bluuebunny/crossref_metadata_2025 huggingface dataset:
ENHANCED GRAVITROPISM 2encodes a STERILE ALPHA MOTIVE containing protein that controls root growth angle in barley and wheat
Authors: Kirschner Gwendolyn K. , Rosignoli Serena , Vardanega Isaia , Guo Li , Imani Jafargholi , Altmüller Janine , Milner Sara G. , Balzano Raffaella , Nagel Kerstin A. , Pflugfelder Daniel , Forestan Cristian , Bovina Riccardo , Koller Robert , Stöcker Tyll G. , Mascher Martin , Simmonds James , Uauy Cristobal , Schoof Heiko , Tuberosa Roberto , Salvi Silvio , Hochholdinger Frank
Published: January 2021

The root growth angle defines how roots grow towards the gravity vector and is among the most important determinants of root system architecture. It controls water uptake capacity, nutrient use efficiency, stress resilience and as a consequence yield of crop plants. We demonstrated that theegt2(enhanced gravitropism 2) mutant of barley exhibits steeper root growth of seminal and lateral roots and an auxin independent higher responsiveness to gravity compared to wild type plants. We cloned theEGT2gene by a combination of bulked segregant analysis and whole genome sequencing. Subsequent validation experiments by an independent CRISPR/Cas9 mutant allele demonstrated thategt2encodes a STERILE ALPHA MOTIF domain containing protein.In situhybridization experiments illustrated thatEGT2is expressed from the root cap to the elongation zone. Subcellular localization experiments revealed thatEGT2localizes to the nucleus and cytoplasm. We demonstrated the evolutionary conserved role ofEGT2in root growth angle control between barley and wheat by knocking out theEGT2orthologs in the A and B genomes of tetraploid durum wheat. By combining laser capture microdissection with RNA-seq, we observed that seven expansin genes were transcriptionally downregulated in the elongation zone. This is consistent with a role ofEGT2in this region of the root where the effect of gravity sensing is executed by differential cell elongation. Our findings suggest thatEGT2is an evolutionary conserved regulator of root growth angle in barley and wheat that could be a valuable target for root-based crop improvement strategies in cereals.

Significance Statement

To date the potential of utilizing root traits in plant breeding remains largely untapped. In this study we cloned and characterized theENHANCED GRAVITROPISM2(EGT2) gene of barley that encodes a STERILE ALPHA MOTIF domain containing protein. We demonstrated thatEGT2is a key gene of root growth angle regulation in response to gravity which is conserved in barley and wheat and could be a promising target for crop improvement in cereals.
Why are viral genomes so fragile? The bottleneck hypothesis
Authors: Merleau Nono S. C. , Pénisson Sophie , Gerrish Philip J. , Elena Santiago F. , Smerlak Matteo
Published: January 2021

If they undergo new mutations at each replication cycle, why are RNA viral genomes so fragile, with most mutations being either strongly deleterious or lethal? Here we provide theoretical evidence for the hypothesis that genetic fragility evolves as a consequence of the pervasive population bottlenecks experienced by viral populations at various stages of their life cycles. Modelling within-host viral populations as multi-type branching processes, we show that mutational fragility lowers the rate at which Muller’s ratchet clicks and increases the survival probability through multiple bottlenecks. In the context of a susceptible-exposed-infectious-recovered epidemiological model, we find that the attack rate of fragile viral strains can exceed that of more robust strains, particularly at low infectivities and high mutation rates. Our findings highlight the importance of demographic events such as transmission bottlenecks in shaping the genetic architecture of viral pathogens.
Variation analysis of SARS-CoV-2 complete sequences from Iran
Authors: Moradi Jale , Moghoofei Mohsen , Alvandi Amir Houshang , Abiri Ramin
Published: January 2021

The SARS-CoV-2 is a new emerging coronavirus initially reported in China at the late December 2019 and rapidly spread to the whole of the world. To date, 1261903 total case and 55830 deaths are reported from Iran as 8 January. In this study, we investigated all the complete sequences of SARS-CoV-2 that publicly reported from Iran. Twenty-four sequences between March to September 2020 were analyzed to identify genome variations and phylogenetic relationships. Furthermore, we assessed the amino acid changes related to the spike glycoprotein as an important viral factor associated with the entry to the host cells and as a vaccine target. Most of the variations are occurred in the ORF1ab, S, N, intergenic and ORF7 regions. The analysis of spike protein mutations demonstrated that D614G mutation could be detected from the May and beyond. Phylogenetic analysis showed that most of the circulated viruses in Iran are belong to the B.4 lineage. Although, we found a limited number of variants associated to the B.1 lineage carrying D614G mutation. Furthermore, we detected a variant characterize as the B.1.36 lineage with sixteen mutations in the spike protein region. This study showed the frequency of the viral populations in Iran as September, therefore, there is an emergent need to genomic surveillance to track viral lineage shift in the country beyond the September. These data would help to predict future situation and apply better strategy to control of the pandemic.
A targeted and tuneable DNA damage tool using CRISPR/Cas9
Authors: Emmanouilidis Ioannis , Fili Natalia , Cook Alexander W. , Hari-Gupta Yukti , dos Santos Ália , Wang Lin , Martin-Fernandez Marisa , Ellis Peter J.I. , Toseland Christopher P.
Published: January 2021

Mammalian cells are constantly subjected to a variety of DNA damaging events that lead to the activation of DNA repair pathways. Understanding the molecular mechanisms of the DNA damage response allows the development of therapeutics which target elements of these pathways.

