bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper bioreduction and nanoparticle synthesis by an enrichment culture from a former copper mine
Authors: Kimber Richard L. , Elizondo Gretta , Jedyka Klaudia , Boothman Christopher , Cai Rongsheng , Bagshaw Heath , Haigh Sarah J. , Coker Victoria S. , Lloyd Jonathan R.
Published: September 2023

Microorganisms can facilitate the reduction of Cu2+, altering its speciation and mobility in environmental systems and producing Cu‐based nanoparticles with useful catalytic properties. However, only a few model organisms have been studied in relation to Cu2+ bioreduction and little work has been carried out on microbes from Cu‐contaminated environments. This study aimed to enrich for Cu‐resistant microbes from a Cu‐contaminated soil and explore their potential to facilitate Cu2+ reduction and biomineralisation from solution. We show that an enrichment grown in a Cu‐amended medium, dominated by species closely related to Geothrix fermentans, Azospira restricta and Cellulomonas oligotrophica, can reduce Cu2+ with subsequent precipitation of Cu nanoparticles. Characterisation of the nanoparticles with (scanning) transmission electron microscopy, energy‐dispersive x‐ray spectroscopy and electron energy loss spectroscopy supports the presence of both metallic Cu(0) and S‐rich Cu(I) nanoparticles. This study provides new insights into the diversity of microorganisms capable of facilitating copper reduction and highlights the potential for the formation of distinct nanoparticle phases resulting from bioreduction or biomineralisation reactions. The implications of these findings for the biogeochemical cycling of copper and the potential biotechnological synthesis of commercially useful copper nanoparticles are discussed.
Authentic leadership, psychological capital, acceptance of change, and innovative work behaviour in non‐profit organisations
Authors: Brunetto Yvonne , Kominis Georgios , Ashton‐Sayers Julia
Published: September 2023

This paper examines whether authentic leadership provides the resources employees need to build their psychological capacities and well‐being so that they can embrace organisational change and engage in innovative work behaviour (IWB) within non‐profit organisation (NPO). The paper builds on previous research examining the antecedents of IWB such as ‘innovation‐enabling culture’ and psychological capital (PsyCap). The new variables examined in this study are authentic leadership and acceptance of change. Utilising a structural equation modelling methodology, 248 surveys from Australian not‐for‐profit employees were analysed revealing that authentic leadership accounted for more than a fifth of the variance of PsyCap; PsyCap, age, and authentic leadership accounted for 40% of employees’ well‐being; and age, leadership, and acceptance of change accounted for a quarter of their IWB, although acceptance of change was not directly related to IWB. The main contribution of this paper is in explaining why authentic leadership is an important ingredient for building an ‘innovation‐enabling culture’ for NPO employees, suggesting that such leadership provides a pathway for developing effective workplace relationships built on trust and ethical decision making. Such behaviour builds a supportive culture for developing employees’ personal resources, which promotes the conditions for promoting IWB.

Points for practitioners

Authentic leadership behaviour provides a platform for developing the psychological capacities of employees in non‐profit organisations (NPOs) contracted to deliver social services to Australians.

Authentic leadership behaviours and psychological capital enhance employees’ well‐being.

Authentic leadership behaviours and psychological capital are significant building blocks of an innovation‐enabling culture in NPOs.
What influences public decision‐makers? An Australian case study
Authors: Bolton Mitzi
Published: September 2023

Limited or incomplete achievement of societal aspirations, such as the realisation of sustainable development, can lead to distrust in government and the public sector. This paper takes an empirical approach to uncover (1) what factors influence public decision‐makers, (2) if such factors apply equally irrespective of the decision, and (3) which are most important. Thirty‐five interviews of public servants within the subnational State of Victoria, Australia, yield 40 common influences upon decision‐makers. Collectively, these influences result in an unmanageably complex operating environment. Statistical and network mapping analyses further demonstrate decision context and decision‐maker self‐efficacy impact influence importance.

Points for practitioners

Forty different influences make the public sector operating environment incredibly complex; they explain why public outcomes can deviate from stated objectives.

These influences vary in impact (barriers, enablers), scale, and importance, pending the decision context and the self‐efficacy of the decision‐makers involved.

While distinct factors, the 40 influences often operate in concert, with some masking others; decision‐makers themselves may not recognise the most important factors upon their work without deep reflection.

Far from being at the mercy of the influences, decision‐makers can shape public outcomes by recognising the influences on their decisions and seeking to engage them as enablers of optimal decisions.

