bluuebunny/crossref_metadata_2025 huggingface dataset:
Methadone pharmacogenetics in vitro and in vivo: Metabolism by CYP2B6 polymorphic variants and genetic variability in paediatric disposition
Authors: Wang Pan‐Fen , Sharma Anshuman , Montana Michael , Neiner Alicia , Juriga Lindsay , Reddy Kavya Narayana , Tallchief Dani , Blood Jane , Kharasch Evan D.
Published: May 2022

Aims

Methadone metabolism and clearance are determined principally by polymorphic cytochrome P4502B6 (CYP2B6). Some CYP2B6 allelic variants affect methadone metabolism in vitro and disposition in vivo. We assessed methadone metabolism by CYP2B6 minor variants in vitro. We also assessed the influence of CYP2B6 variants, and P450 oxidoreductase (POR) and CYP2C19 variants, on methadone clearance in surgical patients in vivo.

Methods

CYP2B6 and P450 oxidoreductase variants were coexpressed with cytochrome b5. The metabolism of methadone racemate and enantiomers was measured at therapeutic concentrations and intrinsic clearances were determined. Adolescents receiving methadone for surgery were genotyped for CYP2B6, CYP2C19 and POR, and methadone clearance and metabolite formation clearance were determined.

Results

In vitro, CYP2B6.4 was more active than wild‐type CYP2B6.1. CYPs 2B6.5, 2B6.6, 2B6.7, 2B6.9, 2B6.17, 2B6.19 and 2B6.26 were less active. CYPs 2B6.16 and 2B6.18 were inactive. CYP2B6.1 expressed with POR variants POR.28, POR.5 and P228L had lower rates of methadone metabolism than wild‐type reductase. In vivo, methadone clinical clearance decreased linearly with the number of CYP2B6 slow metabolizer alleles, but was not different in CYP2C19 slow or rapid metabolizer phenotypes, or in carriers of the POR*28 allele.

Conclusions

Several CYP2B6 and POR variants were slow metabolizers of methadone in vitro. Polymorphisms in CYP2B6, but not CYP2C19 or P450 reductase, affected methadone clearance in vivo. CYP2B6 polymorphisms 516G>T and 983T>C code for canonical loss of function variants and should be assessed when considering genetic influences on clinical methadone disposition. These complementary translational in vitro and in vivo results inform on pharmacogenetic variability affecting methadone disposition in patients.
Motivation towards novel learning content: Perceived similarity of learning content, but not need for cognition, moderates the generalization of motivation
Authors: Gorges Julia , Schmidt Leonie Christina
Published: May 2022

Background

The generalization of established motivation hypothesis states that individuals use established motivational beliefs to predict motivational beliefs regarding novel learning content on the basis of the perceived similarity between academic domains.

Aims

This study tests the generalization hypothesis by investigating the assumed moderating role of the extent of perceived similarity between known and novel learning content and need for cognition (NFC).

Sample(s)

Participants were adult students (n = 576) from various study programs (Study 1) and non‐students (n = 628) of whom the majority held at least a bachelor's degree (Study 2).

Methods

In this prospective correlational survey study, we used online self‐report measures to assess participants’ self‐concept of ability (SCA) and intrinsic task value (ITV) regarding their established and anticipated motivational beliefs regarding a set of school subjects (known learning content) and fields of study (novel learning content), perceptions of similarity, and their NFC. Data was analysed using structural equation modelling with latent interaction variables.

Results

We found support for the generalization hypothesis and documented that the perceived similarity moderated the generalizing effect (i.e., SCA and ITV had stronger predictive validity for learning content that was perceived as more similar). However, the results obtained for the moderating effect of NFC were mostly nonsignificant.

Conclusion

Individuals generalize established motivation regarding known learning content to anticipated motivation regarding novel learning content perceived as being similar. The extent of perceived similarity enhances this effect, whereas NFC does not. Future research should address the underlying automatic and deliberate cognitive processes of generalization.
For to all those who have, will more be given? Evidence from the adoption of the SELFIE tool for the digital capacity of schools in Spain
Authors: Castaño Muñoz Jonatan , Pokropek Artur , Weikert García Lilian
Published: May 2022

