from 0 to 18 points using the CDR-SB. Based on our predictive equation, it takes 116.5 months to progress from SCI to AMCI and 56.2 months to progress from AMCI to ADD. The rate of CDR-SB progression was different according to education level. The lower-education group showed faster CDR-SB progression from SCI to AMCI compared to the higher-education group, and this trend disappeared from AMCI to ADD. In the present study, we developed a disease progression model of AD spectrum from SCI to the end stage of ADD. Our disease modeling provides us with more understanding of the effect of education on cognitive trajectories.
The wasted chewing gum bacteriome
Authors: Satari Leila , Guillén Alba , Vidal-Verdú Àngela , Porcar Manuel
Published: October 2020

Here we show the bacteriome of wasted chewing gums from five different countries and the microbial successions on wasted gums during three months of outdoors exposure. In addition, a collection of bacterial strains from wasted gums was set, and the biodegradation capability of different gum ingredients by the isolates was tested. Our results reveal that the oral microbiota present in gums after being chewed, characterised by the presence of species such as Streptococcus spp. or Corynebacterium spp., evolves in a few weeks to an environmental bacteriome characterised by the presence of Acinetobacter spp., Sphingomonas spp. and Pseudomonas spp. Wasted chewing gums collected worldwide contain a typical sub-aerial biofilm bacteriome, characterised by species such as Sphingomonas spp., Kocuria spp., Deinococcus spp. and Blastococcus spp. Our findings have implications for a wide range of disciplines, including forensics, contagious disease control, or bioremediation of wasted chewing gum residues.
Targeted delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells overexpressing epithelial growth factor receptor (EGFR) using virus-like nanoparticles
Authors: Gan Bee Koon , Rullah Kamal , Yong Chean Yeah , Ho Kok Lian , Omar Abdul Rahman , Alitheen Noorjahan Banu , Tan Wen Siang
Published: October 2020

Chemotherapy is widely used in cancer treatments. However, non-specific distribution of chemotherapeutic agents to healthy tissues and normal cells in the human body always leads to adverse side effects and disappointing therapeutic outcomes. Therefore, the main aim of this study was to develop a targeted drug delivery system based on the hepatitis B virus-like nanoparticle (VLNP) for specific delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells expressing epithelial growth factor receptor (EGFR). 5-FA was synthesized from 5-fluorouracil (5-FU), and it was found to be less toxic than the latter in cancer cells expressing different levels of EGFR. The cytotoxicity of 5-FA increased significantly after being conjugated on the VLNP. A cell penetrating peptide (CPP) of EGFR was displayed on the VLNP via the nanoglue concept, for targeted delivery of 5-FA to A431, HT29 and HeLa cells. The results showed that the VLNP displaying the CPP and harboring 5-FA internalized the cancer cells and killed them in an EGFR-dependent manner. This study demonstrated that the VLNP can be used to deliver chemically modified 5-FU derivatives to cancer cells overexpressing EGFR, expanding the applications of the VLNP in targeted delivery of chemotherapeutic agents to cancer cells overexpressing this transmembrane receptor.
Genome-wide genetic diversity yields insights into genomic responses of candidate climate-selected loci in an Andean wetland plant
Authors: Bertin Angéline , Espinosa Mara I. , Bustamante Catalina A. , Troncoso Alejandra J. , Gouin Nicolas
Published: October 2020

Assessing population evolutionary potential has become a central tenet of conservation biology. Since adaptive responses require allelic variation at functional genes, consensus has grown that genetic variation at genes under selection is a better surrogate for adaptive evolutionary potential than neutral genetic diversity. Although consistent with prevailing theory, this argument lacks empirical support and ignores recent theoretical advances questioning the very concept of neutral genetic diversity. In this study, we quantified genome-wide responses of single nucleotide polymorphism loci linked to climatic factors over a strong latitudinal gradient in natural populations of the high Andean wetland plant, Carex gayana, and then assessed whether genetic variation of candidate climate-selected loci better predicted their genome-wide responses than genetic variation of non-candidate loci. Contrary to this expectation, genomic responses of climate-linked loci only related significantly to environmental variables and genetic diversity of non-candidate loci. The effects of genome-wide genetic diversity detected in this study may be a result of either the combined influence of small effect variants or neutral and demographic factors altering the adaptive evolutionary potential of C. gayana populations. Regardless of the processes involved, our results redeem genome-wide genetic diversity as a potentially useful indicator of population adaptive evolutionary potential.
The SensorOverlord predicts the accuracy of measurements with ratiometric biosensors
Authors: Stanley Julian A. , Johnsen Sean B. , Apfeld Javier
Published: October 2020

