bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome prediction with a social cognitive battery: a multicenter longitudinal study
Authors: Brunet-Gouet Eric , Decaix-Tisserand Capucine , Urbach Mathieu , Bazin Nadine , Aouizerate Bruno , Brunel Lore , Capdevielle Delphine , Chereau Isabelle , Dubertret Caroline , Dubreucq Julien , Fond Guillaume , Lançon Christophe , Leignier Sylvain , Mallet Jasmina , Misdrahi David , Pires Sylvie , Schneider Priscille , Schurhoff Franck , Yazbek Hanan , Zinetti-Bertschy Anna , Passerieux Christine , Roux Paul
Published: May 2021

The interest in social cognition in schizophrenia is justified by the relationship between deficits in these skills and negative functional outcomes. Although assessment batteries have already been described, there is no consensus about which measures are useful in predicting patient functioning or quality of life (QoL). We investigated a set of five measures of recognition of facial emotions, theory of mind (ToM), and empathy in a cohort of 143 patients with schizophrenia or schizoaffective disorder at inclusion and, amongst whom 79 were reassessed 1 year later. The distribution was satisfactory for the TREF (Facial Emotion Recognition Task), V-SIR (Versailles-Situational Intention Reading), and QCAE (Questionnaire of Cognitive and Affective Empathy). Internal consistency was satisfactory for the TREF, V-SIR, V-Comics (Versailles Intention Attribution Task), and QCAE. Sensitivity to change was acceptable for the TREF. The TREF and V-SIR showed a cross-sectional relationship with functioning beyond the clinical symptoms of schizophrenia but not beyond neurocognition. Moreover, the TREF and V-SIR at inclusion could not predict functioning one year later, whereas most neurocognitive and clinical dimensions at inclusion could. Finally, only affective QCAE showed a significant cross-sectional, but not longitudinal, association with QoL. In conclusion, the TREF had satisfactory psychometric properties and showed a cross-sectional, but not longitudinal, association with objective outcome measures, thus appearing to be reliable in clinical practice and research. The V-SIR also showed promising psychometric properties, despite a possible weakness to detect change. However, these measures should be interpreted within the context of the good predictive power of the neurocognitive and clinical status on the outcome.
Investigating the reliability and sex differences of digit lengths, ratios, and hand measures in infants
Authors: Ernsten Luisa , Körner Lisa M. , Heil Martin , Richards Gareth , Schaal Nora K.
Published: May 2021

Hands and digits tend to be sexually dimorphic and may reflect prenatal androgen exposure. In the past years, the literature introduced several hand and digit measures, but there is a lack of studies in prepubertal cohorts. The available literature reports more heterogeneous findings in prepubertal compared to postpubertal cohorts. The comparability of the available studies is further limited by the study design and different measurement techniques. The present study compared the reliability and sex differences of available hand and digit measures, namely digit lengths of 2D, 3D, 4D, 5D, digit ratios 2D:4D, 2D:5D, 3D:4D, 3D:5D, 4D:5D, relative digit lengths rel2, rel3, rel4, rel5, directional asymmetry of right and left 2D:4D (Dr-l), hand width, length, and index of 399 male and 364 female 6-month-old German infants within one study using only indirect and computer-assisted measurements. The inter-examiner reliability was excellent while the test-retest reliability of hand scans was only moderate to high. Boys exhibited longer digits as well as wider and longer hands than girls, but smaller digit ratios, with ratios comprising the fifth digit revealing the largest effect sizes. Other hand and digit ratios revealed sex differences to some extent. The findings promote the assumption of sexual dimorphic hand and digit measures. However, by comparing the results of the available literature, there remains an uncertainty regarding the underlying hypothesis. Specifically in prepubertal cohorts, i.e. before the influence of fluctuating hormones, significant effects should be expected. It seems like other factors than the influence of prenatal androgens contribute to the sexual dimorphism in hand and digit lengths.
Sensorineural hearing loss and risk of stroke: a systematic review and meta-analysis
Authors: Khosravipour Masoud , Rajati Fatemeh
Published: May 2021

The aim of this systematic review and meta-analysis study was to clarify the effects of sensorineural hearing loss (SNHL) on the incidence of stroke. In line with this, PubMed, Scopus, Web of Science, and ScienceDirect databases were searched using related keywords and MeSH terms from inception to March 1, 2020. Out of the 1961 initial records, eight cohort studies comprising 4,564,202 participants were included, and their qualities were assessed using the Newcastle-Ottawa Scale (NOS). Then, the random-effects model was used to pool HR (95% CI) for risk of stroke; and heterogeneity was presented with I2 index. Subgroup analysis and publication bias tests were performed, and the pooled HR (95% CI) of stroke in SNHL was estimated as 1.31 (1.08, 1.53) for the unadjusted model and 1.33 (1.18, 1.49) for the adjusted model. Subgroup analysis indicates a significantly higher risk of stroke in patients with sudden SNHL (SSNHL) in comparison to age-related HL (ARHL) both in the unadjusted model, [HR = 1.46; 95% CI (1.08, 1.63)] versus [HR = 1.14; 95% CI (0.64, 1.65)], and in the adjusted model, [HR = 1.44; 95% CI (1.15, 1.74)] versus [HR = 1.29; 95% CI (1.24, 1.34)]. Our study showed that patients with SNHL face a higher risk of stroke than those without SNHL. It is necessary to perform hematologic and neurological examinations to help clinicians detect patients who are potentially at risk for stroke.
Heatline visualization of MHD natural convection heat transfer of nanofluid in a prismatic enclosure
Authors: Islam Tarikul , Alam Md. Nur , Asjad Muhammad Imran , Parveen Nazma , Chu Yu-Ming
Published: May 2021

