bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in brain structure and function in a multisport cohort of retired female and male athletes, many years after suffering a concussion. The ICHIRF-BRAIN Study
Authors: Turner Michael , Belli Antonio , Castellani Rudolph J. , McCrory Paul
Published: July 2022

Mild traumatic brain injury is widely regarded as a misnomer: it is globally a major cause of disability and is hypothesized as a potential causal factor in subsequent neurodegeneration. Commonly arising in sport, mounting evidence of varying degrees of cognitive impairment in retired athletes exposed to repeated concussions motivates close examination of its cumulative effects on the brain. Studying a cohort of 125 retired athletes with a mean of 11 reported concussions and 36 matched controls with none, here we evaluated whole-brain volumetric and subcortical morphological effects with Bayesian regression models and functional connectivity effects with network-based statistics. Estimates of potential cognitive impact were derived from meta-analytic functional mapping based on 13,459 imaging studies. Across the array of brain structural and functional effects identified, regions significantly lower in volume in the concussed group included, in order of greatest effect size, the middle frontal gyrus, hippocampus, supramarginal gyrus, temporal pole, and inferior frontal gyrus. Conversely, brain regions significantly larger within the athlete group included, in order of greatest effect size, the hippocampal and collateral sulcus, middle occipital gyrus, medial orbital gyrus, caudate nucleus, lateral orbital gyrus, and medial segment to the postcentral gyrus (all significant with 95% Bayesian credible interval). Subcortical morphology analysis corroborated these findings, revealing a significant, age-independent relationship between inward deformation of the hippocampus and the number of concussions sustained (corrected-p<0.0001). Functional connectivity analyses revealed a distinct brain network with significantly increased edge strength in the athlete cohort comprising 150 nodes and 400 edges (corrected-p=0.02), with the highest degree nodes including the pre-central and post-central gyri and right insula. The functional communities of the greatest eigenvector centralities corresponded to motor domains. Numerous edges of this network strengthened in athletes were significantly weakened with increasing bouts of concussion, which included disengagement of the frontal pole, superior frontal, and middle frontal gyri (p=0.04). Aligned to meta-analytic neuroimaging data, the observed changes suggest possible functional enhancement within the motor, sensory, coordination, balance, and visual processing domains in athletes, attenuated by concussive head injury with a negative impact on memory and language. That such changes are observed many years after retirement from impact sport suggests strong repetition effects and/or underpinning genetic selection factors. These findings suggest that engagement in sport may benefit the brain across numerous domains, but also highlights the potentially damaging effects of concussive head injury.
Perceived Barriers and Facilitators of Using Synchronous Telerehabilitation of Physical and Occupational Therapy in Musculoskeletal Disorders: A Scoping Review
Authors: Tao Lydia , Carboni-Jiménez Andrea , Turner Kimberly , Østbø Nora , Aguila Kylene , Boruff Jill , Carrier Marie-Eve , Krishnan Ankur , Azar Christiane , Guindon Andréanne , Viens Natacha , Ahmed Sara , Thombs Brett D. , Kwakkenbos Linda
Published: July 2022

Purpose

Physical and occupational therapy interventions are increasingly delivered through videoconferencing to overcome barriers related to face-to-face delivery. The objective of this scoping review was to identify barriers and facilitators of using synchronous telerehabilitation to deliver these interventions for musculoskeletal disorders.

Materials and Methods

MEDLINE, EMBASE, PsycInfo, CINAHL, Cochrane Library, and ProQuest Dissertations and Theses databases were searched in May 2020. Qualitative and quantitative studies in any language that described barriers and facilitators of using synchronous videoconferencing for physical or occupational interventions or assessments for individuals with musculoskeletal diseases were eligible.

Results

Twenty-three publications were included that reported 59 facilitators and 41 barriers to using telerehabilitation. All included studies (100%) reported on facilitators, and 20 (87%) studies also reported on barriers. Most commonly reported facilitators included convenience and accessibility of services, audio and visual quality, and financial and time savings. Most commonly reported barriers included technological issues, privacy concerns, impersonal connection, and difficulty establishing rapport between patients and healthcare professionals.

Conclusions

Factors including quality and user-friendliness may facilitate the delivery of physical or occupational therapy interventions or assessments for musculoskeletal diseases using telerehabilitation. Strategies to address key barriers should be considered when developing and implementing such interventions or assessments.

Implications for rehabilitation

Videoconferencing with a healthcare professional can be an effective way to deliver patient-centered physical or occupational therapy telerehabilitation interventions.

Strategies to combat barriers to using telerehabilitation may include using a stable, high-quality videoconferencing platform, enhancing self-efficacy to using videoconferencing amongst patients and health care providers, and addressing concerns related to privacy.

During the current COVID-19 pandemic, the present study provides insight into the successful development and delivery of physical or occupational telerehabilitation interventions for at-risk populations.
STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: a structured protocol
Authors: Forshaw Denise , Wall Emma C , Prescott Gordon , Dehbi Hakim-Moulay , Green Angela , Attree Emily , Hismeh Lyth , Strain William D , Crooks Michael G , Watkins Caroline , Robson Chris , Banerjee Rajarshi , Lorgelly Paula , Heightman Melissa , Banerjee Amitava ,   the STIMULATE-ICP trial team
Published: July 2022

Introduction

Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway (ICP) approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace.