Applying systems thinking may enable widespread public decision‐making improvements, through the identification of high‐value leverage points.
Partitioning of casein and fat in Cheddar cheese manufacturing as affected by cheese milk standardisation: A review
Authors: Kayihura Joseph F
Published: September 2023

Cheesemaking offers the opportunity to exploit the unique nutritional, sensory, biological and other functionalities of both cheese and whey‐derived products. Milk standardisation is one of the essential cheesemaking operations designed to preserve the intrinsic cheese quality and may also improve whey composition because of its impact on partitioning of milk constituents between the two coproducts. The effectiveness of cheese milk standardisation in controlling constituent partitioning depends on the method and ingredients selected. This review explores how and why cheese milk standardisation affects the partitioning of casein and fat in Cheddar cheese and provides some perspective on a better approach.
What motivates users to adopt cybersecurity practices? A survey experiment assessing protection motivation theory
Authors: Dodge Cassandra E. , Fisk Nathan , Burruss George W. , Moule Richard K. , Jaynes Chae M.
Published: September 2023

Research Summary

A 2 × 2 × 3 fully crossed factorial experiment is used to examine the linkages between key dimensions of protection motivation theory (PMT; perceived severity of risk, vulnerability to risk, and response costs) and the intentions to adopt information technology (IT) cybersecurity recommendations after being informed of degrees of risk in the vignettes. Data in this study consist of a nationwide sample of 720 American adults. Results from a series of fractional logistic regressions indicate support for many of the core mechanisms within PMT. Seventy percent of respondents indicated they were likely to follow IT recommendations to mitigate a cyber threat. Self‐efficacy and response costs affected intentions to do so.

Policy Implications

The study's findings have important implications for improving cybersecurity and reducing vulnerabilities to cyber threats. Current training programs need more effective communication strategies and engagement tools. Perceptions of users as security threats rather than potential contributors hinder progress in the ability of organizations to improve cybersecurity. Collaborative, user‐centered approaches can enhance users’ self‐efficacy and improve cybersecurity by aligning user and IT professional needs and capabilities. Strategies like gamified simulations and tailored interventions can create a more security‐focused culture and encourage user participation in defending an organization. Recognizing individual differences among users and further examining personal characteristics that may impact user interactions with technology and cybersecurity interventions is crucial. Overall, more personalized, adaptable approaches to cybersecurity policies and technical solutions, accounting for diverse user needs and characteristics, should be a priority for improving cybersecurity practices.
The patchwork governance of ecologically available water: A case study in the Upper Missouri Headwaters, Montana, United States
Authors: Cravens Amanda E. , Goolsby Julia B. , Jedd Theresa , Bathke Deborah J. , Crausbay Shelley , Cooper Ashley E. , Dunham Jason , Haigh Tonya , Hall Kimberly R. , Hayes Michael J. , McEvoy Jamie , Nelson Rebecca L. , Poděbradská Markéta , Ramirez Aaron , Wickham Elliot , Zoanni Dionne
Published: September 2023

Institutional authority and responsibility for allocating water to ecosystems (“ecologically available water” [EAW]) is spread across local, state, and federal agencies, which operate under a range of statutes, mandates, and planning processes. We use a case study of the Upper Missouri Headwaters Basin in southwestern Montana, United States, to illustrate this fragmented institutional landscape. Our goals are to (a) describe the patchwork of agencies and institutional actors whose intersecting authorities and actions influence the EAW in the study basin; (b) describe the range of governance mechanisms these agencies use, including laws, policies, administrative programs, and planning processes; and (c) assess the extent to which the collective governance regime creates gaps in responsibility. We find the water governance regime includes a range of nested mechanisms that in various ways facilitate or hinder the governance of EAW. We conclude the current multilevel governance regime leaves certain aspects of EAW unaddressed and does not adequately account for the interconnections between water in different parts of the ecosystem, creating integrative gaps. We suggest that more intentional and robust coordination could provide a means to address these gaps.
Late‐life plasma proteins associated with prevalent and incident frailty: A proteomic analysis
Authors: Liu Fangyu , Austin Thomas R. , Schrack Jennifer A. , Chen Jingsha , Walston Jeremy , Mathias Rasika A. , Grams Morgan , Odden Michelle C. , Newman Anne , Psaty Bruce M. , Ramonfaur Diego , Shah Amil M. , Windham B. Gwen , Coresh Josef , Walker Keenan A.
Published: September 2023

Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross‐sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 × 10−5) among 3838 older adults aged ≥65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17%) and 82 (46%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; pprefrailty = 1 × 10−15, pfrailty = 2 × 10−19), transgelin (TAGLN; pprefrailty = 2 × 10−12, pfrailty = 6 × 10−22), and insulin‐like growth factor‐binding protein 2 (IGFBP2; pprefrailty = 5 × 10−15, pfrailty = 1 × 10−15) and with a lower level of growth hormone receptor (GHR, pprefrailty = 3 × 10−16, pfrailty = 2 × 10−18). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 10−5). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty‐acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.
Life years lost for users of specialized mental healthcare
Authors: Konings Stefan R. A. , Mierau Jochen O. , Visser Ellen , Bruggeman Richard , Feenstra Talitha L.
Published: September 2023

