bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the Effect of Relaxation on Interfacial Area Development in Multiphase Flow
Authors: Meisenheimer Douglas E. , Wildenschild Dorthe
Published: March 2021

A variety of two‐phase flow experiments, currently available in the literature, are compared to study the effect of fluid relaxation on interfacial area generation. Interfacial area is an important parameter that controls mass transfer in many engineered multiphase systems, so it is important to develop accurate predictive tools describing multiphase flow to engineer efficient processes. An empirical predictive relationship was developed describing a specific interfacial area‐wetting saturation relationship that depends on the number of quasi‐equilibrium relaxation points obtained during a drainage or imbibition experiment. The empirical expression was tested and verified using a number of existing datasets. We found that different relationships were needed depending on the fluid properties as well as the porous medium. However, clear trends were observed that can, once a predictive relationship is established for the system, allow us to design multiphase flow systems to produce a desired amount of interfacial area tailored to a particular application.
Glass crystallization making red phosphor for high-power warm white lighting
Authors: Hu Tao , Ning Lixin , Gao Yan , Qiao Jianwei , Song Enhai , Chen Zitao , Zhou Yayun , Wang Jing , Molokeev Maxim S. , Ke Xiaoxing , Xia Zhiguo , Zhang Qinyuan
Published: March 2021

Rapid development of solid-state lighting technology requires new materials with highly efficient and stable luminescence, and especially relies on blue light pumped red phosphors for improved light quality. Herein, we discovered an unprecedented red-emitting Mg2Al4Si5O18:Eu2+ composite phosphor (λex = 450 nm, λem = 620 nm) via the crystallization of MgO–Al2O3–SiO2 aluminosilicate glass. Combined experimental measurement and first-principles calculations verify that Eu2+ dopants insert at the vacant channel of Mg2Al4Si5O18 crystal with six-fold coordination responsible for the peculiar red emission. Importantly, the resulting phosphor exhibits high internal/external quantum efficiency of 94.5/70.6%, and stable emission against thermal quenching, which reaches industry production. The maximum luminous flux and luminous efficiency of the constructed laser driven red emitting device reaches as high as 274 lm and 54 lm W−1, respectively. The combinations of extraordinary optical properties coupled with economically favorable and innovative preparation method indicate, that the Mg2Al4Si5O18:Eu2+ composite phosphor will provide a significant step towards the development of high-power solid-state lighting.
Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer
Authors: Shen Tong , Liu Jing-Lin , Wang Chu-Yi , Rixiati Youlutuziayi , Li Shi , Cai Ling-Dong , Zhao Yuan-Yuan , Li Jian-Ming
Published: March 2021

The mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear. Here, using clinical samples from lung metastases of CRC patients, we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC. Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin, one member of the leucine-rich repeat and PDZ domain (LAP) family, was involved in the lung metastases. Erbin deletion in B cells suppressed lung metastasis of CRC in vivo. And, deletion of Erbin in B cells enhanced the killing effects of CD8+ T cells on tumor cells. Mechanistically, Erbin knockout attenuated TGFβ-mediated suppression of migration of CXCR5+ IgA+ cells and STAT6-mediated PD1 expression. Our study uncovered a key role of Erbin in regulating PD1+ IgA+ B cells in lung metastasis of CRC. Targeting Erbin as well as combined use of neutralizing B cells and antibodies neutralizing PD1 suppresses lung metastasis of CRC in mice, suggesting the potential option for treatment of lung metastasis of CRC.
Linking metabolic dysfunction with cardiovascular diseases: Brn-3b/POU4F2 transcription factor in cardiometabolic tissues in health and disease
Authors: Budhram-Mahadeo Vishwanie S. , Solomons Matthew R. , Mahadeo-Heads Eeshan A. O.
Published: March 2021

Metabolic and cardiovascular diseases are highly prevalent and chronic conditions that are closely linked by complex molecular and pathological changes. Such adverse effects often arise from changes in the expression of genes that control essential cellular functions, but the factors that drive such effects are not fully understood. Since tissue-specific transcription factors control the expression of multiple genes, which affect cell fate under different conditions, then identifying such regulators can provide valuable insight into the molecular basis of such diseases. This review explores emerging evidence that supports novel and important roles for the POU4F2/Brn-3b transcription factor (TF) in controlling cellular genes that regulate cardiometabolic function. Brn-3b is expressed in insulin-responsive metabolic tissues (e.g. skeletal muscle and adipose tissue) and is important for normal function because constitutive Brn-3b-knockout (KO) mice develop profound metabolic dysfunction (hyperglycaemia; insulin resistance). Brn-3b is highly expressed in the developing hearts, with lower levels in adult hearts. However, Brn-3b is re-expressed in adult cardiomyocytes following haemodynamic stress or injury and is necessary for adaptive cardiac responses, particularly in male hearts, because male Brn-3b KO mice develop adverse remodelling and reduced cardiac function. As a TF, Brn-3b regulates the expression of multiple target genes, including GLUT4, GSK3β, sonic hedgehog (SHH), cyclin D1 and CDK4, which have known functions in controlling metabolic processes but also participate in cardiac responses to stress or injury. Therefore, loss of Brn-3b and the resultant alterations in the expression of such genes could potentially provide the link between metabolic dysfunctions with adverse cardiovascular responses, which is seen in Brn-3b KO mutants. Since the loss of Brn-3b is associated with obesity, type II diabetes (T2DM) and altered cardiac responses to stress, this regulator may provide a new and important link for understanding how pathological changes arise in such endemic diseases.
Combinatorial mechanical gradation and growth factor biopatterning strategy for spatially controlled bone-tendon-like cell differentiation and tissue formation
Authors: Wang Dan , Ker Dai Fei Elmer , Ng Ka Wai , Li Ke , Gharaibeh Burhan , Safran Marc , Cheung Emilie , Campbell Phil , Weiss Lee , Yang Yunzhi Peter
Published: March 2021

