bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal and early-life factors associated with stable and unstable trajectories of psychopathic traits across childhood
Authors: Bégin Vincent , Fontaine Nathalie M.G. , Vitaro Frank , Boivin Michel , Tremblay Richard E. , Côté Sylvana M.
Published: May 2021

Background

This study aimed to identify perinatal and early-life factors associated with trajectories of psychopathic traits across childhood.

Methods

Participants were 1631 children (51.5% girls) from the Quebec Longitudinal Study of Child Development. A wide range of perinatal and early-life factors were assessed from pregnancy to age 2.5 years using medical files and mothers’ reports. Psychopathic traits were assessed via teachers’ reports at ages 6, 7, 8, 10, and 12 years. Latent class growth analyses and multinomial logistic regressions controlling for child sex were conducted. Two-way interaction effects between perinatal/early-life factors and child sex were explored.

Results

Four trajectories of psychopathic traits were identified: High-stable (4.48%), Increasing (8.77%), Decreasing (11.46%), and Low-stable (75.29%). A few perinatal factors and most child-level and family-level early-life factors significantly increased the odds of following the High-stablev.the Low-stable trajectory. Higher levels of psychotropic exposures during pregnancy, socioeconomic adversity, child's physical aggression, child's opposition, mother's depressive symptoms, and hostile parenting increased the likelihood of following the Increasing instead of the Low-stable trajectory. Higher socioeconomic adversity, mother's depressive symptoms, and inconsistent parenting were associated with membership to the High-stable instead of the Decreasing trajectory. Most associations were not moderated by child sex.

Conclusions

These results shed light on the perinatal and early-life factors that are associated with specific pathways of psychopathic traits during childhood and suggest that different factors could be targeted to prevent the exacerbation (v.low and stable levels) or the stability at high levels (v.attenuation) of these traits.
Profiling Social Cognition in Premanifest Huntington's Disease
Authors: Turner Kate , Bartlett Danielle , Grainger Sarah A. , Eddy Clare , Reyes Alvaro , Kordsachia Catarina , Turner Mitchell , Stout Julie C. , Georgiou-Karistianis Nellie , Henry Julie D. , Ziman Mel , Cruickshank Travis
Published: May 2021

Objective:

Discrepancies exist in reports of social cognition deficits in individuals with premanifest Huntington’s disease (HD); however, the reason for this variability has not been investigated. The aims of this study were to (1) evaluate group- and individual-level social cognitive performance and (2) examine intra-individual variability (dispersion) across social cognitive domains in individuals with premanifest HD.

Method:

Theory of mind (ToM), social perception, empathy, and social connectedness were evaluated in 35 individuals with premanifest HD and 29 healthy controls. Cut-off values beneath the median and 1.5 × the interquartile range below the 25th percentile (P25 – 1.5 × IQR) of healthy controls for each variable were established for a profiling method. Dispersion between social cognitive domains was also calculated.

Results:

Compared to healthy controls, individuals with premanifest HD performed worse on all social cognitive domains except empathy. Application of the profiling method revealed a large proportion of people with premanifest HD fell below healthy control median values across ToM (>80%), social perception (>57%), empathy (>54%), and social behaviour (>40%), with a percentage of these individuals displaying more pronounced impairments in empathy (20%) and ToM (22%). Social cognition dispersion did not differ between groups. No significant correlations were found between social cognitive domains and mood, sleep, and neurocognitive outcomes.

Conclusions:

Significant group-level social cognition deficits were observed in the premanifest HD cohort. However, our profiling method showed that only a small percentage of these individuals experienced marked difficulties in social cognition, indicating the importance of individual-level assessments, particularly regarding future personalised treatments.
Perspectives on organic transition from transitioning farmers and farmers who decided not to transition
Authors: Stephenson Garry , Gwin Lauren , Schreiner Chris , Brown Sarah
Published: May 2021

Despite continuous growth in demand for organic food and farm products, US domestic supply is not keeping pace. Increasing domestic supply requires, in part, that more farms transition to certified organic production. This in turn requires a better understanding of the transition process. This paper reports on a national survey of farmers transitioning to organic certification through participation in the United States Department of Agriculture's (USDA) Natural Resources Conservation Service (NRCS) Environmental Quality Incentives Program Organic Initiative (EQIP-OI). Our analysis focuses on what motivates farmers to undertake transition to organic certification and what obstacles they confront in the process. The survey population included farmers in the midst of the transition process and farmers who began transition but decided not to pursue organic farming, allowing us to compare both groups to farmers who successfully transitioned to certified organic. Because farmers do not control all of the factors that influence their success, we use a ‘spheres of influence’ framework to analyze obstacles at four levels: the farm, local and regional infrastructure, the marketplace and policy. Our results improve our understanding of the transition process and apply to a wide range of stakeholders and service providers who support farmers in different ways, through crop research, infrastructure development, market development and policy.
WRF Gray‐Zone Simulations of Precipitation Over the Middle‐East and the UAE: Impacts of Physical Parameterizations and Resolution
Authors: Taraphdar Sourav , Pauluis Olivier M. , Xue Lulin , Liu Changhai , Rasmussen Roy , Ajayamohan R. S. , Tessendorf Sarah , Jing Xiaoqin , Chen Sisi , Grabowski Wojciech W.
Published: May 2021