Background

Mental disorders are burdensome and are associated with increased mortality. Mortality has been researched for various mental disorders, especially in countries with national registries, including the Nordic countries. Yet, knowledge gaps exist around national differences, while also relatively less studies compare mortality of those seeking help for mental disorders in specialized mental healthcare (SMH) by diagnosis. Additional insight into such mortality distributions for SMH users would be beneficial for both policy and research purposes. We aim to describe and compare the mortality in a population of SMH users with the mortality of the general population. Additionally, we aim to investigate mortality differences between sexes and major diagnosis categories: anxiety, depression, schizophrenia spectrum and other psychotic disorders, and bipolar disorder.

Methods

Mortality and basic demographics were available for a population of N = 10,914 SMH users in the north of The Netherlands from 2010 until 2017. To estimate mortality over the adult lifespan, parametric Gompertz distributions were fitted on observed mortality using interval regression. Life years lost were computed by calculating the difference between integrals of the survival functions for the general population and the study sample, thus correcting for age. Survival for the general population was obtained from Statistics Netherlands (CBS).

Results

SMH users were estimated to lose 9.5 life years (95% CI: 9.4–9.6). Every major diagnosis category was associated with a significant loss of life years, ranging from 7.2 (95% CI: 6.4–7.9) years for anxiety patients to 11.7 (95% CI: 11.0–12.5) years for bipolar disorder patients. Significant differences in mortality were observed between male SMH users and female SMH users, with men losing relatively more life years: 11.0 (95% CI: 10.9–11.2) versus 8.3 (95% CI: 8.2–8.4) respectively. This difference was also observed between sexes within every diagnosis, although the difference was insignificant for bipolar disorder.

Conclusion

There were significant differences in mortality between SMH users and the general population. Substantial differences were observed between sexes and between diagnoses. Additional attention is required, and possibly specific interventions are needed to reduce the amount of life years lost by SMH users.
Evidence collection and use when making management decisions
Authors: Criado‐Perez Christian , Jackson Chris , Collins Catherine G.
Published: September 2023

Evidence‐based management (EBM) is a useful framework to assist managers in making organizational decisions based on the best available evidence. EBM use is nevertheless marginal among managers, and little is known about the enablers that can facilitate and effectively increase its use. We use two experimental studies to examine the effect of cognitive reflection, learning goals, and social norms in predicting EBM usage. We also propose an objective assessment task to measure the collection and use of evidence in the context of EBM. Results from both studies provide support for the importance of cognitive reflection and social norms to enable EBM. Surprisingly, learning goals were not associated with EBM use. This research increases our understanding of EBM, provides indications of how to increase its usage, and presents a methodology to investigate evidence collection and use objectively.
Plasmatic thinking and tourism: Plasmatic modernity
Authors: Ong Chin Ee
Published: September 2023

This paper builds on assemblage theory to propose a new theoretical understanding of modernity. While the conceptual framing is meant for modernity at large, this paper locates its conceptual discussion in the context of tourism in Macao and illustrates how plasmatic thinking, the new conceptual framework proposed, advances analysis of aspiration, exploitation and freedom of its tour guides. Plasmatic thinking helps examinations of tourism labour to engage with the fragile and fluid nature of the sociomaterial environments. Instead of structures, networks or fluidities, plasmatic thinking sees the world as composed of ‘plasmas’ – ‘charged’ sociomaterial clustering of objects, humans and the processes between them. Plasmas are a form of charged matter falling outside solid, liquid and gaseous states and metaphorises the fragility and impermanence of sociomaterial situations for plasmas disintegrates when discharged. The attention to charges and fragility of plasmas helps describes both pandemic levels shocks and everyday disruptions. Through a plasmatic analysis of the falling apart and coming together of such plasmas and how they bring about significant consequences to Macao's tourism, I showcase plasmatic thinking as a theoretical approach which vividly uncovers the fragility and fluidity of modernity and the workings of power in our sociomaterial worlds.
Characterisation of obsidian subsource variability at El Paredón, Mexico
Authors: Vicencio A. Gabriel , López Corral Aurelio , Mitrani Alejandro , Arciniega Armando , Carballo David M.
Published: September 2023

Portable X‐ray fluorescence (pXRF) geochemical analysis on obsidian from five Formative period (1200 BCE to AC 100) sites from Tlaxcala, Mexico, has revealed that most of the material had similar values to those found in the closest obsidian source, named El Paredón, Puebla. Nevertheless, initial analyses did not resolve whether these materials came from the same caldera or from a specific obsidian deposit. Here we present a methodology that allows the identification of obsidian subsources. The results reveal that Tlaxcalan populations took advantage of a specific obsidian deposit called Tres Cabezas, Puebla, providing valuable new data to identify associated regional exchange networks.
Lead isotope ratio analysis of lead ingots and bronze wares unearthed from Yinxu
Authors: Li Qiang , Wei Guofeng , Huang Haiyan , Tang Jigen , Zhang Bingjian
Published: September 2023

