bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2-specific Cell-mediated Immunity in Kidney Transplant Recipients Recovered From COVID-19
Authors: Fernández-Ruiz Mario , Olea Beatriz , Giménez Estela , Laguna-Goya Rocío , Trujillo Hernando , Caravaca-Fontán Fernando , Gutiérrez Eduardo , López-Medrano Francisco , Remigia María José , Almendro-Vazquez Patricia , Polanco Natalia , González Esther , Ruiz-Merlo Tamara , Parra Patricia , San Juan Rafael , Andrés Amado , Navarro David , Aguado José María
Published: February 2021

Background.

The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2–specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown.

Methods.

We enumerated SARS-CoV-2-specific interferon-γ-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6.

Results.

Detectable (≥0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P = 0.086) but not CD4+ subsets (P = 0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P = 0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P = 0.087).

Conclusions.

Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.
A Novel Multidrug Combination Mitigates Rat Liver Steatosis Through Activating AMPK Pathway During Normothermic Machine Perfusion
Authors: Xu Min , Zhou Fangyu , Ahmed Ola , Upadhya Gundumi A. , Jia Jianluo , Lee Choonghee , Xing Jianwei , Ye Li , Shim So Hee , Zhang Zhengyan , Byrnes Kathleen , Wong Brian , Kim Jae-Sung , Lin Yiing , Chapman William C.
Published: February 2021

Background.

Hepatic steatosis is now the leading cause of liver discards in deceased donors. Previous studies [Yarmush formula (Y) defatting] have successfully reduced the fat content by treating rat steatotic livers on extracorporeal normothermic machine perfusion (NMP) with a multidrug combination including the GW compounds that were linked to an increased risk of carcinogenesis.

Methods.

We developed a novel multidrug combination by replacing the GW compounds with 2 polyphenols, epigallocatechin-3-gallate (E) and resveratrol (R). Sixteen rat livers were placed on NMP and assigned to control, Y defatting, Y + E + R defatting, or Y′−GW + E + R defatting groups (Y′−GW = 90% dose-reduced Y defatting, n = 4/group).

Results.

All livers in defatting groups had significant decreases in hepatic triglyceride content at the end of the experiment. However, livers treated with our novel Y′−GW + E + R combination had evidence of increased metabolism and less hepatocyte damage and carcinogenic potential. Our Y′−GW + E + R combination had increased phosphorylation of AMP-activated protein kinase (P = 0.019) and acetyl-CoA carboxylase (P = 0.023) compared with control; these were not increased in Y + E + R group and actually decreased in the Y group. Furthermore, the Y′−GW + E + R group had less evidence of carcinogenic potential with no increase in AKT phosphorylation compared with control (P = 0.089); the Y (P = 0.031) and Y + E + R (P = 0.035) groups had striking increases in AKT phosphorylation. Finally, our Y′−GW + E + R showed less evidence of hepatocyte damage with significantly lower perfusate alanine aminotransferase (P = 0.007) and aspartate aminotransferase (P = 0.014) levels.

Conclusions.

We have developed a novel multidrug combination demonstrating promising defatting efficacy via activation of the AMP-activated protein kinase pathway with an optimized safety profile and reduced hepatotoxicity during ex vivo NMP.
Rituximab Was Effective for Treatment of Anti–N-Methyl-d-Aspartate Receptor Encephalitis in Early Adolescence in Initially Suspected Dissociative Disorder
Authors: Shibata Takashi , Kawai Hiroki , Sakamoto Shinji , Tsutsui Ko , Kanbayashi Takashi , Tanaka Keiko , Takaki Manabu
Published: February 2021

Objectives

Anti–N-methyl-d-aspartate receptor (NMDAR) encephalitis is an increasingly recognized etiology of psychiatric symptoms. Because patients with anti-NMDAR encephalitis frequently show aggression, mania, hallucination, depression, or delusion, they are initially diagnosed with schizophrenia or mood disorders. There is only 1 case report of an initially diagnosed dissociative disorder.

Methods

We obtained consent for the presentation and have not identified individuals for ethical reasons.

Results

We first report an adolescent female patient with anti-NMDAR encephalitis who was initially suspected of having dissociative disorder but was responsive to immunotherapies including rituximab. In this case, her symptoms and electroencephalogram findings were proportional to the antibody titer in the cerebrospinal fluid.

