bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Retroviruses and TDP-43 Proteinopathy Form a Sustaining Feedback to Drive the Intercellular Spread of Neurodegeneration
Authors: Chang Yung-Heng , Dubnau Josh
Published: July 2022

Neurodegenerative disorders are thought to initiate focally and then spread over time through neural circuits. A mechanism that has been proposed to explain this is the inter-cellular movement of misfolded “prion-like” proteins that then recruit normally folded proteins in recipient cells to also adopt pathological conformations. Such a mechanism has been proposed, for example, to explain the propagation of abnormally phosphorylated cytoplasmic inclusions of TAR-DNA-Binding protein (TDP-43) during the progression of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). But unlike transmissible prion diseases such as mad cow disease, which can be caused by ingestion or by injection into animal brains of misfolded PrP, ALS and FTD are not infectious and the injection of phosphorylated and aggregated TDP-43 protein into rodent brains is not sufficient to cause disease phenotypes unless those animals also express high levels of transgenic TDP-43 protein. This suggests a missing component of a positive feedback that is necessary to sustain disease progression. We provide evidence that endogenous retroviruses (ERVs) are that missing component. We demonstrate that ERV expression and TDP-43 proteinopathy are mutually reinforcing. Expression of either the Drosophila ERV, gypsy (mdg4) or the human ERV, HERV-K (HML-2) are each sufficient to stimulate cytoplasmic aggregation of human TDP-43. Importantly. We also demonstrate that viral ERV transmission causes propagation of such TDP-43 pathology to cells that express physiological levels of TDP-43, whether they are in contact or at a distance. This mechanism underlies the toxicity of glial cells to neurons and other glia in a Drosophila in vivo model.
Freshwater connectivity transforms spatially integrated signals of biodiversity
Authors: Littlefair Joanne E. , Hleap José S. , Palace Vince , Rennie Michael D. , Paterson Michael J. , Cristescu Melania E.
Published: July 2022

Aquatic ecosystems offer a continuum of water flow from headwater streams to inland lakes and coastal marine systems. This spatial connectivity influences the structure, function and dynamics of aquatic communities, which are among the most threatened and degraded on earth. Environmental DNA achieves biodiversity surveys in these habitats in a high-throughput, spatially integrated way. Here, we determine the spatial resolution of eDNA in dendritic freshwater networks that are typical of aquatic habitats. Our intensive sampling campaign comprised over 430 eDNA samples across 21 connected lakes, allowing us to analyse detections at a variety of scales, from different habitats within a lake to entire lake networks. We found strong signals of within-lake variation in eDNA distribution reflective of typical habitat use by both fish and zooplankton. Most importantly, we also found that connecting channels between lakes resulted in an accumulation of downstream eDNA detections in lakes with a higher number of inflows, and as networks increased in length. These findings have profound implications for the interpretation of eDNA detections in aquatic ecosystems in global-scale biodiversity monitoring observations.
Genome-wide SNPs reveal the social structure and invasion pathways of the invasive tropical fire ant (Solenopsis geminata)
Authors: Lenancker P , Walsh T , Metcalfe S , Gotzek D , Hoffmann BD , Lach L , Tay WT , Elfekih S
Published: July 2022

Elucidating invasion pathways of invasive species is often challenging because invasive populations frequently have low genetic diversity caused by genetic bottlenecks during introduction events. Genome-wide sequencing such as Restriction Site-Associated DNA Sequencing (RADseq) can overcome these challenges by generating thousands of genome-wide single nucleotide polymorphic (SNP) markers. The tropical fire ant,Solenopsis geminata, is a global invader with low genetic diversity in its introduced range, making RADseq one of the best available methods to investigate its population genetics. We used double digest RADseq to generate 3,834 SNPs to compare the genetic diversity ofS. geminatain its introduced range to its most likely source of introduction, determined the invasion pathways among populations at an unprecedented level of detail for this species, and determined the social structure ofS. geminataworkers collected in 13 locations worldwide. We found that introducedS. geminatawent through a strong genetic bottleneck. We also identified multiple secondary introduction events amongS. geminatapopulations, indicating that the bridgehead effect is an important driver in the global spread of this species. We found that all colonies in the introduced range were polygyne (i.e., with more than one queen) which may increase their invasion success and potential to cause adverse effects.
Host cell neddylation facilitates alphaherpesvirus entry in a virus-specific and cell-dependent manner
Authors: Lee Becky H. , Tebaldi Giulia , Pritchard Suzanne M. , Nicola Anthony V.
Published: July 2022