This study gives the element compositions and Pb isotope ratios of three lead ingots and three bronze artefacts unearthed from Yinxu, Anyang, Henan province, and two lead vessels from Zhengxiaozhuang tomb, Anhui province, China. The results of composition analysis show that three lead ingots in Yinxu may be the primary product of lead smelting. The lead wares unearthed in Zhengxiaozhuang tomb could be a kind of Mingqi‐funerary replicas. The results of Pb isotope analysis indicate that the culture exchanges between the Central Plains and the Jianghuai area in the late Shang dynasty. The decrease of bronzes with the highly radiogenic lead is consistent with the increase of Pb content in Yinxu bronzes simultaneously, which could be related to the change of lead source.
Exotic blue pigments in the polychrome interior of Yongle Taoist Temple: A case of international trade during the Yuan and Qing Dynasties
Authors: Zheng Yihua , Guo Weijia , Li Luke , Xi Jiulong , Zhang Morun , Jiang Yutong , Liu Xin
Published: September 2023

Previous studies have established the use of various blue pigments, including both local and imported varieties, in the decoration of architecture in ancient China. However, the application of these pigments in local religious architecture has been understudied. In this study, the chemical analysis of ultramarine blue pigments was conducted on a mural painting retrieved from Yongle Taoist Temple in ancient China. The results showed that both imported and local pigments were used individually in the initial drawing period of the Yuan Dynasty (AD 1271–1368), whereas they were mixed in a later restoration in the Qing Dynasty (AD 1636–1912). Of particular significance, the analysis revealed the presence of lapis lazuli in a local religious relic of the Yuan Dynasty for the first time. Further analysis of the elemental proportions and associated minerals led to speculation about the origin of the lapis lazuli, which is believed to have come from Badakhshan, the northeastern region of Afghanistan, and been transported to Central China through the Silk Road. This finding shed light on the trade routes and usage of these pigments in the construction of religious architecture from the Yuan to the Qing dynasties.
Decolonising ecological research: A generative discussion between Global North geographers and Global South field ecologists
Authors: Soares Bruno Eleres , Franco Ana Clara Sampaio , Leal Juliana S. , Lima Romullo Guimarães de Sá Ferreira , Baker Kate , Griffiths Mark
Published: September 2023

In this article we draw on recent debates in ecology and human geography on the project of decolonising academic practice. Our objective is to address two key questions via a generative discussion across disciplines: what can ecologists learn from ongoing debates in human geography? And how might those learnings translate back into geographical praxis? We make the central argument that vibrant debates in human geography can push ecologists to take more radical steps towards a decolonial vision that, in turn, can guide geographers to a more material decolonising praxis. We build this argument by working through various dis/connections—between ecology/human geography, theory/praxis, South/North—in the wider project of decolonising academia to provoke critical reflection around the themes of (i) language and publishing; (ii) collaboration and ‘inclusion’; and (iii) the geographies of ecological research.
Tools and guidelines to assess the appropriateness of medication and aid deprescribing: An umbrella review
Authors: Anlay Degefaye Zelalem , Paque Kristel , Van Leeuwen Ellen , Cohen Joachim , Dilles Tinne
Published: September 2023

Aims

The aim of this umbrella review was to identify tools and guidelines to aid the deprescribing process of potentially inappropriate medications (PIMs), evaluate development and validation methods, and describe evidence levels for medication inclusion.

Methods

Searches were conducted on MEDLINE (Ovid), Embase.com, Cochrane CDSR, CINAHL (EBSCO), Web of Science Core Collection and guideline databases from the date of inception to 7 July 2022. Following the initial search, an additional search was conducted to identify an updated versions of tools on 17 July 2023. We analysed the contents of tools and guidelines.

Results

From 23 systematic reviews and guidelines, we identified 95 tools (72 explicit, 12 mixed and 11 implicit) and nine guidelines. Most tools (83.2%) were developed to use for older persons, including 14 for those with limited life expectancy. Seven tools were for children <18 years (7.37%). Most explicit/mixed tools (78.57%) and all guidelines were validated. We found 484 PIMs and 202 medications with different appropriateness independent of disease for older persons with normal and limited life expectancy, respectively. Only two tools and eight guidelines reported the evidence level, and a quarter of medications had high‐quality evidence.