Temperature transfer by virtue of natural convection for visualizing heat transport characteristics through heatline method within a prismatic cavity filled with Cu-H2O nanofluid considering two different temperature boundary conditions is performed numerically. Two top inclined walls are warmed-up at low temperature whilst the bottom wall is heated two different heated conditions such as uniform temperature condition and linear temperature condition. Two vertical walls are insulated. Finite element technique of Galerkin weighted residual form is employed for solving nonlinear partial differential equations for numerical calculation. Heatlines, isotherm contours, streamline contours, and Nusselt number are employed for displaying numerical simulated results for the model parameters entitled nanoparticles volume fraction, Hartmann number and Rayleigh number. The outcomes indicate that heat transfer rate has a significant impact on thermal boundary condition and shape of the nanoparticles. The temperature transfer value enhances significantly for higher Rayleigh number as well as nanoparticles volume fraction. Hartmann number has a positive impact on fluid flow and temperature transport. The characteristics of heat transport using heatlines method are also performed for predicting the better energy transform compared to isotherm contours. In addition, different types of nanofluids are also employed to examine the best heat transport performance.
Coalescence dynamics in oil-in-water emulsions at elevated temperatures
Authors: Bera Bijoy , Khazal Rama , Schroën Karin
Published: May 2021

Emulsion stability in a flow field is an extremely important issue relevant for many daily-life applications such as separation processes, food manufacturing, oil recovery etc. Microfluidic studies can provide micro-scale insight of the emulsion behavior but have primarily focussed on droplet breakup rather than on droplet coalescence. The crucial impact of certain conditions such as increased pressure or elevated temperature frequently used in industrial processes is completely overlooked in such micro-scale studies. In this work, we investigate droplet coalescence in flowing oil-in-water emulsions subjected to higher than room temperatures namely between 20 to 70 $$^{\circ }$$∘C. We use a specifically designed lab-on-a-chip application for this purpose. Coalescence frequency is observed to increase with increasing temperature. We associate with this observation the change in viscosity at higher temperatures triggering a stronger perturbation in the thin aqueous film separating the droplets. Using the scaling law for rupture time of such a thin film, we establish a mechanism leading to a higher coalescence frequency at elevated temperatures.
Influenza vaccination and the risk of COVID-19 infection and severe illness in older adults in the United States
Authors: Huang Kelly , Lin Shu-Wen , Sheng Wang-Huei , Wang Chi-Chuan
Published: May 2021

The coronavirus disease of 2019 (COVID-19) has caused a global pandemic and led to nearly three million deaths globally. As of April 2021, there are still many countries that do not have COVID-19 vaccines. Before the COVID-19 vaccines were developed, some evidence suggested that an influenza vaccine may stimulate nonspecific immune responses that reduce the risk of COVID-19 infection or the severity of COVID-19 illness after infection. This study evaluated the association between influenza vaccination and the risk of COVID-19 infection. We conducted a retrospective cross-sectional study with data from July 1, 2019, to June 30, 2020 with the Claims data from Symphony Health database. The study population was adults age 65 years old or older who received influenza vaccination between September 1 and December 31 of 2019. The main outcomes and measures were odds of COVID-19 infection and severe COVID-19 illness after January 15, 2020. We found the adjusted odds ratio (aOR) of COVID-19 infection risk between the influenza-vaccination group and no-influenza-vaccination group was 0.76 (95% confidence interval (CI), 0.75–0.77). Among COVID-19 patients, the aOR of developing severe COVID-19 illness was 0.72 (95% CI, 0.68–0.76) between the influenza-vaccination group and the no-influenza-vaccination group. When the influenza-vaccination group and the other-vaccination group were compared, the aOR of COVID-19 infection was 0.95 (95% CI, 0.93–0.97), and the aOR of developing a severe COVID-19 illness was 0.95 (95% CI, 0.80–1.13). The influenza vaccine may marginally protect people from COVID-19 infection.
Improving the longevity of optically-read quantum dot physical unclonable functions
Authors: Longmate Kieran D. , Abdelazim Nema M. , Ball Elliott M. , Majaniemi Joonas , Young Robert J.
Published: May 2021