Engineering scaffolds to augment the repair of hard-to-soft multitissue musculoskeletal tissue units, such as bone-tendon, to simultaneously support tissue healing and functional movement has had limited success. Overcoming this challenge will require not only precise spatial control of bone- and tendon-like biomechanical properties, but also consideration of the resultant biomechanical cues, as well as the embedded biochemical cues imparted by these scaffolds. Here, we report on the effects of a spatially engineered combination of stiffness and growth factor (GF) cues to control bone-tendon-like differentiation in vitro and tissue formation in vivo. This was achieved using mechanically graded, bone- and tendon-like QHM polyurethane (QHM: Q: Quadrol; H: hexamethylene diisocyanate; M: methacrylic anhydride) scaffolds selectively biopatterned with osteogenic bone morphogenetic protein-2 (BMP-2) and tenogenic fibroblast growth factor-2 (FGF-2). First, material characterization, including porosity, surface roughness, contact angle, and microindentation measurements, was performed. Second, in vitro studies demonstrated that increased material stiffness promoted GF-mediated osteoblast differentiation and reduced tenocyte differentiation. Sustained GF exposure masked this stiffness effect. Third, in vivo studies involving subcutaneous implantation of mechanically graded and biochemically patterned QHM scaffolds (composed of these bone- and tendon-promoting GFs biopatterned on biphasic bone and tendon biomechanically mimicking regions) in mice demonstrated spatial control of bone- and tendon-like tissue formation. Altogether, these data provide new insights for future engineering of scaffolds to augment hard-to-soft multitissue repair.
Light-activated shape morphing and light-tracking materials using biopolymer-based programmable photonic nanostructures
Authors: Wang Yu , Li Meng , Chang Jan-Kai , Aurelio Daniele , Li Wenyi , Kim Beom Joon , Kim Jae Hwan , Liscidini Marco , Rogers John A. , Omenetto Fiorenzo G.
Published: March 2021

Natural systems display sophisticated control of light-matter interactions at multiple length scales for light harvesting, manipulation, and management, through elaborate photonic architectures and responsive material formats. Here, we combine programmable photonic function with elastomeric material composites to generate optomechanical actuators that display controllable and tunable actuation as well as complex deformation in response to simple light illumination. The ability to topographically control photonic bandgaps allows programmable actuation of the elastomeric substrate in response to illumination. Complex three-dimensional configurations, programmable motion patterns, and phototropic movement where the material moves in response to the motion of a light source are presented. A “photonic sunflower” demonstrator device consisting of a light-tracking solar cell is also illustrated to demonstrate the utility of the material composite. The strategy presented here provides new opportunities for the future development of intelligent optomechanical systems that move with light on demand.
Digital proximity tracing on empirical contact networks for pandemic control
Authors: Cencetti G. , Santin G. , Longa A. , Pigani E. , Barrat A. , Cattuto C. , Lehmann S. , Salathé M. , Lepri B.
Published: March 2021

Digital contact tracing is a relevant tool to control infectious disease outbreaks, including the COVID-19 epidemic. Early work evaluating digital contact tracing omitted important features and heterogeneities of real-world contact patterns influencing contagion dynamics. We fill this gap with a modeling framework informed by empirical high-resolution contact data to analyze the impact of digital contact tracing in the COVID-19 pandemic. We investigate how well contact tracing apps, coupled with the quarantine of identified contacts, can mitigate the spread in real environments. We find that restrictive policies are more effective in containing the epidemic but come at the cost of unnecessary large-scale quarantines. Policy evaluation through their efficiency and cost results in optimized solutions which only consider contacts longer than 15–20 minutes and closer than 2–3 meters to be at risk. Our results show that isolation and tracing can help control re-emerging outbreaks when some conditions are met: (i) a reduction of the reproductive number through masks and physical distance; (ii) a low-delay isolation of infected individuals; (iii) a high compliance. Finally, we observe the inefficacy of a less privacy-preserving tracing involving second order contacts. Our results may inform digital contact tracing efforts currently being implemented across several countries worldwide.
Circadian control of hepatitis B virus replication
Authors: Zhuang Xiaodong , Forde Donall , Tsukuda Senko , D’Arienzo Valentina , Mailly Laurent , Harris James M. , Wing Peter A. C. , Borrmann Helene , Schilling Mirjam , Magri Andrea , Rubio Claudia Orbegozo , Maidstone Robert J. , Iqbal Mudassar , Garzon Miguel , Minisini Rosalba , Pirisi Mario , Butterworth Sam , Balfe Peter , Ray David W. , Watashi Koichi , Baumert Thomas F. , McKeating Jane A.
Published: March 2021