Double-Strand Breaks (DSB) are particularly deleterious to cell viability and genome stability. Typically, DSB repair is studied using DNA damaging agents such as ionising irradiation or genotoxic drugs. These induce random lesions at non-predictive genome sites, where damage dosage is difficult to control. Such interventions are unsuitable for studying how different DNA damage recognition and repair pathways are invoked at specific DSB sites in relation to the local chromatin state.

The RNA-guided Cas9 (CRISPR associated protein 9) endonuclease enzyme, is a powerful tool to mediate targeted genome alterations. Cas9-based genomic intervention is attained through DSB formation in the genomic area of interest. Here, we have harnessed the power to induce DSBs at defined quantities and locations across the human genome, using custom-designed promiscuous guide RNAs, based onin silicopredictions. This was achieved using electroporation of recombinant Cas9-guide complex which provides a generic, low-cost and rapid methodology for inducing controlled DNA damage in cell culture models.
Long range, high-gamma phase coherence in the human brain during overt and covert speech
Authors: Valiante Taufik A. , Garic Bojan
Published: January 2021

Using intracranial electroencephalography (iEEG) in patients undergoing diagnostic workup for epilepsy, we show that during reading, phase coherent high-gamma activity emerges between spatially distant regions of proven involvement in vocalization. Using the novel metric of “phase-dependent power-causal correlations”, causal interactions were shown to be maximal at high-gamma frequencies, and displayed stronger correlations to power fluctuations near the optimal time delay, with this delay potentially accounted for by axonal conduction. We conclude that high-gamma activity may represents propagated, directed, large-scale integration between task related regions of the human brain.
De novogenome assembly of the land snailCandidula unifasciata(Mollusca: Gastropoda)
Authors: Chueca Luis J. , Schell Tilman , Pfenninger Markus
Published: January 2021

Among all molluscs, land snails are an economically and scientifically interesting group comprising edible species, alien species and agricultural pests. Yet, despite its high diversity, the number of whole genomes publicly available is still scarce. Here, we present the draft genome assembly of the land snailCandidula unifasciata, a widely distributed species along central Europe, which belongs to Geomitridae family, a group highly diversified in the Western-Palearctic region. We performed a whole genome sequencing, assembly and annotation of an adult specimen based on PacBio and Oxford Nanopore long read sequences as well as Illumina data. A genome of about 1.29 Gb was generated with a N50 length of 246 kb. More than 60% of the assembled genome was identified as repetitive elements, and 22,464 protein-coding genes were identified in the genome, where the 62.27% were functionally annotated. This is the first assembled and annotated genome for a geometrid snail and will serve as reference for further evolutionary, genomic and population genetic studies of this important and interesting group.
In silico investigation of the new UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 variants with a focus at the ACE2-Spike RBD interface
Authors: Villoutreix Bruno O. , Calvez Vincent , Marcelin Anne-Genevieve , Khatib Abdel-Majid
Published: January 2021

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor and several in silico methods to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both UK and South African strains) should be favorable for the interaction with ACE2 while the K417N and E484K substitutions (South African) would seem unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the predicted less favorable (regarding binding) K417N and E484K Spike replacements. Our finding suggests that, if indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions outside the direct Spike-ACE2 interface.

Hihglights

Transmission of the UK and possibly South African SARS-CoV-2 strains appears substantially increased compared to other variants

This could be due, in part, to increased affinity between the variant Spike proteins and ACE2

We investigated in silico the 3D structure of the Spike-ACE2 complex with a focus on Spike K417N, E484K and N501Y

The N501Y substitution is predicted to increase the affinity toward ACE2 (UK strain) with subsequent enhanced transmissibility and possibly pathogenicity

Additional substitutions at positions 417 and 484 (South African strain) may pertub the interaction with ACE2 raising questions about transmissibility and pathogenicity
Shedding light on the contribution of amygdalar excitatory projections to prepulse inhibition of the auditory startle reflex
Authors: Cano Jose Carlos , Huang Wanyun , Fénelon Karine
Published: January 2021

Background

Sensorimotor gating is a fundamental neural filtering process that allows attention to be focused on a given stimulus. Sensory gating, commonly measured using the prepulse inhibition (PPI) of the auditory startle reflex task, is impaired in patients suffering from various neurological and psychiatric disorders, including schizophrenia. Because PPI deficits are often associated with attention and cognitive impairments, they are widely used as biomarkers in pre-clinical research for anti-psychotic drug screening. Yet, the neurotransmitter systems and synaptic mechanisms underlying PPI are still not resolved, even under physiological conditions. Recent evidence ruled out the longstanding hypothesis that PPI is mediated by midbrain cholinergic inputs to the caudal pontine reticular nucleus (PnC). Instead, glutamatergic, glycinergic and GABAergic inhibitory mechanisms are now suggested to be crucial for PPI, at the PnC level. Since amygdalar dysfunctions affect PPI and are common to pathologies displaying sensorimotor gating deficits, the present study was designed to test that direct projections to the PnC originating from the amygdala, contribute to PPI.