Herpes simplex virus 1 (HSV-1) commandeers the host cell proteasome at several steps of its replication cycle, including entry. Here we demonstrate that HSV-2, pseudorabies virus (PRV), and bovine herpesvirus 1 (BoHV-1) entry are blocked by bortezomib, a proteasome inhibitor that is a FDA-approved cancer drug. Proteasome-dependent entry of HSV-1 is thought to be ubiquitin-independent. To interrogate further the proteasomal mechanism of entry, we determined the involvement of the ubiquitin-like molecule NEDD8 and the neddylation cascade in alphaherpesvirus entry and infection. MLN4924 is a small-molecule inhibitor of neddylation that binds directly to the NEDD8-activating enzyme. Cell treatment with MLN4924 inhibited plaque formation and infectivity by HSV-1, PRV and BoHV-1 at non-cytotoxic concentrations. Thus, the neddylation pathway is broadly important for alphaherpesvirus infection. However, the neddylation inhibitor had little effect on entry of the veterinary viruses but had a significant inhibitory effect on entry of HSV-1 and HSV-2 into seven different cell types. Wash-out experiments indicated that MLN4924’s effect on viral entry was reversible. Time-of-addition assay suggested that the drug was acting on an early step in the entry process. siRNA knockdown of NEDD8 significantly inhibited HSV entry. In probing the neddylation-dependent step in entry, we found that MLN4924 dramatically blocked endocytic uptake of HSV from the plasma membrane by >90%. In contrast, the rate of HSV entry into cells that support direct fusion of HSV with the cell surface was unaffected by MLN4924. Interestingly, proteasome activity was less important for the endocytic internalization of HSV from the cell surface. The results suggest that the NEDD8 cascade is critical for the internalization step of HSV entry.

IMPORTANCE

Alphaherpesviruses are ubiquitous pathogens of humans and veterinary species that cause lifelong latent infections and significant morbidity and mortality. Host cell neddylation is important for cell homeostasis and for the infection of many viruses, including HSV-1, HSV-2, PRV, and BoHV-1. Inhibition of neddylation by a pharmacologic inhibitor or siRNA blocked HSV infection at the entry step. Specifically, the NEDD8 pathway was critically important for HSV-1 internalization from the cell surface by an endocytosis mechanism. The results expand our limited understanding of cellular processes that mediate HSV internalization. To our knowledge, this is the first demonstration of a function for the neddylation cascade in virus entry.
Comparison of Bayesian Networks, G-estimation and linear models to estimate causal treatment effects in aggregated N-of-1 trials with carry-over effects
Authors: Gärtner Thomas , Schneider Juliana , Arnrich Bert , Konigorski Stefan
Published: July 2022

Abstract

The aggregation of a series of N-of-1 trials presents an innovative and efficient study design, as an alternative to traditional randomized clinical trials. Challenges for the statistical analysis arise when there is carry-over or complex dependencies of the treatment effect of interest.

In this study, we evaluate and compare methods for the analysis of aggregated N-of-1 trials in different scenarios with carry-over and complex dependencies of treatment effects on covariates. For this, we simulate data of a series of N-of-1 trials for Chronic Nonspecific Low Back Pain based on assumed causal relationships parameterized by directed acyclic graphs. In addition to existing statistical methods such as regression models, Bayesian Networks, and G-estimation, we introduce a carry-over adjusted parametric model (COAPM).

The results show that all evaluated existing models have a good performance when there is no carry-over and no treatment dependence. When there is carry-over, COAPM yields unbiased and more efficient estimates while all other methods show some bias in the estimation. When there is known treatment dependence, all approaches that are capable to model it yield unbiased estimates. Finally, the efficiency of all methods decreases slightly when there are missing values, and the bias in the estimates can also increase.

This study presents a systematic evaluation of existing and novel approaches for the statistical analysis of a series of N-of-1 trials. We derive practical recommendations which methods may be best in which scenarios.
A pro-oxidant combination of resveratrol and copper down-regulates hallmarks of cancer and immune checkpoints in patients with advanced oral cancer: Results of an exploratory study (RESCU 004)
Authors: Pilankar Aishwarya , Singhavi Hitesh , Raghuram Gorantla V. , Siddiqui Sophiya , Khare Naveen Kumar , Jadhav Vishalkumar , Tandel Harshali , Pal Kavita , Bhattacharjee Atanu , Chaturvedi Pankaj , Mittra Indraneel
Published: July 2022

Background

Our earlier studies have shown that cell-free chromatin particles (cfChPs) that are released from dying cancer cells are readily internalised by bystander cells leading to activation of two hallmarks of cancer viz. genome instability and inflammation. These hallmarks could be down-regulated by deactivating cfChPs via medium of oxygen radicals generated upon admixing small quantities of the nutraceuticals resveratrol (R) and copper (Cu). In this exploratory study, we investigated whether oral administration of R and Cu (R-Cu) would down-regulate the hallmarks of cancer and immune checkpoints in advanced squamous cell carcinoma of oral cavity (OSCC).

Patients and methods

The study comprised of 25 patients divided into 5 equal groups. Five patients acted as controls; the remaining 20 were given R-Cu in four escalating doses. The lowest dose of R-Cu was 5.6mg and 560ng respectively, and the highest dose was 500mg and 5mg respectively. An initial biopsy was taken from patients at first presentation, and a second biopsy was taken 2 weeks later on the operating table. R-Cu was administered orally twice daily in the intervening period. Confocal microscopy was performed on tumour sections after fluorescent immuno-staining with anti-DNA and anti-histone antibodies to detect presence of cfChPs in the tumour micro-environment (TME). Immunofluorescence analysis was performed for 23 biomarkers representing the 10 Hallmarks of cancer, including 5 immune checkpoints, defined by Hanahan and Weinberg.

Results

Confocal microscopy detected copious presence of cfChPs in TME of OSCC, which were eradicated / deactivated following two-week treatment with R-Cu. Eradication of cfChPs from TME was associated with marked down-regulation of 21 / 23 biomarkers, including the five immune checkpoints. The lower two doses of R-Cu were more effective than the higher doses. No adverse effects attributable to R-Cu were observed.