Several single‐year‐long (2017) simulations with different configurations of the Weather Research and Forecasting (WRF) model over the United Arab Emirates (UAE) and the Middle‐East at the convective gray‐zone resolution (9 km) are evaluated in their ability to capture the temporal and spatial distributions of precipitation. Annual rainfall over the Middle‐East is dominated by wintertime precipitation and is mostly initiated by the frontal systems intrusion. WRF at 9 km resolution shows good skill in capturing the synoptic and meso‐scale precipitation distributions. The aerosol‐aware Thompson microphysics scheme outperforms the WRF double moment 6 class microphysics by about 20% in annual mean precipitation over the Middle‐East. Different Planetary Boundary Layer (PBL) physics leads to large differences in the annual rainfall over both the Middle‐East (about 30%) and the UAE (about 45%). The Quasi‐Normal Scale Elimination (QNSE) PBL scheme produces stronger precipitation than the Asymmetrical Convective Model and is in better agreement with observations. This difference is attributed to the former scheme producing a warmer and moister lower‐level atmosphere that builds more substantial instability. Regions of stronger instability also depict decreases in lifting condensation level heights and increases in boundary layer height, suggesting that the boundary layer reaching the cloud base helps to trigger the convection and increase precipitation. Refinement in grid spacing (5 km) marginally improves the summertime precipitation over the Middle‐East but significantly increases the computational cost. Current study also indicates that gray‐zone simulations can perform as good as convection‐permitting simulations by carefully choosing the right model physics packages for the synoptic and meso‐scale precipitation.
Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas
Authors: Hübschmann Daniel , Kleinheinz Kortine , Wagener Rabea , Bernhart Stephan H. , López Cristina , Toprak Umut H. , Sungalee Stephanie , Ishaque Naveed , Kretzmer Helene , Kreuz Markus , Waszak Sebastian M. , Paramasivam Nagarajan , Ammerpohl Ole , Aukema Sietse M. , Beekman Renée , Bergmann Anke K. , Bieg Matthias , Binder Hans , Borkhardt Arndt , Borst Christoph , Brors Benedikt , Bruns Philipp , Carrillo de Santa Pau Enrique , Claviez Alexander , Doose Gero , Haake Andrea , Karsch Dennis , Haas Siegfried , Hansmann Martin-Leo , Hoell Jessica I. , Hovestadt Volker , Huang Bingding , Hummel Michael , Jäger-Schmidt Christina , Kerssemakers Jules N. A. , Korbel Jan O. , Kube Dieter , Lawerenz Chris , Lenze Dido , Martens Joost H. A. , Ott German , Radlwimmer Bernhard , Reisinger Eva , Richter Julia , Rico Daniel , Rosenstiel Philip , Rosenwald Andreas , Schillhabel Markus , Stilgenbauer Stephan , Stadler Peter F. , Martín-Subero José I. , Szczepanowski Monika , Warsow Gregor , Weniger Marc A. , Zapatka Marc , Valencia Alfonso , Stunnenberg Hendrik G. , Lichter Peter , Möller Peter , Loeffler Markus , Eils Roland , Klapper Wolfram , Hoffmann Steve , Trümper Lorenz ,   ICGC MMML-Seq consortium,   ICGC DE-Mining consortium,   BLUEPRINT consortium, Küppers Ralf , Schlesner Matthias , Siebert Reiner
Published: May 2021

B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR. We show that not only SHM, but presumably also CSR causes off-target mutations in non-IG genes. Kataegis clusters with high mutational density mainly affected early replicating regions and were enriched for SHM- and CSR-mediated off-target mutations. Moreover, they often co-occurred in loci physically interacting in the nucleus, suggesting that mutation hotspots promote increased mutation targeting of spatially co-localized loci (termed hypermutation by proxy). Only around 1% of somatic small variants were in protein coding sequences, but in about half of the driver genes, a contribution of B-cell specific mutational processes to their mutations was found. The B-cell-specific mutational processes contribute to both lymphoma initiation and intratumoral heterogeneity. Overall, we demonstrate that mutational processes involved in the development of gcBCL are more complex than previously appreciated, and that B cell-specific mutational processes contribute via diverse mechanisms to lymphomagenesis.
Population dynamics of microbial cross-feeding are determined by co-localization probabilities and cooperation-independent cheater growth
Authors: van Tatenhove-Pel Rinke J , de Groot Daan H , Bisseswar Anjani S , Teusink Bas , Bachmann Herwig
Published: May 2021