Quantum dot physically unclonable functions (QD-PUFs) provide a promising solution to the issue of counterfeiting. When quantum dots are deposited on a surface to create a token, they form a unique pattern that is unlikely to ever be reproduced in another token that is manufactured using the same process. It would also be an extreme engineering challenge to deterministically place quantum dots to create a forgery of a specific device. The degradation of the optical response of quantum dots over time, however, places a limitation on their practical usefulness. Here we report methods to minimise the degradation of photoluminescence (PL) from InP/ZnS quantum dots suspended in a polymer and demonstrate reliable authentication using a fingerprinting technique to extract a signature from PL, even after significant degradation has occurred. Using these techniques, it was found that the addition of a polylauryl methacrylate (PLMA) copolymer improved the longevity of devices. The best performing example of this was the Polystyrene-PLMA based material. From this, it is projected that 1000 bits of information could be extracted and read after a period of years, therefore providing a compelling solution to the issue of counterfeiting.
A novel method for dendrochronology of large historical wooden objects using line trajectory X-ray tomography
Authors: Bossema Francien G. , Domínguez-Delmás Marta , Palenstijn Willem Jan , Kostenko Alexander , Dorscheid Jan , Coban Sophia Bethany , Hermens Erma , Batenburg K. Joost
Published: May 2021

Dendrochronology is an essential tool to determine the date and provenance of wood from historical art objects. As standard methods to access the tree rings are invasive, X-ray computed tomography (CT) has been proposed for non-invasive dendrochronological investigation. While traditional CT can provide clear images of the inner structure of wooden objects, it requires their full rotation, imposing strong limitations on the size of the object. These limitations have previously encouraged investigations into alternative acquisition trajectories, including trajectories with only linear movement. In this paper, we use such a line-trajectory (LT) X-ray tomography technique to retrieve tree-ring patterns from large wooden objects. We demonstrate that by moving a wooden artifact sideways between the static X-ray source and the detector during acquisition, sharp reconstruction images of the tree rings can be produced. We validate this technique using computer simulations and two wooden test planks, and demonstrate it on a large iconic chest from the Rijksmuseum collection (Amsterdam, The Netherlands). The LT scanning method can be easily implemented in standard X-ray imaging units available at museum research facilities. Therefore, this scanning technique represents a major step towards the standard implementation of non-invasive dendrochronology on large wooden cultural heritage objects.
Genetic variant of TTLL11 gene and subsequent ciliary defects are associated with idiopathic scoliosis in a 5-generation UK family
Authors: Mathieu Hélène , Patten Shunmoogum A. , Aragon-Martin Jose Antonio , Ocaka Louise , Simpson Michael , Child Anne , Moldovan Florina
Published: May 2021

Idiopathic scoliosis (IS) is a complex 3D deformation of the spine with a strong genetic component, most commonly found in adolescent girls. Adolescent idiopathic scoliosis (AIS) affects around 3% of the general population. In a 5-generation UK family, linkage analysis identified the locus 9q31.2-q34.2 as a candidate region for AIS; however, the causative gene remained unidentified. Here, using exome sequencing we identified a rare insertion c.1569_1570insTT in the tubulin tyrosine ligase like gene, member 11 (TTLL11) within that locus, as the IS causative gene in this British family. Two other TTLL11 mutations were also identified in two additional AIS cases in the same cohort. Analyses of primary cells of individuals carrying the c.1569_1570insTT (NM_194252) mutation reveal a defect at the primary cilia level, which is less present, smaller and less polyglutamylated compared to control. Further, in a zebrafish, the knock down of ttll11, and the mutated ttll11 confirmed its role in spine development and ciliary function in the fish retina. These findings provide evidence that mutations in TTLL11, a ciliary gene, contribute to the pathogenesis of IS.
Extracellular DNA of slow growers of mycobacteria and its contribution to biofilm formation and drug tolerance
Authors: Ilinov Aleksandr , Nishiyama Akihito , Namba Hiroki , Fukushima Yukari , Takihara Hayato , Nakajima Chie , Savitskaya Anna , Gebretsadik Gebremichal , Hakamata Mariko , Ozeki Yuriko , Tateishi Yoshitaka , Okuda Shujiro , Suzuki Yasuhiko , Vinnik Yuri S. , Matsumoto Sohkichi
Published: May 2021

DNA is basically an intracellular molecule that stores genetic information and carries instructions for growth and reproduction in all cellular organisms. However, in some bacteria, DNA has additional roles outside the cells as extracellular DNA (eDNA), which is an essential component of biofilm formation and hence antibiotic tolerance. Mycobacteria include life-threating human pathogens, most of which are slow growers. However, little is known about the nature of pathogenic mycobacteria’s eDNA. Here we found that eDNA is present in slow-growing mycobacterial pathogens, such as Mycobacterium tuberculosis, M. intracellulare, and M. avium at exponential growth phase. In contrast, eDNA is little in all tested rapid-growing mycobacteria. The physiological impact of disrupted eDNA on slow-growing mycobacteria include reduced pellicle formation, floating biofilm, and enhanced susceptibility to isoniazid and amikacin. Isolation and sequencing of eDNA revealed that it is identical to the genomic DNA in M. tuberculosis and M. intracellulare. In contrast, accumulation of phage DNA in eDNA of M. avium, suggests that the DNA released differs among mycobacterial species. Our data show important functions of eDNA necessary for biofilm formation and drug tolerance in slow-growing mycobacteria.
Flow of long chain hydrocarbons through carbon nanotubes (CNTs)
Authors: Asai Pranay , Panja Palash , Velasco Raul , Deo Milind
Published: May 2021