Methods and analysis

This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an ICP (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that ICP interventions are delivered as “standard of care” in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 NHS LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes (e.g. EQ-5D-5L, GAD-7, PHQ-9, WSAS, PDQ-5, CFQ, SF-12, MRC Dyspnoea score) at 3 months. The trial also includes an economic evaluation which will be described separately.

Ethics and dissemination

The protocol was reviewed by South Central - Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™has UKCA certification (752965). The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations.

Trial registration number

ISRCTN10665760
Methods and Outcomes Reporting in Exercise-Based Cardiovascular Rehabilitation Research: a cross-sectional analysis
Authors: Freccia Guilherme W , dos Santos Rafaella Zulianello , De Lucca Leonardo , Korbes Andrea Schaefer , de Carvalho Tales
Published: July 2022

The poor reporting quality of methods and outcomes is relatively recognized in the biomedical field. Its prevalence and implications have been studied in the cardiovascular rehabilitation literature but not so extensively in exercise-based trials. Our main objective was to cross-sectionally estimate the prevalence of both methodological and outcome reporting items in CVR trials with EBI. We also searched for associations (secondary outcomes) between (1) the effect size reported and the direction of the primary outcome, as well as (2) associations with the frequency of Spin. We cross-sectionally screened the sample of eligible trials dated between 2017 and 2021, and then collected the prevalence of methodological and outcome characteristics, independent and blinded manner. Our study shows that there was an insufficient reporting of methods and outcomes. Also, studies reporting effect size measures had a lower chance of Spin. The primary outcome effect size was not reported in 35% of the studies SES. However, more than 2/3 of the sample (69%) had a statement in the discussion or conclusion sections mentioning clinical relevance or meaningful benefit of the statistically significant results. Selective outcome reporting has important implications for translating science into practice, once not so threatens the validity of an intervention effectiveness, but also frustrates the use of its evidence in meta-analyses.

What is new?

Our study shows that randomized controlled trials with cardiovascular rehabilitation based on exercise insufficiently reported the various methods and outcomes characteristics.

Although nearly 70% studies had stated its outcomes as clinically meaningful within our sample, about 41%of the studies clearly stated the primary outcome confidence intervals.

More than half of the sample presented at least one spin in the results section, and studies reporting effect size measures had a lower chance of Spin.

40% of the studies within our sample did not report a priori sample size calculation, with 1/4 not stating the number of randomized subjects that could meet the intended power.

We did not find any associations regarding the direction of the results (positive or negative) and the prevalence of spin, contrary to what have been found in the literature.
Symbiosis-driven development in an early branching metazoan
Authors: Ohdera Aki H. , Darymple Justin , Avila-Magaña Viridiana , Sharp Victoria , Watson Kelly , McCauley Mark , Steinworth Bailey , Diaz-Almeyda Erika M. , Kitchen Sheila A. , Poole Angela Z. , Bellantuono Anthony , Haridas Sajeet , Grigoriev Igor V. , Goentoro Lea , Vallen Elizabeth , Baker David M. , LaJeunesse Todd C. , Loesgen Sandra , Martindale Mark Q. , DeGennaro Matthew , Fitt William K. , Medina Mónica
Published: July 2022

Microbes can initiate developmental gene regulatory cascades in animals. The molecular mechanisms underlying microbe-induced animal development and the evolutionary steps to integrate microbial signals into regulatory programs remain poorly understood. In the upside-down jellyfishCassiopea xamachana, a dinoflagellate endosymbiont initiates the life stage transition from the sessile polyp to the sexual medusa. We found that metabolic products derived from symbiont carotenoids may be important to initiateC. xamachanadevelopment, in addition to expression of conserved genes involved in medusa development of non-symbiotic jellyfish. We also revealed the transcription factor COUP is expressed during metamorphosis, potentially as a co-regulator of nuclear receptor RXR. These data suggest relatively few steps may be necessary to integrate symbiont signals into gene regulatory networks and cements the role of the symbiont as a key trigger for life history transition inC. xamachana.
Microaerophilic activated sludge system for ammonia recovery from high-strength nitrogenous wastewater: Performance and microbial communities
Authors: Tsukamoto Hiroki , Phan Hop Van , Suenaga Toshikazu , Yasuda Shohei , Kuroiwa Megumi , Riya Shohei , Ogata Atsushi , Hori Tomoyuki , Terada Akihiko
Published: July 2022