As natural selection acts on individual organisms the evolution of costly cooperation between microorganisms is an intriguing phenomenon. Introduction of spatial structure to privatize exchanged molecules can explain the evolution of cooperation. However, in many natural systems cells can also grow to low cell concentrations in the absence of these exchanged molecules, thus showing “cooperation-independent background growth”. We here serially propagated a synthetic cross-feeding consortium of lactococci in the droplets of a water-in-oil emulsion, essentially mimicking group selection with varying founder population sizes. The results show that when the growth of cheaters completely depends on cooperators, cooperators outcompete cheaters. However, cheaters outcompete cooperators when they can independently grow to only ten percent of the consortium carrying capacity. This result is the consequence of a probabilistic effect, as low founder population sizes in droplets decrease the frequency of cooperator co-localization. Cooperator-enrichment can be recovered by increasing the founder population size in droplets to intermediate values. Together with mathematical modelling our results suggest that co-localization probabilities in a spatially structured environment leave a small window of opportunity for the evolution of cooperation between organisms that do not benefit from their cooperative trait when in isolation or form multispecies aggregates.
Synaptic metaplasticity in binarized neural networks
Authors: Laborieux Axel , Ernoult Maxence , Hirtzlin Tifenn , Querlioz Damien
Published: May 2021

While deep neural networks have surpassed human performance in multiple situations, they are prone to catastrophic forgetting: upon training a new task, they rapidly forget previously learned ones. Neuroscience studies, based on idealized tasks, suggest that in the brain, synapses overcome this issue by adjusting their plasticity depending on their past history. However, such “metaplastic” behaviors do not transfer directly to mitigate catastrophic forgetting in deep neural networks. In this work, we interpret the hidden weights used by binarized neural networks, a low-precision version of deep neural networks, as metaplastic variables, and modify their training technique to alleviate forgetting. Building on this idea, we propose and demonstrate experimentally, in situations of multitask and stream learning, a training technique that reduces catastrophic forgetting without needing previously presented data, nor formal boundaries between datasets and with performance approaching more mainstream techniques with task boundaries. We support our approach with a theoretical analysis on a tractable task. This work bridges computational neuroscience and deep learning, and presents significant assets for future embedded and neuromorphic systems, especially when using novel nanodevices featuring physics analogous to metaplasticity.
Loss of Ambra1 promotes melanoma growth and invasion
Authors: Di Leo Luca , Bodemeyer Valérie , Bosisio Francesca M. , Claps Giuseppina , Carretta Marco , Rizza Salvatore , Faienza Fiorella , Frias Alex , Khan Shawez , Bordi Matteo , Pacheco Maria P. , Di Martino Julie , Bravo-Cordero Jose J. , Daniel Colin J. , Sears Rosalie C. , Donia Marco , Madsen Daniel H. , Guldberg Per , Filomeni Giuseppe , Sauter Thomas , Robert Caroline , De Zio Daniela , Cecconi Francesco
Published: May 2021

Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma.
Data-driven reaction coordinate discovery in overdamped and non-conservative systems: application to optical matter structural isomerization
Authors: Chen Shiqi , Peterson Curtis W. , Parker John A. , Rice Stuart A. , Ferguson Andrew L. , Scherer Norbert F.
Published: May 2021

Optical matter (OM) systems consist of (nano-)particle constituents in solution that can self-organize into ordered arrays that are bound by electrodynamic interactions. They also manifest non-conservative forces, and the motions of the nano-particles are overdamped; i.e., they exhibit diffusive trajectories. We propose a data-driven approach based on principal components analysis (PCA) to determine the collective modes of non-conservative overdamped systems, such as OM structures, and harmonic linear discriminant analysis (HLDA) of time trajectories to estimate the reaction coordinate for structural transitions. We demonstrate the approach via electrodynamics-Langevin dynamics simulations of six electrodynamically-bound nanoparticles in an incident laser beam. The reaction coordinate we discover is in excellent accord with a rigorous committor analysis, and the identified mechanism for structural isomerization is in very good agreement with the experimental observations. The PCA-HLDA approach to data-driven discovery of reaction coordinates can aid in understanding and eventually controlling non-conservative and overdamped systems including optical and active matter systems.
Regression plane concept for analysing continuous cellular processes with machine learning
Authors: Szkalisity Abel , Piccinini Filippo , Beleon Attila , Balassa Tamas , Varga Istvan Gergely , Migh Ede , Molnar Csaba , Paavolainen Lassi , Timonen Sanna , Banerjee Indranil , Ikonen Elina , Yamauchi Yohei , Ando Istvan , Peltonen Jaakko , Pietiäinen Vilja , Honti Viktor , Horvath Peter
Published: May 2021

Biological processes are inherently continuous, and the chance of phenotypic discovery is significantly restricted by discretising them. Using multi-parametric active regression we introduce the Regression Plane (RP), a user-friendly discovery tool enabling class-free phenotypic supervised machine learning, to describe and explore biological data in a continuous manner. First, we compare traditional classification with regression in a simulated experimental setup. Second, we use our framework to identify genes involved in regulating triglyceride levels in human cells. Subsequently, we analyse a time-lapse dataset on mitosis to demonstrate that the proposed methodology is capable of modelling complex processes at infinite resolution. Finally, we show that hemocyte differentiation in Drosophila melanogaster has continuous characteristics.
CopulaNet: Learning residue co-evolution directly from multiple sequence alignment for protein structure prediction
Authors: Ju Fusong , Zhu Jianwei , Shao Bin , Kong Lupeng , Liu Tie-Yan , Zheng Wei-Mou , Bu Dongbo
Published: May 2021