Results

Using Wild Type and transgenic mice expressing eGFP under the control of the glycine transporter type 2 promoter (GlyT2-eGFP mice), we first employed tract-tracing, morphological reconstructions and immunohistochemical analyses to demonstrate that the central nucleus of the amygdala (CeA) sends glutamatergic inputs latero-ventrally to PnC neurons, including GlyT2+cells. Then, we showed the contribution of the CeA-PnC excitatory synapses to PPIin vivoby demonstrating that optogenetic inhibition of this connection decreases PPI, and optogenetic activation induces partial PPI. Finally, in GlyT2-Cre mice, whole-cell recordings of GlyT2+PnC neuronsin vitropaired with optogenetic stimulation of CeA fibers, as well as photo-inhibition of GlyT2+PnC neuronsin vivo, allowed us to implicate GlyT2+neurons in the PPI pathway.

Conclusions

Our results uncover a feed-forward inhibitory mechanism within the brainstem startle circuit by which amygdalar glutamatergic inputs and GlyT2+PnC neurons play a key role in meditating PPI. We are providing new insights to the clinically-relevant theoretical construct of PPI, which is disrupted in various neuropsychiatric and neurodevelopmental diseases.
Emergence and fast spread of B.1.1.7 lineage in Lebanon
Authors: Younes Mahmoud , Hamze Kassem , Nassar Hassan , Makki Mohamad , Ghadar Maysaa , Nguewa Paul , Sater Fadi Abdel
Published: January 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a rapid spread emerging disease. Recently, a new variant of this virus called SARS-CoV-2 VOC 202012/01 (or B.1.1.7 lineage), described in the United Kingdom (UK), has become highly prevalent in several countries. Its rate of transmission has been estimated to be greatly higher. B.1.1.7 lineage harbors 23 mutations co-existed for the first time in the same variant. Herein, we are interested only by the deletion mutation ΔH69/ΔV70 in the spike protein.

In the UK they were able to identify the increase of this new variant through the increase in the false negative result for the spike target of a three-target RT-PCR assay from Thermo Fisher Scientific (TaqPath kit). Later, the manufacturer announced that this false negative result is because of the deletion ΔH69/ΔV70 in the area targeted by the TaqPath Kit. Furthermore, The European CDC recommended that the use of this kit help to track the new variant.

Genome sequencing is the gold method to confirm the new variant, but observational studies provide also stronger evidence if similar models are observed in multiple countries, especially when randomized studies are not possible. In Lebanon, the highest number of confirmed cases were reported in first week of 2021. In the present study, we show the emergence and the fast spreading of the new variant in Lebanon and a relationship between SARS-CoV-2 transmission intensity and the frequency of the new variant during the first twelve days of January.
IceBear: an intuitive and versatile web application for research-data tracking from crystallization experiment to PDB deposition
Authors: Daniel Ed , Maksimainen Mirko M. , Smith Neil , Ratas Ville , Biterova Ekaterina , Murthy Sudarshan N. , Rahman M. Tanvir , Kiema Tiila-Riikka , Sridhar Shruthi , Cordara Gabriele , Dalwani Subhadra , Venkatesan Rajaram , Prilusky Jaime , Dym Orly , Lehtiö Lari , Koski M. Kristian , Ashton Alun W. , Sussman Joel L. , Wierenga Rik K.
Published: January 2021

The web-based IceBear software is a versatile tool to monitor the results of crystallization experiments and is designed to facilitate supervisor and student communications. It also records and tracks all relevant information from crystallization setup to PDB deposition in protein crystallography projects. Fully automated data collection is now possible at several synchrotrons, which means that the number of samples tested at the synchrotron is currently increasing rapidly. Therefore, the protein crystallography research communities at the University of Oulu, Weizmann Institute of Science and Diamond Light Source have joined forces to automate the uploading of sample metadata to the synchrotron. In IceBear, each crystal selected for data collection is given a unique sample name and a crystal page is generated. Subsequently, the metadata required for data collection are uploaded directly to the ISPyB synchrotron database by a shipment module, and for each sample a link to the relevant ISPyB page is stored. IceBear allows notes to be made for each sample during cryocooling treatment and during data collection, as well as in later steps of the structure determination. Protocols are also available to aid the recycling of pins, pucks and dewars when the dewar returns from the synchrotron. The IceBear database is organized around projects, and project members can easily access the crystallization and diffraction metadata for each sample, as well as any additional information that has been provided via the notes. The crystal page for each sample connects the crystallization, diffraction and structural information by providing links to the IceBear drop-viewer page and to the ISPyB data-collection page, as well as to the structure deposited in the Protein Data Bank.
Ab initio determination of the shape of membrane proteins in a nanodisc
Authors: Orioli Simone , Henning Hansen Carl G. , Arleth Lise
Published: January 2021

