bluuebunny/crossref_metadata_2025 huggingface dataset:
The DEAD-box protein p68 and β-catenin: the crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer
Authors: Tabassum Shaheda , Basu Malini , Ghosh Mrinal K
Published: October 2022

Forkhead box M1 (FOXM1), a vital member of the Forkhead box family of transcription factors, helps in mediating oncogenesis. However, limited knowledge exists regarding the mechanistic insights into the FOXM1 gene regulation. p68, an archetypal member of the DEAD-box family of RNA helicases, shows multifaceted action in cancer progression by arbitrating RNA metabolism and transcriptionally coactivating transcription factors. Here, we report a novel mechanism of alliance between p68 and the Wnt/β-catenin pathway in regulating FOXM1 gene expression and driving colon carcinogenesis. Initial bioinformatic analyses highlighted elevated expression levels of FOXM1 and p68 in colorectal cancer datasets. Immunohistochemical assays confirmed that FOXM1 showed a positive correlation with p68 and β-catenin in both normal and colon carcinoma patient samples. Overexpression of p68 and β-catenin increased the protein and mRNA expression profiles of FOXM1, and the converse correlation occurred during downregulation. Mechanistically, overexpression and knockdown of p68 and β-catenin elevated and diminished FOXM1 promoter activity respectively. Additionally, Chromatin immunoprecipitation assay demonstrated the occupancy of p68 and β-catenin at the TCF4/LEF binding element (TBE) sites on the FOXM1 promoter. Thiostrepton delineated the effect of FOXM1 inhibition on cell proliferation and migration. Colony formation assay, migration assay, and cell cycle data reveal the importance of the p68/β-catenin/FOXM1 axis in oncogenesis. Collectively, our study mechanistically highlights the regulation of FOXM1 gene expression by p68 and β-catenin in colorectal cancer.
Effects of supply chain disruptions due to COVID-19 on shareholder value
Authors: Choudhury Nishat Alam , Kim Seongtae , Ramkumar M.
Published: October 2022

Purpose

The purpose of this research work is to examine the financial effect of supply chain disruptions (SCDs) caused by coronavirus disease 2019 (COVID-19) and how the magnitude of such effects depends on event time and space that may moderate the signaling environment for shareholder behaviors during the pandemic.

Design/methodology/approach

This study analyses a sample of 206 SCD events attributed to COVID-19 made by 145 publicly traded firms headquartered in 21 countries for a period between 2020 and 2021. Change in shareholder value is estimated by employing a multi-country event study, followed by estimating the differential effect of SCDs due to the pandemic by event time and space.

Findings

On average, SCDs due to pandemic decrease shareholder value by −2.16%, which is similar to that of pre-pandemic SCDs (88 events for 2018–2019). This negative market reaction remains unchanged regardless of whether stringency measures of the firm's country become more severe. Supply-side disruptions like shutdowns result in a more negative stock market reaction than demand-side disruptions like price hikes. To shareholder value, firm's upstream or downstream position does not matter, but supply chain complexity serves as a positive signal.

Originality/value

This study provides the first empirical evidence on the financial impact of SCDs induced by COVID-19. Combining with signaling theory and event system theory, this study provides a new boundary condition that explains the impact mechanism of SCDs caused by the pandemic.
Organisational capabilities for successful digital transformation: a global analysis of national football associations in the digital age
Authors: Merten Sebastian , Schmidt Sascha L. , Winand Mathieu
Published: October 2022

Purpose

The aim of this study is to identify organisational capabilities (OC) for a successful digital transformation (DT) and associated structures of internal teams to orchestrate and support DT.

Design/methodology/approach

An explorative, qualitative study, comprising semi-structured interviews with 82 executives from 43 diverse National Football Associations (NFA) spread across five continents was conducted.

Findings

The results show that organisational culture, strategic sensitivity, up-to-date ICT-infrastructure, a digitally skilled workforce, leadership support, knowledge management and internal DT-teams are important capabilities to enable successful DT.

Research limitations/implications

Due to the different levels of maturity of digitalisation and the financial constraints, not every NFA intends or is able to assign a full-time staff member exclusively to digital issues. Therefore, the most appropriate person was interviewed in each NFA.

Practical implications

Adapting an organisational culture to the requirements of the digital age is one of the most important steps in implementing DT. It is equally important for the leadership to form the strategic framework and enable the necessary training of employees to improve the results of the digitalisation processes.

Originality/value

This is the first study investigating NFA's DT from a worldwide perspective, identifying the most important factors for successful DT-processes.
Documenting the knowledge of pro-environmental travel behaviour research: a visual analysis using CiteSpace
Authors: Zhang Jiale , Quoquab Farzana
Published: October 2022

Purpose

The purpose of this study is to present a comprehensive knowledge mapping and an in-depth analysis of pro-environmental travel behaviour research to better understand the global trend in this field that have emerged between 2000 and 2021.