Residue co-evolution has become the primary principle for estimating inter-residue distances of a protein, which are crucially important for predicting protein structure. Most existing approaches adopt an indirect strategy, i.e., inferring residue co-evolution based on some hand-crafted features, say, a covariance matrix, calculated from multiple sequence alignment (MSA) of target protein. This indirect strategy, however, cannot fully exploit the information carried by MSA. Here, we report an end-to-end deep neural network, CopulaNet, to estimate residue co-evolution directly from MSA. The key elements of CopulaNet include: (i) an encoder to model context-specific mutation for each residue; (ii) an aggregator to model residue co-evolution, and thereafter estimate inter-residue distances. Using CASP13 (the 13th Critical Assessment of Protein Structure Prediction) target proteins as representatives, we demonstrate that CopulaNet can predict protein structure with improved accuracy and efficiency. This study represents a step toward improved end-to-end prediction of inter-residue distances and protein tertiary structures.
Protein analysis of extracellular vesicles to monitor and predict therapeutic response in metastatic breast cancer
Authors: Tian Fei , Zhang Shaohua , Liu Chao , Han Ziwei , Liu Yuan , Deng Jinqi , Li Yike , Wu Xia , Cai Lili , Qin Lili , Chen Qinghua , Yuan Yang , Liu Yi , Cong Yulong , Ding Baoquan , Jiang Zefei , Sun Jiashu
Published: May 2021

Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). However, the analysis of EV protein markers has been confounded by the presence of soluble protein counterparts in peripheral blood. Here we use a rapid, sensitive, and low-cost thermophoretic aptasensor (TAS) to profile cancer-associated protein profiles of plasma EVs without the interference of soluble proteins. We show that the EV signature (a weighted sum of eight EV protein markers) has a high accuracy (91.1 %) for discrimination of MBC, non-metastatic breast cancer (NMBC), and healthy donors (HD). For MBC patients undergoing therapies, the EV signature can accurately monitor the treatment response across the training, validation, and prospective cohorts, and serve as an independent prognostic factor for progression free survival in MBC patients. Together, this work highlights the potential clinical utility of EVs in management of MBC.
Effect of bisphenol A on alterations of ICAM-1 and HLA-G genes expression and DNA methylation profiles in cumulus cells of infertile women with poor response to ovarian stimulation
Authors: Aftabsavad Somayeh , Noormohammadi Zahra , Moini Ashraf , Karimipoor Morteza
Published: May 2021

This study aimed to investigate the relationship between follicular fluid Bisphenol A (BPA) concentrations with alterations of ICAM-1 and HLA-G genes and proteins expression as well as methylation profiles in the cumulus cells of poor ovarian response (POR) women based on their healthy lifestyle habit. Eighty women under the age of 35 were divided into two groups: 1—POR without using plastic containers (n = 40) and 2—POR with using plastic containers (n = 40). The ICAM-1 and HLA-G genes and protein expressions were examined by the quantitative PCR and western blotting technique. The methylation pattern was investigated by the methylation-specific PCR. Total BPA in follicular fluid was measured with high-performance liquid chromatography technique and the detection limit was 1.14 ng/ml. ICAM-1 and HLA-G genes were differentially expressed between the two groups studied. ICAM-1, HLA-G genes, and protein expressions in group 1 were up-regulated compared to the second group (P < 0.05). While DNA methylation status in group 1 were decreased compared to the other group (P < 0.05). The concentration of BPA in the follicular fluid of group 1 was lower compared to the second group (P < 0.05). The oocyte quality and clinical pregnancy ratio showed significantly higher in group 1 than in the other ones (P < 0.05). The alteration of ICAM-1 and HLA-G gene expressions in POR women is probably related to BPA concentration. As a result Lifestyle habits may also affect the methylation pattern and protein levels in the cumulus cells of POR women. Additionally, lifestyle habits may be considered as a marker for ovulation, oocyte maturation, preimplantation, and clinical pregnancy process.
Community composition and functional prediction of prokaryotes associated with sympatric sponge species of southwestern Atlantic coast
Authors: Hardoim C. C. P. , Ramaglia A. C. M. , Lôbo-Hajdu G. , Custódio M. R.
Published: May 2021

Prokaryotes contribute to the health of marine sponges. However, there is lack of data on the assembly rules of sponge-associated prokaryotic communities, especially for those inhabiting biodiversity hotspots, such as ecoregions between tropical and warm temperate southwestern Atlantic waters. The sympatric species Aplysina caissara, Axinella corrugata, and Dragmacidon reticulatum were collected along with environmental samples from the north coast of São Paulo (Brazil). Overall, 64 prokaryotic phyla were detected; 51 were associated with sponge species, and the dominant were Proteobacteria, Bacteria (unclassified), Cyanobacteria, Crenarchaeota, and Chloroflexi. Around 64% and 89% of the unclassified operational taxonomical units (OTUs) associated with Brazilian sponge species showed a sequence similarity below 97%, with sequences in the Silva and NCBI Type Strain databases, respectively, indicating the presence of a large number of unidentified taxa. The prokaryotic communities were species-specific, ranging 56%–80% of the OTUs and distinct from the environmental samples. Fifty-four lineages were responsible for the differences detected among the categories. Functional prediction demonstrated that Ap. caissara was enriched for energy metabolism and biosynthesis of secondary metabolites, whereas D. reticulatum was enhanced for metabolism of terpenoids and polyketides, as well as xenobiotics’ biodegradation and metabolism. This survey revealed a high level of novelty associated with Brazilian sponge species and that distinct members responsible from the differences among Brazilian sponge species could be correlated to the predicted functions.
Effects of urethane and isoflurane on the sensory evoked response and local blood flow in the early postnatal rat somatosensory cortex
Authors: Shumkova Viktoria , Sitdikova Violetta , Rechapov Ildar , Leukhin Alexey , Minlebaev Marat
Published: May 2021