The pressure-driven flow of long-chain hydrocarbons in nanosized pores is important in energy, environmental, biological, and pharmaceutical applications. This paper examines the flow of hexane, heptane, and decane in carbon nanotubes (CNTs) of pore diameters 1–8 nm using molecular dynamic simulations. Enhancement of water flow in CNTs in comparison to rates predicted by continuum models has been well established in the literature. Our work was intended to observe if molecular dynamic simulations of hydrocarbon flow in CNTs produced similar enhancements. We used the OPLS-AA force field to simulate the hydrocarbons and the CNTs. Our simulations predicted the bulk densities of the hydrocarbons to be within 3% of the literature values. Molecular sizes and shapes of the hydrocarbon molecules compared to the pore size create interesting density patterns for smaller sized CNTs. We observed moderate flow enhancements for all the hydrocarbons (1–100) flowing through small-sized CNTs. For very small CNTs the larger hydrocarbons were forced to flow in a cork-screw fashion. As a result of this flow orientation, the larger molecules flowed as effectively (similar enhancements) as the smaller hydrocarbons.
Real-time multi-task diffractive deep neural networks via hardware-software co-design
Authors: Li Yingjie , Chen Ruiyang , Sensale-Rodriguez Berardi , Gao Weilu , Yu Cunxi
Published: May 2021

Deep neural networks (DNNs) have substantial computational requirements, which greatly limit their performance in resource-constrained environments. Recently, there are increasing efforts on optical neural networks and optical computing based DNNs hardware, which bring significant advantages for deep learning systems in terms of their power efficiency, parallelism and computational speed. Among them, free-space diffractive deep neural networks (D2NNs) based on the light diffraction, feature millions of neurons in each layer interconnected with neurons in neighboring layers. However, due to the challenge of implementing reconfigurability, deploying different DNNs algorithms requires re-building and duplicating the physical diffractive systems, which significantly degrades the hardware efficiency in practical application scenarios. Thus, this work proposes a novel hardware-software co-design method that enables first-of-its-like real-time multi-task learning in D22NNs that automatically recognizes which task is being deployed in real-time. Our experimental results demonstrate significant improvements in versatility, hardware efficiency, and also demonstrate and quantify the robustness of proposed multi-task D2NN architecture under wide noise ranges of all system components. In addition, we propose a domain-specific regularization algorithm for training the proposed multi-task architecture, which can be used to flexibly adjust the desired performance for each task.
Transcriptional analysis of the response of C. elegans to ethanol exposure
Authors: Sterken Mark G. , van Wijk Marijke H. , Quamme Elizabeth C. , Riksen Joost A. G. , Carnell Lucinda , Mathies Laura D. , Davies Andrew G. , Kammenga Jan E. , Bettinger Jill C.
Published: May 2021

Ethanol-induced transcriptional changes underlie important physiological responses to ethanol that are likely to contribute to the addictive properties of the drug. We examined the transcriptional responses ofCaenorhabditis elegansacross a timecourse of ethanol exposure, between 30 min and 8 h, to determine what genes and genetic pathways are regulated in response to ethanol in this model. We found that short exposures to ethanol (up to 2 h) induced expression of metabolic enzymes involved in metabolizing ethanol and retinol, while longer exposure (8 h) had much more profound effects on the transcriptome. Several genes that are known to be involved in the physiological response to ethanol, including direct ethanol targets, were regulated at 8 h of exposure. This longer exposure to ethanol also resulted in the regulation of genes involved in cilia function, which is consistent with an important role for the effects of ethanol on cilia in the deleterious effects of chronic ethanol consumption in humans. Finally, we found that food deprivation for an 8-h period induced gene expression changes that were somewhat ameliorated by the presence of ethanol, supporting previous observations that worms can use ethanol as a calorie source.
Whole brain functional recordings at cellular resolution in zebrafish larvae with 3D scanning multiphoton microscopy
Authors: Bruzzone Matteo , Chiarello Enrico , Albanesi Marco , Miletto Petrazzini Maria Elena , Megighian Aram , Lodovichi Claudia , dal Maschio Marco
Published: May 2021

Optical recordings of neuronal activity at cellular resolution represent an invaluable tool to investigate brain mechanisms. Zebrafish larvae is one of the few model organisms where, using fluorescence-based reporters of the cell activity, it is possible to optically reconstruct the neuronal dynamics across the whole brain. Typically, leveraging the reduced light scattering, methods like lightsheet, structured illumination, and light-field microscopy use spatially extended excitation profiles to detect in parallel activity signals from multiple cells. Here, we present an alternative design for whole brain imaging based on sequential 3D point-scanning excitation. Our approach relies on a multiphoton microscope integrating an electrically tunable lens. We first apply our approach, adopting the GCaMP6s activity reporter, to detect functional responses from retinal ganglion cells (RGC) arborization fields at different depths within the zebrafish larva midbrain. Then, in larvae expressing a nuclear localized GCaMP6s, we recorded whole brain activity with cellular resolution. Adopting a semi-automatic cell segmentation, this allowed reconstructing the activity from up to 52,000 individual neurons across the brain. In conclusion, this design can easily retrofit existing imaging systems and represents a compact, versatile and reliable tool to investigate neuronal activity across the larva brain at high resolution.
Novel human neutralizing mAbs specific for Spike-RBD of SARS-CoV-2
Authors: Passariello Margherita , Gentile Chiara , Ferrucci Veronica , Sasso Emanuele , Vetrei Cinzia , Fusco Giovanna , Viscardi Maurizio , Brandi Sergio , Cerino Pellegrino , Zambrano Nicola , Zollo Massimo , De Lorenzo Claudia
Published: May 2021

Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein represent good candidates to interfere in the Spike/ACE2 interaction, preventing virus cell entry. Since anti-spike mAbs, used individually, might be unable to block the virus entry in the case of resistant mutations, we designed an innovative strategy for the isolation of multiple novel human scFvs specific for the binding domain (RBD) of Spike. By panning a large phage display antibody library on immobilized RBD, we obtained specific binders by eluting with ACE2 in order to identify those scFvs recognizing the epitope of Spike interacting with its receptor. We converted the novel scFvs into full size IgG4, differently from the previously isolated IgG1 mAbs, to avoid unwanted potential side effects of IgG1 potent effector functions on immune system. The novel antibodies specifically bind to RBD in a nanomolar range and interfere in the interaction of Spike with ACE2 receptor, either used as purified protein or when expressed on cells in its native conformation. Furthermore, some of them have neutralizing activity for virus infection in cell cultures by using two different SARS-CoV-2 isolates including the highly contagious VOC 202012/01 variant and could become useful therapeutic tools to fight against the SARS-CoV-2 virus.
EGCG promotes PRKCA expression to alleviate LPS-induced acute lung injury and inflammatory response
Authors: Wang Mian , Zhong Hua , Zhang Xian , Huang Xin , Wang Jing , Li Zihao , Chen Mengshi , Xiao Zhenghui
Published: May 2021

Acute lung injury (ALI), which could be induced by multiple factors such as lipopolysaccharide (LPS), refer to clinical symptoms of acute respiratory failure, commonly with high morbidity and mortality. Reportedly, active ingredients from green tea have anti-inflammatory and anticancer properties, including epigallocatechin-3-gallate (EGCG). In the present study, protein kinase C alpha (PRKCA) is involved in EGCG protection against LPS-induced inflammation and ALI. EGCG treatment attenuated LPS-stimulated ALI in mice as manifested as improved lung injury scores, decreased total cell amounts, neutrophil amounts and macrophage amounts, inhibited the activity of MPO, decreased wet-to-dry weight ratio of lung tissues, and inhibited release of inflammatory cytokines TNF-α, IL-1β, and IL-6. PRKCA mRNA and protein expression showed to be dramatically decreased by LPS treatment while reversed by EGCG treatment. Within LPS-stimulated ALI mice, PRKCA silencing further aggravated, while PRKCA overexpression attenuated LPS-stimulated inflammation and ALI through MAPK signaling pathway. PRKCA silencing attenuated EGCG protection. Within LPS-induced RAW 264.7 macrophages, EGCG could induce PRKCA expression. Single EGCG treatment or Lv-PRKCA infection attenuated LPS-induced increases in inflammatory factors; PRKCA silencing could reverse the suppressive effects of EGCG upon LPS-stimulated inflammatory factor release. In conclusion, EGCG pretreatment inhibits LPS-induced ALI in mice. The protective mechanism might be associated with the inhibitory effects of PRKCA on proinflammatory cytokine release via macrophages and MAPK signaling pathway.
Frequency domain measurements of melt pool recoil force using modal analysis
Authors: Cullom Tristan , Lough Cody , Altese Nicholas , Bristow Douglas , Landers Robert , Brown Ben , Hartwig Troy , Barnard Andrew , Blough Jason , Johnson Kevin , Kinzel Edward
Published: May 2021

Recoil pressure is a critical factor affecting the melt pool dynamics during Laser Powder Bed Fusion (LPBF) processes. Recoil pressure depresses the melt pool. When the recoil pressure is low, thermal conduction and capillary forces may be inadequate to provide proper fusion between layers. However, excessive recoil pressure can produce a keyhole inside the melt pool, which is associated with gas porosity. Direct recoil pressure measurements are challenging because it is localized over an area proportionate to the laser spot size producing a force in the mN range. This paper reports a vibration-based approach to quantify the recoil force exerted on a part in a commercial LPBF machine. The measured recoil force is consistent with estimates from high speed synchrotron imaging of entrained particles, and the results show that the recoil force scales with applied laser power and is inversely related to the laser scan speed. These results facilitate further studies of melt pool dynamics and have the potential to aid process development for new materials.
Genome-wide identification of potential biomarkers in multiple myeloma using meta-analysis of mRNA and miRNA expression data
Authors: Katiyar Amit , Kaur Gurvinder , Rani Lata , Jena Lingaraja , Singh Harpreet , Kumar Lalit , Sharma Atul , Kaur Punit , Gupta Ritu
Published: May 2021