Conclusions

Tools are available for a diversity of populations. There were discrepancies, with the same medication being classified as inappropriate in some tools and appropriate in others, possibly due to low‐quality evidence. In particular, tools for patients with limited life expectancy were developed based on very limited evidence, and research to generate this evidence is urgently needed. Our medication lists, along with the level of evidence, could facilitate efforts to strengthen the evidence.
Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma
Authors: Williams Connor M. D. , Noll Jacqueline E. , Bradey Alanah L. , Duggan Jvaughn , Wilczek Vicki J. , Masavuli Makutiro G. , Grubor‐Bauk Branka , Panagopoulos Romana A. , Hewett Duncan R. , Mrozik Krzysztof M. , Zannettino Andrew C. W. , Vandyke Kate , Panagopoulos Vasilios
Published: September 2023

Expression of myeloperoxidase (MPO), a key inflammatory enzyme restricted to myeloid cells, is negatively associated with the development of solid tumours. Activated myeloid cell populations are increased in multiple myeloma (MM); however, the functional consequences of myeloid‐derived MPO within the myeloma microenvironment are unknown. Here, the role of MPO in MM pathogenesis was investigated, and the capacity for pharmacological inhibition of MPO to impede MM progression was evaluated. In the 5TGM1‐KaLwRij mouse model of myeloma, the early stages of tumour development were associated with an increase in CD11b+ myeloid cell populations and an increase in Mpo expression within the bone marrow (BM). Interestingly, MM tumour cell homing was increased towards sites of elevated myeloid cell numbers and MPO activity within the BM. Mechanistically, MPO induced the expression of key MM growth factors, resulting in tumour cell proliferation and suppressed cytotoxic T‐cell activity. Notably, tumour growth studies in mice treated with a small‐molecule irreversible inhibitor of MPO (4‐ABAH) demonstrated a significant reduction in overall MM tumour burden. Taken together, our data demonstrate that MPO contributes to MM tumour growth, and that MPO‐specific inhibitors may provide a new therapeutic strategy to limit MM disease progression.
Prevalence of urolithiasis in China: a systematic review and meta‐analysis
Authors: Tan Songsong , Yuan Dongbo , Su Hao , Chen Weihong , Zhu Siqi , Yan Bo , Sun Fa , Jiang Kehua , Zhu Jianguo
Published: September 2023

Objective

To estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China.

Materials and Methods

We conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random‐effects meta‐analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates.

Results

A total of 46 studies conducted in 22 provinces across China were included in this meta‐analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6–11.1%), 7.8% (95% CI 5.8–10.0%), 3.2% (95% CI 0.6–5.7%), 0.5% (95% CI 0.1–0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46–1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis.

Conclusions

The prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time.
Outsource to India: The impact of service outsourcing to India on the labor market in the United States
Authors: Park Jiwon
Published: September 2023

Service offshoring raises the fear of job loss for high‐skilled workers, unlike goods offshoring, because workers at home compete with highly educated workers in low‐income countries. This paper examines whether the increase in the United States's service offshoring to India has reduced the domestic employment of the occupations with greater exposure to Indian service imports. To account for endogeneity, I instrument for the growth of the United States's service imports from India by exploiting the change in Indian exports to European countries. Service offshoring reduces total employment from 2000 to 2006; however, this effect disappears overall and becomes positive for college‐educated workers in the later period from 2006 to 2016. Unlike goods offshoring, the employment effect is largely driven by college‐educated workers, and the employment growth in the later period is larger.
Flucloxacillin worsens while imipenem–cilastatin protects against vancomycin‐induced kidney injury in a translational rat model
Authors: Pais Gwendolyn M. , Marianski Sylwia , Valdez Kimberly , Melicor Renz Paulo , Liu Jiajun , Rohani Roxane , Chang Jack , Tong Steven Y. C. , Davis Joshua S. , Scheetz Marc H.
Published: September 2023

Background and Purpose

Vancomycin is one of the most common clinical antibiotics, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin‐induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem–cilastatin on kidney injury when combined with vancomycin in our translational rat model.

Experimental Approach

Male Sprague–Dawley rats received allometrically scaled (1) vancomycin, (2) flucloxacillin, (3) vancomycin + flucloxacillin, (4) vancomycin + imipenem–cilastatin or (5) saline for 4 days. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule‐1 (KIM‐1), clusterin and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored.

Key Results

Urinary output increased every study day for vancomycin + flucloxacillin, but after the first dose only in the vancomycin group. In the vancomycin + flucloxacillin group, urinary KIM‐1 increased on all days compared with vancomycin. In the vancomycin + imipenem–cilastatin group, urinary KIM‐1 was decreased on Days 1 and 2 compared with vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin + flucloxacillin compared with vancomycin and vancomycin + imipenem–cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM‐1.