Functional studies in the central nervous system are often conducted using anesthesia. While the dose-dependent effects of anesthesia on neuronal activity have been extensively characterized in adults, little is known about the effects of anesthesia on cortical activity and cerebral blood flow in the immature central nervous system. Substitution of electrophysiological recordings with the less-invasive technique of optical intrinsic signal imaging (OIS) in vivo allowed simultaneous recordings of sensory-evoked functional response and local blood flow changes in the neonatal rat barrel cortex. Using OIS we characterize the effects of two widely used anesthetics—urethane and isoflurane. We found that both anesthetics suppressed the sensory-evoked optical intrinsic signal in a dose-dependent manner. Dependence of the cortical response suppression matched the exponential decay model. At experimental levels of anesthesia, urethane affected the evoked cortical response less than isoflurane, which is in agreement with the results of electrophysiological recordings demonstrated by other authors. Changes in oxygenation and local blood flow also showed negative correlation with both anesthetics. The high similarity in immature patterns of activity recorded in different regions of the developing cortex suggested similar principles of development regardless of the cortical region. Therefore the indicated results should be taken into account during functional explorations in the entire developing cortex. Our results also point to urethane as the anesthetic of choice in non-survival experimental recordings in the developing brain as it produces less prominent impairment of cortical neuronal activity in neonatal animals.
The epidemiological characteristics and effectiveness of countermeasures to contain coronavirus disease 2019 in Ningbo City, Zhejiang Province, China
Authors: Lao Xuying , Luo Li , Lei Zhao , Fang Ting , Chen Yi , Liu Yuhui , Ding Keqin , Zhang Dongliang , Wang Rong , Zhao Zeyu , Rui Jia , Zhu Yuanzhao , Xu Jingwen , Wang Yao , Yang Meng , Yi Bo , Chen Tianmu
Published: May 2021

A novel coronavirus (SARS-CoV-2) has spread worldwide and led to high disease burden around the world. This study aimed to explore the key parameters of SARS-CoV-2 infection and to assess the effectiveness of interventions to control the coronavirus disease 2019 (COVID-19). A susceptible—exposed—infectious—asymptomatic—recovered (SEIAR) model was developed for the assessment. The information of each confirmed case and asymptomatic infection was collected from Ningbo Center for Disease Control and Prevention (CDC) to calculate the key parameters of the model in Ningbo City, China. A total of 157 confirmed COVID-19 cases (including 51 imported cases and 106 secondary cases) and 30 asymptomatic infections were reported in Ningbo City. The proportion of asymptomatic infections had an increasing trend. The proportion of elder people in the asymptomatic infections was lower than younger people, and the difference was statistically significant (Fisher’s Exact Test, P = 0.034). There were 22 clusters associated with 167 SARS-CoV-2 infections, among which 29 cases were asymptomatic infections, accounting for 17.37%. We found that the secondary attack rate (SAR) of asymptomatic infections was almost the same as that of symptomatic cases, and no statistical significance was observed (χ2 = 0.052, P = 0.819) by Kruskal–Wallis test. The effective reproduction number (Reff) was 1.43, which revealed that the transmissibility of SARS-CoV-2 was moderate. If the interventions had not been strengthened, the duration of the outbreak would have lasted about 16 months with a simulated attack rate of 44.15%. The total attack rate (TAR) and duration of the outbreak would increase along with the increasing delay of intervention. SARS-CoV-2 had moderate transmissibility in Ningbo City, China. The proportion of asymptomatic infections had an increase trend. Asymptomatic infections had the same transmissibility as symptomatic infections. The integrated interventions were implemented at different stages during the outbreak, which turned out to be exceedingly effective in China.
Determinants of peripapillary retinal nerve fiber layer’s grayscale value in normal eyes by spectral domain optical coherence tomography
Authors: Xie Xiaolin , Chen Binyao , Yang Jianling , Huang Chukai , Qiu Kunliang , Zheng Ce , Zhang Mingzhi
Published: May 2021