Conclusion

These results suggest that cfChPs released into TME from dying cancer cells are global instigators for cancer hallmarks and immune checkpoints in surviving cancer cells. The ability of R-Cu to deactivate cfChPs raises the prospect of a novel and non-toxic form of cancer treatment which sans killing of cancer cells, and instead induces healing by down-regulating cancer hallmarks and immune check-points.

Clinical Trial Registration

http://ctri.nic.in/Clinicaltrials/login.php,(CTRI/2018/03/012459)
Air and surface sampling for monkeypox virus in UK hospitals
Authors: Gould Susan , Atkinson Barry , Onianwa Okechukwu , Spencer Antony , Furneaux Jenna , Grieves James , Taylor Caroline , Milligan Iain , Bennett Allan , Fletcher Tom , Dunning Jake ,   NHS England Airborne HCID Network
Published: July 2022

Background

An unprecedented outbreak of monkeypox virus (MPXV) infections in non-endemic countries has been recognised since 12 May 2022. More than 6000 cases have been identified globally with more than 1500 in the UK by July 2022. Transmission of MPXV is believed to be predominantly through direct contact with lesions or infected body fluids, with possible involvement of fomites and large respiratory droplets. Importantly, a case of monkeypox in a UK healthcare worker in 2018 was suspected to be due to virus exposure while changing bedding.

Methods

We investigated environmental contamination with MPXV from infected patients admitted to isolation rooms in the UK, to inform infection prevention and control measures. Surface swabs of high-touch areas in isolation rooms, of healthcare worker personal protective equipment (PPE) in doffing areas, and from air samples collected before and during bedding change were analysed using MPXV qPCR to assess contamination levels. Virus isolation was performed to confirm presence of infectious virus in key positive samples.

Findings

We identified widespread surface contamination (66 positive out of 73 samples) in occupied patient rooms (MPXV DNA Ct values 24·7-38·6), on healthcare worker personal protective equipment after use, and in doffing areas (Ct 26·3-34·3). Five out of fifteen air samples taken were positive. Significantly, three of four air samples collected during a bed linen change in one patient’s room were positive (Ct 32·7-35·8). Replication-competent virus was identified in two of four samples selected for viral isolation, including from air samples collected during the bed linen change.

Interpretation

These data demonstrate significant contamination in isolation facilities and potential for aerosolisation of MPXV during specific activities. PPE contamination was observed after clinical contact and changing of bed linen. Additionally, contamination of hard surfaces in doffing areas supports the importance of cleaning protocols, PPE use and doffing procedures.

Funding

No funding source for this study
TREK-1 knock-down in human atrial fibroblasts leads to a myofibroblastic phenotype: a role in phenoconversion and over-view of mechano-sensitive channel mRNA expression in cardiac diseases
Authors: Darkow Elisa , Yusuf Dilmurat , Rajamani Sridharan , Backofen Rolf , Kohl Peter , Ravens Ursula , Peyronnet Rémi
Published: July 2022

Cardiac cell mechanical environment changes on a beat-by-beat basis and also in the course of various cardiac diseases. Cells sense and adapt to such mechanical cues via specialized mechano-sensors mediating adaptive signaling cascades. Here, we report TREK-1 mRNA expression and activity in human atrial fibroblasts and reveal a cross talk between TREK-1 and fibroblast phenoconversion. With the aim to reveal additional candidates underlying mechano-transduction relevant to cardiac diseases, we investigated mechano-sensitive ion channels (MSC) mRNA expression in diseased and non-diseased human hearts.

Our results showed higher TREK-1 expression and activity in fibroblasts compared to myofibroblasts and we found that TREK-1 down-regulation leads a more myofibroblastic phenotype suggesting a role for this mechano-sensor in phenoconversion. In addition, TREK-1 is preferentially expressed in the left atrium compared to the right one and its expression is not significantly changed when fibroblasts from patients in sinus rhythm vs. sustained atrial fibrillation are compared. At the whole-heart level, numerous MSC were differentially expressed between atrial and ventricular or between non-diseased and diseased tissue samples.

Thus, we identify atrial fibroblast-specific TREK-1 expression and activity and reveal a role of TREK-1 in atrial fibroblast pheno-conversion. We also provide a comprehensive overview of cardiac MSC mRNA expression in atrial and ventricular tissue from diseased and non-diseased patients, identifying potential novel candidates underlying mechanotransduction in cardiac diseases.
Mechanistic basis for targeting homologous recombination defective liver cancer via synthetic lethality
Authors: Zeng Ming , Tang Zizhi , Ren Laifeng , Wang Haibin , Wang Xiaojun , Zhu Wenyuan , Mao Xiaobing , Li Zeyang , Mo Xianming , Chen Jun , Han Junhong , Kong Daochun , Ji Jianguo , Carr Antony M. , Liu Cong
Published: July 2022