Conclusions

It is important to consider the possibility of autoimmune encephalitis and immunotherapy including rituximab in cases of not only acute psychosis but also dissociation.
Pseudomonas piscium sp. nov., Pseudomonas pisciculturae sp. nov., Pseudomonas mucoides sp. nov. and Pseudomonas neuropathica sp. nov. isolated from rainbow trout
Authors: Duman Muhammed , Mulet Magdalena , Altun Soner , Saticioglu Izzet Burcin , Gomila Margarita , Lalucat Jorge , Garcia-Valdes Elena
Published: February 2021

Six Gram negative, motile bacteria were isolated from rainbow trout (Oncorhynchus mykiss). The 16S rRNA sequence similarity values grouped them in thePseudomonas mandelii(strains P49, P50T, 154aTand P154b),Pseudomonas fluorescens(strain P115T) andPseudomonas koreensis(strain P155T) phylogenetic subgroups in the genusPseudomonas. The DNA G+C content ranged from 58.5 to 60 mol%. The strains were characterized phenotypically using API 20NE and Biolog GENIII tests, and chemotaxonomically by their whole-cell MALDI-TOF MS protein profiles and fatty acid contents. Multi-locus sequence analysis with four housekeeping gene sequences (rpoD,rpoB,gyrBand 16S rRNA) together with genome comparisons by average nucleotide identity and genome-to-genome distance calculations were performed. Results showed that the similarity values of these strains to known species type strains were lower than the thresholds established for species in the genusPseudomonas. Based on these data, we concluded that strains P49, P50T, P115T, P154aT, P154b and P155Tbelonged to four novel species. The names proposed are:Pseudomonas pisciumsp. nov. for strains P49 and P50Twith P50T(=CECT 30175T=CCUG 74871T) as the type strain;Pseudomonas pisciculturaesp. nov. for strain P115T(CECT 30173T=CCUG 74873T); Pseudomonas mucoidessp. nov. for strains P154aTand P154b with P154aT(=CECT 30177T=CCUG 74874T) as the type strain; andPseudomonas neuropathicasp. nov. for strain P155T(=CECT 30178T=CCUG 74875T).
Grimontia sedimenti sp. nov., isolated from benthic sediments near coral reefs south of Kuwait
Authors: Mahmoud Huda , Jose Liny , Eapen Susan
Published: February 2021

A Gram-stain-negative, rod and rod-curved shaped motile bacterium designated strain S25T was obtained from benthic sediment collected near the Kubbar Island coral reefs south of Kuwait. Phenotypic analysis revealed that strain S25T was slightly halophilic, mesophilic and facultative anaerobic, fermenting d-glucose, d-ribose, d-mannose, d-mannitol, maltose, fructose, gentiobiose, cellobiose, melibiose, trehalose and sucrose. It was positive for oxidase and indole production and negative for arginine dihydrolase and lysine and ornithine decarboxylases. It contained C16 : 1
 ω7c/C16 : 1
 ω6c (summed feature 3), C18 : 1 ω7c (summed feature 8) and C16 : 0 as the major fatty acids. Strain S25T grew optimally at 30 °C and pH 8 in the presence of 3 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA sequences revealed that strain S25T is related to species of the genus

Grimontia

, having 99.15 % similarity to ‘Grimontia indica’ AK16T, 99.08 % to

Grimontia celer

96-237T and 98.66 % to

Grimontia marina

IMCC 5001T. The DNA G+C content was 48.8 mol% and the full genome analysis for the strain S25T showed that the bacterium has a genome size of 5 158 621 bp and contains 4730 predicted protein-encoding genes. The average nucleotide identity values between the S25T genome and the genomes of its nearest matches ranged between 81.39 and 94.16 %. The strain was distinguishable from the phylogenetically related genera through differences in several phenotypic properties. On the basis of the phenotypic, phylogenetic and genetic data, strain S25T represents a novel species in the genus

Grimontia

, for which the name Grimontia sedimenti sp. nov. is proposed. The type strain of Grimontia sedimenti is S25T (=DSM 28878T=LMG 28315T).
Genomic evolution and local epidemiology of Klebsiella pneumoniae from a major hospital in Beijing, China, over a 15 year period: dissemination of known and novel high-risk clones
Authors: Palmieri Mattia , Wyres Kelly L. , Mirande Caroline , Qiang Zhao , Liyan Ye , Gang Chen , Goossens Herman , van Belkum Alex , Yan Ping Luo
Published: February 2021

Klebsiella pneumoniae

is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical

K. pneumoniae

isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.
Miltefosine enhances infectivity of miltefosine-resistantLeishmania infantumby attenuating innate immune recognition
Authors: Bulté Dimitri , Bockstal Lieselotte Van , Dirkx Laura , Van den Kerkhof Magali , Trez Carl De , Timmermans Jean-Pierre , Hendrickx Sarah , Maes Louis , Caljon Guy
Published: February 2021