Design/methodology/approach

In this study, a visual analysis of 187 scholarly articles between the year 2000 and 2021 related to pro-environmental travel behaviour (PETB) is presented. Using the knowledge mapping based on CiteSpace it presents the current research status, which contains the analysis of collaboration network, co-citation network, and emerging trends.

Findings

The results revealed that the PETB is an emerging topic, which has an increased number of publications in recent years. Though the collaboration network between scholars is dispersed, some countries exert stronger collaboration network. Researchers from England, USA and China have worked more on this topic comparatively. “Pro-environmental norm” is found to be the major concern in regard to PETB, and the theory of planned behaviour (TPB) is the most common theory used by the scholars around the world. Ten articles with the highest citations are found to be the most valuable articles. COVID-19, value orientation, negative spillover, carbon footprints, biospheric and adolescent are some of the latest keywords based on the past two years' literature review, all of which have huge research potential in the future.

Originality/value

This study is among the pioneers to shed some light on the current research progress of PETB by using a bibliometric analysis to provide research directions for scholars. Moreover, this study utilized latest data from 2000 to 2021. The studies which are published before and during the pandemic are also incorporated.
Different facets of bacterial and fungal communities drive soil multifunctionality in grasslands spanning a 3500 km transect
Authors: Ma Linna , Zhang Chaoxue , Xu Xiaofeng , Wang Congwen , Liu Guofang , Liang Cunzhu , Zuo Xiaoan , Wang Chengjie , Lv Yixia , Wang Renzhong
Published: October 2022

Soil microbial communities are essential in regulating ecosystem functions and services. However, the importance of bacterial and fungal communities as predictors of multiple soil functions (i.e. soil multifunctionality) in grassland ecosystems has not been studied systematically.

Here, we measured soil microbial diversity, community composition, biomass and multiple soil functions of 41 sites in five grassland ecosystems spanning a 3500 km northeast–southwest transect. The random forest algorithm was adopted to determine the importance of geographical location, climatic, altitude, edaphic, plant and microbial predictors in driving a proxy of soil multifunctionality (seven soil functions in this study). Moreover, structural equation models were employed to examine the direct and indirect effects of those predictors on soil multifunctionality.

Our results demonstrated that soil multifunctionality was positively driven by soil fungal diversity but not by bacterial diversity. Fungal phylogenetic diversity (presence of different evolutionary lineages) showed stronger positive relationships with soil multifunctionality than taxonomic diversity (richness of species). Dominant bacterial taxa, particularly of phyla Actinobacteria and Proteobacteria, were positively associated with soil multifunctionality, while none of the fungal taxa were found to regulate soil multifunctionality. Furthermore, both fungal and bacterial biomass had significant effects on soil multifunctionality, while the effect of microbial biomass was weaker than that of fungal diversity and bacterial taxa. Importantly, the direct positive effects of soil fungal diversity, dominant bacterial taxa, and fungal and bacterial biomass were maintained after accounting for multiple predictors in grassland ecosystems.

This study provided strong empirical evidence that soil multifunctionality was driven by different facets of the bacterial and fungal communities in the grassland ecosystems. Our results also highlighted that any loss of fungal diversity, dominant bacterial taxa and microbial biomass might reduce soil multifunctionality, exacerbating ecosystem functions and services such as soil fertility, primary production and climate mitigation in grassland ecosystems.

Read the free Plain Language Summary for this article on the Journal blog.
Physical activity knowledge and confidence of education staff in a special education setting
Authors: Bellamy J. , Fensom S. , van Doorn N.
Published: October 2022

Children with intellectual disabilities (ID) are less likely to meet physical activity (PA) guidelines and have higher tendencies towards sedentary behaviors. Considering a large proportion of a child's day is spent at school, this setting provides a promising environment for increasing PA levels. Staff often significantly impact the success of PA within schools. Limited research has focused on PA knowledge and confidence of staff in a special education setting. In this study, staff from two Schools for Specific Purposes in Sydney, Australia, were invited to complete a questionnaire regarding their knowledge of child PA guidelines, and their confidence in delivering PA to children with ID. Questions were derived from the validated Schools Physical Activity & Nutrition Survey (SPANS). Descriptive analyses were completed on all variables. The questionnaire was completed by 55 of the 74 participants. Although 40.0% reported knowledge of Australian PA guidelines for children, only 20% correctly identified these guidelines. PA was perceived to be ‘extremely important’ (4.69/5) for children with ID, and staff reported ‘confidence’ (3.78/5) in delivering PA for children with ID. Only seven (12.7%) participants reported meeting the New South Wales Department of Education PA requirements (mean = 100 minutes per week). We conclude that despite confidence in delivery of PA and its perceived importance, staff within special education settings have little knowledge of child PA guidelines and are unlikely to meet current Department of Education requirements. We suggest a targeted intervention to improve staff knowledge of PA guidelines, which may enhance the delivery of PA for children with ID.
Murdoch on ethical formation in a changing world
Authors: Hämäläinen Nora
Published: October 2022