A transition to ammonia recovery from wastewater has started; however, a technology for sustainable nitrogen retention in the form of ammonia is still in development. This study validated a microaerophilic activated sludge (MAS) system to efficiently retain ammonia from high-strength nitrogenous wastewater. The MAS is based on conventional activated sludge (CAS) with aerobic and settling compartments. Low dissolved oxygen (DO) concentrations (<0.1 mg/L) and short solid retention times (SRTs) (<5 d) eliminated nitrifying bacteria. The two parallel MASs were successfully operated for 300 d and had ammonia retention of 101.7 ± 24.9% and organic carbon removal of 85.5 ± 8.9%. The MASs mitigated N2O emissions with an emission factor of <0.23%, much lower than the default value of CAS (1.6%). A short-term step-change test demonstrated that N2O indicated the initiation of nitrification and the completion of denitrification in the MAS. The parallel MASs had comparable microbial diversity, promoting organic carbon oxidation while inhibiting ammonia-oxidizing microorganisms (AOMs), as revealed by 16S rRNA gene amplicon sequencing, qPCR of functional genes, and fluorescent in situ hybridization of β-Proteobacteria AOB. The microbial analyses also uncovered that filamentous bacteria were positively correlated with effluent turbidity. Together, controlling DO and SRT achieved successful ammonia retention, mainly by suppressing AOM activity. This process represents a new nitrogen management paradigm.

Synopsis

Moving from nitrogen removal to nitrogen recovery is critical for establishing a sustainable society. We provided proof-of-the-concept for a novel ammonia retention technology by retrofitting an activated sludge system.
Effects ofWolbachiaon transposable element activity largely depend onDrosophila melanogasterhost genotype
Authors: Eugénio Ana T. , Marialva Marta S. P. , Beldade Patrícia
Published: July 2022

Transposable elements (TEs) are repetitive DNA sequences capable of changing position in host genomes, thereby causing mutations. TE insertions typically have deleterious effects but they can also be beneficial. Increasing evidence of the contribution of TEs to adaptive evolution further raises interest in understanding what factors impact TE activity. Based on previous studies associating the bacterial endosymbiontWolbachiato changes in the abundance of piRNAs, a mechanism for TE repression, and to transposition of specific TEs, we hypothesized thatWolbachiainfection would interfere with TE activity. We tested this hypothesis by studying expression of 14 TEs in a panel of 25Drosophila melanogasterhost genotypes, naturally infected withWolbachiaand annotated for TE insertions. The host genotypes differed significantly inWolbachiatiters inside individual flies, with broad-sense heritability around 20%, and in the number of TE insertions, which depended greatly on TE identity. By removingWolbachiafrom the target host genotypes, we generated a panel of 25 pairs ofWolbachia-positive andWolbachia-negative lines in which we quantified transcription levels our target TEs. We found variation in TE expression that was dependent onWolbachiastatus, TE identity, and host genotype. Comparing between pairs ofWolbachia-positive andWolbachia-negative flies, we found thatWolbachiaremoval affected TE expression in 23.7% of the TE-genotype combinations tested, with up to 4.6 times differences in median level of transcript. Our data shows thatWolbachiacan impact TE activity in host genomes, underscoring the importance this endosymbiont can have in the generation of genetic novelty in hosts.
Single-molecule localization microscopy reveals the ultrastructural root constitution of distal appendages in expanded mammalian centrioles
Authors: Chang Ting-Jui Ben , Hsu Jimmy Ching-Cheng , Yang T. Tony
Published: July 2022

Distal appendages (DAPs) are vital in cilia formation, mediating vesicular and ciliary docking to the plasma membrane during early ciliogenesis. Although numerous DAP proteins arranging a nine-fold symmetry have been studied using superresolution microscopy analyses, the extensive ultrastructural understanding of the DAP root structure developing from the centriole wall remains elusive owing to insufficient resolution. Here, we proposed a pragmatic imaging strategy for two-color single-molecule localization microscopy of swellable mammalian DAP proteins. Importantly, our imaging workflow enables us to push the resolution limit of a light microscope well close to an electron microscopy level, thus achieving an unprecedented λ/200 mapping precision inside intact cells. Upon this workflow, we unravel the ultraresolved higher-order protein complexes of the core DAP. Intriguingly, C2CD3, microtubule triplet, and ODF2 jointly constitute the spatial basis of DAP, suggesting a unique configuration of the DAP assembly. Moreover, our results show that the distal-layered ODF2 labeled at the N- and C-terminus construct a fastening unit encircling the microtubule triplets. Together, we develop an organelle-based drift correction protocol and a two-color solution with minimum crosstalk, allowing a robust localization microscopy imaging of expanded cellular structures deep into the gel-specimen composites.
Cohesin is involved in transcriptional repression of stage-specific genes in the human malaria parasite
Authors: Rosa Catarina , Singh Parul , Sinha Ameya , Preiser Peter R , Dedon Peter C , Baumgarten Sebastian , Scherf Artur , Bryant Jessica M
Published: July 2022