Miltefosine (MIL) is currently the only oral drug available to treat visceral leishmaniasis but its use as first-line monotherapy has been compromised by an increasing treatment failure. Despite the scarce number of resistant clinical isolates, MIL-resistance by mutations in a single aminophospholipid transporter gene can easily be selected in a laboratory environment. These mutations result in a reduced survival in the mammalian host, which can partially be restored by exposure to MIL, suggesting a kind of drug-dependency. To enable a combined study of the infection dynamics and underlying immunological events for differentialin vivosurvival, firefly luciferase (PpyRE9) / red fluorescent protein (DsRed) double-reporter strains were generated of MIL-resistant (MIL-R) and syngeneic MIL-sensitive (MIL-S)Leishmania infantum. Results in C57Bl/6 and BALB/c mice show that MIL-R parasites induce an increased innate immune response that is characterized by enhanced influx and infection of neutrophils, monocytes and dendritic cells in the liver and elevated serum IFN-γ levels, finally resulting in a less efficient establishment in liver macrophages. The elevated IFN-γ levels were shown to originate from an increased response of hepatic NK and NKT cells to the MIL-R parasites. In addition, we demonstrated that MIL could increase thein vivofitness of MIL-R parasites by lowering NK and NKT cell activation, leading to a reduced IFN-γ production. These data provide an immunological basis for the MIL-R-associated attenuated phenotype and for the peculiar drug-dependency that may constitute one of the mechanisms of treatment failure.

Importance

Recently, our laboratory demonstrated anin vivofitness loss of experimentally selected MIL-R parasites in both the sand fly vector and vertebrate host. These findings could explain the scarce number of MIL-R clinical isolates. Surprisingly, MIL-R parasites developed a MIL-dependency which could partially rescue their fitness loss and which may constitute a mechanism of treatment failure. This research aimed to better understand the immunological basis of the attenuated phenotype and the effect of MIL on infectivity traits. Together, this study provides new insights into the complex interplay between the parasite, drug and host and discloses an immune-related mechanism of treatment failure.
A comparison of denoising methods in dynamic MRS using pseudo-synthetic data
Authors: Rowland Benjamin C. , Sreepada Lasya , Lin Alexander P.
Published: February 2021

Purpose

MR spectroscopy of dynamic systems is limited by low signal to noise. Denoising along a series of acquired spectra exploits their temporal correlation to improve the quality of individual spectra, and reduce errors in fitting metabolite peaks. In this study we compare the performance of several denoising methods.

Methods

Six different denoising methods were considered: SIFT (Spectral Improvement by Fourier Thresholding), HSVD (Hankel Singular Value Decomposition), spline, wavelet, sliding window and sliding Gaussian. Pseudo-synthetic data was constructed to mimic 31Phosphorus spectra from exercising muscle. For each method the optimal tuning parameters were determined for SNRs of 2, 5, 10 and 20 using a Monte Carlo approach. Denoised data from each method was then fitted using the AMARES algorithm and the results compared to the pseudo-synthetic ground truth.

Results

All six methods produced improvements in both fitting accuracy and agreement with the ground truth, compared to unprocessed noisy data. The least effective methods, SIFT and HSVD, achieved around 10-20% reduction in RMS error, while the most effective, Spline, reduced RMS error by 70%. The improvement from denoising was typically greater for lower SNR data.

Conclusions

Indirect time domain denoising of dynamic MR spectroscopy data can substantially improve subsequent metabolite fitting. Spline-based denoising was found to be the most flexible and effective technique.
The nonstructural protein 5 of coronaviruses antagonizes GSDMD-mediated pyroptosis by cleaving and inactivating its pore-forming p30 fragment
Authors: Shi Fushan , Lv Qian , Wang Tingjun , Xu Jidong , Xu Wei , Shi Yuhua , Fu Xinyu , Yang Tianming , Yang Yang , Zhuang Lenan , Fang Weihuan , Gu Jinyan , Li Xiaoliang
Published: February 2021

Coronaviruses (CoV) are a family of RNA viruses that typically cause respiratory, enteric and hepatic diseases in animals and humans. Here, we used porcine epidemic diarrhea virus (PEDV) as a model of coronaviruses (CoVs) to illustrate the reciprocal regulation between CoVs infection and pyroptosis. For the first time, we clarified the molecular mechanism of porcine Gasdermin D (pGSDMD)-mediated pyroptosis and demonstrated that amino acids T239 and F240 within pGSDMD-p30 are critical for pyroptosis. Furthermore, 3C-like protease Nsp5 from SARS-CoV-2, MERS-CoV, PDCoV and PEDV can cleave human/porcine GSDMD at the Q193-G194 junction upstream of the caspase-1 cleavage site to produce two fragments which fail to trigger pyroptosis or inhibit viral replication. Thus, we provide clear evidence that coronoviruses may utilize viral Nsp5-GSDMD pathway to help their host cells escaping from pyroptosis, protecting the replication of the virus during the initial period, which suggest an important strategy for coronoviruses infection and sustain.
Quasi-species evolution maximizes genotypic reproductive value (not fitness or flatness)
Authors: Smerlak Matteo
Published: February 2021