In the past few years, we have seen emerging new work that brings into focus the role of historical change and its moral implications in Iris Murdoch's philosophy. This paper strengthens this reading of her work and investigates the implications of this aspect of Murdoch's thinking for education in general and for moral education in particular. It resituates the Platonic imagery of the individual's ascent towards the true and the good in a framework where our conceptions of the true and the good are in a process of historical reconfiguration.
Identification of a fatty acid synthase gene (FAS1) from Laodelphax striatellus planthoppers contributing to fecundity
Authors: Cheng Jia‐Yan , Yu Pei‐Han , Xia Xue , Zhang Ru , Wang Li‐Hua , Fang Ji‐Chao , Hoffmann Ary A. , Luo Guang‐Hua
Published: October 2022

Fatty acid synthase (FAS) is a multifunctional enzyme that plays an important role in the formation of fatty acids. The fatty acids take part in many processes, such as cell signaling and energy metabolism, and in insects they are important in both cuticular hydrocarbon (CHC) formation and reproduction. Here we characterized the sequence structure and function of an FAS from the small brown planthopper (SBPH), Laodelphax striatellus. The full‐length open reading frame (ORF) sequence of LsFAS1 was 7122 bp, encoding a predicted protein of 2373 amino acid residues. There were 7 functional domains in the LsFAS1 protein sequence. Gene expression screening by real‐time quantitative polymerase chain reaction (RT‐qPCR) showed that LsFAS1 was expressed in all developmental stages. Relative expression was highest at the 4th‐instar and female adult stages. Among different tissues, the expression level of LsFAS1 in the ovary was the highest. Phylogenetic analysis showed that LsFAS1 clustered in a clade with 2 FASs from Nilaparvata lugens. Furthermore, these 3 FASs are related to cockroach BgFAS and locust LmFAS. After RNA interference‐mediated knock‐down, most treated insects died at eclosion. In addition, the lifespan of dsFAS1‐treated female adults was shorter than that of the dsGFP‐injected control, and offspring production decreased. Also, the expression of vitellogenin (Vg) and vitellogenin receptor (VgR) genes decreased. Virgin females dissected at days 2 and 4 post‐eclosion showed many matured oocytes in planthoppers treated with dsGFP but not with dsFAS1. These data highlight the importance of LsFAS1 in SBPH, including a role in reproduction.
Forecasting trait responses in novel environments to aid seed provenancing under climate change
Authors: Putra Andhika R. , Yen Jian D. L. , Fournier‐Level Alexandre
Published: October 2022

Revegetation projects face the major challenge of sourcing optimal plant material. This is often done with limited information about plant performance and increasingly requires factoring resilience to climate change. Functional traits can be used as quantitative indices of plant performance and guide seed provenancing, but trait values expected under novel conditions are often unknown. To support climate‐resilient provenancing efforts, we develop a trait prediction model that integrates the effect of genetic variation with fine‐scale temperature variation. We train our model on multiple field plantings of Arabidopsis thaliana and predict two relevant fitness traits—days‐to‐bolting and fecundity—across the species' European range. Prediction accuracy was high for days‐to‐bolting and moderate for fecundity, with the majority of trait variation explained by temperature differences between plantings. Projection under future climate predicted a decline in fecundity, although this response was heterogeneous across the range. In response, we identified novel genotypes that could be introduced to genetically offset the fitness decay. Our study highlights the value of predictive models to aid seed provenancing and improve the success of revegetation projects.
Phenological growth stages of Magnolia ×soulangeana according to the extended BBCH scale
Authors: Li Jia , Yang Aixiang , Nie Tangjie , Sun Liyong , Chen Yao , Jiang Zheng , Yin Zengfang
Published: October 2022

Magnolia × soulangeana, one of the most famous ornamental trees of Magnoliaceae, is widely cultivated around the world. However, its phenological characteristics at life‐cycle scale have never been detailedly reported so far. In this article, the extended BBCH (Biologische Bundesanstalt, Bundessortenamt, und Chemische Industrie) scale was applied to divide the growth and development cycle of M. × soulangeana in both juvenile phase and adult phase, and describe the characteristics of phenological development stage, so as to provide theoretical guidance for its cultivation measures implementation. Based on the BBCH phenological scale, the processes of germination (0), leaf development (1), main stem elongation (3) and dormancy (9) were observed in the juvenile phase. Likewise, the morphological changes of organs in adult phase were abundant, and eight principal growth stages were described: vegetative bud development (0), leaf development (1), shoot development (3), reproductive development (5), flowering (6), fruit development (7), maturity of fruit (8) and dormancy (9). Our newly developed scale provides a unified standard for describing and identifying the phenological period of M. × soulangeana. In addition, it is of great significance to understand the phenological characteristics of M. × soulangeana for its breeding and cultivation management.
Drunken snakes and sober owls: ancient authors on the relationship between animals and wine
Authors: Kostuch Lucyna
Published: October 2022

Aims

In the article, ancient concepts linking animals and wine are discussed. This paper provides a description of animals that in antiquity were considered to be especially fond of grapes and wine, as well as animals that were, for various reasons, given wine to drink by humans, and animals that in ancient literature had an averse association with wine. In the paper, the author attempts to answer the following questions, what was the conceptual framework for the tales about drunk animals? In what circumstances were observations of animals becoming inebriated conducted? Which animal species were considered as most susceptible to the effects of wine? Last, was wine believed to affect animals and humans in a similar way?