The most virulent human malaria parasite, Plasmodium falciparum, has a complex life cycle between its human host and mosquito vector. Each stage is driven by a specific transcriptional program, but with a relatively high ratio of genes to specific transcription factors, it is unclear how genes are activated or silenced at specific times. The P. falciparum genome is relatively euchromatic compared to the mammalian genome, except for specific genes that are uniquely heterochromatinized via HP1. There seems to be an association between gene activity and spatial organization; however, the molecular mechanisms behind genome organization are unclear. While P. falciparum lacks key genome-organizing proteins found in metazoans, it does have all core components of the cohesin complex. In other eukaryotes, cohesin is involved in sister chromatid cohesion, transcription, and genome organization. To investigate the role of cohesin in P. falciparum, we combined genome editing, mass spectrometry, chromatin immunoprecipitation and sequencing (ChIP-seq), and RNA sequencing to functionally characterize the cohesin subunit Structural Maintenance of Chromosomes protein 3 (SMC3). SMC3 knockdown in early stages of the intraerythrocytic developmental cycle (IDC) resulted in significant upregulation of a subset of genes involved in erythrocyte egress and invasion, which are normally expressed at later stages. ChIP-seq of SMC3 revealed that over the IDC, enrichment at the promoter regions of these genes inversely correlates with their expression and chromatin accessibility levels. These data suggest that SMC3 binding helps to repress specific genes until their appropriate time of expression, revealing a new mode of stage-specific, HP1-independent gene repression in P. falciparum.
Blood Chemistry Analysis in an Active Pneumocystis Pneumonia (PCP) Model Treated with Selective CARD9 Inhibitor BRD5529
Authors: Kottom Theodore J. , Schaefbauer Kyle , Limper Andrew H.
Published: July 2022

Background

Pneumocystis pneumonia (PCP) in AIDS and other immunosuppressive states that result from absence of CD4 lymphocytic immunity, continues to be a significant cause of morbidity and mortality. We and others have shown the importance of CARD9 in PCP and other fungal infections, respectively. BRD5529 has been shown to be an effective in vitro and in vivo (18 hour) inhibitor of Pneumocystis β-glucans induced proinflammatory response. These recent results, along with recent general safety and toxicology assessments suggests the application of BRD5529 in an active PCP mouse model of infection to assess initial blood toxicology parameters.

Methods

To assess preliminary blood toxicology, mice were injected intraperitoneally (IP) daily either with vehicle or BRD5529 at 1.0 mg/kg for one week starting at the 6th week of the PCP mouse model. After one week, mice were sacrificed, and blood collection postmortem was performed for blood chemistry analysis.

Results

Analysis of blood chemistry showed a significant reduction in blood urea nitrogen (BUN) in the BRD5529 IP treated PCP mice cohort compared to the vehicle control group. All other blood chemistry parameters were not significantly different between the two groups.

Conclusions

BRD5529 in this preliminary PCP treatment model displayed only significant changes in BUN levels in the BRD5529 treatment group versus the vehicle control group. All other blood chemistry parameters were statistically similar between the two groups.
A synthetic C2 auxotroph of Pseudomonas putida for evolutionary engineering of alternative sugar catabolic routes
Authors: Wirth Nicolas T. , Gurdo Nicolás , Krink Nicolas , Verdú Àngela Vidal , Férnandez-Cabezón Lorena , Wulff Tune , Nikel Pablo I.
Published: July 2022

Acetyl-coenzyme A (AcCoA) is a metabolic hub in virtually all living cells, serving as both a key precursor of essential biomass components and a metabolic sink for catabolic pathways of a large variety of substrates. Owing to this dual role, tight growth-production coupling schemes can be implemented around the AcCoA node. Inspired by this concept, a synthetic C2 auxotrophy was implemented in the platform bacterium Pseudomonas putida through an in silico-guided engineering approach. A growth-coupling strategy, driven by AcCoA demand, allowed for direct selection of an alternative sugar assimilation route—the phosphoketolase (PKT) shunt from bifidobacteria. Adaptive laboratory evolution forced the synthetic auxotroph to integrate the PKT shunt to restore C2 prototrophy. Large-scale structural chromosome rearrangements were identified as possible mechanisms for adjusting the network-wide proteome profile, resulting in improved PKT-dependent growth phenotypes. 13C-based metabolic flux analysis revealed an even split between the native Entner-Doudoroff and the synthetic PKT pathway for glucose processing, leading to enhanced carbon conservation. These results demonstrate that the P. putida metabolism can be radically rewired to incorporate a synthetic C2 metabolism, creating novel network connectivities and highlighting the importance of unconventional engineering strategies to support efficient microbial production.
Ezh2knockout in B cells impairs plasmablast differentiation and ameliorates lupus-like disease in MRL/lprmice
Authors: Zheng Xiaoqing , Dozmorov Mikhail G , Strohlein Colleen E , Bastacky Sheldon , Sawalha Amr H
Published: July 2022

Objectives

Enhancer of zeste homolog 2 (EZH2) regulates B cell development and differentiation. We have previously demonstrated increased EZH2 expression in peripheral blood mononuclear cells isolated from lupus patients. The goal of this study was to evaluate the role of B cell EZH2 expression in lupus pathogenesis.

Methods

We generated an MRL/lprmouse with floxedEzh2, which was crossed with CD19-Cre mice to examine the effect of B cell EZH2 deficiency in MRL/lprlupus-prone mice. Differentiation of B cells was assessed by flow cytometry. Single cell RNA sequencing and single cell B cell receptor sequencing were used to investigate compositional and functional changes of B cell subsets.In vitroB cell culture with an XBP1 inhibitor was performed. EZH2 and XBP1 mRNA levels in CD19+B cells isolated from SLE patients and healthy controls were analyzed.