Growing efforts to measure fitness landscapes in molecular and microbial systems are motivated by a longstanding goal to predict future evolutionary trajectories. Sometimes under-appreciated, however, is that the fitness landscape and its topography do not by themselves determine the direction of evolution: under sufficiently high mutation rates, populations can climb the closest fitness peak (survival of the fittest), settle in lower regions with higher mutational robustness (survival of the flattest), or even fail to adapt altogether (error catastrophes). I show that another measure of reproductive success, Fisher’sreproductive value, resolves the trade-off between fitness and robustness in the quasi-species regime of evolution: to forecast the motion of a population in genotype space, one should look for peaks in the (mutation-rate dependent) landscape of genotypic reproductive values—whether or not these peaks correspond to local fitness maxima or flat fitness plateaus. This new landscape picture turns quasi-species dynamics into an instance of non-equilibrium dynamics, in the physical sense of Markovian processes, potential landscapes, entropy production, etc.
Genetic variation in haemoglobin alters breathing in high-altitude deer mice
Authors: Ivy Catherine M. , Wearing Oliver H. , Natarajan Chandrasekhar , Schweizer Rena M. , Gutiérrez-Pinto Natalia , Velotta Jonathan P. , Campbell-Staton Shane C. , Petersen Elin E. , Fago Angela , Cheviron Zachary A. , Storz Jay F. , Scott Graham R.
Published: February 2021

Physiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated thein vivoeffects on respiratory physiology of genetic variants in haemoglobin (Hb) that contribute to hypoxia adaptation in high-altitude deer mice (Peromyscus maniculatus). We created F2inter-population hybrids of highland and lowland deer mice to test the phenotypic effects of α- and β-globin variants on a mixed genetic background. High-altitude genotypes were associated with breathing phenotypes that enhance O2uptake in hypoxia, including a deeper more effective breathing pattern and an augmented hypoxic ventilatory response. These effects could not be explained by erythrocyte Hb-O2affinity or globin gene expression in the brainstem. Therefore, adaptive variation in haemoglobin can have unexpected effects on physiology that are distinct from the canonical function of this protein in circulatory O2transport.
Low rank approximation of difference between correlation matrices by using inner product
Authors: Tanioka Kensuke , Hiwa Satoru
Published: February 2021

Introduction

In the domain of functional magnetic resonance imaging (fMRI) data analysis, given two correlation matrices between regions of interest (ROIs) for the same subject, it is important to reveal relatively large differences to ensure accurate interpretations. However, clustering results based only on difference tend to be unsatisfactory, and interpreting features is difficult because the difference suffers from noise. Therefore, to overcome these problems, we propose a new approach for dimensional reduction clustering.

Methods

Our proposed dimensional reduction clustering approach consists of low rank approximation and a clustering algorithm. The low rank matrix, which reflects the difference, is estimated from the inner product of the difference matrix, not only the difference. In addition, the low rank matrix is calculated based on the majorize-minimization (MM) algorithm such that the difference is bounded from 1 to 1. For the clustering process, ordinalk-means is applied to the estimated low rank matrix, which emphasizes the clustering structure.

Results

Numerical simulations show that, compared with other approaches that are based only on difference, the proposed method provides superior performance in recovering the true clustering structure. Moreover, as demonstrated through a real data example of brain activity while performing a working memory task measured by fMRI, the proposed method can visually provide interpretable community structures consisted of well-known brain functional networks which can be associated with human working memory system.

Conclusions

The proposed dimensional reduction clustering approach is a very useful tool for revealing and interpreting the differences between correlation matrices, even if the true difference tends to be relatively small.
Spontaneous Facet Joint Osteoarthritis in NFAT1-Mutant Mice
Authors: Wang Jinxi , Lu Qinghua , Mackay Matthew J. , Liu Xiangliang , Feng Yi , Burton Douglas C. , Asher Marc A.
Published: February 2021

Objectives

Although rodent models of traumatically or chemically induced intervertebral facet joint osteoarthritis (FJOA) were previously described, the characteristics of spontaneous FJOA animal models have not been documented. This study aimed to identify the characteristics of a murine model of spontaneous FJOA and its underlying mechanisms.

Methods

The lumbar facet joints of mutant mice carrying a disrupted NFAT1 (nuclear factor of activated T cells 1) allele and of wild-type control mice were examined by histochemistry, quantitative gene expression analysis, immunohistochemistry, and histomorphometry using a novel FJOA scoring system at 2, 6, 12, and 18 months of age. The reproducibility of the FJOA scoring system was analyzed by inter-observer and intra-observer variability tests. Tissue-specific histomorphometric and gene expression changes were statistically analyzed.