Methods

Ancient literature provides a set of extant information about animals that willingly become inebriated with grapes or are given wine by humans, which deserves a separate analysis. The ancient authors commonly interspersed narration with information about the animals and invoked personal experiences of contact with the described animal and information obtained from those who had the opportunity to conduct ‘zoological’ observations or even medical experiments.

Results

There is a large group of animals that appear in ancient accounts consuming alcohol in the form of fermented fruit and wine. The ancients held the mostly incorrect belief that snakes had an enormous predilection for wine; moreover, contemporary research confirms that, as the ancients rightly observed, insects and birds do display a fondness for fermented fruit and wine. It was correctly observed that an excess of wine induced extreme states, such as sleepiness and aggression in animals, in a manner similar to humans.

Conclusions

Accounts in ancient literature show a close association between animals and wine existed among the Greeks and Romans.
Dysregulated lipidome of sebum in patients with atopic dermatitis
Authors: Yin Huibin , Qiu Zhuoqiong , Zhu Ronghui , Wang Shangshang , Gu Chaoying , Yao Xu , Li Wei
Published: October 2022

Background

Lipids are the major components of skin barrier, mainly produced by keratinocytes and sebaceous glands. Previous studies on barrier dysfunction of atopic dermatitis (AD) mainly focus on the lipids from keratinocytes, whereas the role of sebaceous gland‐derived lipids in AD has long been underrecognized.

Methods

The sebum secreted on the skin surface of AD patients was measured using the Delfin Sebum Scale. Sebum was collected using Sebutape patches and subjected for liquid chromatography tandem‐mass spectrometry (LC–MS/MS) analysis. Multivariate data analysis was applied to explore the relationship among the lipidome, clinical features, and sebaceous gland‐related molecules.

Results

The amount of sebum secreted from sebaceous glands was decreased in AD patients and was negatively correlated with the barrier function and disease severity. LC–MS/MS revealed the lipidome of sebum, which clustered distinctly between AD patients and healthy individuals. Among the differential lipid subclasses, triglycerides (TG) were exclusively decreased in AD patients and correlated with disease severity. The first principal component scores of AD patients, which represented the main signature of the lipidome, were positively correlated with the SCORAD scores and were significantly different across the patient groups with differential clinical symptoms such as skin dryness and pruritus. Further analysis on the previously published transcriptome data revealed aberrant expression of lipid metabolism‐related genes in non‐lesional skin of AD patients, which was associated with skin inflammation and barrier dysfunction and mainly derived from inner root sheath keratinocytes and sebaceous gland cells.

Conclusion

Atopic dermatitis patients demonstrated a deviated lipidome of sebum and aberrant lipid metabolism in sebaceous glands, indicating a possible role of lipids from sebaceous glands in the pathogenesis of AD.
Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence
Authors: Andrews Christopher N. , Rehak Renata , Woo Matthew , Walker Ian , Ma Christopher , Forbes Nauzer , Rittenbach Katherine , Hathaway Joshua , Wilsack Lynn , Liu Andy , Nasser Yasmin , Sharkey Keith A.
Published: October 2022

Background

Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use.

Aims

To characterise patients experiencing CHS in North America and to obtain a population‐based estimate of CHS treatment prevalence in Canada before and during the Covid‐19 pandemic

Methods

Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017–2018), after recreational legalisation (2018–2019) and during the first year of the Covid‐19 pandemic (2020–2021).

Results

Problematic cannabis use (defined as a CUDIT‐R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14–17) prior to legalisation, to 21 (95% CI, 20–23) after legalisation, to 32 (95% CI, 31–35) during the beginning of the Covid‐19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16–24 age group.