Multiple myeloma (MM) is a plasma cell malignancy with diverse clinical phenotypes and molecular heterogeneity not completely understood. Differentially expressed genes (DEGs) and miRNAs (DEMs) in MM may influence disease pathogenesis, clinical presentation / drug sensitivities. But these signatures overlap meagrely plausibly due to complexity of myeloma genome, diversity in primary cells studied, molecular technologies/ analytical tools utilized. This warrants further investigations since DEGs/DEMs can impact clinical outcomes and guide personalized therapy. We have conducted genome-wide meta-analysis of DEGs/DEMs in MM versus Normal Plasma Cells (NPCs) and derived unified putative signatures for MM. 100 DEMs and 1,362 DEGs were found deranged between MM and NPCs. Signatures of 37 DEMs (‘Union 37’) and 154 DEGs (‘Union 154’) were deduced that shared 17 DEMs and 22 DEGs with published prognostic signatures, respectively. Two miRs (miR-16–2-3p, 30d-2-3p) correlated with survival outcomes. PPI analysis identified 5 topmost functionally connected hub genes (UBC, ITGA4, HSP90AB1, VCAM1, VCP). Transcription factor regulatory networks were determined for five seed DEGs with ≥ 4 biomarker applications (CDKN1A, CDKN2A, MMP9, IGF1, MKI67) and three topmost up/ down regulated DEMs (miR-23b, 195, let7b/ miR-20a, 155, 92a). Further studies are warranted to establish and translate prognostic potential of these signatures for MM.
Eye-blink artifact removal from single channel EEG with k-means and SSA
Authors: Maddirala Ajay Kumar , Veluvolu Kalyana C
Published: May 2021

In recent years, the usage of portable electroencephalogram (EEG) devices are becoming popular for both clinical and non-clinical applications. In order to provide more comfort to the subject and measure the EEG signals for several hours, these devices usually consists of fewer EEG channels or even with a single EEG channel. However, electrooculogram (EOG) signal, also known as eye-blink artifact, produced by involuntary movement of eyelids, always contaminate the EEG signals. Very few techniques are available to remove these artifacts from single channel EEG and most of these techniques modify the uncontaminated regions of the EEG signal. In this paper, we developed a new framework that combines unsupervised machine learning algorithm (k-means) and singular spectrum analysis (SSA) technique to remove eye blink artifact without modifying actual EEG signal. The novelty of the work lies in the extraction of the eye-blink artifact based on the time-domain features of the EEG signal and the unsupervised machine learning algorithm. The extracted eye-blink artifact is further processed by the SSA method and finally subtracted from the contaminated single channel EEG signal to obtain the corrected EEG signal. Results with synthetic and real EEG signals demonstrate the superiority of the proposed method over the existing methods. Moreover, the frequency based measures [the power spectrum ratio ($$\Gamma $$Γ) and the mean absolute error (MAE)] also show that the proposed method does not modify the uncontaminated regions of the EEG signal while removing the eye-blink artifact.
Microfluidic-based processors and circuits design
Authors: Azizbeigi Kasra , Zamani Pedram Maysam , Sanati-Nezhad Amir
Published: May 2021

Droplets produced within microfluidics have not only attracted the attention of researchers to develop complex biological, industrial and clinical testing systems but also played a role as a bit of data. The flow of droplets within a network of microfluidic channels by stimulation of their movements, trajectories, and interaction timing, can provide an opportunity for preparation of complex and logical microfluidic circuits. Such mechanical-based circuits open up avenues to mimic the logic of electrical circuits within microfluidics. Recently, simple microfluidic-based logical elements such as AND, OR, and NOT gates have been experimentally developed and tested to model basic logic conditions in laboratory settings. In this work, we develop new microfluidic networks, control the shape of channels and speed of droplet movement, and regulate the size of bubbles in order to extend the logical elements to six new logic gates, including AND/OR type 1, AND/OR type 2, NOT type 1, NOT type 2, Flip-Flop, Synchronizer, and a parametric model of T-junction as a bubble generator. We further designed and simulated a novel microfluidic Decoder 1 to 2, a Decoder 2 to 4, and a microfluidic circuit that combines several individual logic gates into one complex circuit. Further fabrication and experimental testing of these newly introduced logic gates within microfluidics enable implementing complex circuits in high-throughput microfluidic platforms for tissue engineering, drug testing and development, and chemical synthesis and process design.
High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma
Authors: Li Songwei , Huang Jian , Yang Fan , Zeng Haiping , Tong Yuyun , Li Kejia
Published: May 2021

Hepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identified PARD3 as one of the most significantly differentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infiltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p < 0.001). High PARD3 expression was associated with poor clinicopathologic feathers, such as advanced pathologic stage (p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45–2.98, p < 0.001) and disease-specific survival (DSS, HR = 2.00, 95% CI = 1.27–3.16, p = 0.003). 242 up-regulated and 71 down-regulated genes showed significant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infiltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs). Altogether, PARD3 could be a potential prognostic biomarker and therapeutic target of HCC.
MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
Authors: Zalosnik M. I. , Fabio M. C. , Bertoldi M. L. , Castañares C. N. , Degano A. L.
Published: May 2021