Results

NFAT1-mutant facet joints displayed dysfunction of articular chondrocytes and synovial cells with aberrant gene and protein expression in cartilage and synovium as early as 2 months, followed by osteoarthritic structural changes such as articular surface fissuring and chondro-osteophyte formation at 6 months. Deeper cartilage lesions, synovitis, separation of cartilage from thickened subchondral bone, and tissue-specific molecular and cellular alterations in NFAT1-mutant facet joints became evident at 12 and 18 months. Osteoarthritic structural changes were not detected in wild-type facet joints at any ages, though age-related cartilage degeneration was observed at 18 months.

Conclusions

Using NFAT1-mutant mice, this study has identified for the first time an animal model of spontaneous FJOA with age-dependent osteoarthritic characteristics, developed the first FJOA scoring system, and elucidated the molecular mechanisms of NFAT1 mutation-mediated FJOA.
Unsupervised Clustering characterizes the CPG dinucleotides distribution of the Andes hantavirus
Authors: Mastriani Emilio , Liu Shu-Lin
Published: February 2021

Hantaviruses belong to the family ofBunyaviridae, and small mammals host them. Humans are infected either by inhaling virus-containing aerosols or through contact with animal droppings. Even if rodents host the pathogenic species and humans are dead-end hosts, they get accidentally infected. Andes Orthohantavirusus (ANDV) seems to be the only species with documented person-to-person transmission. Hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are both serious syndromes associated with hantavirus infections. For both syndromes, the mortality rate is near 40%. Decades of studies already highlighted the CpG repression in RNA viruses, and both the estimation of the CpG odds ratio and the correlation with their genome polarity were dominant factors to figure out the CpG bias. We conducted the differential analysis of the CpG odds ratio for all the orthohantaviruses on the full segmented genomes (L, M, S). The results suggested the statistical significance of the three groups. The“Small”genomes resulted in the more informative from the CpG odd ratio point of view. We calculated the CpG odds ratio for all the Orthohantaviruses within these segments, and besides, we estimated the correlation coefficient with the relative coding sequences (CDS). Preliminary results firstly confirmed the CpG odds ratio as the lowest among all the nucleotides. Second, highlighted the Andes virus as that whose CpG odds ratio within CDS is highest. The use of these two measures as features for unsupervised clustering algorithms has brought to the identification of four different sub-groups inside of theOrthohantaviridaefamily. The evidence is that the Andes Hantavirus exhibits a peculiar CpG odds ratio distribution, probably linked to its unique prerogative to pass from human-to-human.
Development of Tribo-Electroceutical Fabrics for Potential Application in Self-sanitizing Personal Protective Equipment (PPE)
Authors: Bayan Sayan , Adhikari Aniruddha , Pal Uttam , Ghosh Ria , Mondal Susmita , Darbar Soumendra , Saha-Dasgupta Tanusri , Ray Samit Kumar , Pal Samir Kumar
Published: February 2021

Attachment of microbial bodies including coronavirus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a novel tribo-electroceutical fabric (TECF) consisting of commonly available materials namely Nylon, and Silicone Rubber (SR) for the fabrication of protective gloves on Nitrile platform, as a model wearable PPE. A small triboelectric device (2 cm × 2 cm) consisting of SR and Nylon on Nitrile can generate more than 20 volt transient or 41 µW output power, which is capable of charging a capacitor up to 65 V in only ∼50 sec. The novelty of the present work relies on the TECF led anti-microbial activity through the generation of an electric current in saline water. The fabrication of TECF based functional prototype gloves can generate hypochlorite ions through the formation of electrolysed water upon rubbing them with saline water. Further a computational modelling has been employed to reveal the optimum structure and mechanistic pathway of anti-microbial hypochlorite generation. Detailed anti-microbial assays have been performed to establish effectiveness of such TECF based gloves to reduce the risk from life threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other material with comparable properties, as material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19.
Effect of in-hospital treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on mortality and complications in patients hospitalized for COVID-19: a large Spanish cohort study
Authors: Roy-Vallejo Emilia , Sánchez Purificación Aquilino , Torres Peña José David , Sánchez Moreno Beatriz , Arnalich Francisco , García Blanco María José , Miranda José López , Cabrera Juan Luis Romero , Gil Carmen Rosario Herrero , Bascunana J , Rubio-Rivas Manuel , Otero Sara Pintos , Sempere Verónica Martínez , Rodríguez-Solís Jesús Ballano , Sánchez Ricardo Gil , del Pino Jairo Luque , González Noya Amara , Navas-Alcántara MS , Rodríguez Begoña Cortés , Alcalá José N. , Suárez-Lombraña Ana , Andrés Soler Jorge , Gómez Huelgas Ricardo , Casas Rojo José Manuel , Núñez-Cortés Jesús Millán ,   for the SEMI-COVID-19 Network^
Published: February 2021

Background

The use of ACEI (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin II Receptor Blocker) in COVID-19 remains controversial. Our main aim was to describe the effect of ACEI/ARB treatment during COVID-19 hospitalization on mortality and complications.