Conclusion

Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid‐19 pandemic.
Antioxidant activities of artesunate–procyanidin hybrid compound in erythrocyte and liver of Plasmodium berghei NK65‐infected mice
Authors: Tijjani Habibu , Adebayo Joseph O.
Published: October 2022

Resistance of malaria parasites to conventionally used antimalarial drugs has necessitated the search for new potent antimalarials, especially those that can also ameliorate oxidative stress‐mediated secondary complications. This has led to the synthesis of an antimalarial artesunate–procyanidin hybrid compound (PC14), but it has not been evaluated for its antioxidant activity. This study was carried out to evaluate the antioxidant activities of PC14 in the erythrocyte and liver of Plasmodium berghei NK65‐infected mice. A hundred mice were randomly divided into 10 equal groups (A–J). Mice in Groups B–J were inoculated with P. berghei NK65 while group A mice were not inoculated. Starting from Day 3 post‐inoculation, dimethyl sulfoxide (DMSO) (5%) was administered to mice in Groups A and B (normal and negative controls, respectively), while various doses of chloroquine, artesunate, procyanidin, and PC14 were administered to their respective groups for 3 days. Thereafter, antioxidant parameters were determined in the erythrocyte and liver on Days 6 and 10 post‐inoculation. A significant increase (P < 0.05) was observed in malondialdehyde levels in the erythrocyte and liver of negative control on Day 10 post‐inoculation compared to normal controls. Significant reduction (P < 0.05) was observed in activities of liver catalase and superoxide dismutase and erythrocyte glutathione peroxidase and glutathione‐S‐transferase of negative control on Days 6 and 10 compared to normal controls. However, PC14 at various doses significantly (P < 0.05) reversed these alterations. The results suggest that PC14 possesses antioxidant activity, and it enhanced antioxidant defense in the erythrocyte and liver of P. berghei‐infected mice.
In conversation with Peter Macheroux
Authors: Skourti Eleni , Macheroux Peter
Published: October 2022

Peter Macheroux is Professor of Biochemistry and Head of the Institute of Biochemistry at Graz University of Technology in Austria. Peter's research spans a diverse selection of topics, and his work has contributed significantly towards advancing our understanding of bacterial enzymology, plant physiology and the molecular pathways that underlie human pathophysiology. Among Peter's many scientific achievements, he has led the team that recognised DPP3 as a biomarker for cardiovascular diseases, with the subsequent therapeutic implications of the development of DPP3 inhibitors. In this interview‐based article, Peter provides an overview of his research focus and goals, recalls some of his great scientific breakthroughs and describes what the key current challenges in his research field are.
The importance of establishing a core outcome set for endodontic clinical trials and outcomes studies
Authors: El‐Karim Ikhlas , Duncan Henry F. , Nagendrababu Venkateshbabu , Clarke Mike
Published: October 2022

Endodontic therapy aims to preserve teeth by preventing and treating apical disease, therefore, evaluation of treatment outcome in clinical trials and outcomes studies should effectively assess if it achieves these aims. Traditionally, treatment outcomes have been reported by clinicians after history and clinical examination in what is known as clinician‐reported outcomes (CROs). Much less commonly employed however, are patient‐reported outcomes (PROs) in which patients directly report on their condition. Endodontic treatment outcome reporting is evolving from a focus on CROs to increasing consideration for patient and disease‐focused outcomes, with different criteria being proposed for assessment of treatment outcomes. Unfortunately, this has led to considerable variability and a lack of consensus on the definition, appropriate measurement and reporting of these outcomes. Heterogeneity in outcome reporting in clinical research provides a significant major barrier to conduct meta‐analysis, guidelines development, clinical decision making, and ultimately affecting patient care. These effects could, however, be reduced by the establishment of a core outcome set (COS) in endodontics, which is defined as an agreed, standardized set of outcomes that should be included, measured and reported as a minimum in all trials and outcome studies. COS development is a regulated and validated process requiring involvement of appropriate stakeholders as well as a rigorous methodology. To date, COS has been developed for the management of traumatic dental injuries, orthodontic and periodontal treatment and is currently being developed for endodontic treatment. The aim of this review is to discuss the importance of COS in endodontics with focus on the evidence for and impact of heterogeneity in reporting endodontic treatment outcomes. An overview of an ongoing process for development of COS for different endodontic treatment modalities will also be provided.
A recent glance on the valorisation of cheese whey for industrial prerogative: high‐value‐added products development and integrated reutilising strategies
Authors: Arshad Umm‐e‐Tazeem , Hassan Ali , Ahmad Talha , Naeem Maha , Chaudhary Maryam T. , Abbas Syed Qamar , Randhawa Muhammad Atif , Pimentel Tatiana C. , da Cruz Adriano Gomes , Aadil Rana Muhammad
Published: October 2022