Rett syndrome is a severe and progressive neurological disorder linked to mutations in the MeCP2 gene. It has been suggested that immune alterations may play an active role in the generation and/or maintenance of RTT phenotypes. However, there is no clear consensus about which pathways are regulated in vivo by MeCP2 in the context of immune activation. In the present work we set to characterize the role of MeCP2 during the progression of Experimental Autoimmune Encephalomyelitis (EAE) using the MeCP2308/y mouse model (MUT), which represents a condition of “MeCP2 function deficiency”. Our results showed that MeCP2 deficiency increased the susceptibility to develop EAE, along with a defective induction of anti-inflammatory responses and an exacerbated MOG-specific IFNγ expression in immune sites. In MUT-EAE spinal cord, we found a chronic increase in pro-inflammatory cytokines gene expression (IFNγ, TNFα and IL-1β) and downregulation of genes involved in immune regulation (IL-10, FoxP3 and CX3CR1). Moreover, our results indicate that MeCP2 acts intrinsically upon immune activation, affecting neuroimmune homeostasis by regulating the pro-inflammatory/anti-inflammatory balance in vivo. These results are relevant to identify the potential consequences of MeCP2 mutations on immune homeostasis and to explore novel therapeutic strategies for MeCP2-related disorders.
HDAC6 inhibitors sensitize non-mesenchymal triple-negative breast cancer cells to cysteine deprivation
Authors: Alothaim Tahiyat , Charbonneau Morgan , Tang Xiaohu
Published: May 2021

Triple-negative breast cancer (TNBC) is a highly malignant type of breast cancer and lacks effective therapy. Targeting cysteine-dependence is an emerging strategy to treat the mesenchymal TNBC. However, many TNBC cells are non-mesenchymal and unresponsive to cysteine deprivation. To overcome such resistance, three selective HDAC6 inhibitors (Tubacin, CAY10603, and Tubastatin A), identified by epigenetic compound library screening, can synergize with cysteine deprivation to induce cell death in the non-mesenchymal TNBC. Despite the efficacy of HDAC6 inhibitor, knockout of HDAC6 did not mimic the synthetic lethality induced by its inhibitors, indicating that HDAC6 is not the actual target of HDAC6 inhibitor in this context. Instead, transcriptomic profiling showed that tubacin triggers an extensive gene transcriptional program in combination with erastin, a cysteine transport blocker. Notably, the zinc-related gene response along with an increase of labile zinc was induced in cells by the combination treatment. The disturbance of zinc homeostasis was driven by PKCγ activation, which revealed that the PKCγ signaling pathway is required for HDAC6 inhibitor-mediated synthetic lethality. Overall, our study identifies a novel function of HDAC6 inhibitors that function as potent sensitizers of cysteine deprivation and are capable of abolishing cysteine-independence in non-mesenchymal TNBC.
Impact of US vaccination strategy on COVID-19 wave dynamics
Authors: Cot Corentin , Cacciapaglia Giacomo , Islind Anna Sigridur , Óskarsdóttir María , Sannino Francesco
Published: May 2021

We employ the epidemic Renormalization Group (eRG) framework to understand, reproduce and predict the COVID-19 pandemic diffusion across the US. The human mobility across different geographical US divisions is modelled via open source flight data alongside the impact of social distancing for each such division. We analyse the impact of the vaccination strategy on the current pandemic wave dynamics in the US. We observe that the ongoing vaccination campaign will not impact the current pandemic wave and therefore strict social distancing measures must still be enacted. To curb the current and the next waves our results indisputably show that vaccinations alone are not enough and strict social distancing measures are required until sufficient immunity is achieved. Our results are essential for a successful vaccination strategy in the US.
Seagrass blue carbon stocks and sequestration rates in the Colombian Caribbean
Authors: Serrano Oscar , Gómez-López Diana Isabel , Sánchez-Valencia Laura , Acosta-Chaparro Andres , Navas-Camacho Raul , González-Corredor Juan , Salinas Cristian , Masque Pere , Bernal Cesar A. , Marbà Núria
Published: May 2021