Conclusions and Implications

Vancomycin + flucloxacillin caused more kidney injury compared with vancomycin alone and vancomycin + imipenem–cilastatin in a translational rat model. The combination of vancomycin + imipenem–cilastatin was nephroprotective.
The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease
Authors: He Mingyue , Lian Tenghong , Guo Peng , Zhang Weijiao , Zhang Yanan , Huang Yue , Liu Gaifen , Guan Huiying , Li Jinghui , Luo Dongmei , Zhang Weijia , Zhang Wenjing , Qi Jing , Yue Hao , Wang Xiaomin , Zhang Wei
Published: September 2023

Aims

To explore the roles of apolipoprotein E (APOE) ε4 on the neuropathology and neuroinflammation in Alzheimer's disease (AD) patients.

Methods

AD patients were divided into the APOE ε4 carrier and the APOE ε4 non‐carrier groups according to APOE genotype. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) were compared between the two groups, and their correlations were subsequently analyzed.

Results

β amyloid protein (Aβ)1–42 level from the APOE ε4 carrier group was significantly lower than that from the non‐carrier group (p = 0.023), which was associated with worse cognitive function. The nitric oxide (NO) level was significantly elevated in the APOE ε4 carrier group compared to the non‐carrier group (p = 0.016), which was significantly and positively correlated with the Trail Making Test (TMT)‐A‐time (r = 0.21, p = 0.026) and TMT‐B‐time (r = 0.38, p < 0.01).

Conclusion

APOE ε4 is associated with poorer cognition, particularly the early symptoms of memory, language, and attention. APOE ε4 is associated with lower Aβ1–42 level, and the more numbers of APOE ε4 are carried, the lower level of Aβ1–42 is measured. APOE ε4 is associated with elevated NO level, which is linked to the impaired attention and executive function.
Human umbilical cord mesenchymal stem cell‐derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF‐κB/NLRP3 pathway
Authors: Che Ji , Wang Hui , Dong Jing , Wu Yuanyuan , Zhang Haichao , Fu Lei , Zhang Jun
Published: September 2023

Aims

We investigated whether human umbilical cord mesenchymal stem cell (hUC‐MSC)‐derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)‐induced neuroinflammation.

Methods

Exosomes were isolated from hUC‐MSC supernatant by ultra‐high‐speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV‐2 cells, primary microglial cultures, and C57BL/6J mice. H2O2 was also used to induce inflammation and oxidative stress in BV‐2 cells. The effects of hUC‐MSC‐derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting.

Results

Treatment with hUC‐MSC‐derived exosomes significantly decreased the LPS‐ or H2O2‐induced oxidative stress and expression of pro‐inflammatory cytokines (IL‐6 and TNF‐α) in vitro, while promoting an anti‐inflammatory (classical M2) phenotype in an LPS‐treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS‐induced NF‐κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF‐κB inhibitor BAY 11–7082 also inhibited the LPS‐induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti‐inflammatory and anti‐oxidative effects of the exosomes.

Conclusion

hUC‐MSC‐derived exosomes ameliorated LPS/H2O2‐induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF‐κB/NLRP3 signaling pathway.
GRECCAR 14 – a multicentric, randomized, phase II–III study evaluating the tailored management of locally advanced rectal carcinoma after a favourable response to induction chemotherapy: Study protocol
Authors: Rouanet Philippe , Castan Florence , Mazard Thibault , Lemanski Claire , Nougaret Stephanie , Deshayes Emmanuel , Chalbos Patrick , Gourgou Sophie , Taoum Christophe ,   the GRECCAR, PRODIGE study group
Published: September 2023

Aim

Total neoadjuvant treatment (TNT) is becoming standard in patients with locally advanced rectal carcinoma (LARC). Preoperative chemoradiotherapy (CRT) has proven side effects on bowel and genitourinary function. An early tumoral response to induction chemotherapy demonstrates its high prognostic value. Tailored management could be used as an alternative to systematic CRT. The GRECCAR 14 trial will attempt to personalize treatment strategy according to the patient's early tumour response to intensive chemotherapy with the aim of achieving the best toxicity–efficiency ratio.

Method

GRECCAR 14 is a multicentric, randomized, two‐arm, phase II–III noninferiority trial. Patients with mid or low LARC with a predictive circumferential resection margin ≤2 mm or T3c‐d stage with extramural venous invasion will be included. Evaluation of the tumoral response will be performed after six courses of high‐dose FOLFIRINOX chemotherapy. Good responders (GRs) will be defined by a 60% decrease in tumoral volume on magnetic resonance imaging. Patients will be randomized to CRT before surgery. The primary endpoints will be R0 resection for phase II and the 3‐year disease‐free survival (DFS) for phase III.

Results

Tailored management of LARC is becoming an exciting challenge for the modality of neoadjuvant treatment and for the type of surgery or its omission. Neoadjuvant FOLFIRINOX has established efficacy, with a significant increase in the 3‐year DFS. Better control of systemic disease must be accompanied by the same locoregional control, with the lowest morbidity. Our previous GRECCAR 4 trial demonstrated the high value of the early tumoral response after induction chemotherapy and the long‐term safety of tailored management for GRs.