This review article explores recent advancements in converting cheese whey (CW) into high‐value‐added products, focusing on producing biofuels, bioelectricity and different whey‐based food items, as well as other potential uses. Additionally, new integrated reutilising strategies are proposed to utilise CW to develop innovative products with various applications, mainly focusing on sustainable alternatives at the industrial level. CW could be utilised with the help of different processes, for example separation of main protein components from cheese whey, like separation and purification of α‐lactalbumin, production of polysaccharides (lactose and lactulose), volatile fatty acids (VFAs), other organic acids and bioethanol. Besides these products, CW could also be utilised in the fermentation process, in the production of alcoholic drinks (whey sprite and white whisky), in the production of whey protein concentrate and as poultry feed. Biotechnological approaches for whey utilisation are the most recent alternatives. They can produce important products for the industries, such as whey‐based products, bioplastics, biofuels, bioelectricity, organic acids, bioactive compounds and whey‐based food items.
Delivery of topical gentamicin cream via platform wound device to reduce wound infection—A prospective, controlled, randomised, clinical study
Authors: Cooley Jennifer , Obaidi Noor , Diaz Victoria , Anselmo Kristin , Eriksson Elof , Carlsson Anders H. , Chan Rodney K. , Nuutila Kristo
Published: October 2022

The platform wound device (PWD) is a wound coverage system that is designed to decrease wound infection rates by allowing for direct delivery of topical antibiotics and antimicrobials while creating a sealed, protective barrier around the area of injury. This study evaluated the safety and efficacy of the PWD as a protective dressing and a delivery system for topical antibiotics compared to the current standard of care (SoC). This was a multi‐center, prospective, randomised, controlled clinical trial. The wounds were treated with the PWD with gentamicin cream or SoC dressings. The wounds were evaluated before the start of treatment and after 48–96 hours via clinical assessment, photographs, and qualitative bacterial swabs for bacterial analysis. The delivery of gentamicin via the PWD was safe and did not cause any adverse effects. The treatment decreased both inflammation and bacterial growth during the study period. No significant differences in the SoC were observed. The PWD is a transparent and impermeable polyurethane chamber that encloses and protects the injured area. The delivery of topical gentamicin via the PWD was safe and effective. Clinical assessment for infection found the PWD to be non‐inferior to the current SoC treatment options.
Autologous wound margin point columnar full‐thickness skin grafting combined with negative pressure wound therapy improves wound healing in refractory diabetic foot ulcers
Authors: Mo Jianming , Huang Yuanjing , Wang Qiu , Zhong Hua , Zhai Zhenwei , Nong Yuechou , Yan Xiaodong , Huang Xiulu , Huang Jianhao , Yang Suping , Sun Jingxia , Han Jiaxia , Zhou Xing , Lu Wensheng
Published: October 2022

Diabetic lower extremity ulcers (DLEUs) are a severe complication of diabetes mellitus (DM) and are difficult to heal. This study aimed to explore the efficacy of autologous point columnar full‐thickness skin graft taken from the ulcer wound margin combined with negative pressure wound therapy (NPWT) in refractory DLEUs. This is a prospective cohort study. A total of 40 inpatients with refractory DLEUs were recruited in the Diabetes Foot Center of Guangxi Zhuang Autonomous Region People's Hospital from October 2019 to November 2021. According to the doctors' professional suggestions and the patients' personal wishes, these enrolled patients were divided into two groups based on different topical wound management: the graft group (n = 18) and the conventional wound therapeutic (CWT) group (n = 22). The efficacy evaluations included the time to complete re‐epithelialization of the wound and healing speed within 14 days of graft treatment or after 14 days of graft treatment in the two groups. Before the treatment, the graft group had a significantly larger ulcer area than the CWT group [27.22 (15.28, 46.59) versus 10.92 (7.00, 24.93) cm2, P < .01]. However, the time to complete wound re‐epithelialization in the graft group was shorter than in the CWT group [58.22 ± 30.60 versus 86.09 ± 49.54 d, P < .05]. Meanwhile, the healing speed in graft group was markedly faster than in CWT group, whether within 14 days [0.60 (0.40, 0.92) versus 0.16 (0.07, 0.34) cm2/d, P < .01] or after 14 days of graft treatment [0.57 (0.45, 0.91) versus 0.13 (0.08, 0.27) cm2/d, P < .01]. However, the total treatment cost in the graft group was lower than in the CWT group [419.59 ± 137.20 versus 663.97 ± 497.02 $, P < .05]. The novel treatment modality of autologous full‐thickness skin graft taken from the ulcer wound margin combined with NPWT has hereby proposed for the first time, and is a safe, effective, and reliable method with a good performance‐to‐cost ratio to promote wound healing and shorten the healing time for DLEUs.
IL‐17A promotes lung fibrosis through impairing mitochondrial homeostasis in type II alveolar epithelial cells
Authors: Xiao Huijuan , Peng Liang , Jiang Dingyuan , Liu Yuan , Zhu Lili , Li Zhen , Geng Jing , Xie Bingbing , Huang Xiaoxi , Wang Jing , Dai Huaping , Wang Chen
Published: October 2022