New software, called Marbles, is introduced that employs SAXS intensities to predict the shape of membrane proteins embedded into membrane nanodiscs. To gain computational speed and efficient convergence, the strategy is based on a hybrid approach that allows one to account for the contribution of the nanodisc to the SAXS intensity through a semi-analytical model, while the embedded membrane protein is treated as a set of beads, similarly to as in well known ab initio methods. The reliability and flexibility of this approach is proved by benchmarking the code, implemented in C++ with a Python interface, on a toy model and two proteins with very different geometry and size.
Tokugawa Confucian Sermons as Popular Emotional Education: The Moral and Pedagogical Philosophy of Hosoi Heishū*
Authors: Takao Makoto Harris
Published: January 2021

This article contributes to the growing literature on the nexus of religion and emotion, thinking through the ways in which historians of Japan can make interventions in the field, and exploring research methodologies that speak to a pre‐modern and non‐Christian milieu. In looking to the moral and pedagogical philosophy of Hosoi Heishū (1728–1801), a Tokugawa Confucian teacher and itinerant preacher, this article places an emphasis on the use of contextualised and historically‐specific emic categories of belief and feeling. To do so, it explores the popularising movement of Japanese Confucianism in the late eighteenth century, tracing Hosoi's development of vernacular sermonising and his identification of emotion as both a subject and object of instruction. His rhetorical style and pedagogy is unpacked, followed by an analysis of his popular reception, before turning to a sermon case study to observe these ideas in action. This article offers new insights into the viewing habits and emotional expectations of Tokugawa audiences, underscoring the ways in which emotion terms and concepts can change meaning in how they are defined, embodied, expressed, and valued as part of a broader habitus.
Active packaging films and edible coatings based on polyphenol‐rich propolis extract: A review
Authors: Yong Huimin , Liu Jun
Published: January 2021

The development of active packaging films and edible coatings based on biopolymers and natural bioactive substances has received increasing attention in recent years. Propolis, also called bee glue, is a natural resin substance collected by worker‐bees from the mucilage, gum, and resin of several plants. In food industry, propolis is commonly extracted in solvents to afford polyphenol‐rich extract with potent antimicrobial and antioxidant activities. The prepared propolis extract can be mixed with biopolymers, plasticizers, emulsifiers, and reinforcing agents to develop active packaging films and edible coatings. The functionality of active packaging films and edible coatings is closely related to the type, harvesting method, geographic origin, extraction method and extraction conditions of propolis, the content and composition of polyphenolic compounds in the extract, and the presence of other bioactive substances. Active packaging films and edible coatings based on propolis extract can impact the physical, biochemical, and sensory properties of food (e.g., fruits, vegetables, meat, and fish) during storage. This review focuses on the recent advances of active packaging films and edible coatings based on polyphenol‐rich propolis extract. The impact of polyphenol‐rich propolis extract on the structural characterization, functionality, and potential food applications of the films and edible coatings is summarized.
UV treatment for degradation of chemical contaminants in food: A review
Authors: He Jiang , Evans Natasha Marie , Liu Huaizhi , Zhu Yan , Zhou Ting , Shao Suqin
Published: January 2021

Application of ultraviolet (UV) irradiation for the degradation of chemical contaminants in food products has gained more and more interest in the past two decades. The majority of the research in this field was on mycotoxins, especially aflatoxins and patulin, with limited studies on pesticide residues and other chemical contaminants in food. These studies have been focused on identifying the structure and toxicity of degradation products, investigating the influence of UV treatment factors on the degradation efficiency, determining the impact of UV treatment on the quality of food products, and developing updated UV treatment methods such as TiO2 induced photocatalytic degradation. The summary of published literatures provided insights into future research opportunities in this area, which include determining a standard for the UV treatment description, working with naturally contaminated samples rather than artificially spiked samples, conducting pilot plant or industrial scale studies, examining more targets and conducting multi‐targets studies, and developing more innovative methods for UV treatment.
Chitinase‐3‐like protein 1 is an independent risk factor for the early failure of forearm autologous arteriovenous fistulas in uremic patients
Authors: Liang Liming , Chen Qinlan , Cao Wei , Tang Lijun , Wei Yong , Ding Nannan , Kong Xianglei , Xu Dongmei
Published: January 2021

Chitinase‐3‐like protein 1 (CHI3L1) has been introduced as a marker of inflammation in different diseases, which can promote cell proliferation and differentiation. It has also been demonstrated that elevated serum CHI3L1 concentration can independently predict all‐cause mortality in uremic patients. However, the impact of CHI3L1 on the early failure of autologous arteriovenous fistulas (AVFs) in uremic patients remains unknown. We conducted a prospective observational cohort study of 109 uremic patients (mean age 53.2 ± 14.7 years, 67.9% males), who received forearm AVF surgery, and were consecutively enrolled with a median follow‐up time of 15 months. The early failure was defined as a fistula that never developed adequately for dialysis or that failed within the first 3 months of use. Serum CHI3L1 concentration was determined by the ELISA method. Among 109 uremic patients, 24 patients had AVF failure. The optimal cutoff value based on the receiver operating characteristics analysis of CHI3L1 was 122.6 ng/mL, with the area under the curve of 0.73 (P = 0.001). The Kaplan–Meier survival analysis demonstrated that patients with CHI3L1 < 122.6 ng/mL had better AVF patency than patients with CHI3L1 ≥ 122.6 ng/mL (Log–rank test, P = 0.001). Multivariable Cox proportional hazards regression analysis showed that baseline CHI3L1 level (≥ 122.6 ng/mL vs. < 122.6 ng/mL) was significantly associated with AVF failure after adjustment for confounders (adjusted hazard ratio [HR], 3.67; 95% CI, 1.44–9.36). The study demonstrated that Increased baseline serum level of CHI3L1 is independently associated with higher risk of the early failure of forearm AVFs.
Process and product characteristics of refractance window dried Curcuma longa
Authors: Talukdar Preetisagar , Uppaluri Ramagopal
Published: January 2021