Results

We show thatEzh2deletion in B cells significantly decreased autoantibody production and improved glomerulonephritis. B cell development was altered in the bone marrow and spleen of EZH2-deficient mice. Differentiation of plasmablasts was impaired. Single cell RNA sequencing showed that XBP1, a key transcription factor in B cell development, is downregulated in the absence of EZH2. Inhibiting XBP1in vitroimpairs plasmablast development similar to EZH2-deficient mice. Single cell B cell receptor RNA sequencing revealed defective immunoglobulin class switch recombination in EZH2-deficient mice. In human lupus B cells, we observed a strong correlation between EZH2 and XBP1 mRNA expression levels.

Conclusion

EZH2 overexpression in B cells contributes to disease pathogenesis in lupus.
Frequent pulse disturbances influence resistance and resilience in tropical marine microbial communities
Authors: Wijaya Winona , Suhaimi Zahirah , Xin’Er Cherlyn Chua , Sunil Rohan Shawn , Kolundžija Sandra , Bin Rohaizat Ahmad Muzakkir , Md. Azmi Norzarifah Binti , Hazrin-Chong Nur Hazlin , Lauro Federico M.
Published: July 2022

The Johor Strait separates the island of Singapore from Peninsular Malaysia. A 1-kilometer causeway built in the early 1920s in the middle of the Strait effectively blocks water flowing to/from either side, resulting in low water turnover rates and build-up of nutrients in the inner Strait. We have previously shown that short-term rather than seasonal environmental changes influence microbial community composition in the Johor Strait. Here, we present a temporally-intensive study that uncovers the drivers keeping the microbial populations in check. We sampled the surface water at four sites in the inner Eastern Johor Strait every other day for two months, measured various water quality parameters, and analysed 16S amplicon sequences and flow-cytometry counts. We discovered that microbial community succession revolves around a common stable state resulting from frequent pulse disturbances. Among these, sporadic riverine freshwater input and regular tidal currents influence bottom-up controls including the availability of the limiting nutrient nitrogen and its biological release in readily available forms. From the top-down, marine viruses and predator bacteria (e.g. Saprospiraceae family) limit the proliferation of microbes in the water. Harmful algal blooms, which have been observed historically in these waters, may occur when there are gaps in the top-down and bottom-up controls. This study uncovers the complex interaction between these factors contributing to a low-resistance but high-resilience microbial community and speculate about the rare events that could lead to the occurrence of an algal bloom.
Extracellular Vesicles derived from Apis mellifera Royal Jelly promote wound healing by modulating inflammation and cellular responses
Authors: Alvarez S. , Contreras-Kallens P. , Aguayo S. , Ramirez O. , Vallejos C. , Ruiz J. , Carrasco-Gallardo E. , Troncoso-Vera S. , Morales B. , Schuh C.M.A.P.
Published: July 2022

Apis mellifera Royal Jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. Several active compounds have been identified, however, the mechanisms of action still remain widely unknown. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs) and in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing associated effects. Molecular analysis of RJEVs verified the presence of important conserved exosomal markers such as CD63 and syntenin, as well as cargo molecules MRJP1, defensin-1 and jellein-3. RJEV internalization analysis demonstrated the involvement of membrane fusion as well as macropinocytosis or clathrin-dependent endocytosis into mammalian cells. Furthermore, RJEVs have demonstrated to modulate MSCs differentiation and secretome, as well as decrease LPS-induced inflammation in RAW 264.7 macrophages by blocking the MAPK pathway. In vivo studies confirmed anti-bacterial effects of RJEVs, and demonstrated an acceleration of wound healing in a splinted mouse model. Summarizing, this study suggests that RJEVs of potentially exosomal origin play a crucial role in the known effects of RJ by modulating the inflammatory phase and cellular response in wound healing.
Fluorogenic U-rich internal loop (FLURIL) tagging with bPNA enables intracellular RNA and DNA tracking
Authors: Liang Yufeng , Willey Sydney , Chung Yu-Chieh , Lo Yi-Meng , Miao Shiqin , Rundell Sarah , Tu Li-Chun , Bong Dennis
Published: July 2022

We introduce herein a new strategy for intracellular RNA and DNA tracking that is robust, orthogonal and complementary to existing methods:FluorogenicU-RichInternalLoop (FLURIL) tagging with cell-permeable fluorophore-labeled bifacial Peptide Nucleic Acids (fbPNAs). Our approach uses an 8-nt (U4xU4) U-rich internal loop (URIL) in the RNA of interest (ROI) as a compact labeling site for fluorogenic triplex hybridization with a bPNA probe (~1 kD). FLURIL tagging thus replaces a 4 bp duplex stem with a labeled 4-base-triple hybrid stem of similar structure and mass. In contrast to existing strategies for RNA tracking, FLURIL tagging can be applied to internal, genetically encoded URIL RNA siteswith minimal structural perturbation, co-expression of protein-fusion labels or significant increase in molecular weight and steric bulk. We demonstrate effective FLURIL tagging of intracellular (HEK-293) RNAs, ribonucleoprotein (RNP) complexes and live cell (U2-OS) tracking of genomic loci. FLURIL tracking was internally validated by direct comparison with the most widely used live-cell RNA labeling method, MS2-labeling with MCP-HaloTag and Janelia Fluor dyes. In addition, FLURIL-tagging correctly reported on the endogenous RNP in HEK293 cells formed from TAR DNA binding protein 43 (TDP-43-tdTomato) and UG repeat RNA. The FLURIL strategy was also successfully applied to guide RNA (gRNA) in CRISPR-dCas complexes to enable live cell tracking of a low-copy number genomic locus (IDR3), internally benchmarked against MS2/HaloTag labeling of CRISPR-Sirius gRNA targeted to a proximal locus (IDR2). Notably, FLURIL-tagged IDR2 exhibited similar brightness as loci targeted by CRISPR-Sirius gRNA complexes, which bear 8-MS2 hairpins for protein labeling. Together, these experiments show that FLURIL tagging can simply and reliably track intracellular RNA, RNPs, and DNA, with a streamlined molecular footprint relative to other methods. Importantly, these data also indicate that FLURIL tagging is fully compatible with existing labeling methods without crosstalk and may be used to broaden the scope of intracellular RNA and DNA tracking.