The dysfunction of type II alveolar epithelial cells (AECIIs), mainly manifested by apoptosis, has emerged as a major component of idiopathic pulmonary fibrosis (IPF) pathophysiology. A pivotal mechanism leading to AECIIs apoptosis is mitochondrial dysfunction. Recently, interleukin (IL)‐17A has been demonstrated to have a pro‐fibrotic role in IPF, though the mechanism is unclear. In this study, we report enhanced expression of IL‐17 receptor A (IL‐17RA) in AECIIs in lung samples of IPF patients, which may be related to the accumulation of mitochondria in AECIIs of IPF. Next, we investigated this relationship in bleomycin (BLM)‐induced PF murine model. We found that IL‐17A knockout (IL‐17A−/−) mice exhibited decreased apoptosis levels of AECIIs. This was possibly a result of the recovery of mitochondrial morphology from the improved mitochondrial dynamics of AECIIs, which eventually contributed to alleviating lung fibrosis. Analysis of in vitro data indicates that IL‐17A impairs mitochondrial function and mitochondrial dynamics of mouse primary AECIIs, further promoting apoptosis. PTEN‐induced putative kinase 1 (PINK1)/Parkin signal‐mediated mitophagy is an important aspect of mitochondria homeostasis maintenance. Our data demonstrate that IL‐17A inhibits mitophagy and promotes apoptosis of AECIIs by decreasing the expression levels of PINK1. We conclude that IL‐17A exerts its pro‐fibrotic effects by inducing mitochondrial dysfunction in AECIIs by disturbing mitochondrial dynamics and inhibiting PINK1‐mediated mitophagy, thereby leading to apoptosis of AECIIs.
Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK‐Ay mice
Authors: Oda Kaori , Miyamoto Satoshi , Kodera Ryo , Wada Jun , Shikata Kenichi
Published: October 2022

Aims/Introduction

Nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL‐18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL‐18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg‐Ay/TaJcl (KK‐Ay) mice against DKD progression.

Materials and Methods

Suramin or saline was administered i.p. to KK‐Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin.

Results

Suramin treatment significantly suppressed the increase in the urinary albumin‐to‐creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK‐Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome‐related genes and proteins in the renal cortex of KK‐Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK‐Ay mice and mainly distributed in the glomerular mesangial cells of KK‐Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP‐induced NLRP3 complex formation and the downstream expression of caspase‐1 and IL‐18 in MMCs.

Conclusions

These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.
Decimal reduction value (D) from fraction negative experiments via maximum likelihood estimation: An enabling spreadsheet and its implications on methodology and current standards
Authors: Moruzzi Guido , Lou Yuqian , Fritz Ronald D.
Published: October 2022

Resistance of biological indicators for sterilization in pharma and food applications is often determined via fraction negative experiments. The ISO 11138 standards prescribe the Holcomb–Spearman–Karber procedure (HSKP) for calculating D value using these methods. However, HSKP imposes limitations on experimental designs. While ISO 11138 requires inactivation kinetics to not significantly deviate from first order, the HSKP does not provide a step to check such departure, or its extent. Maximum likelihood estimation (MLE) is an alternative approach for D value determination from fraction negative experiments. Compared to HSKP, it allows researchers to tailor the experimental design to practical needs, potentially reducing overall sample size in the process. This work presents a development of a 2004 published worksheet for MLE calculation, providing tighter confidence intervals and an improved way for Improbability calculation. Ways to exploit the design flexibility of MLE approach are presented, including simulated experiments and examples on how to optimize experimental design according to various situational needs, also in cases where expected D values are of the order of one or a few seconds as is commonly encountered in the sterilization of aseptic fillers for food. Detection of deviation from first‐order kinetics using the enhanced Improbability methods is discussed; one of the examples provided by ISO 11138‐1 for D value determination by HSKP contains data that deviate significantly from first order.
Association between social integration and risk of dementia: A systematic review and meta‐analysis of longitudinal studies
Authors: Wang Shanshan , Molassiotis Alex , Guo Chunlan , Leung Isaac Sze Him , Leung Angela Yee Man
Published: October 2022

Background

Dementia is an emerging public health issue. Growing evidence emerged on the association between social integration and the risk of dementia. However, the magnitude of the association between different aspects of social integration and the risk of dementia is unclear.

Methods

Five databases were systematically searched. Newcastle–Ottawa scale for assessing the quality of the reporting was used for quality appraisal. Longitudinal cohort studies examining the association between social integration and the risk of dementia were analyzed using random effects model. A series of sensitivity analyses was conducted to enhance the robustness of the findings.

Results

Forty publications generated from 32 studies/databases were included. The meta‐analysis showed that strong social engagement (overall RR = 0.81, 95% CI = 0.74–0.89, p < 0.001) and frequent social contact (overall RR = 0.86, 95% CI = 0.76–0.97, p = 0.018) were positively associated with decreased risk of dementia. The influence of social support (overall RR = 0.92, 95% CI = 0.80–1.06, p = 0.238) and close social contact (overall RR = 0.74, 95% CI = 0.48–1.13, p = 0.167) was not significant. Loneliness was significantly associated with an increased risk of dementia (overall RR = 1.42, 95% CI = 1.26–1.60, p < 0.001), whereas the influence of social isolation (overall RR = 1.58, 95% CI = 0.80–3.12, p = 0.192) was not significant. A larger social network size (RR = 0.75, 95% CI = 0.59–0.97, p = 0.028) was a promising influencing factor even though the number of studies was insufficient for a meta‐analysis. However, the heterogeneity among studies was generally high even though sensitivity analysis was conducted.