Methods

Retrospective, observational, multicenter study, part of the SEMI-COVID-19 Registry, comparing patients with COVID-19 treated with ACEI/ARB during hospitalization to those not treated. The primary endpoint was incidence of the composite outcome of prognosis (IMV [Invasive Mechanical Ventilation], NIMV [Non-Invasive Mechanical Ventilation], ICU admission [Intensive Care Unit], and/or all-cause mortality). The secondary endpoint was incidence of MACE (Major Adverse Cardiovascular Events). We evaluated both outcomes in patients whose treatment with ACEI/ARB continued or was withdrawn during hospitalization.

Results

Between February and June 2020, 11,205 patients were included, with mean age 67 years (SD=16.3) and 43.1% female; 2,162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed a protective effect on all-cause mortality (p<.0001). In hypertensive patients it was also protective in terms of IMV, ICU admission, and the composite outcome of prognosis (p<.0001 for all). No differences were found in incidence of MACE. Patients previously treated with ACEI/ARB who continued treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB had a more beneficial effect on survival than ACEI (HR 0.77, 95%CI 0.62-0.96).

Conclusion

ACEI/ARB treatment during COVID-19 hospitalization had a protective effect on mortality. The benefits were greater in hypertensive patients, those who continued treatment during hospitalization, and those taking ARB.

Treatment with ACEI/ARB during COVID-19 hospitalization showed a beneficial effect on mortality in the general population. The benefit was greater in hypertensive patients, in those who maintained treatment during hospitalization and those taking ARB.
Longitudinal high-resolution imaging through a flexible intravital imaging window
Authors: Jacquemin Guillaume , Benavente-Diaz Maria , Djaber Samir , Bore Aurélien , Dangles-Marie Virginie , Surdez Didier , Tajbakhsh Shahragim , Fre Silvia , Lloyd-Lewis Bethan
Published: February 2021

Intravital microscopy (IVM) is a powerful technique that enables imaging of internal tissues at (sub)cellular resolutions in living animals. Here, we present a silicone-based imaging window consisting of a fully flexible, suture-less design that is ideally suited for long-term, longitudinal IVM of growing tissues and tumors. Crucially, we show that this window, without any customization, is suitable for numerous anatomical locations in mice using a rapid and standardized implantation procedure. This low-cost device represents a substantial technological and performance advance that facilitates intravital imaging in diverse contexts in higher organisms, opening new avenues forin vivoimaging of soft and fragile tissues.

One-sentence summary

This study presents a versatile, fully flexible imaging window that acts as an implantable transparent ‘second skin’ for small laboratory animalin vivoimaging.
More comprehensive proprioceptive stimulation of the hand amplifies its cortical processing
Authors: Hakonen Maria , Nurmi Timo , Vallinoja Jaakko , Jaatela Julia , Piitulainen Harri
Published: February 2021

Corticokinematic coherence (CKC) quantifies the phase coupling between limb kinematics and cortical neurophysiological signals reflecting proprioceptive feedback to the primary sensorimotor (SM1) cortex. We studied CKC to proprioceptive stimulation (i.e. movement-actuator-evoked movements) of right-hand digits (index, middle, ring and little) performed simultaneously or separately. CKC was computed between magnetoencephalography (MEG) and finger acceleration signals. The strongest CKC was obtained by stimulating the fingers simultaneously at fixed 3-Hz frequency, and can, therefore, be recommended as design for fast functional localization of the hand area in the primary sensorimotor (SM1) cortex using MEG. The peaks of CKC sources were concentrated in the hand region of the SM1 cortex, but did not follow consistent somatotopic order. This result suggests that spatial specificity of MEG is not sufficient to separate proprioceptive finger representations of the same hand adequately or that their representations are overlapping.
Outcomes of Progranulin Gene Therapy in the Retina are Dependent on Time of Delivery
Authors: Zin Emilia A. , Han Daisy , Tran Jennifer , Morisson-Welch Nikolas , Visel Meike , Kuronen Mervi , Flannery John G.
Published: February 2021