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The major challenge in curing infection is eradicating or silencing the covalent closed circular DNA (cccDNA) form of the viral genome. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the liver transcriptome and yet their role in HBV replication is unknown. We establish a circadian cycling liver cell-model and demonstrate that REV-ERB directly regulates NTCP-dependent hepatitis B and delta virus particle entry. Importantly, we show that pharmacological activation of REV-ERB inhibits HBV infection in vitro and in human liver chimeric mice. We uncover a role for BMAL1 to bind HBV genomes and increase viral promoter activity. Pharmacological inhibition of BMAL1 through REV-ERB ligands reduces pre-genomic RNA and de novo particle secretion. The presence of conserved E-box motifs among members of the Hepadnaviridae family highlight an evolutionarily conserved role for BMAL1 in regulating this family of small DNA viruses.
Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans
Authors: Izotova Natalia , Rivat Christine , Baricordi Cristina , Blanco Elena , Pellin Danilo , Watt Eleanor , Gkazi Athina S. , Adams Stuart , Gilmour Kimberly , Bayford Jinhua , Booth Claire , Gaspar H. Bobby , Thrasher Adrian J. , Biasco Luca
Published: March 2021

Our mathematical model of integration site data in clinical gene therapy supported the existence of long-term lymphoid progenitors capable of surviving independently from hematopoietic stem cells. To date, no experimental setting has been available to validate this prediction. We here report evidence of a population of lymphoid progenitors capable of independently maintaining T and NK cell production for 15 years in humans. The gene therapy patients of this study lack vector-positive myeloid/B cells indicating absence of engineered stem cells but retain gene marking in both T and NK. Decades after treatment, we can still detect and analyse transduced naïve T cells whose production is likely maintained by a population of long-term lymphoid progenitors. By tracking insertional clonal markers overtime, we suggest that these progenitors can support both T and NK cell production. Identification of these long-term lymphoid progenitors could be utilised for the development of next generation gene- and cancer-immunotherapies.
Global discovery of lupus genetic risk variant allelic enhancer activity
Authors: Lu Xiaoming , Chen Xiaoting , Forney Carmy , Donmez Omer , Miller Daniel , Parameswaran Sreeja , Hong Ted , Huang Yongbo , Pujato Mario , Cazares Tareian , Miraldi Emily R. , Ray John P. , de Boer Carl G. , Harley John B. , Weirauch Matthew T. , Kottyan Leah C.
Published: March 2021

Genome-wide association studies of Systemic Lupus Erythematosus (SLE) nominate 3073 genetic variants at 91 risk loci. To systematically screen these variants for allelic transcriptional enhancer activity, we construct a massively parallel reporter assay (MPRA) library comprising 12,396 DNA oligonucleotides containing the genomic context around every allele of each SLE variant. Transfection into the Epstein-Barr virus-transformed B cell line GM12878 reveals 482 variants with enhancer activity, with 51 variants showing genotype-dependent (allelic) enhancer activity at 27 risk loci. Comparison of MPRA results in GM12878 and Jurkat T cell lines highlights shared and unique allelic transcriptional regulatory mechanisms at SLE risk loci. In-depth analysis of allelic transcription factor (TF) binding at and around allelic variants identifies one class of TFs whose DNA-binding motif tends to be directly altered by the risk variant and a second class of TFs that bind allelically without direct alteration of their motif by the variant. Collectively, our approach provides a blueprint for the discovery of allelic gene regulation at risk loci for any disease and offers insight into the transcriptional regulatory mechanisms underlying SLE.
Interplay of BAF and MLL4 promotes cell type-specific enhancer activation
Authors: Park Young-Kwon , Lee Ji-Eun , Yan Zhijiang , McKernan Kaitlin , O’Haren Tommy , Wang Weidong , Peng Weiqun , Ge Kai
Published: March 2021