Conclusions

Our findings reveal that high social engagement and frequent social contact are significantly associated with a lower risk of dementia, whereas loneliness is associated with a higher risk. The promising impact of large social network size is also identified. Substantial heterogeneity appeared in most of the analysis, making the inference tentative. Nevertheless, the sensitivity analysis provided valuable implications that enhancing social engagement and reducing loneliness may prevent or delay the onset of dementia among middle‐aged and older adults.
Hyperkyphosis and mortality risk in older men: The osteoporotic fractures in men study
Authors: Cours Alexandra , Huang Mei‐Hua , Fink Howard , Ensrud Kristine E. , Schousboe John T. , Katzman Wendy , Schneider Diane , Lane Nancy E. , Cawthon Peggy , Kado Deborah M.
Published: October 2022

Introduction

Hyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk.

Methods

Men aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks‐measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all‐cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self‐reported health, alcohol use, medical co‐morbidities, and physical activity.

Results

During a mean follow‐up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0–1 block kyphosis, increasing blocks‐measured kyphosis was associated with increased mortality (HR: 1.26–1.53, p trend <0.001). With addition of prevalent vertebral fracture to adjusted models, the association remained significant in participants with severe kyphosis (3+ blocks‐measured). Similarly, with addition of chair stand performance the association remained significant for 4+ blocks kyphosis. Walking speed did not attenuate the association of kyphosis and mortality. In the secondary cohort, there were no significant associations between radiographic Cobb angle kyphosis and mortality.

Conclusions

Increasing blocks‐measured kyphosis was associated with a greater risk of mortality in older men, indicating that hyperkyphosis identified on physical exam should be considered a clinically significant finding that may warrant further evaluation and treatment.
Low copy numbers for mitochondrial DNA moderates the strength of nuclear–cytoplasmic incompatibility in plants
Authors: Zhang Liguang , Ma Jin , Shen Zhaorui , Wang Bo , Jiang Qingling , Ma Fei , Ju Yan , Duan Guangxing , Zhang Quan , Su Xiaodong , Sodmergen
Published: October 2022

Plant cells contain only small amounts of mitochondrial DNA (mtDNA), with the genomic information shared among multiple mitochondria. The biological relevance and molecular mechanism underlying this hallmark of plant cells has been unclear. Here, we report that Arabidopsis thaliana plants exhibited significantly reduced growth and mitochondrial dysfunction when the mtDNA copy number was increased to the degree that each mitochondrion possessed DNA. The amounts of mitochondrion‐encoded transcripts increased several fold in the presence of elevated mtDNA levels. However, the efficiency of RNA editing decreased with this excess of mitochondrion‐encoded transcripts, resulting in impaired assembly of mitochondrial complexes containing mtDNA‐encoded subunits, such as respiratory complexes I and IV. These observations indicate the occurrence of nuclear–mitochondrial incompatibility in the cells with increased amounts of mtDNA and provide an initial answer to the fundamental question of why plant cells have much lower mtDNA levels than animal cells. We propose that keeping mtDNA levels low moderates nuclear–mitochondrial incompatibility and that this may be a crucial factor driving plant cells to restrict the copy numbers of mtDNA.
An assessment of the variation of the intramuscular innervation of the gracilis muscle, with the aim of determining its neuromuscular compartments
Authors: Kurtys Konrad , Podgórski Michał , Gonera Bartosz , Vazquez Teresa , Olewnik Łukasz
Published: October 2022

Some muscles present neuromuscular compartments, one of which is the gracilis muscle. The aim of the present study is to determine the number of compartments present within the gracilis muscle based on its intramuscular innervation patterns; such knowledge could be of value in free functional muscle transfer. The study comprised 72 gracilis muscles (38 women, 34 men), fixed in 10% formalin solution. The muscles were removed and then stained using Sihler's method. When sufficient transparency was achieved, some measurements were made. Three different types of intramuscular innervation were distinguished. Type I (70.8%) was featured by at least one direct proximal nerve branch. Type II (23.6%) presented at least one indirect proximal nerve branch. Type III (5.6%) did not possess any proximal nerve branch. The median of descended nerve branches was five. Considerable anatomical variation is possible within the intramuscular innervation of the gracilis muscle. The muscle presents neuromuscular compartments, but the exact number depends on the type of its intramuscular innervation and the number of the main descendent nerve branches. All three types seem to be appropriate for free functional muscle transfer. Our findings may be of great value for surgeons carrying out complex reconstructions with the use of the gracilis muscle.