Abstract Figure

Scheme 1.

FLURIL-tagging of RNAs with bPNA probes.

(a) Triplex hybridization of a U-rich internal loop (URIL) with bPNA (blue) via base triple formation between the melamine base (M) and two uracil bases (inset). (b) General schematic of labeling strategy described herein. An RNA of interest is engineered to contain an URIL and expressed within the cell, with a fluorogenic bPNA probe introduced via cell culture media. Successful URIL targeting is reported by an increase in emission (green) and confirmed by a previously established RNA binding protein with a fluorescent protein (red) fusion.
Molecular dynamics study of phospholipid membrane electroporation induced by bipolar pulses with different intervals
Authors: Guo Fei , Zhou Jiong , Wang Ji , Qian Kun , Qu Hongchun
Published: July 2022

In this study, PM-EP induced by bipolar pulses with different intervals was investigated by all-atom molecular dynamics simulation. Firstly, PM-EP was formed during the positive pulse of 2ns and 0.5V/nm, then the effects of various intervals of 0, 1, 5, 10ns on PM-EP evolution were investigated, and the dynamic changes of different degrees of PM-EP induced by following negative pulses of 2ns and 0.5V/nm were analyzed. The elimination of the PM-EP during the interval of bipolar pulses were determined and it was related to the degrees of PM-EP and the time of intervals, then the degrees of PM-EP at the end of the intervals were classified and quantitatively defined, namely, Resealing, Destabilizing and Retaining state. These three states appeared due to the combined effect of both the preceding positive pulse and the interval. Furthermore, the evolution of PM-EP in resealing state under negative pulses was similar to that of positive pulses as evidenced by EP formation time and degree of PM-EP, the destabilizing state had the same trends as the resealing state except that the re-electroporation of phospholipid membrane appeared faster and larger degree of EP obtained with the same pulse exposure time. Regarding the retaining state, the negative pulses enhanced PM-EP with more profound water bridges, which can be considered as the effect of electric field superposition. These results can improve our understanding of the fundamental mechanism of bipolar pulse-induced PM-EP.

Graphical Abstract

Highlights

Quantitative and qualitative definition of the three states of the phospholipid membrane electroporation at the end of the intervals.

Clarification that the states of phospholipid membrane electroporation were generated due to the combined effect of positive pulses and intervals.

Quantitative and qualitative comparison the evolution of the states of phospholipid membrane electroporation during the negative pulses.
Impact of health warning labels and calorie labels on selection and purchasing of alcoholic and non-alcoholic drinks: a randomised controlled trial
Authors: Clarke Natasha , Ferrar Jennifer , Pechey Emily , Ventsel Minna , Pilling Mark A , Munafò Marcus R , Marteau Theresa M , Hollands Gareth J
Published: July 2022

Objective

Health warning and calorie labels on alcohol have the potential to reduce consumption at population level but remain unevaluated using robust designs with behavioural outcomes. The aim of the current study is to estimate the impact on selection and actual purchasing of (a) health warning labels (text-only and image-and-text) on alcoholic drinks and (b) calorie labels on alcoholic and non-alcoholic drinks.

Design

Parallel-groups randomised controlled trial.

Setting

Participants selected drinks in a simulated online supermarket, before purchasing them in an actual online supermarket.

Participants

Adults in England and Wales who regularly consumed and purchased beer or wine online (n= 644).

Interventions

Participants were randomised to one of six groups in a between-subjects 3 (Health warning labels (HWLs): i. image-and-text HWL, ii. text-only HWL, iii. no HWL) x 2 (Calorie labels: present vs absent) factorial design.

Main outcome measures

The number of alcohol units selected (with intention to purchase); secondary outcomes included alcohol units purchased and calories selected and purchased.

Results

608 participants completed the study and were included in the primary analysis. There was no evidence of an overall difference for either (a) HWLs, or (b) calorie labels on the number of alcohol units selected [HWLs: F(2,599) = 0.406, p = .666; calorie labels: F(1,599) = 0.002, p = .961]. There was also no evidence of an overall difference on any secondary outcomes, including the number of alcohol units purchased [HWLs: F(2,462) = 1.85, p = .159; calorie labels: F(1,462) = 0.193, p = .661].