Two-state ratiometric biosensors change conformation and spectral properties in response to specific biochemical inputs. Much effort over the past two decades has been devoted to engineering biosensors specific for ions, nucleotides, amino acids, and biochemical potentials. The utility of these biosensors is diminished by empirical errors in fluorescence-ratio signal measurement, which reduce the range of input values biosensors can measure accurately. Here, we present a formal framework and a web-based tool, the SensorOverlord, that predicts the input range of two-state ratiometric biosensors given the experimental error in measuring their signal. We demonstrate the utility of this tool by predicting the range of values that can be measured accurately by biosensors that detect pH, NAD+, NADH, NADPH, histidine, and glutathione redox potential. The SensorOverlord enables users to compare the predicted accuracy of biochemical measurements made with different biosensors, and subsequently select biosensors that are best suited for their experimental needs.
Preemptive interleukin-6 blockade in patients with COVID-19
Authors: Guillén Lucía , Padilla Sergio , Fernández Marta , Agulló Vanesa , García José Alberto , Telenti Guillermo , García-Abellán Javier , Botella Ángela , Gutiérrez Félix , Masiá Mar
Published: October 2020

Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes.
Tracking cortical representations of facial attractiveness using time-resolved representational similarity analysis
Authors: Kaiser Daniel , Nyga Karen
Published: October 2020

When we see a face, we rapidly form an impression of its attractiveness. Here, we investigated how rapidly representations of facial attractiveness emerge in the human brain. In an EEG experiment, participants viewed 100 face photographs and rated them for their attractiveness. Using time-resolved representational similarity analysis on the EEG data, we reveal representations of facial attractiveness after 150–200 ms of cortical processing. Interestingly, we show that these representations are related to individual participants’ personal attractiveness judgments, suggesting that already early perceptual representations of facial attractiveness convey idiosyncratic attractiveness preferences. Further, we show that these early representations are genuinely related to attractiveness, as they are neither explained by other high-level face attributes, such as face sex or age, nor by features extracted by an artificial deep neural network model of face processing. Together, our results demonstrate early, individually specific, and genuine representations of facial attractiveness, which may underlie fast attractiveness judgments.
Rural–urban scaling of age, mortality, crime and property reveals a loss of expected self-similar behaviour
Authors: Sutton Jack , Shahtahmassebi Golnaz , Ribeiro Haroldo V. , Hanley Quentin S.
Published: October 2020

The urban scaling hypothesis has improved our understanding of cities; however, rural areas have been neglected. We investigated rural–urban population density scaling in England and Wales using 67 indicators of crime, mortality, property, and age. Most indicators exhibited segmented scaling about a median critical density of 27 people per hectare. Above the critical density, urban regions preferentially attract young adults (25–40 years) and lose older people (> 45 years). Density scale adjusted metrics (DSAMs) were analysed using hierarchical clustering, networks, and self-organizing maps (SOMs) revealing regional differences and an inverse relationship between excess value of property transactions and a range of preventable mortality (e.g. diabetes, suicide, lung cancer). The most striking finding is that age demographics break the expected self-similarity underlying the urban scaling hypothesis. Urban dynamism is fuelled by preferential attraction of young adults and not a fundamental property of total urban population.
Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice
Authors: Charles-Schoeman Christina , Wang Jennifer , Shahbazian Ani , Lee Yuen Yin , Wang Xiaoyan , Grijalva Victor , Brahn Ernest , Shih Diana M. , Devarajan Asokan , Montano Christy , Lusis Aldons J. , Reddy Srinivasa T.
Published: October 2020

Paraoxonase 1(PON1) is an HDL-associated protein, which metabolizes inflammatory, oxidized lipids associated with atherosclerotic plaque development. Because oxidized lipid mediators have also been implicated in the pathogenesis of rheumatoid arthritis (RA), we evaluated the role of PON1 in murine inflammatory arthritis. K/BxN serum transfer (STIA) or collagen antibody transfer (CAIA) was used for arthritis induction in B6 mice homozygous for the PON1 human transgene [PON1Tg], PON1 knock-out mice [PON1KO], and wild type littermate control mice [WT]. Experiments were also performed in K/BxN mice with chronic arthritis, and in RA patients and healthy controls. Arthritis activity in K/BxN mice was associated with a marked dyslipidemia, lower PON1 activity and higher bioactive lipid mediators (BLM), as well as a dysregulated hepatic lipid gene expression profile. Higher serum PON1 activity correlated with lower BLM and lower arthritis activity in both K/BxN mice and RA patients. Overexpression of the human PON1 transgene was associated with reduced inflammatory arthritis, which correlated strongly with higher circulating PON1 activity, upregulation of the hepatic glutathione pathway, and reduction of circulating BLM. These results implicate PON1 as a potential novel therapeutic target for joint disease in RA with potential for vascular benefit, which warrants further investigation.
Implication of single year seasonal sampling to genetic diversity fluctuation that coordinates with oceanographic dynamics in torpedo scads near Taiwan
Authors: Su Yong-Chao , Su Shan-Hui , Li Han-Yun , Wang Hurng-Yi , Lee Sin-Che
Published: October 2020