To determine and evaluate the distribution, variation, and determinants of peripapillary retinal nerve fiber layer (pRNFL) grayscale value with spectral-domain optical coherence tomography (SD-OCT) in normal eyes. In this cross-sectional study, three hundred ninety-seven normal eyes from 397 healthy Chinese adults aged 18–80 were consecutively recruited from a tertiary eye care center. An SD-OCT instrument took pRNFL imaging. We used a customized software to measure pRNFL parameters, including thickness and grayscale value. Univariable and multiple linear regression analyses were performed to examine the relationship between pRNFL grayscale value with ocular (e.g., axial length [A.L.], spherical equivalent [S.E.], intraocular pressure [IOP]), and systemic (e.g., age, sex) factors. A total of 397 eyes from 397 healthy subjects were included in the final analysis with mean (± SD) age 44.63 ± 16.43 years (range 18–80 years) and 196 (49.4%) males. The mean average of pRNFL grayscale value and thickness 164.82 ± 5.69 and 106.68 ± 8.89 μm, respectively. pRNFL grayscale value in nasal sectors (163.26 ± 9.31) was significantly lower comparing those in all other five sectors (all with p < 0.001)]. In multivariable analysis, average pRNFL grayscale value was independently correlated to older age (β = − 0.053, p = 0.002), longer axial length (β = − 0.664, p = 0.003), lower RPE grayscale value (β = 0.372, p < 0.001) and lower ImageQ (β = 0.658, p < 0.001). In this study, we provided normative SD-OCT data on the pRNFL grayscale value profile in nonglaucomatous eyes. Lower average pRNFL grayscale value was independently correlated to older age, longer axial length, lower RPE grayscale value, and lower ImageQ. These determinants should be considered when interpreting pRNFL grayscale value in glaucoma assessment.
A cautionary tale about using the apparent carbon accumulation rate (aCAR) obtained from peat cores
Authors: Young Dylan M. , Baird Andy J. , Gallego-Sala Angela V. , Loisel Julie
Published: May 2021

The carbon (C) accumulation histories of peatlands are of great interest to scientists, land users and policy makers. Because peatlands contain more than 500 billion tonnes of C, an understanding of the fate of this dynamic store, when subjected to the pressures of land use or climate change, is an important part of climate-change mitigation strategies. Information from peat cores is often used to recreate a peatland’s C accumulation history from recent decades to past millennia, so that comparisons between past and current rates can be made. However, these present day observations of peatlands’ past C accumulation rates (known as the apparent rate of C accumulation - aCAR) are usually different from the actual uptake or loss of C that occurred at the time (the true C balance). Here we use a simple peatland model and a more detailed ecosystem model to illustrate why aCAR should not be used to compare past and current C accumulation rates. Instead, we propose that data from peat cores are used with existing or new C balance models to produce reliable estimates of how peatland C function has changed over time.
A morphological analysis of activity-dependent myelination and myelin injury in transitional oligodendrocytes
Authors: Toth Eszter , Rassul Sayed Muhammed , Berry Martin , Fulton Daniel
Published: May 2021

Neuronal activity is established as a driver of oligodendrocyte (OL) differentiation and myelination. The concept of activity-dependent myelin plasticity, and its role in cognition and disease, is gaining support. Methods capable of resolving changes in the morphology of individual myelinating OL would advance our understanding of myelin plasticity and injury, thus we adapted a labelling approach involving Semliki Forest Virus (SFV) vectors to resolve and quantify the 3-D structure of OL processes and internodes in cerebellar slice cultures. We first demonstrate the utility of the approach by studying changes in OL morphology after complement-mediated injury. SFV vectors injected into cerebellar white matter labelled transitional OL (TOL), whose characteristic mixture of myelinating and non-myelinating processes exhibited significant degeneration after complement injury. The method was also capable of resolving finer changes in morphology related to neuronal activity. Prolonged suppression of neuronal activity, which reduced myelination, selectively decreased the length of putative internodes, and the proportion of process branches that supported them, while leaving other features of process morphology unaltered. Overall this work provides novel information on the morphology of TOL, and their response to conditions that alter circuit function or induce demyelination.
A novel RLIM/RNF12 variant disrupts protein stability and function to cause severe Tonne–Kalscheuer syndrome
Authors: Bustos Francisco , Espejo-Serrano Carmen , Segarra-Fas Anna , Toth Rachel , Eaton Alison J. , Kernohan Kristin D. , Wilson Meredith J. , Riley Lisa G. , Findlay Greg M.
Published: May 2021

Tonne–Kalscheuer syndrome (TOKAS) is an X-linked intellectual disability syndrome associated with variable clinical features including craniofacial abnormalities, hypogenitalism and diaphragmatic hernia. TOKAS is caused exclusively by variants in the gene encoding the E3 ubiquitin ligase gene RLIM, also known as RNF12. Here we report identification of a novel RLIM missense variant, c.1262A>G p.(Tyr421Cys) adjacent to the regulatory basic region, which causes a severe form of TOKAS resulting in perinatal lethality by diaphragmatic hernia. Inheritance and X-chromosome inactivation patterns implicate RLIM p.(Tyr421Cys) as the likely pathogenic variant in the affected individual and within the kindred. We show that the RLIM p.(Tyr421Cys) variant disrupts both expression and function of the protein in an embryonic stem cell model. RLIM p.(Tyr421Cys) is correctly localised to the nucleus, but is readily degraded by the proteasome. The RLIM p.(Tyr421Cys) variant also displays significantly impaired E3 ubiquitin ligase activity, which interferes with RLIM function in Xist long-non-coding RNA induction that initiates imprinted X-chromosome inactivation. Our data uncover a highly disruptive missense variant in RLIM that causes a severe form of TOKAS, thereby expanding our understanding of the molecular and phenotypic spectrum of disease severity.
Future changes to the upper ocean Western Boundary Currents across two generations of climate models
Authors: Sen Gupta Alex , Stellema Annette , Pontes Gabriel M. , Taschetto Andréa S. , Vergés Adriana , Rossi Vincent
Published: May 2021