Cell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF chromatin remodeling complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Using adipogenesis as a model system, we identify BAF as the major SWI/SNF complex that colocalizes with MLL4 and LDTFs on active enhancers and is required for cell differentiation. In contrast, the promoter enriched SWI/SNF complex PBAF is dispensable for adipogenesis. By depleting BAF subunits SMARCA4 (BRG1) and SMARCB1 (SNF5) as well as MLL4 in cells, we show that BAF and MLL4 reciprocally regulate each other’s binding on active enhancers before and during adipogenesis. By focusing on enhancer activation by the adipogenic pioneer transcription factor C/EBPβ without inducing cell differentiation, we provide direct evidence for an interdependent relationship between BAF and MLL4 in activating cell type-specific enhancers. Together, these findings reveal a positive feedback between BAF and MLL4 in promoting LDTF-dependent activation of cell type-specific enhancers.
Theory of optical responses in clean multi-band superconductors
Authors: Ahn Junyeong , Nagaosa Naoto
Published: March 2021

Electromagnetic responses in superconductors provide valuable information on the pairing symmetry as well as physical quantities such as the superfluid density. However, at the superconducting gap energy scale, optical excitations of the Bogoliugov quasiparticles are forbidden in conventional Bardeen-Cooper-Schrieffer superconductors when momentum is conserved. Accordingly, far-infrared optical responses have been understood in the framework of a dirty-limit theory by Mattis and Bardeen for over 60 years. Here we show, by investigating the selection rules imposed by particle-hole symmetry and unitary symmetries, that intrinsic momentum-conserving optical excitations can occur in clean multi-band superconductors when one of the following three conditions is satisfied: (i) inversion symmetry breaking, (ii) symmetry protection of the Bogoliubov Fermi surfaces, or (iii) simply finite spin-orbit coupling with unbroken time reversal and inversion symmetries. This result indicates that clean-limit optical responses are common beyond the straightforward case of broken inversion symmetry. We apply our theory to optical responses in FeSe, a clean multi-band superconductor with inversion symmetry and significant spin-orbit coupling. This result paves the way for studying clean-limit superconductors through optical measurements.
Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications
Authors: Xiao Nan , Nie Meng , Pang Huanhuan , Wang Bohong , Hu Jieli , Meng Xiangjun , Li Ke , Ran Xiaorong , Long Quanxin , Deng Haijun , Chen Na , Li Shao , Tang Ni , Huang Ailong , Hu Zeping
Published: March 2021

Cytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.
SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance
Authors: Kutter Jasmin S. , de Meulder Dennis , Bestebroer Theo M. , Lexmond Pascal , Mulders Ard , Richard Mathilde , Fouchier Ron A. M. , Herfst Sander
Published: March 2021

SARS-CoV-2 emerged in late 2019 and caused a pandemic, whereas the closely related SARS-CoV was contained rapidly in 2003. Here, an experimental set-up is used to study transmission of SARS-CoV and SARS-CoV-2 through the air between ferrets over more than a meter distance. Both viruses cause a robust productive respiratory tract infection resulting in transmission of SARS-CoV-2 to two of four indirect recipient ferrets and SARS-CoV to all four. A control pandemic A/H1N1 influenza virus also transmits efficiently. Serological assays confirm all virus transmission events. Although the experiments do not discriminate between transmission via small aerosols, large droplets and fomites, these results demonstrate that SARS-CoV and SARS-CoV-2 can remain infectious while traveling through the air. Efficient virus transmission between ferrets is in agreement with frequent SARS-CoV-2 outbreaks in mink farms. Although the evidence for virus transmission via the air between humans under natural conditions is absent or weak for SARS-CoV and SARS-CoV-2, ferrets may represent a sensitive model to study interventions aimed at preventing virus transmission.
Adeno-associated virus capsid assembly is divergent and stochastic
Authors: Wörner Tobias P. , Bennett Antonette , Habka Sana , Snijder Joost , Friese Olga , Powers Thomas , Agbandje-McKenna Mavis , Heck Albert J. R.
Published: March 2021

Adeno-associated viruses (AAVs) are increasingly used as gene therapy vectors. AAVs package their genome in a non-enveloped T = 1 icosahedral capsid of ~3.8 megaDalton, consisting of 60 subunits of 3 distinct viral proteins (VPs), which vary only in their N-terminus. While all three VPs play a role in cell-entry and transduction, their precise stoichiometry and structural organization in the capsid has remained elusive. Here we investigate the composition of several AAV serotypes by high-resolution native mass spectrometry. Our data reveal that the capsids assemble stochastically, leading to a highly heterogeneous population of capsids of variable composition, whereby even the single-most abundant VP stoichiometry represents only a small percentage of the total AAV population. We estimate that virtually every AAV capsid in a particular preparation has a unique composition. The systematic scoring of the simulations against experimental native MS data offers a sensitive new method to characterize these therapeutically important heterogeneous capsids.
Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures
Authors: Li Jiao , Seidlitz Jakob , Suckling John , Fan Feiyang , Ji Gong-Jun , Meng Yao , Yang Siqi , Wang Kai , Qiu Jiang , Chen Huafu , Liao Wei
Published: March 2021