Conclusion

If GRECCAR 14 demonstrates the ability to tailor TNT for LARC, this could lead to changes in clinical practice.
Methylthio‐substituted coumarin‐based fluorescent probe for highly specific and fast detection of hypochlorite and bioimaging application
Authors: Zhao Baijun , Wang Wenwen , Song Yanxi , Li Hongqi , Jiang Lin , Chu Lingling
Published: September 2023

Hypochlorite is a kind of endogenously produced reactive oxygen species (ROS) in the human immune system and plays a crucial role in many pathophysiological processes. In this work a novel fluorescent probe derived from 6‐methylthio coumarin was designed and synthesised for detection of hypochlorite in acetonitrile/phosphate‐buffered saline (MeCN/PBS) (1:1, v/v, pH 7.4) medium. The probe displayed high specificity toward hypochlorite over other ROS analytes, rapid response to hypochlorite within 30 s, and a broad applicable range of pH 3–8. The detection limit was calculated to be 1.48 μM. Application of this probe for in vitro Hecat cell imaging to detect hypochlorite ions was confirmed. A sensing mechanism based on thioether to sulfoxide oxidation by hypochlorite was proposed and demonstrated. The study presented an effective approach for construction of highly efficient hypochlorite chemosensors from hydrophilic methylthio‐substituted coumarins considering their facile access.
Notochordal cells: A potential therapeutic option for intervertebral disc degeneration
Authors: Li Yanhu , Zhang Haijun , Zhu Daxue , Yang Fengguang , Wang Zhaoheng , Wei Ziyan , Yang Zhili , Jia Jingwen , Kang Xuewen
Published: September 2023

Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal degenerative disorder worldwide, and ~40% of chronic low back pain cases are associated with IDD. Although the pathogenesis of IDD remains unclear, the reduction in nucleus pulposus cells (NPCs) and degradation of the extracellular matrix (ECM) are critical factors contributing to IDD. Notochordal cells (NCs), derived from the notochord, which rapidly degrades after birth and is eventually replaced by NPCs, play a crucial role in maintaining ECM homeostasis and preventing NPCs apoptosis. Current treatments for IDD only provide symptomatic relief, while lacking the ability to inhibit or reverse its progression. However, NCs and their secretions possess anti‐inflammatory properties and promote NPCs proliferation, leading to ECM formation. Therefore, in recent years, NCs therapy targeting the underlying cause of IDD has emerged as a novel treatment strategy. This article provides a comprehensive review of the latest research progress on NCs for IDD, covering their biological characteristics, specific markers, possible mechanisms involved in IDD and therapeutic effects. It also highlights significant future directions in this field to facilitate further exploration of the pathogenesis of IDD and the development of new therapies based on NCs strategies.
Polarity reversal of canine intestinal organoids reduces proliferation and increases cell death
Authors: Csukovich Georg , Wagner Maximilian , Walter Ingrid , Burger Stefanie , Tschulenk Waltraud , Steinborn Ralf , Pratscher Barbara , Burgener Iwan Anton
Published: September 2023

Apical‐out intestinal organoids are a relatively simple method of gaining access to the apical cell surface and have faced increasing scientific interest over the last few years. Apical‐out organoids can thus be used for disease modelling to compare differing effects on the basolateral versus the apical cell surface. However, these ‘inside‐out’ organoids die relatively quickly and cannot be propagated as long as their basal‐out counterparts. Here, we show that apical‐out organoids have drastically reduced proliferative potential, as evidenced by immunohistochemical staining and the incorporation of the thymidine analogue EdU. At the same time, cell death levels are increased. Nevertheless, these phenomena cannot be explained by an induction of differentiation, as the gene expression of key marker genes for various cell types does not change over time.
Apoptotic vesicles derived from human red blood cells promote bone regeneration via carbonic anhydrase 1
Authors: Shao Yuzi , Jiang Yuhe , Yang Kunkun , Zhu Yuan , Liu Yunsong , Zhang Ping , Lv Longwei , Zhang Xiao , Zhou Yongsheng
Published: September 2023