Western Boundary Currents (WBCs) are important for the oceanic transport of heat, dissolved gases and nutrients. They can affect regional climate and strongly influence the dispersion and distribution of marine species. Using state-of-the-art climate models from the latest and previousClimate Model Intercomparison Projects, we evaluate upper ocean circulation and examine future projections, focusing on subtropical and low-latitude WBCs. Despite their coarse resolution, climate models successfully reproduce most large-scale circulation features with ensemble mean transports typically within the range of observational uncertainty, although there is often a large spread across the models and some currents are systematically too strong or weak. Despite considerable differences in model structure, resolution and parameterisations, many currents show highly consistent projected changes across the models. For example, the East Australian Current, Brazil Current and Agulhas Current extensions are projected to intensify, while the Gulf Stream, Indonesian Throughflow and Agulhas Current are projected to weaken. Intermodel differences in most future circulation changes can be explained in part by projected changes in the large-scale surface winds. In moving to the latest model generation, despite structural model advancements, we find little systematic improvement in the simulation of ocean transports nor major differences in the projected changes.
FoldAffinity: binding affinities from nDSF experiments
Authors: Niebling Stephan , Burastero Osvaldo , Bürgi Jérôme , Günther Christian , Defelipe Lucas A. , Sander Simon , Gattkowski Ellen , Anjanappa Raghavendra , Wilmanns Matthias , Springer Sebastian , Tidow Henning , García-Alai María
Published: May 2021

Differential scanning fluorimetry (DSF) using the inherent fluorescence of proteins (nDSF) is a popular technique to evaluate thermal protein stability in different conditions (e.g. buffer, pH). In many cases, ligand binding increases thermal stability of a protein and often this can be detected as a clear shift in nDSF experiments. Here, we evaluate binding affinity quantification based on thermal shifts. We present four protein systems with different binding affinity ligands, ranging from nM to high μM. Our study suggests that binding affinities determined by isothermal analysis are in better agreement with those from established biophysical techniques (ITC and MST) compared to apparent Kds obtained from melting temperatures. In addition, we describe a method to optionally fit the heat capacity change upon unfolding ($$\Delta {C}_{p}$$

Δ

C
p

) during the isothermal analysis. This publication includes the release of a web server for easy and accessible application of isothermal analysis to nDSF data.
The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
Authors: Tamiya Motohiro , Tamiya Akihiro , Okamoto Norio , Taniguchi Yoshihiko , Nishino Kazumi , Atagi Shinji , Hirashima Tomonori , Imamura Fumio , Kumagai Toru , Suzuki Hidekazu
Published: May 2021

The most frequent mechanism of resistance after 1st/2nd-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is secondary point mutation Thr790Met (T790M) in EGFR. Afatinib followed by osimertinib (Afa group) may provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-G EGFR-TKI followed by osimertinib (1st-G group). We studied 111 consecutive NSCLC patients with T790M mutation treated with osimertinib after progression following 1st/2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed the ratio of T790M to EGFR-activating mutation (T790M ratio) in post EGFR-TKI resistance re-biopsy tissue using droplet digital polymerase chain reaction. And investigated whether afatinib purified the T790M mutation more than 1st-G EGFR-TKI. Among 60 patients with preserved re-biopsy tissue, we analyzed 38 having adequate DNA content. The response rate in Afa group was 81.8% (n = 11) and 1st-G group was 85.2% (n = 27). The mean T790M ratio in total population was 0.3643. The ratio in those with response to osimertinib was significantly higher than in the non-responders (0.395, 0.202; p = 0.0231) and was similar in Afa and 1st-G group (0.371, 0.362; p = 0.9693). T790M ratio significantly correlated with osimertinib response and was similar between the 1st/2nd-G EGFR-TKIs in 1st/2nd-G EGFR-TKI-refractory tumors.
Enabling exercise prescription for survivors of cancer
Authors: White Katherine R. , Lu Jana , Ibrahim Zara , Furth Priscilla A.
Published: May 2021

Although exercise is widely recommended for survivors of cancer, readily implementable approaches for evaluating exercise tolerance enabling exercise prescriptions at appropriate levels of cardiovascular exertion are not always available. We evaluated the utility of modified Harvard Step tests within the context of a standard physical examination for fitness evaluation and exercise prescription for survivors of cancer across a range of age, BMI and exercise history. While 52% of presenting individuals with a past cancer diagnosis were able to complete a 3-min test at pace with a reduced 9-in. step, adoption of self-determined pacing, test duration and completion on a flat surface enabled relative fitness rating and appropriate exercise prescription for the remaining survivors. Younger age and more vigorous exercise histories correlated with completion of the standard 3-min test at pace, but all 9-in. formats led to exercise prescriptions more vigorous than current activity. The physical examination setting expedited inclusion of core and specific muscle group strength testing. The approach is adaptable to a range of health care settings, providers, and patients, providing a shared opportunity for providers and patients to evaluate exercise tolerance. It can be used to further expand incorporation of exercise testing and prescription into routine care.
The use of spent coffee grounds and spent green tea leaves for the removal of cationic dyes from aqueous solutions
Authors: Jóźwiak Tomasz , Filipkowska Urszula , Struk-Sokołowska Joanna , Bryszewski Kamil , Trzciński Karol , Kuźma Joanna , Ślimkowska Monika
Published: May 2021