Major depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.
Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana
Authors: Andronico Alessio , Tran Kiem Cécile , Paireau Juliette , Succo Tiphanie , Bosetti Paolo , Lefrancq Noémie , Nacher Mathieu , Djossou Félix , Sanna Alice , Flamand Claude , Salje Henrik , Rousseau Cyril , Cauchemez Simon
Published: March 2021

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June–July 2020 in French Guiana that relied on curfews, targeted lockdowns, and other measures. We find that the combination of these interventions coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modelling can be used to support healthcare planning in a context of high uncertainty.
A deep learning method for HLA imputation and trans-ethnic MHC fine-mapping of type 1 diabetes
Authors: Naito Tatsuhiko , Suzuki Ken , Hirata Jun , Kamatani Yoichiro , Matsuda Koichi , Toda Tatsushi , Okada Yukinori
Published: March 2021

Conventional human leukocyte antigen (HLA) imputation methods drop their performance for infrequent alleles, which is one of the factors that reduce the reliability of trans-ethnic major histocompatibility complex (MHC) fine-mapping due to inter-ethnic heterogeneity in allele frequency spectra. We develop DEEP*HLA, a deep learning method for imputing HLA genotypes. Through validation using the Japanese and European HLA reference panels (n = 1,118 and 5,122), DEEP*HLA achieves the highest accuracies with significant superiority for low-frequency and rare alleles. DEEP*HLA is less dependent on distance-dependent linkage disequilibrium decay of the target alleles and might capture the complicated region-wide information. We apply DEEP*HLA to type 1 diabetes GWAS data from BioBank Japan (n = 62,387) and UK Biobank (n = 354,459), and successfully disentangle independently associated class I and II HLA variants with shared risk among diverse populations (the top signal at amino acid position 71 of HLA-DRβ1; P = 7.5 × 10−120). Our study illustrates the value of deep learning in genotype imputation and trans-ethnic MHC fine-mapping.
A systematic review of movement and muscular activity biomarkers to discriminate non-specific chronic low back pain patients from an asymptomatic population
Authors: Moissenet Florent , Rose-Dulcina Kevin , Armand Stéphane , Genevay Stéphane
Published: March 2021

The identification of relevant and valid biomarkers to distinguish patients with non-specific chronic low back pain (NSCLBP) from an asymptomatic population in terms of musculoskeletal factors could contribute to patient follow-up and to evaluate therapeutic strategies. Several parameters related to movement and/or muscular activity impairments have been proposed in the literature in that respect. In this article, we propose a systematic and comprehensive review of these parameters (i.e. potential biomarkers) and related measurement properties. This systematic review (PROSPERO registration number: CRD42020144877) was conducted in Medline, Embase, and Web of Knowledge databases until July 2019. In the included studies, all movements or muscular activity parameters having demonstrated at least a moderate level of construct validity were defined as biomarkers, and their measurement properties were assessed. In total, 92 studies were included. This allowed to identify 121 movement and 150 muscular activity biomarkers. An extensive measurement properties assessment was found in 31 movement and 14 muscular activity biomarkers. On the whole, these biomarkers support the primary biomechanical concepts proposed for low back pain. However, a consensus concerning a robust and standardised biomechanical approach to assess low back pain is needed.
Wireless power transfer system rigid to tissue characteristics using metamaterial inspired geometry for biomedical implant applications
Authors: Pokharel Ramesh K. , Barakat Adel , Alshhawy Shimaa , Yoshitomi Kuniaki , Sarris Costas
Published: March 2021

Conventional resonant inductive coupling wireless power transfer (WPT) systems encounter performance degradation while energizing biomedical implants. This degradation results from the dielectric and conductive characteristics of the tissue, which cause increased radiation and conduction losses, respectively. Moreover, the proximity of a resonator to the high permittivity tissue causes a change in its operating frequency if misalignment occurs. In this report, we propose a metamaterial inspired geometry with near-zero permeability property to overcome these mentioned problems. This metamaterial inspired geometry is stacked split ring resonator metamaterial fed by a driving inductive loop and acts as a WPT transmitter for an in-tissue implanted WPT receiver. The presented demonstrations have confirmed that the proposed metamaterial inspired WPT system outperforms the conventional one. Also, the resonance frequency of the proposed metamaterial inspired TX is negligibly affected by the tissue characteristics, which is of great interest from the design and operation prospects. Furthermore, the proposed WPT system can be used with more than twice the input power of the conventional one while complying with the safety regulations of electromagnetic waves exposure.
Ketone body 3-hydroxybutyrate as a biomarker of aggression
Authors: Whipp A. M. , Vuoksimaa E. , Korhonen T. , Pool R. , But A. , Ligthart L. , Hagenbeek F. A. , Bartels M. , Bogl L. H. , Pulkkinen L. , Rose R. J. , Boomsma D. I. , Kaprio J.
Published: March 2021