Many cancers harbour homologous recombination defects (HRD). The identification of PARP inhibitors as synthetic lethal with HRD has led to new therapeutic strategies for HRD cancers. Here we report a subtype of HRD that is caused by the perturbation of a previously uncharacterised proteasome variant, CDW19S, in hepatitis virus B (HBV) positive hepatocellular carcinoma (HBVHCC). CDW19S contains the 19S complex decorated with a Cullin 4 ubiquitin ligase (CRL4WDR70) that is assembled at broken chromatin and regulates end processing nucleases. The HBV oncoprotein, HBx, prevents integration of the CRL4 backbone into CDW19S. We show that CDW19S directly ubiquitinates ADRM1Rpn13, targeting it for degradation, and that HBx interferes with this, leading to the imposition of a novel ADRM1Rpn13-dependent resection barrier that results in HRD and promotes carcinogenesis with concurrent TP53 loss. Using cellular and patient-derived xenograft models we demonstrate that HRD in HBVHCC can be exploited to restrict tumour progression. Our work clarifies the mechanism of a virally-induced HRD and suggests a new route for targeted HBVHCC therapy.
Crown-of-thorns starfish in captivity experience sustained large-scale changes in gene expression
Authors: Morin Marie , Jönsson Mathias , Wang Conan K. , Craik David J. , Degnan Sandie M. , Degnan Bernard M.
Published: July 2022

Marine animals in the wild are often difficult to access, so that biologists have to extrapolate from the study of animals in captivity. However, the implicit assumption that physiological and cellular processes of animals in artificial environments are not significantly different from those in the wild has rarely been tested. Here we investigate the extent to which the biological state of an animal is impacted by captivity by comparing global gene expression in wild and captive crown-of-thorns starfish (COTS). We compare transcriptomes of three external tissues obtained from wild COTS with captive COTS maintained in aquaria for at least one week. On average, an astonishingly large 24% of the coding sequences in the genome are differentially expressed. Comparing transcriptomes from coelomocytes – cells in internal coelomic fluid – in wild and captive COTS, we find that 20% of the coding sequences in the genome rapidly change expression. These captive transcriptomes remained markedly different from the wild ones for more than 30 days in captivity, and showed no indication of reverting back to a wild state. Genes consistently upregulated in captivity include those involved in oxidative stress and energy metabolism, whereas genes downregulated are involved in intercellular signalling. These extensive changes in gene expression in captive COTS suggest that captivity has a profound and sustained impact on the physiology, behaviour and health of these echinoderms. The potential for such dramatic changes should be accounted for when designing studies seeking to understand wild animals.
Crystal structure and Hirshfeld surface analysis of (Z)-4-(4-hydroxybenzylidene)-3-methylisoxazol-5(4H)-one. Corrigendum
Authors: Zemamouche Wissame , Laroun Rima , Hamdouni Noudjoud , Brihi Ouarda , Boudjada Ali , Debache Abdelmadjid
Published: July 2022

In the paper by Zemamouche et al. [Acta Cryst. (2018), E74, 926–930], there is an error in the name of the first author.
Crystal structure and Hirshfeld surface analysis of N-[(2-hydroxynaphthalen-1-yl)(3-methylphenyl)methyl]acetamide. Corrigendum
Authors: Boudebbous Khawla , Zemamouche Wissame , Debache Abdelmadjid , Hamdouni Noudjoud , Boudjada Ali
Published: July 2022

In the paper by Boudebbous et al. [Acta Cryst. (2018), E74, 1002–1005], there is an error in the name of the second author.
Crystal structure of (2E)-1-(4-ethoxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one
Authors: Bernhard Merle , Lutter Jacob C. , Predecki Allison
Published: July 2022

The title molecule, C17H15FO2, was synthesized by a Claisen–Schmidt condensation with 4-fluorobenzaldehyde and 4′-ethoxyacetophenone. The torsion angles between the 4-fluorophenyl ring and the alkene and the 4′-ethoxyphenyl ring and the 2-propen-1-one are −1.2 (4) and 1.2 (3)°, respectively; however, there is a larger torsion between the bonds comprising the 2-propen-1-one unit of 12.0 (4)°. The crystal packing is stabilized by intermolecular C—H...O/F hydrogen bonding, π–π stacking, and H–π interactions.
Employer attractiveness, employee engagement and employee performance
Authors: Nguyen Ha Minh , Nguyen Luan Vinh
Published: July 2022

Purpose

This study examines the effects of employer attractiveness (EA) on employee engagement (EE) and employee performance (EP).

Design/methodology/approach

Mixed method. The analytical technique is the Partial Least Squares Structural Equation Modeling through survey questionnaires collected from 937 respondents as employees from 37 enterprises in Vietnam.

Findings

EA has a positive impact on EE and EP factors. However, EE has no statistically significant impact on EP.

Practical implications

This study helps managers build solutions toward retaining talent and improving EP through the strategy of building EA. Concurrently, this study guides the important factors to build an effective EA.

Originality/value

This study explores the relationship between three factors: EA, EE and EP. This has added a new research direction of EA to existing employees. In addition, the study results provide a new perspective on the relationship between EE and EP.
Selective search and new-to-market process innovation
Authors: Aliasghar Omid , Kanani Moghadam Venus
Published: July 2022

Purpose

Searching for knowledge from outside firms' boundaries has been proved to be a critical strategy to develop innovation. However, the existing body of research has mainly focused on the high-tech sector in developed countries, largely neglecting the considerable role of low- and medium-technology sectors (LMT) in emerging contexts. The authors discuss the fact that knowledge search patterns and the role of internal R&D intensity differ for firms operating in LMT sectors.