This study aimed to examine sorption effectiveness of cationic dyes: Basic Red 46 (BR46) and Basic Violet 10 (BV10) onto spent coffee ground (CG) and spent green tea leaves (GTL). The scope of the study included, i.a.: sorbent FTIR spectra analysis, determination of pH effect on dye sorption effectiveness, analysis of dye sorption kinetics, and determination of maximal sorption capacity of the sorbents. The effectiveness of BR46 sorption on the sorbents tested was the highest at pH 6 and that of BV10 at pH 3. Both sorbents caused changes in solution pH during the sorption process, due to the system tending to reach the pH value approximating the pHZPC (pHPZC = 7.55 for CG and pHPZC = 7.05 for GTL). The time needed to reach BR46 and BV10 sorption equilibrium onto CG and GTL ranged from 180 to 240 min. The intramolecular diffusion model demonstrated that the sorption of cationic dyes onto CG and GTL proceeded in three phases differing in the intensity and duration. The maximal sorption capacity of CG reached 179.4 mg/g for BR46 and 59.3 mg/g for BV10. The sorption capacity of GTL was lower and reached 58.0 mg/g for BR46 and 26.7 mg/g for BV10.
Aerodynamics of the newly approved football for the English Premier League 2020–21 season
Authors: Asai Takeshi , Hong Sungchan
Published: May 2021

Footballs are typically constructed with 32 panels. Recently, the number of panels has been successively reduced to 14, 8, and 6 panels, and official balls have been adopted with complex panel shapes and aerodynamics that differ from those of 32-panel balls. The official ball for the 2020–21 season of the English Premier League comprises just four panels with a complex panel shape and surface groove design; however, its aerodynamics have not yet been clarified. This study aims to clarify the aerodynamic characteristics (drag, side force, lift force, their deviations, and critical Reynolds number) of the new 4-panel ball (Flight 2020, Nike) in comparison to a 6-panel ball (Tsubasa 2020, Adidas) and conventional 32-panel ball (Pelada 2020, Molten) using a wind tunnel test, surface design measurement, and a simple 2D flight simulation. The results showed that Flight 2020 has greater surface roughness and smaller critical Reynolds number than Pelada 2020 and Tsubasa 2020, resulting to its marginally greater drag force in the supercritical region, and slightly smaller fluctuations of the side and lift forces. Furthermore, Flight with a symmetrical orientation exhibits a significantly higher drag coefficient in the supercritical region, suggesting its greater air resistance during flight under this condition.
Thermal decomposition of ammonium perchlorate-based molecular perovskite from TG-DSC-FTIR-MS and ab initio molecular dynamics
Authors: Zhai Pengfei , Shi Chengying , Zhao Shengxiang , Liu Wenbin , Wang Wenxin , Yao Lina
Published: May 2021

Organic components realize a more efficient autocatalytic chain propagation for degradation of ClO4− in the thermal decomposition process of DAP.
Bio-mass derived functionalized graphene aerogel: a sustainable approach for the removal of multiple organic dyes and their mixtures
Authors: Kaushik Jaidev , Kumar Vishrant , Garg Anjali Kumari , Dubey Prashant , Tripathi Kumud Malika , Sonkar Sumit Kumar
Published: May 2021

Herein, fabrication of a functionalized graphene aerogel (f-GA) from a biomass (pear fruit)-derived graphene aerogel (GA) is described. f-GA is showing better adsorption capacity towards CV, MB and RhB dyes than GA and activated charcoal.
Latin American databases of natural products: biodiversity and drug discovery against SARS-CoV-2
Authors: Núñez Marvin J. , Díaz-Eufracio Bárbara I. , Medina-Franco José L. , Olmedo Dionisio A.
Published: May 2021

We performed a cheminfomatic analysis of four databases in Latin America and evaluated its potential in silico against SARS-CoV-2.
Facial controlled synthesis of Pt/MnO2 catalysts with high efficiency for VOCs combustion
Authors: Hu Jing , Gao Xiangling , Fan Qingfeng , Gao Xingmin
Published: May 2021

Two sets of experiments were initially implemented to explore the best impregnation method and the best morphology substrate.
Sustainable aromatic polyesters with 1,5-disubstituted indole units
Authors: Wang Ping , Zhang Baozhong
Published: May 2021

1,5-disubstituted indole was investigated as new sustainable aromatic units for polyesters to enhance thermal stability.
Improving light absorption and photoelectrochemical performance of thin-film photoelectrode with a reflective substrate
Authors: Xiao Jingran , Peng Lingling , Gao Le , Zhong Jun , Huang Zhongliang , Yuan Enxian , Srinivasapriyan Vijayan , Zhou Shu-Feng , Zhan Guowu
Published: May 2021

The charge separation/transport efficiency is relatively high in thin-film hematite photoanodes in which the distance for charge transport is short, but simultaneously the high loss of light absorption due to transmission is confronted.