In pre-specified subgroup analyses comparing the ‘calorie label only’ group (n = 101) to the ‘no label’ group (n = 104) there was no evidence that calorie labels reduced the number of calories selected [unadjusted means: 1913 calories vs 2203 calories, p = .643]. Amongst the 75% of participants who went on to purchase drinks, those in the ‘calorie label only’ group (n = 74) purchased fewer calories than those in the ‘no label’ group (n = 79) [unadjusted means: 1532 calories vs 2090, p = .028].

Conclusion

There was no evidence that health warning labels reduced the number of alcohol units selected or purchased in an online purchasing setting. There was some evidence suggesting that calorie labels on alcoholic and non-alcoholic drinks may reduce calories purchased. Further evaluation is warranted in suitably powered studies in real world settings.

Trial registration

Pre-registered protocol (https://osf.io/ch2sm/) and prospective ISCRTN registration:https://www.isrctn.com/ISRCTN10313219

Funding

This study was funded by Wellcome [Grant number 206853/Z/17/Z].
Preventing iatrogenic HCV infection: A quantitative risk assessment based on observational data in an Egyptian hospital
Authors: Henriot Paul , Anwar Wagida , El Gaafary Maha , Abdo Samia , Rafik Mona , Hussein Wafaa , Sos Dalia , Magdy Isis , Jean Kevin , Temime Laura
Published: July 2022

When compliance with infection control recommendations is non-optimal, hospitals may play an important role in hepatitis C (HCV) transmission. However, few studies have analysed HCV acquisition risk based on detailed empirical data in order to identify high-risk patient profiles or transmission hotspots.
We used data from a prospective cohort study conducted on 500 patients in the internal medicine and surgery departments of Ain Shams hospital (Cairo, Egypt). We first performed a sequence analysis to describe patient trajectory profiles. Second, we estimated each patient individual risk of HCV acquisition based on ward-specific prevalence and procedures undergone. We then identified within-hospital risk hotspots by computing ward-level risks. A beta regression model was used to highlight upon-admission factors linked to HCV acquisition risk. Finally, ward-focused and patient-focused strategies were assessed for their ability to reduce HCV infection risk.
Sequence analysis identified 4 distinct patient profiles. The estimated HCV acquisition risk varied widely between patients and patient profiles. The risk was found to be higher in the internal medicine hospital compared to the surgery hospital (median: 0.188% IQR [0.142%-0.235%] vs. 0.043%, CI 95%: [0.036%-0.050%]). Upon-admission risk predictors included source of admission, age, reason for hospitalization, and history of anti-schistosomiasis treatment, injection and endoscopy. Patient-focused interventions were found to be most effective to reduce HCV infection risk.
Our results might help reduce the risk of HCV acquisition during hospitalisation in Egypt by targeting enhanced control measures to ward-level transmission hotspots and to at-risk patients identified upon admission.
An unexpected histone chaperone function for the MIER1 histone deacetylase complex
Authors: Wang Siyu , Fairall Louise , Pham Khoa , Ragan Timothy J , Vashi Dipti , Collins Mark O. , Dominguez Cyril , Schwabe John W.R.
Published: July 2022

Histone deacetylases 1 and 2 (HDAC1/2) serve as the catalytic subunit of six distinct families of nuclear complexes. These complexes repress gene transcription through removing acetyl groups from lysine residues in histone tails. In addition to the deacetylase subunit, these complexes typically contain transcription factor and/or chromatin binding activities. The MIER:HDAC complex has hitherto been poorly characterized. Here we show that MIER1 unexpectedly co-purifies with an H2A:H2B histone dimer. We show that MIER1 is also able to bind a complete histone octamer. Intriguingly, we found that a larger MIER1:HDAC1:BAHD1:C1QBP complex additionally co-purifies with an intact nucleosome on which H3K27 is either di- or tri-methylated. Together this suggests that the MIER1 complex acts downstream of PRC2 to expand regions of repressed chromatin and to deposit histone octamer onto nucleosome-depleted regions of DNA.
Sharīʿah scrutiny of Islamic Banks' Financial Compensation Fund in Bangladesh: governance principles in the COVID-19 perspective
Authors: Masum Abdullah , Islam S M Shariful
Published: July 2022

Purpose

The purpose of this study is to critically analyze the Financial Compensation Funds being accumulated by Islamic Banks of Bangladesh in credit-based transactions. In this connection, due to the evolved liquidity crisis amidst the COVID-19, industry opinions are observed that suggest including the compensations or the donation funds directly into the bank's income account. But the Sharīʿah does not permit it. Such alternative proposals of using compensation or donation fund during crises are scrutinized under Sharīʿah principles to come to a logical conclusion.

Design/methodology/approach

The approach followed in the study is textual and discourse analysis through descriptions of ideal Sharīʿah-compliant methods for handling late payment of credit and comparison with the industry practices.