Design/methodology/approach

A sample of 1,365 firms operating in LMT sectors in Iran was used to test the proposed conceptual model, using logistic regression analysis.

Findings

The findings show that a firm will learn from its collaboration with value chain partners only if it has a strong in-house R&D capacity. In addition, while a high level of internal research development capacity increases the impact of knowledge acquired from value chain partners, the authors did not find evidence for complementarity between the investment in internal technology development and knowledge acquired from university and science-based partners.

Originality/value

Unlike previous studies in open innovation that have mainly investigated the role of knowledge search on product innovation in developed countries, this study contributes to the literature by connecting the concepts of R&D intensity and selective search, discussing that businesses operating in challenging contexts follow different knowledge search strategies to develop process-related innovation activities.
The influence of YouTube videos on human tolerance of sharks
Authors: Beall J. M. , Pharr L. D. , von Furstenberg R. , Barber A. , Casola W. R. , Vaughn A. , Peterson M. N. , Larson L. R.
Published: July 2022

Sharks are often depicted in the media as violent killers that actively seek out opportunities to harm humans. This framing may impact human tolerance and support of shark conservation, underscoring the need to identify strategies that counteract these negative representations. Social media, given its widespread use, could be an effective platform for shaping public tolerance for sharks and other wildlife species. In this experimental study, we conducted an online pre‐post survey in Spring 2020 to determine how viewing shark‐related YouTube videos impacted tolerance for sharks among residents (n = 335) in the coastal state of North Carolina (NC), USA and neighboring states. The study employed framing theory, which suggests that the ways in which information is presented influence how it is processed and the actions that result from it. Participants were randomly assigned to one of two video treatments where sharks were framed positively or negatively. Each video treatment impacted tolerance for sharks in the direction of their framing: positive framing influenced positive changes in tolerance (70% more positive attitudes toward sharks, a 130% increase in acceptance of sharks and a 46% increase in intended shark conservation behaviors), and negative framing influenced negative changes (25% more negative attitudes toward sharks, a 18% decrease in acceptance of sharks and a 3% decrease in intended shark conservation behaviors). These findings suggest positive messages about sharks on social media promote tolerance of sharks and can be more impactful than negative messages. At least one form of social media, YouTube, appears to be a valuable tool for encouraging tolerance for sharks.
Influence of moderate hypothermia on renal and cerebral haemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep
Authors: Jufar Alemayehu H. , May Clive N. , Evans Roger G. , Cochrane Andrew D. , Marino Bruno , Hood Sally G. , McCall Peter R. , Bellomo Rinaldo , Lankadeva Yugeesh R.
Published: July 2022

Aim

Cardiac surgery requiring cardiopulmonary bypass (CPB) can result in renal and cerebral injury. Intraoperative tissue hypoxia could contribute to such organ injury. Hypothermia, however, may alleviate organ hypoxia. Therefore, we tested whether moderate hypothermia (30°C) improves cerebral and renal tissue perfusion and oxygenation during ovine CPB.

Methods

Ten sheep were studied while conscious, under stable anesthesia, and during 3 h of CPB. In a randomized within‐animal cross‐over design, five sheep commenced CPB at a target body temperature of 30°C (moderate hypothermia). After 90 min, the body temperature was increased to 36°C (standard procedure). The remaining five sheep were randomized to the opposite order of target body temperature.

Results

Compared with the standard procedure, moderately hypothermic CPB reduced renal oxygen delivery (−34.8% ± 19.6%,P = 0.003) and renal oxygen consumption (−42.7% ± 35.2%,P = 0.04). Nevertheless, moderately hypothermic CPB did not significantly alter either renal cortical or medullary tissue PO2. Moderately hypothermic CPB also did not significantly alter cerebral perfusion, cerebral tissue PO2, or cerebral oxygen saturation compared with the standard procedure. Compared with the anesthetized state, the standard procedure reduced renal medullary PO2(−21.0 ± 13.8 mmHg,P = 0.014) and cerebral oxygen saturation (65.0% ± 7.0% to 55.4% ± 9.6%,P = 0.022) but did not significantly alter either renal cortical or cerebral PO2.

Conclusion

Ovine experimental CPB leads to renal medullary tissue hypoxia. Moderately hypothermic CPB did not improve cerebral or renal tissue oxygenation. In the kidney, this is probably because renal tissue oxygen consumption is matched by reduced renal oxygen delivery.
Feasibility of a multiple‐component mindfulness intervention for Chinese adolescents living with overweight: A pilot randomized trial
Authors: Zhang Qian , O'Connor Daryl B. , Hugh‐Jones Siobhan
Published: July 2022