This work addresses the optimality of hot water bath based refractance window drying (RWD) characteristics of 1 mm Curcuma longa (turmeric) slices. Mylar film thickness (125 to 350 µm) and water bath temperature (65 to 95 °C) have been considered as independent variables to evaluate drying kinetics and nutritional characteristics of the process product combination. Equilibrium drying time, moisture diffusivity, fitness of thin layer models, moisture content, total phenolic content, total flavonoids content, curcumin content, and antioxidant activity have been considered to evaluate the optimality of the RWD process parameters. It has been analyzed that while both parameters critically influence equilibrium drying time, only temperature had profound influence on nutritional characteristics.

Practical Application

There is a need for a fast‐drying method without significant loss in bioactive compounds. Refractance window drying (RWD) method is such a process. The study of RWD of turmeric slices will help in understanding the relations between different drying temperatures and mylar film thickness and its relation to nutritional characteristics of the product.
Measuring the global, regional, and national burden of type 2 diabetes and the attributable risk factors in all 194 countries
Authors: Yu Mei , Zhan Xiaoqing , Yang Zhenxing , Huang Yongmin
Published: January 2021

Background

No detailed quantitative global, regional, or national estimates of the disability‐adjusted life years (DALYs) of type 2 diabetes mellitus (T2DM) are available.

Methods

We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to estimate the global, regional, and national incidence rates and DALYs of T2DM, as well as the associated risk factors, in all 194 countries and territories by age, sex, and sociodemographic status during the period from 2007 to 2017.

Results

Globally, the age‐standardized incidence and DALY rates increased by 3.23% and 5.07% during 2007 to 2017, respectively. The age‐standardized incidence and DALY rates in 2017 and the corresponding percentage changes during 2007 to 2017 were highest in the low‐middle sociodemographic index (SDI) quintile. Regionally, the highest 2017 age‐standardized incidence and DALY rates were observed in Oceania, whereas the largest percentage increases in both rates during 2007 to 2017 were observed in Southeast Asia. Nationally, Iran, the United Kingdom, and Indonesia reported the largest percentage increases in the age‐standardized incidence rates, whereas Georgia, Czech Republic, and Iran showed the largest percentage increases in the age‐standardized DALY rates. Globally, the largest percentage increases in risk‐attributable DALYs were associated with a high body mass index, low physical activity level, high fasting plasma glucose level, and high sugar‐sweetened beverage and red meat consumption.

Conclusions

The global T2DM age‐standardized incidence and DALY rates increased globally between 2007 and 2017, especially in the low‐middle SDI quintile, Southeast Asia.
Health‐related quality of life in rheumatoid arthritis: Systematic review and meta‐analysis of EuroQoL (EQ‐5D) utility scores from Asia
Authors: Haridoss Madhumitha , Bagepally Bhavani Shankara , Natarajan Meenakumari
Published: January 2021

Introduction

Region‐specific health‐related quality of life (HRQoL) scores or utility values are representative and pivotal for economic evaluations as they are influenced by the value judgment of the local population. This study systematically reviewed and pooled EuroQoL‐5 Dimension (EQ‐5D) utility scores of rheumatoid arthritis (RA) across primary studies from Asia.

Methods

Studies reporting EQ‐5D utility scores among adult RA patients from Asian countries were systematically searched in PubMed‐Medline, Scopus and Embase since inception through February 2020. Selected studies were systematically reviewed and study quality assessment was performed. Meta‐analysis was performed using a random‐effect model with subgroup and meta‐regression analysis to explore heterogeneity.

Results

Among 1391 searched articles, 37 studies with 31 983 participants were systematically reviewed and meta‐analysis was conducted among 31 studies. The pooled EQ‐5D scores and EQ‐5D visual analog score were 0.66 (95% CI 0.63‐0.69, I2 = 99.65%) and 61.21 (50.73‐71.69, I2 = 99.56%) respectively with high heterogeneity. For RA patients with no, low, moderate and high disease activity based on Disease Activity Score (DAS)‐28, the pooled EQ‐5D scores were 0.78 (0.65‐0.90), 0.73 (0.65‐0.80), 0.53 (0.32‐ 0.74), and 0.47 (0.32‐0.62), respectively. On meta‐regression, age of patients (P < .05) was positively associated and use of glucocorticoids (P < .05) was inversely associated with utility values.