Seagrass ecosystems rank amongst the most efficient natural carbon sinks on earth, sequestering CO2through photosynthesis and storing organic carbon (Corg) underneath their soils for millennia and thereby, mitigating climate change. However, estimates of Corgstocks and accumulation rates in seagrass meadows (blue carbon) are restricted to few regions, and further information on spatial variability is required to derive robust global estimates. Here we studied soil Corgstocks and accumulation rates in seagrass meadows across the Colombian Caribbean. We estimated thatThalassia testudinummeadows store 241 ± 118 Mg Corgha−1(mean ± SD) in the top 1 m-thick soils, accumulated at rates of 122 ± 62 and 15 ± 7 g Corgm−2 year−1over the last ~ 70 years and up to 2000 years, respectively. The tropical climate of the Caribbean Sea and associated sediment run-off, together with the relatively high primary production ofT. testudinum, influencing biotic and abiotic drivers of Corgstorage linked to seagrass and soil respiration rates, explains their relatively high Corgstocks and accumulation rates when compared to other meadows globally. Differences in soil Corgstorage among Colombian Caribbean regions are largely linked to differences in the relative contribution of Corgsources to the soil Corgpool (seagrass, algaeHalimeda tuna, mangrove and seston) and the content of soil particles < 0.016 mm binding Corgand enhancing its preservation. Despite the moderate areal extent ofT. testudinumin the Colombian Caribbean (661 km2), it sequesters around 0.3 Tg CO2year−1, which is equivalent to ~ 0.4% of CO2emissions from fossil fuels in Colombia. This study adds data from a new region to a growing dataset on seagrass blue carbon and further explores differences in meadow Corgstorage based on biotic and abiotic environmental factors, while providing the basis for the implementation of seagrass blue carbon strategies in Colombia.
Comprehensive profiling analysis of the N6-methyladenosine-modified circular RNA transcriptome in cultured cells infected with Marek’s disease virus
Authors: Sun Aijun , Wang Rui , Yang Shuaikang , Zhu Xiaojing , Liu Ying , Teng Man , Zheng Luping , Luo Jun , Zhang Gaiping , Zhuang Guoqing
Published: May 2021

Marek’s disease virus (MDV) induces severe immunosuppression and lymphomagenesis in the chicken, its natural host, and results in a condition that investigated the pathogenesis of MDV and have begun to focus on the expression profiling of circular RNAs (circRNAs). However, little is known about how the expression of circRNAs is referred to as Marek’s disease. Previous reports have is regulated during MDV replication. Here, we carried out a comprehensive profiling analysis of N6-methyladenosine (m6A) modification on the circRNA transcriptome in infected and uninfected chicken embryonic fibroblast (CEF) cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that m6A modification was highly conserved in circRNAs. Comparing to the uninfected group, the number of peaks and conserved motifs were not significantly different in cells that were infected with MDV, although reduced abundance of circRNA m6A modifications. However, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses revealed that the insulin signaling pathway was associated with the regulation of m6A modified circRNAs in MDV infection. This is the first report to describe alterations in the transcriptome-wide profiling of m6A modified circRNAs in MDV-infected CEF cells.
In situ photografting during direct laser writing in thermoplastic microchannels
Authors: Han Jung Y. , Warshawsky Sarah , DeVoe Don L.
Published: May 2021

A method for in situ photografting during direct laser writing by two-photon polymerization is presented. The technique serves as a powerful approach to the formation of covalent bonds between 3D photoresist structures and thermoplastic surfaces. By leveraging the same laser for both pattern generation and localized surface reactions, crosslinking between the bulk photoresist and thermoplastic surface is achieved during polymerization. When applied to in-channel direct laser writing for microfluidic device fabrication, the process yields exceptionally strong adhesion and robust bond interfaces that can withstand pressure gradients as high as 7 MPa through proper channel design, photoinitiator selection, and processing conditions.
Thermally tolerant intertidal triplefin fish (Tripterygiidae) sustain ATP dynamics better than subtidal species under acute heat stress
Authors: Willis Jaime R. , Hickey Anthony J. R. , Devaux Jules B. L.
Published: May 2021

Temperature is a key factor that affects all levels of organization. Minute shifts away from thermal optima result in detrimental effects that impact growth, reproduction and survival. Metabolic rates of ectotherms are especially sensitive to temperature and for organisms exposed to high acute temperature changes, in particular intertidal species, energetic processes are often negatively impacted. Previous investigations exploring acute heat stress have implicated cardiac mitochondrial function in determining thermal tolerance. The brain, however, is by weight, one of the most metabolically active and arguably the most temperature sensitive organ. It is essentially aerobic and entirely reliant on oxidative phosphorylation to meet energetic demands, and as temperatures rise, mitochondria become less efficient at synthesising the amount of ATP required to meet the increasing demands. This leads to an energetic crisis. Here we used brain homogenate of three closely related triplefin fish species (Bellapiscis medius, Forsterygion lapillum,andForsterygion varium) and measured respiration and ATP dynamics at three temperatures (15, 25 and 30 °C). We found that the intertidalB. mediusandF. lapillumwere able to maintain rates of ATP production above rates of ATP hydrolysis at high temperatures, compared to the subtidalF. varium, which showed no difference in rates at 30 °C. These results showed that brain mitochondria became less efficient at temperatures below their respective species thermal limits, and that energetic surplus of ATP synthesis over hydrolysis narrows. In subtidal species synthesis matches hydrolysis, leaving no scope to elevate ATP supply.
Comprehensive analysis of competitive endogenous RNA associated with immune infiltration in lung adenocarcinoma
Authors: Chen Wenjie , Li Wen , Liu Zhenkun , Ma Guangzhi , Deng Yunfu , Li Xiaogang , Wang Zhu , zhou Qinghua
Published: May 2021

To identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan–Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, andhas-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that theFKBP3was associated with Monocytes and Macrophages M1, and theGPIwas obviously related with Monocytes and Macrophages M1. Besides, theLOXL2was associated with Monocytes and Activated mast cells, and theIL22RA1was significantly associated with Monocytes and Macrophages M1, while theGPR37and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.