Neuronal ceroid lipofuscinosis (NCL) is a family of neurodegenerative diseases caused by mutations to genes related to lysosomal function. One variant, CNL11, is caused by mutations to the gene encoding the protein progranulin. Primarily secreted by microglia, progranulin regulates neuronal lysosomal function once endocytosed. Absence of progranulin causes cerebellar atrophy, seizures, ataxia, dementia and vision loss. As progranulin gene therapies targeting the brain are developed, it is also advantageous to focus on the retina, as its characteristics are beneficial for gene therapy development: the retina is easily visible through direct imaging, can be assessed through quantitative methodsin vivo, requires smaller amounts of AAV and AAV can be administered via a less invasive surgery. In this study we characterize the retinal degeneration in a progranulin knockout mouse model of CLN11 and study the effects of gene replacement at different time points. All mice heterologously expressing progranulin showed reduction in lipofuscin deposits and microglia infiltration. While mice that receive systemic AAV9.2YF-scCAG-PGRN at post-natal day 3 or 4 show a reduction in retina thinning, mice injected intravitreally at months 1 and 6 with 7m8-scCAG-PGRN show no improvement, and mice injected at 12 months of age show increased retinal thinning in comparison to their controls. Thus, delivery of progranulin proves to be time-sensitive, requiring early administration for optimal therapeutic benefit.
Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape
Authors: Brown Jonathan C. , Goldhill Daniel H. , Zhou Jie , Peacock Thomas P. , Frise Rebecca , Goonawardane Niluka , Baillon Laury , Kugathasan Ruthiran , Pinto Andreia L. , McKay Paul F. , Hassard Jack , Moshe Maya , Singanayagam Aran , Burgoyne Thomas ,   the ATACCC Investigators,   PHE Virology Consortium, Barclay Wendy S.
Published: February 2021

Lineage B.1.1.7 (Variant of Concern 202012/01) is a new SARS-CoV-2 variant which was first sequenced in the UK in September 2020 before becoming the majority strain in the UK and spreading worldwide. The rapid spread of the B.1.1.7 variant results from increased transmissibility but the virological characteristics which underpin this advantage over other circulating strains remain unknown. Here, we demonstrate that there is no difference in viral replication between B.1.1.7 and other contemporaneous SARS-CoV-2 strains in primary human airway epithelial (HAE) cells. However, B.1.1.7 replication is disadvantaged in Vero cells potentially due to increased furin-mediated cleavage of its spike protein as a result of a P681H mutation directly adjacent to the S1/S2 cleavage site. In addition, we show that B.1.1.7 does not escape neutralisation by convalescent or post-vaccination sera. Thus, increased transmission of B.1.1.7 is not caused by increased replication, as measured on HAE cells, or escape from serological immunity.
A mouse model of occult intestinal colonization demonstrating antibiotic-induced outgrowth of carbapenem-resistantEnterobacteriaceae
Authors: Sim Choon K. , Kashaf Sara Saheb , Conlan Sean , Stacy Apollo , Proctor Diana M. , Almeida Alexandre , Bouladoux Nicolas , Chen Mark ,   NISC Comparative Sequencing Program, Finn Robert D. , Belkaid Yasmine , Segre Julia A.
Published: February 2021

Background

The human intestinal microbiome is a complex community that contributes to host health and disease. In addition to normal microbiota, pathogens like carbapenem-resistantEnterobacteriaceaemay be asymptomatically present. When these bacteria are present at very low levels, they are often undetectable in hospital surveillance cultures, known as occult or subclinical colonization. Through the use of antibiotics, these subclinical pathogens can increase to sufficiently high levels to become detectable, in a process called outgrowth. However, little is known about the interaction between gut microbiota andEnterobacteriaceaeduring occult colonization and outgrowth.

Results

We developed a clinically relevant mouse model for studying occult colonization. Conventional wild-type mice without antibiotic pre-treatment were exposed toK. pneumoniaebut rapidly tested negative for colonization. This occult colonization was found to perturb the microbiome as detected by both 16S rRNA amplicon and shotgun metagenomic sequencing. Outgrowth of occultK. pneumoniaewas induced either by a four-antibiotic cocktail or by individual receipt of ampicillin, vancomycin or azithromycin, which all reduced overall microbial diversity. Notably, vancomycin was shown to triggerK. pneumoniaeoutgrowth in only a subset of exposed animals (outgrowth-susceptible). To identify factors that underlie outgrowth susceptibility, we analyzed microbiome-encoded gene functions and were able to classify outgrowth-susceptible microbiomes using pathways associated with mRNA stability. Lastly, an evolutionary approach illuminated the importance of xylose metabolism inK. pneumoniaecolonization, supporting xylose abundance as a second susceptibility indicator. We showed that our model is generalizable to other pathogens, including carbapenem-resistantEscherichia coliandEnterobacter cloacae.

Conclusions

This study suggests that microbiota mRNA and small-molecule metabolites may be used to predict outgrowth-susceptibility. Our modeling of occult colonization and outgrowth could help the development of strategies to mitigate the risk of subsequent infection and transmission in medical facilities and the wider community.
Approximate Bayesian computation untangles signatures of contemporary and historical hybridization between two endangered species
Authors: Dittberner Hannes , Tellier Aurelien , de Meaux Juliette
Published: February 2021