Conclusion

Lower EQ‐5D scores were associated with severe disease activity, increasing age and female gender among RA patients. The study provides pooled EQ‐5D scores for RA patients that are useful inputs for cost‐utility studies in Asia.
A practical approach to measuring the acoustic diversity by community ecology methods
Authors: Zsebők Sándor , Schmera Dénes , Laczi Miklós , Nagy Gergely , Vaskuti Éva , Török János , Zsolt Garamszegi László
Published: January 2021

The study of the diversity of animal signals on within‐ and among‐species levels is the key to uncover mechanisms that shape the evolution of communication systems. However, the methods used to quantify acoustic diversity (like repertoire size) lack to grasp several aspects of acoustic diversity. Here, we propose a new framework for the study of animal communication, in which we decompose the acoustic diversity with the methodological toolbox from community ecology.

We explore how different diversity estimates reflecting different aspects of acoustic diversity can be applied to characterise the complexity of acoustic signals. We propose that this approach can be used in a wide range of animal taxa to derive further insights about the function and evolution of communication systems besides the traditional methods.

To illustrate the use of our approach in a case study, we used the song of the collared flycatcher Ficedula albicollis as model system. Based on three frequency and time variables, we calculated three functional diversity indices (FRic, FEve and FDiv) to characterise the distribution of song elements (syllables) in the acoustic parameter space. We aimed to uncover the interrelations of diversity indices, reveal the degree of among‐individual consistency and investigate their relationships with certain aspects of individual quality (body condition, age and arrival date).

We found that the diversity indices were largely independent of each other and showed different consistency patterns that were time‐scale dependent, indicating different signalling potential of individual‐specific attributes. We also found that FEve strongly related to the age of males. Our case study showed that decomposing the diversity into different components can reveal additional biologically meaningful aspects of birdsong.
The consequences of checking for zero‐inflation and overdispersion in the analysis of count data
Authors: Campbell Harlan
Published: January 2021

Count data are ubiquitous in ecology and the Poisson generalized linear model (GLM) is commonly used to model the association between counts and explanatory variables of interest. When fitting this model to the data, one typically proceeds by first confirming that the model assumptions are satisfied. If the residuals appear to be overdispersed or if there is zero‐inflation, key assumptions of the Poison GLM may be violated and researchers will then typically consider alternatives to the Poison GLM. An important question is whether the potential model selection bias introduced by this data‐driven multi‐stage procedure merits concern.

Here we conduct a large‐scale simulation study to investigate the potential consequences of model selection bias that can arise in the simple scenario of analysing a sample of potentially overdispersed, potentially zero‐inflated, count data. Specifically, we investigate model selection procedures recently recommended by Blasco‐Moreno et al. (2019) using either a series of score tests or information theoretic criteria to select the best model.

We find that, when sample sizes are small, model selection based on preliminary score tests (or information theoretic criteria, e.g. AIC, BIC) can lead to potentially substantial inflation of false positive rates (i.e. type 1 error inflation). When sample sizes are sufficiently large, model selection based on preliminary score tests, is not problematic.

Ignoring the possibility of overdispersion and zero‐inflation during data analyses can lead to invalid inference. However, if one does not have sufficient power to test for overdispersion and zero‐inflation, post hoc model selection may also lead to substantial bias. This ‘catch‐22’ suggests that, if sample sizes are small, a healthy skepticism is warranted whenever one rejects the null hypothesis of no association between a given outcome and covariate.
Cerebrospinal Fluid Biomarkers in Patients With Alcohol Use Disorder and Persistent Cognitive Impairment
Authors: Azuar Julien , Bouaziz‐Amar Elodie , Cognat Emmanuel , Dumurgier Julien , Clergue‐Duval Virgile , Barré Thomas , Amami Jihed , Hispard Eric , Bellivier Frank , Paquet Claire , Vorspan Florence , Questel Frank
Published: January 2021

Background

The prevalence of cognitive impairment is high among alcohol‐dependent patients. Although the clinical presentation of alcohol‐related cognitive disorder (ARCD) may resemble that of Alzheimer’s disease (AD), the prognosis and treatment of the 2 diseases are different. Cerebrospinal fluid (CSF) biomarkers (tau, phosphorylated tau, and amyloid β) have high diagnostic accuracy in AD and are currently being used to discriminate between psychiatric disorders and AD, but are not used to diagnose ARCD. The aim of this study was to characterize CSF biomarkers in a homogeneous, cognitively impaired alcohol‐dependent population.

Methods

This single‐center study was conducted in an addiction medicine department of a Parisian Hospital. We selected patients with documented persistent cognitive impairment whose MoCA (Montreal Cognitive Assessment) score was below 24/30 after at least 1 month of documented inpatient abstinence from alcohol. We measured the CSF biomarkers (tau, phosphorylated tau, and amyloid β 1‐42 and 1‐40) in 73 highly impaired alcohol‐dependent patients (Alcohol Use Disorders Identification Test score over 11 for women and 12 for men) with.

Results

Patients' average age was 60 ± 9.1 years and 45 (61.6%) had a normal CSF profile, 8 (11.0%) had a typical CSF AD profile, and 20 (27.4%) had an intermediate CSF profile.