Human aggression is a complex behaviour, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983–1987, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the response variable and aggression ratings as predictor variables, and included several potential confounders. All metabolites showed low correlations with aggression, with only one—3-hydroxybutyrate, a ketone body produced during fasting—showing significant (negative) associations with aggression. Effect sizes for different raters were generally similar in magnitude, while teacher-rated (age 12) and self-rated (age 14) aggression were both significant predictors of 3-hydroxybutyrate in multi-rater models. In an independent replication sample of 960 adults from the Netherlands Twin Register, higher aggression (self-rated) was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.
Associations between the gut microbiome and fatigue in cancer patients
Authors: Hajjar Joud , Mendoza Tito , Zhang Liangliang , Fu Siqing , Piha-Paul Sarina A. , Hong David S. , Janku Filip , Karp Daniel D. , Ballhausen Alexej , Gong Jing , Zarifa Abdulrazzak , Peterson Christine B. , Meric-Bernstam Funda , Jenq Robert , Naing Aung
Published: March 2021

Fatigue is the most prevalent symptom of cancer and its treatments. Changes in the intestinal microbiome have been identified in chronic fatigue syndrome and other neuropsychiatric disorders, and cancer patients. However, the association between intestinal microbiome and fatigue in patients with advanced cancers has not been evaluated. Understanding the connection between intestinal microbiome and fatigue will provide interventional and therapeutic opportunities to manipulate the microbiome to improve fatigue and other patients’ reported outcomes. In this project, we aimed to identify associations between microbiome composition and fatigue in advanced cancer patients. In this cross-sectional observational study at a tertiary cancer care center, we included 88 patients with advanced, metastatic, unresectable cancers who were in a washout period from chemotherapy. We measured fatigue using the MD Anderson Symptom Inventory—Immunotherapy fatigue score, and used 16srRNA to analyze intestinal microbiome. Using correlation analysis we found that Eubacterium hallii was negatively associated with fatigue severity scores (r = − 0.30, p = 0.005), whereas Cosenzaea was positively associated with fatigue scores (r = 0.33, p = 0.0002). We identified microbial species that exhibit distinct composition between high-fatigued and low-fatigued cancer patients. Further studies are warranted to investigate whether modulating the microbiome reduces cancer patients’ fatigue severity and improves their quality of life.
Human milk extracellular vesicle miRNA expression and associations with maternal characteristics in a population-based cohort from the Faroe Islands
Authors: Kupsco Allison , Prada Diddier , Valvi Damaskini , Hu Lisa , Petersen Maria Skaalum , Coull Brent , Grandjean Philippe , Weihe Pal , Baccarelli Andrea A.
Published: March 2021

Human milk plays a critical role in infant development and health, particularly in cognitive, immune, and cardiometabolic functions. Milk contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs). We aimed to characterize milk EV-miRNA profiles in a human population cohort, assess potential pathways and ontology, and investigate associations with maternal characteristics. We conducted the first study to describe the EV miRNA profile of human milk in 364 mothers from a population-based mother-infant cohort in the Faroe Islands using small RNA sequencing. We detected 1523 miRNAs with ≥ one read in 70% of samples. Using hierarchical clustering, we determined five EV-miRNA clusters, the top three consisting of 15, 27 and 67 miRNAs. Correlation coefficients indicated that the expression of many miRNAs within the top three clusters was highly correlated. Top-cluster human milk EV-miRNAs were involved in pathways enriched for the endocrine system, cellular community, neurodevelopment, and cancers. miRNA expression was associated with time to milk collection post-delivery, maternal body mass index, and maternal smoking, but not maternal parity. Future studies investigating determinants of human EV-miRNAs and associated health outcomes are needed to elucidate the role of human milk EV-miRNAs in health and disease.
Quantifying mechanical loading and elastic strain energy of the human Achilles tendon during walking and running
Authors: Kharazi Mohamadreza , Bohm Sebastian , Theodorakis Christos , Mersmann Falk , Arampatzis Adamantios
Published: March 2021

The purpose of the current study was to assess in vivo Achilles tendon (AT) mechanical loading and strain energy during locomotion. We measured AT length considering its curve-path shape. Eleven participants walked at 1.4 m/s and ran at 2.5 m/s and 3.5 m/s on a treadmill. The AT length was defined as the distance between its origin at the gastrocnemius medialis myotendinous junction (MTJ) and the calcaneal insertion. The MTJ was tracked using ultrasonography and projected to the reconstructed skin surface to account for its misalignment. Skin-to-bone displacements were assessed during a passive rotation (5°/s) of the ankle joint. Force and strain energy of the AT during locomotion were calculated by fitting a quadratic function to the experimentally measured tendon force–length curve obtained from maximum voluntary isometric contractions. The maximum AT strain and force were affected by speed (p < 0.05, ranging from 4.0 to 4.9% strain and 1.989 to 2.556 kN), yet insufficient in magnitude to be considered as an effective stimulus for tendon adaptation. Besides the important tendon energy recoil during the propulsion phase (7.8 to 11.3 J), we found a recoil of elastic strain energy at the beginning of the stance phase of running (70–77 ms after touch down) between 1.7 ± 0.6 and 1.9 ± 1.1 J, which might be functionally relevant for running efficiency.
Evidence for temporal relationship between the late Mesozoic multistage Qianlishan granite complex and the Shizhuyuan W–Sn–Mo–Bi deposit, SE China
Authors: Liao Yuzhong , Zhao Bo , Zhang Dehui , Danyushevsky Leonid V. , Li Tonglin , Wu Mingqian , Liu Feng
Published: March 2021