The prevalence of obesity among Chinese adolescents is rising rapidly, and theoretically informed, scalable weight management interventions are needed. We developed and evaluated the feasibility and preliminary effects of an mHealth nutrition education and mindful snacking intervention for weight loss and improved dietary practices among Chinese adolescents with overweight. We examined whether including implementation intention formation (using if–then plans) improved outcomes. With user consultation, we created a 3‐week mindful eating intervention delivered as 10 videos to user smartphones. Participants (n = 55) were randomly assigned to mindful eating or mindful eating + planning. Forty‐six (83.6%) participants (age = 16.35 ± 0.48 years; body mass index [BMI] = 25.79 ± 2.05 kg/m2) completed the intervention. Both groups exhibited significant pre‐ to post‐intervention weight loss (M = 1.42 and 1.79 kg, respectively); decreases in snacking frequencies, emotional eating, external eating, and trait craving; and significant increases in mindful eating and eating self‐efficacy. No significant intervention group differences were observed. User experience data (n = 16) indicated acceptability and meaningful behavior change. Findings suggest that a smartphone‐delivered mindfulness‐based intervention for Chinese adolescents living with overweight is feasible and efficacious.
Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity
Authors: Copland Mhairi
Published: July 2022

Despite the success of BCR‐ABL‐specific tyrosine kinase inhibitors (TKIs) such as imatinib in chronic phase (CP) chronic myeloid leukaemia (CML), patients with blast phase (BP)‐CML continue to have a dismal outcome with median survival of less than one year from diagnosis. Thus BP‐CML remains a critical unmet clinical need in the management of CML. Our understanding of the biology of BP‐CML continues to grow; genomic instability leads to acquisition of mutations which drive leukaemic progenitor cells to develop self‐renewal properties, resulting in differentiation block and a poor‐prognosis acute leukaemia which may be myeloid, lymphoid or bi‐phenotypic. Similar advances in therapy are urgently needed to improve patient outcomes; however, this is challenging given the rarity and heterogeneity of BP‐CML, leading to difficulty in designing and recruiting to prospective clinical trials. This review will explore the treatment of BP‐CML, evaluating the data for TKI therapy alone, combinations with intensive chemotherapy, the role of allogeneic haemopoietic stem cell transplantation, the use of novel agents and clinical trials, as well as discussing the most appropriate methods for diagnosing BP and assessing response to therapy, and factors predicting outcome.
Cushioning the blow: role of perirenal fat in renal trauma injury severity
Authors: Hakam Nizar , Lui Jason L. , Shaw Nathan M. , Breyer Benjamin N.
Published: July 2022

Objectives

To explore the association between perirenal fat thickness (PFT) and renal trauma grade. We hypothesise this association is related to a shock‐absorbing effect of adiposity around the kidney.

Patients and Methods

We identified all patients with renal trauma who arrived at the emergency department of a single trauma centre between 2014 and 2020. Radiology images were reviewed to measure the PFT around the uninjured kidney due to disrupted PFT around the traumatised kidney. Patients with no available images or penetrating trauma mechanism were excluded. Logistic regression was used to assess the relation between PFT and high‐grade renal trauma (HGRT; defined as American Association for the Surgery of Trauma Renal Grade IV–V), adjusting for age, sex, and Injury Severity Scale (ISS).

Results

A total of 150 patients with renal trauma were included. The median (interquartile range) age was 38.5 (26–52) years and 106 (70.7%) were males. The PFT ranged between 2.1 and 50.1 mm, and 31 (20.7%) had HGRT. Interestingly, PFT only mildly correlated with body mass index (BMI; Pearson correlation coefficient 0.42, P < 0.001). Those with HGRT had significantly lower PFT compared to those without HGRT (median 9.5 vs 11.9 mm, P = 0.047). In the multivariable analysis adjusting for age, sex, and ISS, increasing PFT was associated with decreased odds (odds ratio 0.91, 95% confidence interval 0.84–0.98; P = 0.015) of HGRT.

Conclusion

Increasing PFT is associated with lower risk of HGRT following blunt injury. These results support a protective cushion role of adiposity in renal trauma. Notably, PFT was not strongly correlated with BMI, underscoring limitations of BMI in measuring adiposity.
The myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid‐induced impaired wound healing
Authors: Nguyen Van Tuan , Ngo Qui Trung , Ramirez Roberto Palacios , Nakamura Toshifumi , Farman Nicolette , Aractingi Sélim , Jaisser Frederic
Published: July 2022

Background and Purpose

Delayed wound healing is among the deleterious consequences of over‐activation of the mineralocorticoid receptor (MR) induced by topical dermocorticoids. The role of dermal inflammation and angiogenesis in the benefits of MR blockade is unknown.

Experimental Approach

Skin wounds were made on C57Bl6 mice after topical pretreatment with the dermocorticoid clobetasol. The impact of topical MR blockade by canrenoate on inflammation, angiogenesis, and the wound macrophage phenotype was analysed 5 days post‐wounding. Similar experiments were conducted on mice with genetic deletion of the MR in myeloid cells.

Key Results

Topical inhibition of the MR with canrenoate improved delayed wound healing through the resolution of prolonged inflammation in glucocorticoid‐pretreated mouse skin. This effect was associated with a higher ratio of anti‐inflammatory macrophages versus pro‐inflammatory macrophages in wounds treated by canrenoate. Furthermore, MR blockade led to upregulated expression of pro‐angiogenic factors and improved impaired angiogenesis in wounds of glucocorticoid‐pretreated skin. Finally, deletion of MR expression by myeloid cells reproduced the benefits of topical pharmacological MR blockade.