Contemporary gene flow, when resumed after a period of isolation, can have crucial consequences for endangered species, as it can both increase the supply of adaptive alleles and erode local adaptation. Determining the history of gene flow and thus the importance of contemporary hybridization, however, is notoriously difficult. Here, we focus on two endangered plant species,Arabis nemorensisandA. sagittata, which hybridize naturally in a sympatric population located on the banks of the Rhine. Using reduced genome sequencing, we determined the phylogeography of the two taxa but report only a unique sympatric population. Molecular variation in chloroplast DNA indicated thatA. sagittatais the principal receiver of gene flow. Applying classical D-statistics and its derivatives to whole-genome data of 35 accessions, we detect gene flow not only in the sympatric population but also among allopatric populations. Using an Approximate Bayesian computation approach, we identify the model that best describes the history of gene flow between these taxa. This model shows that low levels of gene flow have persisted long after speciation. Around 10 000 years ago, gene flow stopped and a period of complete isolation began. Eventually, a hotspot of contemporary hybridization was formed in the unique sympatric population. Occasional sympatry may have helped protect these lineages from extinction in spite of their extremely low diversity.
sweetD: An R package using Hoeffding’s D statistic to visualise the dependence between M and A for large numbers of gene expression samples
Authors: Barton Amber
Published: February 2021

MA plots are frequently used to examine the relationship between gene abundance and differences in gene expression between two samples. In good quality samples without batch effects or outliers, there is generally no or little relationship between intensity and log fold difference. As the number of MA plots increases quadratically with the number of samples, for large datasets the number of potential MA plots becomes prohibitively high for manual examination. Here we present an R package calculating and visualising the dependence between abundance and log fold difference for large numbers of samples using Hoeffding’s D statistic.

Availability and implementation

sweetD is currently available as an R package on Githubhttps://github.com/amberjoybarton/sweetD.
Dynamic expression of smRNA from fecal exosome in disease progression of an inflammatory bowel disorder mouse model
Authors: Manning Sean , Torii Shisui , Atkins Hannah M , Kawasawa Yuka Imamura
Published: February 2021

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract affecting over 3 million adults in the United States. Despite being widespread, reliable early diagnostic tests are not available. We examined exosomal small RNA (smRNA), specifically targeting microRNA (miRNA) and piRNA from the stool samples of IBD model mice, interleukin 10 knockout mice (IL-10 KO), as a potential diagnostic marker. Stool samples were specifically chosen because they are readily available, and collection is noninvasive. At the end of the experimental period, the gastrointestinal (GI) tract was collected, and disease severity was scored. Histopathology showed a significant increase in inflammation and proliferation within the proximal and distal large intestines. smRNA profiles were examined upon conventional housing (start-point) which is a determinant factor of spontaneous IBD progression in the IL-10 KO mice, terminal illness (end-point), and 6 weeks before the end-point (mid-point), when the mice were still phenotypically healthy. We found 504 smRNA that were significantly differentially expressed between before symptom onset and terminal sedation. These changes were not detected in wild-type samples. Moreover, clustering analysis of expression changes over the disease progression identified a unique set of smRNAs that primarily target pro-inflammatory or anti-inflammatory genes. The expression of smRNAs that suppresses pro-inflammatory genes was higher at 6 weeks before terminal sedation, suggesting the downregulation of the pro-inflammatory genes advances the terminal illness of the IBD. In summary, our study proposes that fecal exosomal smRNA profiling offers a new opportunity to monitor the inflammatory status of the gut with a capability of detecting its pro-inflammatory (asymptomatic) status. Our next step is to understand the spatiotemporal interplay of these exosomes and the host cells in the gut as well as the complete biochemical makeup of fecal exosomes, such as mRNA, DNA, protein, and lipids. This will lead to an exciting development of reengineered exosomes that can be utilized to treat or even prevent the pro-inflammatory colonic lesion while the host is still clinically asymptomatic.
Morningness-eveningness assessment from mobile phone communication analysis
Authors: Roy Chandreyee , Monsivais Daniel , Bhattacharya Kunal , Dunbar Robin I.M. , Kaski Kimmo
Published: February 2021

Human behaviour follows a 24-hour rhythm and is known to be governed by the individual chronotypes. Due to the widespread use of technology in our daily lives, it is possible to record the activities of individuals through their different digital traces. In the present study we utilise a large mobile phone communication dataset containing time stamps of calls and text messages to study the circadian rhythms of anonymous users in a European country. After removing the effect of the synchronization of East-West sun progression with the calling activity, we used two closely related approaches to heuristically compute the chronotypes of the individuals in the dataset, to identify them as morning persons or “larks” and evening persons or “owls”. Using the computed chronotyes we showed how the chronotype is largely dependent on age with younger cohorts being more likely to be owls than older cohorts. Moreover, our analysis showed how on average females have distinctly different chronotypes from males. Younger females are more larkish than males while older females are more owlish. Finally, we also studied the period of low calling activity for each of the users which is considered as a marker of their sleep period during the night. We found that while “extreme larks” tend to sleep more than “extreme owls” on the weekends, we do not observe much variation between them on weekdays. In addition, we have observed that women tend to sleep even less than males on weekdays while there is not much difference between them on the weekends.