Findings

It is observed that there are conceptual gaps in the industry as is reflected in the Islamic Banking Guideline of Bangladesh. The funds collected from the debtor due to late payment are named as compensation (Ta‘wīḍ) whereas the nature of the transaction is a donation (Tabarru'). The misconception can lead to various Sharīʿah non-compliant activities later with the funds. The proposals brought out in the industry to use such compensation/donation funds during a crisis are a consequence of this. The proposals of using such funds for banks' purposes in any situation are not supported by Sharīʿah principles and are against the Islamic banking philosophy.

Originality/value

The study is very relevant to the current crisis of COVID-19 in the domestic Islamic Banking Industry and also instrumental for the future guidance to stick to the Sharīʿah principles in managing compensation or donation funds by the Islamic Banks.
Impact of a physician's prosocial behavior on the patient's choice: an empirical investigation in online health community
Authors: Wang Jian-Jun , Liu Huiyuan , Cui Xiaocong , Ye Jiao , Chen Haozhe
Published: July 2022

Purpose

The purpose of this paper is to explore the influence of a physician’s prosocial behavior on a patient's choices in the online health community (OHC) context. Moreover, the authors explore how such effects differ across different online word-of-mouth (WOM) and professional titles.

Design/methodology/approach

Guided by the motivation, opportunity and ability (MOA) framework, this paper develops hypotheses and an econometric model. Then this paper used spline regression to test hypotheses on 6,204 physicians at The Good Doctor (www.Haodf.com), which is one of the largest Chinese OHCs. The authors conducted the propensity score matching and difference-in-difference method (PSM-DID) to address the concern about the bias caused by possible endogeneity concerns.

Findings

The authors’ results show that a physician’s prosocial behavior improves a patient's choice only when the strength of a physician’s prosocial behavior is below the tipping point. In addition, the influence of a physician’s prosocial behavior is heterogeneous for physicians with different online WOM and professional titles. For physicians with higher online WOM, the effect of a physician's prosocial behaviors on a patient's choice is positive, while for physicians with lower online WOM, a physician’s prosocial behavior has no impact on a patient’s choice. For physicians with higher professional titles, the quantity of a physician’s prosocial behavior has a positive impact on a patient’s choice, while for physicians with lower professional titles the quality of a physician’s prosocial behavior has a positive impact on a patient’s choice.

Originality/value

This study contributes new knowledge and provides new perspectives to study a patient's choice by addressing the importance of physician's prosocial behavior. With the effort of explicitly explaining the complex mechanisms, this study encourages physicians' engagement in a physician’s prosocial behavior and gives some implications on how to perform the behaviors strategically.
Industry 4.0: what is the relationship between manufacturing strategies, critical success factors and technology adoption?
Authors: Tortorella Guilherme , Kurnia Sherah , Trentin Marcelo , Oliveira Gilson Adamczuk , Setti Dalmarino
Published: July 2022

Purpose

This paper examines the relationship between different manufacturing strategies and Industry 4.0's (I4.0) critical success factors (CSFs) and technology adoption.

Design/methodology/approach

For that, the authors surveyed 165 practitioners from different manufacturers. Participants provided information about the levels of product customization and production volume in their companies. They also indicated the adoption level of I4.0 technologies and CSFs. Using multivariate data techniques, the authors identified four clusters of different manufacturing strategies and two readiness levels based on the establishment of I4.0 CSFs. The adoption level of I4.0 technologies was then cross compared among clusters to identify which technologies are more likely to be supported.

Findings

The findings indicate that, in low-readiness companies, the adoption level of I4.0 technologies does not significantly differ between manufacturing strategies. However, when companies present a higher I4.0 readiness, the adoption of I4.0 technologies seem to vary according to the existing manufacturing strategy.

Originality/value

This study sheds light on the influence that manufacturing strategies may have on the digital transformation of companies, highlighting which strategies are more likely to offer a context to successfully adopt I4.0 technologies. The identification of these relationships helps to define the expectation regarding the company's digital transformation, determining coherent benchmarks and allowing managers to anticipate potential issues.
The lived experience of Australian public library staff during the COVID-19 library closures
Authors: Garner Jane , Wakeling Simon , Hider Philip , Jamali Hamid R. , Kennan Mary Anne , Mansourian Yazdan , Randell-Moon Holly
Published: July 2022

Purpose

The purpose of this paper is to explore the lived experiences of Australian public library staff during the COVID-19 library closures. The study examines the effect of mandated physical library closures on staff well-being, along with the challenges they faced as library operations moved to a remotely delivered model. The paper includes an examination of staff perceptions of their library's value in the lives of their users.

Design/methodology/approach

Semi-structured interviews were undertaken with 15 Australian library staff from three library networks. A process of inductive coding resulted in a thematic description of the participants' experiences of continuing to work during a period of where their libraries were closed due to COVID-19 restrictions.

Findings

Australian public library workers experienced many challenges that affected their well-being during the period of library closures. These included challenges relating to moving library programming to a virtual delivery model, managing significant change in their work lives, managing the emotions of self and others, and concern for the well-being of library users. Positive outcomes relating to skill development and innovative thinking were also reported.

Originality/value

The operational responses to the COVID-19 library closures in Australia and elsewhere have been well reported. This paper takes a different approach by examining the emotional and well-being outcomes for public library staff during these periods of closure.