Many fisheries management and conservation plans are based on the genetic structure of organisms in pelagic ecosystems; however, these structures tend to vary over time, particularly in cyclic ocean currents. We performed genetic analyses on the populations of the pelagic fish, Megalaspis cordyla (Osteichthyes: Carangidae) in the area surrounding Taiwan during 2000–2001. Genotyping was performed on M. cordyla collected seasonally around Taiwan as well as specimens collected from Singapore (Malacca strait) and Indonesia (Banda Sea). Gonadosomatic indices (GSI) revealed that M. cordyla does not spawn near Taiwan. Data related to the mitochondrial control region revealed that the samples from Singapore and Indonesia represented two distinct genetic cohorts. Genotyping revealed that during the summer (June–August 2000), the Indonesian variant was dominant in eastern Taiwan (presumably following the Kuroshio Current) and in the Penghu region (following the Kuroshio Branch Current). During the same period, the Singapore genotype was dominant along the western coast of Taiwan (presumably following the South China Sea Current); however, the number dropped during the winter (December–February 2001) under the effects of the China Coast Current. Divergence time estimates indicate that the two genetic cohorts split during the last glacial maximum. Despite the fact that these results are based on sampling from a single year, they demonstrate the importance of seasonal sampling in unravelling the genetic diversity in pelagic ecosystems.
Mapping the native interaction surfaces of PREP1 with PBX1 by cross-linking mass-spectrometry and mutagenesis
Authors: Bruckmann Chiara , Tamburri Simone , De Lorenzi Valentina , Doti Nunzianna , Monti Alessandra , Mathiasen Lisa , Cattaneo Angela , Ruvo Menotti , Bachi Angela , Blasi Francesco
Published: October 2020

Both onco-suppressor PREP1 and the oncogene MEIS1 bind to PBX1. This interaction stabilizes the two proteins and allows their translocation into the nucleus and thus their transcriptional activity. Here, we have combined cross-linking mass-spectrometry and systematic mutagenesis to detail the binding geometry of the PBX1-PREP1 (and PBX1-MEIS1) complexes, under native in vivo conditions. The data confirm the existence of two distinct interaction sites within the PBC domain of PBX1 and unravel differences among the highly similar binding sites of MEIS1 and PREP1. The HR2 domain has a fundamental role in binding the PBC-B domain of PBX1 in both PREP1 and MEIS1. The HR1 domain of MEIS1, however, seem to play a less stringent role in PBX1 interaction with respect to that of PREP1. This difference is also reflected by the different binding affinity of the two proteins to PBX1. Although partial, this analysis provides for the first time some ideas on the tertiary structure of the complexes not available before. Moreover, the extensive mutagenic analysis of PREP1 identifies the role of individual hydrophobic HR1 and HR2 residues, both in vitro and in vivo.
Validation of Clinical Treatment Score post-5 years (CTS5) risk stratification in premenopausal breast cancer patients and Ki-67 labelling index
Authors: Lee Janghee , Cha Chihwan , Ahn Sung Gwe , Kim Dooreh , Park Soeun , Bae Soong June , Kim Jeeye , Park Hyung Seok , Park Seho , Kim Seung Il , Park Byeong-Woo , Jeong Joon
Published: October 2020

This study aimed to validate the Clinical Treatment Score post-5 years (CTS5)-based risk stratification in a cohort comprising pre- and postmenopausal patients with estrogen receptor (ER)–positive breast cancer. We investigated the clinicopathologic parameters including Ki-67 labelling index (LI) to identify factors affecting late distant recurrence (DR). Women with ER-positive breast cancer who were free of DR for 5 years were identified between January 2004 and December 2009. We investigated the risk of late DR (5–10 years) according to the CTS5 risk group. Cox regression analysis was used to determine the prognostic performance of CTS5 and identify factors associated with late DR. In all, 680 women were included. Of these, 379 (55.7%) were premenopausal and 301 (44.3%) were postmenopausal. At a median follow-up of 118 months, 32 women had late DR. CTS5 was a significant prognostic factor for late DR in both pre- and postmenopausal women. In the low CTS5 group, high Ki-67 LI (> 20%) was a significant risk factor for late DR. CTS5 is a useful tool for assessing the risk of late DR in pre- and postmenopausal women with ER-positive breast cancer. Extended endocrine therapy can be considered in patients with high Ki-67 LI (> 20%) in the low CTS5 group.
Understanding solute effect on grain boundary strength based on atomic size and electronic interaction
Authors: Huang Zhifeng , Wang Ping , Chen Fei , Shen Qiang , Zhang Lianmeng
Published: October 2020