Conclusions

This study revealed a high prevalence of AD in alcohol‐dependent patients with persistent cognitive deficits and several anomalies in their CSF profiles. Thus, it is important to consider AD in the differential diagnosis of persistent cognitive deficits in patients with alcohol dependence and to use CSF biomarkers in addition to imaging and neuropsychological testing to evaluate alcohol‐related cognitive impairment.
Distinct Whole‐Body Movements in Response to Alcohol and Sexual Content in Alcohol Use Disorder
Authors: Noël Xavier , Dubuson Macha , Rougier Marine , Lelard Thierry , Mouras Harold , Kornreich Charles , Wyckmans Florent , Pereira Maylis , Chatard Armand , Jaafari Némat , Campanella Salvatore
Published: January 2021

Background

Spontaneous motor responses of approach and avoidance toward stimuli are important in characterizing psychopathological conditions, including alcohol use disorder (AUD). However, divergent results have been reported, possibly due to confounded parameters (e.g., using a symbolic vs. a sensorimotor task, implementation of approach–avoidance as a measure vs. a manipulation).

Methods

We studied whole‐body/posturometric changes by using a sensorimotor measure relying on embodied cognition principles to assess forward (approach) and backward (avoidance) spontaneous leaning movements. Over a 12‐second period, 51 male patients with AUD and 29 male control participants were instructed to stand still in response to both alcohol and sexual visual content. Patients with AUD were then divided into “abstainers” and “relapsers,” depending on their continuous abstinence at 2 weeks postdischarge (obtained via a telephone follow‐up interview). The effects of the group, the stimulus type, the experimental period, and their interactions on the posturometric changes were tested using mixed Analyses of variance (ANOVAs), with a significance threshold set at 0.05.

Results

Contrary to our expectations, patients and controls did not show significant difference in their forward/backward micromovements while passively viewing alcohol or sexual content (p > 0.1). However, in line with our hypothesis, patients who relapsed several weeks following discharge from the rehabilitation program were significantly more reactive and more likely to lean back during the first seconds of viewing alcohol cues (p = 0.002). Further, “relapsers” were more likely to lean forward during exposure to sexual content than participants who remained abstinent (p < 0.001).

Conclusions

Among individuals with AUD, there are distinct pattern of spontaneous movements that differentiate “abstainers” and “relapsers,” findings that can be understood in light of existing data and theories on action tendencies.
Efficacy of low‐molecular weight chitosan against Candida albicans biofilm on polymethyl methacrylate resin
Authors: Srimaneepong Viritpon , Thanamee Thanaporn , Wattanasirmkit Kamolporn , Muangsawat Sureeporn , Matangkasombut Oranart
Published: January 2021

Background

Candida biofilm is a major cause of denture stomatitis. We aimed to compare the efficacy of low‐molecular‐weight chitosan solutions against Candida albicans biofilm on polymethyl methacrylate (PMMA) resin.

Methods

Various types of chitosan were tested for anti‐Candida activity by broth dilution. Two types were selected for further testing on 24‐hour C.albicans biofilm formed on PMMA specimens. Specimens were randomly distributed among experimental groups, including 0.1% and 0.2% acetic acid, 3 and 6 mg/mL of oligomer chitosan and 30 kDa chitosan solutions, effervescent tablet (Polident), and 0.2% chlorhexidine, and immersed for 5 min to 12 h. The viability of C. albicans after cleansing were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays. Remaining viability was calculated into percentage relative to respective controls and analyzed using ANOVA with Tukey post‐hoc tests. Live/dead fluorescence microscopy was also performed.

Results

Chitosan solutions had high efficacy against C. albicans biofilm on PMMA. The mean relative viability compared to control after 12‐h immersion was 6.60 ± 4.75% and 12.72 ± 6.96% for 3 and 6 mg/mL oligomer, respectively, and 11.68 ± 4.81% and 18.08 ± 6.20% for 3 and 6 mg/mL 30 kDa chitosan, respectively.

Conclusions

Low‐molecular‐weight chitosan solution is an effective antifungal denture cleanser that can significantly reduce C. albicans viability in biofilm on PMMA.
Unknowing, indifferent, or committed: Relations between age and assessments of the German population’s involvement and inaction during the time of National Socialism
Authors: Papendick Michael , Rees Jonas H. , Zick Andreas
Published: January 2021

We examine German participants’ assessment of the time of National Socialism. Especially for younger generations, shifts in the culture of remembrance may change their assessments of historical events. We argue that factors such as increased formal education about the topic and decreased personal contact with contemporary witnesses can weaken attributional biases (e.g., ingroup favouritism) in the assessment of the role of the German population during the time of National Socialism. We use data from a German representative sample (N = 1,000) and focus on the links between participants’ age and the estimated involvement of the German population under National Socialism as perpetrators, victims, helpers, and “bystanders,” as well as the agreement with explanations why the general population did not act against National Socialist crimes. Younger participants estimated the proportions of perpetrators and bystanders within the German population as higher and were less likely to agree that Germans did not know about the systematic killings. Older participants were more likely to agree with situational explanations for the population’s inaction (i.e., that Germans did not know or did not have an opportunity to act against the crimes). We find a positive relation between a more critical perspective on the involvement of the population in the past and participants’ feelings of responsibility in the present.
Mast cell‐derived serotonin enhances methacholine‐induced airway hyperresponsiveness in house dust mite‐induced experimental asthma
Authors: Mendez‐Enriquez Erika , Alvarado‐Vazquez Perla Abigail , Abma Willem , Simonson Oscar E. , Rodin Sergey , Feyerabend Thorsten B. , Rodewald Hans‐Reimer , Malinovschi Andrei , Janson Christer , Adner Mikael , Hallgren Jenny
Published: January 2021

Background

Airway hyperresponsiveness (AHR) is a feature of asthma in which airways are hyperreactive to stimuli causing extensive airway narrowing. Methacholine provocations assess AHR in asthma patients mainly by direct stimulation of smooth muscle cells. Using in vivo mouse models, mast cells have been implicated in AHR, but the mechanism behind has remained unknown.