Conclusion and Implications

Topical MR antagonism facilitates the switching of macrophages towards an anti‐inflammatory phenotype, which improves prolonged inflammation and induces angiogenesis to accelerate wound healing delayed by glucocorticoid treatment.
Harvesting has variable effects on demographic rates and population growth across three dry forest tree species
Authors: Neeraja U. V. , Saneesh C. S. , Dyda Venkat , Reddy Hemalatha , Yadama Gautam N. , Knight Tiffany M.
Published: July 2022

Understanding how anthropogenic activities, such as harvesting, influence plant populations is important to quantify sustainable practices that conserve species of socioeconomic importance. There is limited knowledge on how harvesting of branches and non‐timber forest products affect populations of trees in the dry tropics. We measure demographic vital rates of three dry tropical tree species in the presence and absence of harvesting and apply integral projection models to quantify population growth rates, which represent the mean fitness across the life cycle. Our results show that the three species vary in their demographic rates and life history. Harvesting significantly decreases the growth of two species. Current levels of harvesting only significantly decreased the population growth rate of one species that experienced both branch and main stem harvesting. Life table response experiments reveal that the negative effect of harvesting on the population growth rate of this species is primarily due to individuals being forced to re‐sprout from their base. Few individuals were observed recruiting from seed, and this might be due to the presence of other threats, such as fire, soil erosion, and grazing. Our results provide knowledge on the demography and the effects of harvesting on endemic tree species of the Eastern Ghats, a region for which few demographic studies are available. These results are relevant to conserving forest biodiversity for the benefits of people and can contribute to quantitative threat assessment for IUCN red listing.
Paediatric asthma and non‐allergic comorbidities: A review of current risk and proposed mechanisms
Authors: Brew Bronwyn K. , Osvald Emma Caffrey , Gong Tong , Hedman Anna M. , Holmberg Kirsten , Larsson Henrik , Ludvigsson Jonas F. , Mubanga Mwenya , Smew Awad I. , Almqvist Catarina
Published: July 2022

It is increasingly recognized that children with asthma are at a higher risk of other non‐allergic concurrent diseases than the non‐asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016–2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome‐wide association studies, gene expression–functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene–environment interactions, such as epi‐genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
Aphelinus nigritus‐induced transgenerational fecundity compensation in parasitized Melanaphis sorghi
Authors: Wright Crys , Lei Jiaxin , Bernal Julio S. , Zhu‐Salzman Keyan , Medina Raul F.
Published: July 2022

Aphids adopt many defensive strategies against natural enemies. While immediate strategies like emitting alarm pheromones or producing secretions are often researched, fewer studies have assessed long‐term defences that include physiological adaptive responses affecting aphid reproduction.

Fecundity compensation is a post‐wounding increase in host reproduction, which benefits the offspring of wounded or parasitized insects. Though fecundity compensation can be expressed by individuals experiencing natural enemy attacks, it can also be transgenerational, wherein the offspring of wounded or parasitized mothers reproduce more than the offspring of unaffected mothers.

The possibility of fecundity compensation was tested on laboratory populations of the sorghum aphid (SA), Melanaphis sorghi (Hemiptera: Aphididae), in response to wounding from a needle puncture or sting by Aphelinus nigritus Howard (Hymenoptera: Aphelinidae).

No evidence of reproductive compensation was found among needle‐wounded, stung and mummified (successfully parasitized), or stung but not mummified SAs in the parental generation, nor in the F1 generation of needle‐wounded or stung but not mummified aphids. However, transgenerational fecundity compensation was observed in F1 daughters of mummified F0 mothers, though this effect did not occur in the F2 generation.

At the molecular level, changes were not detected in the expression of DNA methylation and histone modification genes that potentially mediated transgenerational fecundity compensation in SAs stung by A. nigritus, regardless of whether aphids were successfully parasitized. As SA is a cereal aphid pest, the possibility of fecundity compensation should be tested when assessing the suitability of certain parasitoids as biological control agents.
The lost Missal of Alcuin and the Carolingian sacramentaries of Tours
Authors: Westwell Arthur
Published: July 2022

Letters of Alcuin of York attest that he composed a liturgical book he called a ‘missal’ while he was abbot of St Martin's basilica in Tours. No manuscripts of this missal survive. It has to be recovered from much later sacramentaries copied in Tours, which have been subject to significant subsequent reworking. This article makes a new attempt to draw out the contents of the missal from these later sources, assuming that the later adjustments by others are an equally valid attempt to improve the usability and comprehensiveness of the book as Alcuin's original endeavour. The discovery of fragments of a much earlier sacramentary from Tours in Solothurn Staatsarchiv also makes a significant contribution to the process.
Estimation of the basic reproduction number forStreptococcus equispp.equioutbreaks by meta‐analysis of strangles outbreak reports
Authors: Houben Rosa M. A. C. , van Maanen Kees , Kemp‐Symonds Jeremy G. , Waller Andrew S. , Sloet van Oldruitenborgh‐Oosterbaan Marianne M. , Heesterbeek Hans
Published: July 2022

Background

Streptococcus equispp.equi(S. equi), the cause of strangles in horses, is considered a highly contagious pathogen affecting equines and the equine industry worldwide. Fundamental epidemiological characteristics of outbreaks, such as the basic reproduction number (R0), are not well described.

Objectives

EstimateR0forS. equiin equine populations from outbreak data.

Study design

Systematic review and meta‐analysis of published and unpublished data.