The world-class Shizhuyuan W–Sn–Mo–Bi deposit is spatially related to the Qianlishan granite complex (QGC) in Hunan Province, China. However, the age and classification of the QGC are still debated, and a better understanding of the temporal genetic relationship between the QGC and the Shizhuyuan deposit is essential. Here, we present chemical compositions the intrusive phases of the QGC and the results of detailed zircon U–Pb dating and muscovite Ar–Ar dating of a mineralized greisen vein. Our new zircon laser ablation inductively coupled plasma mass spectrometry U–Pb age data constrain the emplacement of the QGC to 155–151.7 Ma. According to petrological, geochemical and geochronological data and the inferred redox conditions, the QGC can be classified into four phases: P1, porphyritic biotite granites; P2, porphyritic biotite granites; P3, equigranular biotite granite; and P4, granite porphyry dikes. All phases, and especially P1-P3, have elevated concentrations of ore-forming metals and heat-producing elements (U, Th, K; volume heat-producing rate of 5.89–14.03 μWm−3), supplying the metal and heat for the metalogic process of the Shizhuyuan deposit. The Ar–Ar muscovite age (154.0 ± 1.6 Ma) of the mineralized greisen vein in the Shizhuyuan deposit is consistent with the emplacement time of the QGC, suggesting their temporal genetic relationship.
From rumor to genetic mutation detection with explanations: a GAN approach
Authors: Cheng Mingxi , Li Yizhi , Nazarian Shahin , Bogdan Paul
Published: March 2021

Social media have emerged as increasingly popular means and environments for information gathering and propagation. This vigorous growth of social media contributed not only to a pandemic (fast-spreading and far-reaching) of rumors and misinformation, but also to an urgent need for text-based rumor detection strategies. To speed up the detection of misinformation, traditional rumor detection methods based on hand-crafted feature selection need to be replaced by automatic artificial intelligence (AI) approaches. AI decision making systems require to provide explanations in order to assure users of their trustworthiness. Inspired by the thriving development of generative adversarial networks (GANs) on text applications, we propose a GAN-based layered model for rumor detection with explanations. To demonstrate the universality of the proposed approach, we demonstrate its benefits on a gene classification with mutation detection case study. Similarly to the rumor detection, the gene classification can also be formulated as a text-based classification problem. Unlike fake news detection that needs a previously collected verified news database, our model provides explanations in rumor detection based on tweet-level texts only without referring to a verified news database. The layered structure of both generative and discriminative models contributes to the outstanding performance. The layered generators produce rumors by intelligently inserting controversial information in non-rumors, and force the layered discriminators to detect detailed glitches and deduce exactly which parts in the sentence are problematic. On average, in the rumor detection task, our proposed model outperforms state-of-the-art baselines on PHEME dataset by $$26.85\%$$

26.85
%

in terms of macro-f1. The excellent performance of our model for textural sequences is also demonstrated by the gene mutation case study on which it achieves $$72.69\%$$

72.69
%

macro-f1 score.
Isolation and characterization of two virulent Aeromonads associated with haemorrhagic septicaemia and tail-rot disease in farmed climbing perch Anabas testudineus
Authors: Mazumder Abhishek , Choudhury Hrishikesh , Dey Abhinit , Sarma Dandadhar
Published: March 2021

Diseased Anabas testudineus exhibiting signs of tail-rot and ulcerations on body were collected from a fish farm in Assam, India during the winter season (November 2018 to January 2019). Swabs from the infected body parts were streaked on sterilized nutrient agar. Two dominant bacterial colonies were obtained, which were then isolated and labelled as AM-31 and AM-05. Standard biochemical characterisation and 16S rRNA and rpoB gene sequencing identified AM-31 isolate as Aeromonas hydrophila and AM-05 as Aeromonas jandaei. Symptoms similar to that of natural infection were observed on re-infecting both bacteria to disease-free A. testudineus, which confirmed their virulence. LC50 was determined at 1.3 × 104 (A. hydrophila) and 2.5 × 104 (A. jandaei) CFU per fish in intraperitoneal injection. Further, PCR amplification of specific genes responsible for virulence (aerolysin and enterotoxin) confirmed pathogenicity of both bacteria. Histopathology of kidney and liver in the experimentally-infected fishes revealed haemorrhage, tubular degeneration and vacuolation. Antibiotic profiles were also assessed for both bacteria. To the best of our knowledge, the present work is a first report on the mortality of farmed climbing perch naturally-infected by A. hydrophila as well as A. jandaei, with no records of pathogenicity of the latter in this fish.
Patient individual phase gating for stereotactic radiation therapy of early stage non-small cell lung cancer (NSCLC)
Authors: Kraus K. M. , Oechsner M. , Wilkens J. J. , Kessel K. A. , Münch S. , Combs S. E.
Published: March 2021