Methods

Cpa3Cre/+mice, which lack mast cells, were used to assess the role of mast cells in house dust mite (HDM)‐induced experimental asthma. Effects of methacholine in presence or absence of ketanserin were assessed on lung function and in lung mast cells in vitro. Airway inflammation, mast cell accumulation and activation, smooth muscle proliferation, and HDM‐induced bronchoconstriction were evaluated.

Results

Repeated intranasal HDM sensitization induced allergic airway inflammation associated with accumulation and activation of lung mast cells. Lack of mast cells, absence of activating Fc‐receptors, or antagonizing serotonin (5‐HT)2A receptors abolished HDM‐induced trachea contractions. HDM‐sensitized mice lacking mast cells had diminished lung‐associated 5‐HT levels, reduced AHR and methacholine‐induced airway contraction, while blocking 5‐HT2A receptors in wild types eliminated AHR, implying that mast cells contribute to AHR by releasing 5‐HT. Primary mouse and human lung mast cells express muscarinic M3 receptors. Mouse lung mast cells store 5‐HT intracellularly, and methacholine induces release of 5‐HT from lung‐derived mouse mast cells and Ca2+ flux in human LAD‐2 mast cells.

Conclusions

Methacholine activates mast cells to release 5‐HT, which by acting on 5‐HT2A receptors enhances bronchoconstriction and AHR. Thus, M3‐directed asthma treatments like tiotropium may also act by targeting mast cells.
Temporal variability of T‐wave morphology and risk of sudden cardiac death in patients with coronary artery disease
Authors: Rahola Janne T. , Kiviniemi Antti M. , Ukkola Olavi H. , Tulppo Mikko P. , Junttila M. Juhani , Huikuri Heikki V. , Kenttä Tuomas V. , Perkiömäki Juha S.
Published: January 2021

Background

The possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarization and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood.

Methods

The standard deviation of T‐wave morphology dispersion (TMD‐SD), of QRST angle (QRSTA‐SD), and of T‐wave area dispersion (TW‐Ad‐SD) were analyzed on beat‐to‐beat basis from 10 min period of the baseline electrocardiographic recording in ARTEMIS study patients with angiographically verified CAD.

Results

After on average of 8.6 ± 2.3 years of follow‐up, a total of 66 of the 1,678 present study subjects (3.9%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD‐SD was most closely associated with the risk for SCD and was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.61 ± 2.83 vs. 2.64 ± 2.52, p = .008, respectively), but did not differ significantly between the patients who had experienced non‐SCD (n = 71, 4.2%) and those who remained alive (3.20 ± 2.73 vs. 2.65 ± 2.53, p = .077, respectively) or between the patients who succumbed to non‐cardiac death (n = 164, 9.8%) and those who stayed alive (2.64 ± 2.17 vs. 2.68 ± 2.58, p = .853). After adjustments with relevant clinical risk indicators of SCD/SCA, TMD‐SD still predicted SCD/SCA (HR 1.107, 95% CIs 1.035–1.185, p = .003).

Conclusions

Temporal variability of electrocardiographic spatial heterogeneity of repolarization represented by TMD‐SD independently predicts long‐term risk of SCD/SCA in patients with CAD.
Association between circulating furin levels, obesity and pro‐inflammatory markers in children
Authors: Swärd Per , Rosengren Björn E. , Jehpsson Lars , Karlsson Magnus K.
Published: January 2021

Aim

To, in children, investigate the associations between serum furin, obesity, overweight, body fat and circulating markers reflecting adipose tissue or systemic inflammation.

Methods

We analysed furin, leptin, adipocyte fatty acid–binding protein, triglycerides, interleukin (IL)‐6, IL‐8 and C‐reactive protein in serum from 166 children in the Pediatric Osteoporosis Prevention (POP) study collected at mean age (SD) 9.9 (0.6) years. Children were classified as low‐to‐normal weight, overweight or obese. Total body fat mass (kg), trunk fat mass (kg) and total body lean mass (kg) were measured by dual‐energy X‐ray absorptiometry. Body fat percentage (%) was calculated.

Results

We found that circulating furin levels were higher in children with obesity and overweight compared with children with low‐to‐normal weight (p < 0.001 and p = 0.006, respectively). Also, there were positive correlations between circulating furin, total body fat mass, trunk fat mass, body fat percentage, triglycerides, adipokines and pro‐inflammatory markers.

Conclusion

This study indicates associations between furin, adiposity and a pro‐inflammatory milieu in children. We suggest that future studies investigate the role of furin in fat tissue inflammation and associated increased risk of cardiometabolic diseases in children. Studies should also investigate whether higher furin levels could be a link between obesity and severe coronavirus disease 2019 in children.