Solute segregating to grain boundary can stabilize the microstructure of nanocrystalline materials, but a lot of solutes also cause embrittlement effect on interfacial strength. Therefore, uncovering the solute effect on grain boundary strength is very important for nanocrystalline alloys design. In this work, we have systematically studied the effects of various solutes on the strength of a Σ5 (310) grain boundary in Cu by first-principle calculations. The solute effects are closely related to the atomic radius of solutes and electronic interactions between solutes and Cu. The solute with a larger atomic radius is easier to segregate the grain boundary but causes more significant grain boundary embrittlement. The weak electronic interactions between the s- and p-block solutes and Cu play a very limited role in enhancing grain boundary strength. While the strong d-states electronic interactions between transition metallic solutes and Cu can counteract embrittlement caused by size mismatch and significantly improve the grain boundary strength. This work deepens our understanding of solute effects on grain boundary strength based on atomic size and electronic interactions.
Cadherin repeat 5 mutation associated with Bt resistance in a field-derived strain of pink bollworm
Authors: Wang Ling , Ma Yuemin , Wei Wei , Wan Peng , Liu Kaiyu , Xu Min , Cong Shengbo , Wang Jintao , Xu Dong , Xiao Yutao , Li Xianchun , Tabashnik Bruce E. , Wu Kongming
Published: October 2020

Evolution of resistance by pests reduces the benefits of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Here we analyzed resistance to Bt toxin Cry1Ac in a field-derived strain of pink bollworm (Pectinophora gossypiella), a global pest of cotton. We discovered that the r14 allele of the pink bollworm cadherin gene (PgCad1) has a 234-bp insertion in exon 12 encoding a mutant PgCad1 protein that lacks 36 amino acids in cadherin repeat 5 (CR5). A strain homozygous for this allele had 237-fold resistance to Cry1Ac, 1.8-fold cross-resistance to Cry2Ab, and developed from neonate to adult on Bt cotton producing Cry1Ac. Inheritance of resistance to Cry1Ac was recessive and tightly linked with r14. PgCad1 transcript abundance in midgut tissues did not differ between resistant and susceptible larvae. Toxicity of Cry1Ac to transformed insect cells was lower for cells expressing r14 than for cells expressing wild-type PgCad1. Wild-type PgCad1 was transported to the cell membrane, whereas PgCad1 produced by r14 was not. In larval midgut tissue, PgCad1 protein occurred primarily on the brush border membrane only in susceptible larvae. The results imply r14 mediates pink bollworm resistance to Cry1Ac by reduced translation, increased degradation, and/or mislocalization of cadherin.
Gold nanoparticles to enhance ophthalmic imaging
Authors: Chen Fang , Si Peng , de la Zerda Adam , Jokerst Jesse V. , Myung David
Published: October 2020

Gold nanoparticles are promising OCT and PAI contrast agents for ophthalmic imaging because of their high light scattering/absorption from SPR.
Fe-TCPP@CS nanoparticles as photodynamic and photothermal agents for efficient antimicrobial therapy
Authors: Zhang Yufeng , Ma Jing , Wang Dianwei , Xu Caina , Sheng Shu , Cheng Jianfeng , Bao Changjiang , Li Yanhui , Tian Huayu
Published: October 2020

Photodynamic and photothermal agents for efficient antimicrobial therapy.
A metal–organic framework template derived hierarchical Mo-doped LDHs@MOF-Se core–shell array electrode for supercapacitors
Authors: Zhu Yulu , Du Wei , Zhang Qilong , Yang Hui , Zong Quan , Wang Qianqian , Zhou Zheng , Zhan Jianhui
Published: October 2020

A core–shell array electrode displays high areal capacity and rate capability with a highly conductive framework and a high loading of active materials.
Reactivity prediction in aza-Michael additions without transition state calculations: the Ames test for mutagenicity
Authors: Townsend Piers A. , Grayson Matthew N.
Published: October 2020

This work demonstrates a novel method for aza-Michael reactivity prediction using easily calculable intermediate structures instead of time-consuming transition states.
Thermoelectric properties of hydrogenated Sn2Bi monolayer under mechanical strain: a DFT approach
Authors: Mohebpour Mohammad Ali , Izadi Vishkayi Sahar , Bagheri Tagani Meysam
Published: October 2020

We performed a density functional theory calculation combined with the semiclassical Boltzmann transport equation to investigate the thermoelectric properties of the stabilized Sn2Bi monolayer.