Methods

A literature search for outbreak reports was carried out. Depending on data available in the reports, the early epidemic growth rate or final attack rate (AR) approach was used to estimate the basic reproduction number for that outbreak. Other recorded outbreak characteristics were the type of housing (group vs. individual). An overall estimate forR0was computed by meta‐analysis.

Results

Data from eight outbreaks were extracted from peer‐reviewed publications. Data from two additional, non‐published outbreaks was also included in the meta‐analysis. A conservative estimate forR0was 2.2 (95% confidence interval [CI] 1.9–2.5). A less conservative estimate, including outbreaks with a 100% AR for which a lower limitR0was estimated, was 2.7 (95% CI 2.1–3.3).

Main limitations

Few papers describing longitudinal incidence data were found so most estimates were based on the outbreaks' final size. Several outbreaks had a 100% attack rate and could therefore only be included as a lower limit estimate in the meta‐analysis. The reported result therefore may be an underestimation.

Conclusions

This estimate forR0forS. equiinforms parameters for future mathematical modelling, quantifies desired preventive vaccine coverage and helps evaluate the effect of prevention strategies through future modelling studies.
BRD4andMYC: power couple in transcription and disease
Authors: Kotekar Aparna , Singh Amit Kumar , Devaiah Ballachanda N.
Published: July 2022

The MYC proto‐oncogene and BRD4, a BET family protein, are two cardinal proteins that have a broad influence in cell biology and disease. Both proteins are expressed ubiquitously in mammalian cells and play central roles in controlling growth, development, stress responses and metabolic function. As chromatin and transcriptional regulators, they play a critical role in regulating the expression of a burgeoning array of genes, maintaining chromatin architecture and genome stability. Consequently, impairment of their function or regulation leads to many diseases, with cancer being the most predominant. Interestingly, accumulating evidence indicates that regulation of the expression and functions of MYC are tightly intertwined with BRD4 at both transcriptional and post‐transcriptional levels. Here, we review the mechanisms by which MYC and BRD4 are regulated, their functions in governing various molecular mechanisms and the consequences of their dysregulation that lead to disease. We present a perspective of how the regulatory mechanisms for the two proteins could be entwined at multiple points in a BRD4‐MYC nexus that leads to the modulation of their functions and disease upon dysregulation.
Can Spanish programs evaluate oral proficiency gains for all learners? An empirical analysis of traditional and nontraditional Spanish majors' oral proficiency development
Authors: Viera Carolina , Arispe Kelly
Published: July 2022

Higher education Spanish programs in the United States are diverse and complex, especially when it comes to student linguistic background. However, most studies on language proficiency were designed for traditional learners (L2s). In this study, we examine oral proficiency development of 125 Spanish majors in light of four linguistic profiles: Extended Stay Abroad learners, Second Language Learners, Native Speakers, and Spanish Heritage Language Learners. Data were collected using an oral exam based on the ACTFL Oral Proficiency guidelines at the beginning and end of students' upper division coursework. Quantitative analysis reveals significant differences within groups for senior exit oral proficiency exam scores as well as level gains. These findings suggest that oral proficiency exams are a valuable tool for understanding differences in oral proficiency development for the four student categories. This information is pertinent for program assessment and has important research and pedagogical implications.
Usefulness of the Global Leadership Initiative on Malnutrition criteria to predict sarcopenia and mortality in patients with chronic liver disease
Authors: Miwa Takao , Hanai Tatsunori , Nishimura Kayoko , Unome Shinji , Maeda Toshihide , Ogiso Yui , Imai Kenji , Suetsugu Atsushi , Takai Koji , Shimizu Masahito
Published: July 2022

Aim

The Global Leadership Initiative on Malnutrition (GLIM) criteria, a newly developed global consensus around core diagnostic criteria for malnutrition, needs validation studies for use in daily clinical settings. This study aimed to determine whether the GLIM criteria could predict sarcopenia and mortality in patients with chronic liver disease (CLD).

Methods

We retrospectively reviewed 858 patients with CLD who were treated at our hospital between March 2013 and December 2019. Sarcopenia was diagnosed based on the criteria proposed by the Japan Society of Hepatology. Malnutrition was assessed using the GLIM criteria, subjective global assessment (SGA), and Royal Free Hospital‐global assessment (RFH‐GA) and their predictive ability for sarcopenia and mortality were assessed using the logistic regression analysis and the Cox proportional hazards regression model, respectively.

Results

Among the eligible 406 patients, 67% were men, the median age was 74 years, and 26% had sarcopenia. The prevalence of malnutrition according to the GLIM criteria, SGA, and RFH‐GA was 21%, 35%, and 26%, respectively. Comparing malnourished with well‐nourished patients, the odds ratio for complicating sarcopenia was 2.54 (95% confidence interval [CI], 1.44–4.49) for the GLIM criteria, 2.13 (95% CI, 1.09–4.15) for the SGA, and 2.78 (95% CI, 1.56–4.95) for the RFH‐GA. During a median follow‐up period of 2.0 years, 176 (43%) patients died. After adjusting for confounding factors, the GLIM criteria could independently predict mortality (hazard ratio, 1.95; 95% CI, 1.37–2.81).

Conclusions

The GLIM criteria are useful in identifying sarcopenia and predicting mortality in patients with CLD.