Stereotactic body radiotherapy (SBRT) applies high doses and requires advanced techniques to spare surrounding tissue in the presence of organ motion. In this work patient individual phase gating is investigated. We studied peripheral and central primary lung tumors. The internal target volume (ITV) was defined including different numbers of phases picked from a 4D Computed tomography (CT) defining the gating window (gw). Planning target volume (PTV) reductions depending on the gw were analyzed. A treatment plan was calculated on a reference phase CT (rCT) and the dose for each breathing phase was calculated and accumulated on the rCT. We compared the dosimetric results with the dose calculated when all breathing phases were included for ITV definition. GWs including 1 to 10 breathing phases were analyzed. We found PTV reductions up to 38.4%. The mean reduction of the lung volume receiving 20 Gy due to gating was found to be 25.7% for peripheral tumors and 16.7% for central tumors. Gating considerably reduced esophageal doses. However, we found that simple reduction of the gw does not necessarily influence the dose in a clinically relevant range. Thus, we suggest a patient individual definition of the breathing phases included within the gw.
Primary ectocervical epithelial cells display lower permissivity to Chlamydia trachomatis than HeLa cells and a globally higher pro-inflammatory profile
Authors: Tang Chongfa , Liu Chang , Maffei Benoit , Niragire Béatrice , Cohen Henri , Kane Aminata , Donnadieu Anne-Claire , Levy-Zauberman Yael , Vernay Thomas , Hugueny Juliette , Vincens Etienne , Louis-Sylvestre Christine , Subtil Agathe , Wu Yongzheng
Published: March 2021

The tumoral origin and extensive passaging of HeLa cells, a most commonly used cervical epithelial cell line, raise concerns on their suitability to study the cell responses to infection. The present study was designed to isolate primary epithelial cells from human ectocervix explants and characterize their susceptibility toC. trachomatisinfection. We achieved a high purity of isolation, assessed by the expression of E-cadherin and cytokeratin 14. The infectious progeny in these primary epithelial cells was lower than in HeLa cells. We showed that the difference in culture medium, and the addition of serum in HeLa cultures, accounted for a large part of these differences. However, all things considered the primary ectocervical epithelial cells remained less permissive than HeLa cells toC. trachomatisserovar L2 or D development. Finally, the basal level of transcription of genes coding for pro-inflammatory cytokines was globally higher in primary epithelial cells than in HeLa cells. Transcription of several pro-inflammatory genes was further induced by infection withC. trachomatisserovar L2 or serovar D. In conclusion, primary epithelial cells have a strong capacity to mount an inflammatory response toChlamydiainfection. Our simplified purification protocol from human explants should facilitate future studies to understand the contribution of this response to limiting the spread of the pathogen to the upper female genital tract.
Classification of sleep apnea based on EEG sub-band signal characteristics
Authors: Zhao Xiaoyun , Wang Xiaohong , Yang Tianshun , Ji Siyu , Wang Huiquan , Wang Jinhai , Wang Yao , Wu Qi
Published: March 2021

Sleep apnea syndrome (SAS) is a disorder in which respiratory airflow frequently stops during sleep. Alterations in electroencephalogram (EEG) signal are one of the physiological changes that occur during apnea, and can be used to diagnose and monitor sleep apnea events. Herein, we proposed a method to automatically distinguish sleep apnea events using characteristics of EEG signals in order to categorize obstructive sleep apnea (OSA) events, central sleep apnea (CSA) events and normal breathing events. Through the use of an Infinite Impulse Response Butterworth Band pass filter, we divided the EEG signals of C3-A2 and C4-A1 into five sub-bands. Next, we extracted sample entropy and variance of each sub-band. The neighbor composition analysis (NCA) method was utilized for feature selection, and the results are used as input coefficients for classification using random forest, K-nearest neighbor, and support vector machine classifiers. After a 10-fold cross-validation, we found that the average accuracy rate was 88.99%. Specifically, the accuracy of each category, including OSA, CSA and normal breathing were 80.43%, 84.85%, and 95.24%, respectively. The proposed method has great potential in the automatic classification of patients' respiratory events during clinical examinations, and provides a novel idea for the development of an automatic classification system for sleep apnea and normal events without the need for expert intervention.