Apoptotic vesicles (apoVs) are nanoscale vesicles derived from billions of apoptotic cells involved in the maintenance of the human body's homeostasis. Previous researches have shown that some apoVs, such as those derived from mesenchymal stem cells, contribute to bone formation. However, those apoVs cannot be extracted from patients in large quantities, and cell expansion is needed before apoV isolation, which limits their clinical translation. Mature RBCs, which have no nuclei or genetic material, are easy to obtain, showing high biological safety as a source of extracellular vesicles (EVs). Previous studies have demonstrated that RBC‐derived EVs have multiple biological functions, but it is unknown whether RBCs produce apoVs and what effect these apoVs have on bone regeneration. In this study, we isolated and characterized RBC‐derived apoVs (RBC‐apoVs) from human venous blood and investigated their role in the osteogenesis of human bone mesenchymal stem cells (hBMSCs). We showed that RBCs could produce RBC‐apoVs that expressed both general apoVs markers and RBC markers. RBC‐apoVs significantly promoted osteogenesis of hBMSCs and enhanced bone regeneration in rat calvarial defects. Mechanistically, RBC‐apoVs regulated osteogenesis by transferring carbonic anhydrase 1 (CA1) into hBMSCs and activating the P38 MAPK pathway. Our results indicated that RBC‐apoVs could deliver functional molecules from RBCs to hBMSCs and promote bone regeneration, pointing to possible therapeutic use in bone tissue engineering.
Adam Smith's moral foundations of self‐interest and ethical social order
Authors: Arevuo Mikko
Published: September 2023

This article draws on textual evidence from The Theory of Moral Sentiments and The Wealth of Nations to address mistaken interpretations of Adam Smith's fundamental concept of self‐interest as greed that has been said to have had a corrosive influence on markets, commercial behaviour, and widening inequality. To the contrary, Smith's complex set of human motivations, including self‐interest, his economic system that is based on free markets, and institutional frameworks governing productive property rights and the rule of law are argued to increase aggregate wealth, improve the position of those least well off, and maintain ethical social order.
Health human capital formation in the OECD: Exploring the role of welfare state composition
Authors: Santos Marcelo , Simões Marta , Sousa Sílvia
Published: September 2023

This study examines the relationship between welfare state or social expenditure composition and health human capital in 37 OECD countries spanning 1980–2018. Our findings confirm that public health spending has a positive effect on health capital formation. Dissecting social expenditure according to other nine social spending categories reveals a positive influence for old age pensions and unemployment benefits. The results for the remaining social programs vary with the health capital proxy and estimation method used. It thus appears that more comprehensive and universal social programs, possibly by guaranteeing the necessary income, do a better job in improving health human capital.
Perceived confidence of dental students and new graduates in performing tooth extractions—An exploratory study
Authors: Gaballah Kamis , Ali Kamran , Zahra Daniel , Abou Neel Ensanya , Ibrahim Eteman
Published: September 2023

Introduction

The ability to perform uncomplicated tooth extractions is a core clinical skill in undergraduate dental education. The aim of this study was to evaluate pre‐extraction assessment skills of dental students and interns and explore their self‐perceived confidence in performing these tooth extractions.

Materials and Methods

A cross‐sectional survey investigated the self‐perceived confidence to perform the extraction for a set of eight expert‐rated cases. The participants were dental students at three different stages, that is, in Years 4 and 5 of the Bachelor of Dental Surgery (BDS) programme and interns. The participants were asked to rate the difficulty level of each of the eight tooth extraction cases. The self‐perceived confidence of the participants to perform extraction of each was also explored. Finally, the participants were asked to identify the main reason for the perceived lack of confidence.

Results

A total of 199 responded to the survey, yielding a response rate of 94.7%. The effect of grade of extraction (the expert rating of cases) and stage of education on difficulty ratings was assessed using a mixed three stage of education × 4‐grade ANOVA, with response (Difficult = 1, Easy = 0) as the dependent variable. The results showed that there was a correlation between the stage of education and grade of extraction and affected the self‐perceived confidence of the participants. Gender showed a significant impact with females categorizing significantly more cases as difficult. A three‐way contingency table (counts of each confidence‐level response by stage of education by expert rating of cases) suggests a statistically significant association between the three factors. Most participants identified limited clinical exposure as the main reason for their perceived lack of confidence.

Conclusion

The findings of this study show that a majority of the participants were able to recognize tooth extraction cases which were beyond the scope of their training stage with females reporting a lower confidence. Increased clinical exposure to a wider range of tooth extraction cases with varying levels of difficulty may contribute to improving the self‐confidence of undergraduate dental students and interns.
Application of thromboelastography to predict the severity of bleeding after chimeric antigen receptor (CAR)‐T cell therapy in patients with hematological malignancy
Authors: Chen Liu , Ding Shuyi , Cheng Yin , Zhou Linghui , Yan Jiali , Cheng Qiong , Jin Aiyun , Zhou Xiaoyu , Huang He , Hu Yongxian
Published: September 2023

Objectives

We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)‐T cell therapy.

Methods

A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non‐severe bleeding group. The thromboelastography data was collected on the day of CAR‐T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR‐T cell infusion.

Results

The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0–10, opposite on Days 10–20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR‐T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84–0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35–5.32; p = .006) were significantly associated with high bleeding severity.

Conclusions

Thromboelastography was considered to be a good predictor of bleeding severity.