This paper explores participation trends in interventions that promote self‐evaluation exercises on the effective use of digital technologies in schools. We use a unique dataset consisting of 83,185 respondents from 924 Spanish schools that used SELFIE, a tool based on self‐reflection questionnaires that capture different dimensions of school's digital capacity. We benefit from a natural experiment situation caused by the parallel use of SELFIE by two groups of schools. The first group was externally selected as part of a representative sample of Spanish schools. Conversely, the second group voluntarily decided to use SELFIE as a diagnostic tool for a subsequent self‐evaluation exercise. Moreover, a subset of schools were located in regions where authorities embedded SELFIE in broader digitalisation programmes. By comparing these groups, it is shown that schools that decide to participate in SELFIE voluntarily are those with a lower initial digitalisation level. It is also found that the promotion of the use of SELFIE as part of public interventions can increase participation but mainly attracts digitally advanced schools. In conclusion, policy interventions aiming to develop the digital capacity of schools need to plan how to reach those schools that need it more in order to be more equitable.

Practitioner notes

What is already known about this topic

Research has shown the existence of a Matthew effect in the usage of digital technologies in education.

The promotion of schools self‐evaluation exercises on digital education is a common policy intervention that is growing in importance.

There is a surprising lack of attention to the inequitable effects that programmes aiming to incorporate technologies in educational institutions may generate.

What this paper adds

This paper investigates the self‐selection trends and (un)equity effects of SELFIE, an EU programme designed to prompt schools' self‐evaluations of digital capacity.

When schools decide autonomously, schools with low digital capacity levels tend to participate in SELFIE more.

Incorporation of SELFIE into broader public programmes enlarges participation in SELFIE.

Incorporation of SELFIE into broader public programmes over‐attracts digitally advanced schools.

Implications for practice and/or policy

Public policies promoting self‐evaluation exercises on school digital capacity in schools might be a good way for upscaling these exercises.

However, these policies should be carefully designed to reduce inequalities and reach these schools that need digitalisation more.
‘Pulling the Bandage Off’: Using Margaret Warner's ‘Fragile Process’ in the Psychodynamic Approach
Authors: Hauser Holt J.S.
Published: May 2022

This article explores the nature of how therapists work with clients who find it difficult or impossible to be emotionally or relationally present in therapy. In trying to explore how to be with clients in this challenging state, the author draws from person‐centred theorist Margaret Warner's concept of ‘fragile process’, and how it describes the presentation of these clients and the therapists’ role with them. The author then argues for the utility of this person‐centred concept and its applicability in the psychodynamic approach, and wonders how it might be theoretically conceived in psychodynamic terms for use by psychodynamic practitioners. The author draws parallel between Warner's idea of fragile process with fundamental theoretical understandings of the infant–mother relationship from the theories of Donald Winnicott. After exploring a theoretical understanding of this concept, the author explores his own clinical experience of a client exhibiting fragile process, inspecting a single session. The author offers his account on the case study's contents, the transference material, and the practitioner's reflective process to demonstrate how fragile process as a concept might be applied in client work.
An unusual case of comedones
Authors: Haywood Sophia , Barker Ruth , Blakeway-Manning Elizabeth , Walton Shernaz
Published: May 2022

We present the case of a 71-year-old woman with widespread comedones since adolescence. Histological examination revealed branching hyperpigmented rete ridges and cystically dilated follicular infundibulum containing laminated keratinous debris. We explore the differential diagnosis in the context of other reticulate hyperpigmentation disorders.
Heart transplant recipient 1‐year outcomes during the COVID‐19 pandemic
Authors: Esmailian Gabriel , Patel Nikhil , Patel Jignesh K. , Czer Lawrence , Rafiei Matthew , Megna Dominick , Emerson Dominic , Ramzy Danny , Trento Alfredo , Chikwe Joanna , Esmailian Fardad , Kobashigawa Jon A.
Published: May 2022

The COVID‐19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post‐transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1‐year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted during the same months between 2011 and 2019 (n = 482). Endpoints included subsequent 1‐year survival, freedom from cardiac allograft vasculopathy, any‐treated rejection, acute cellular rejection, antibody‐mediated rejection, nonfatal major adverse cardiac events (NF‐MACE), and hospital and ICU length of stay. Patients transplanted during the pandemic had similar 1‐year endpoints compared to those of patients transplanted from years prior apart from 1‐year freedom from NF‐MACE which was significantly higher for patients transplanted during the pandemic. Despite necessary changes being made to outpatient management of heart transplant recipients, heart transplantation continues to be safe and effective with similar 1‐year outcomes to years prior.
Traction‐assisted endoscopic submucosal dissection for esophageal neoplasms using a novel traction device
Authors: Ogura Kanako , Ichijima Ryoji , Ikehara Hisatomo
Published: May 2022

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Pathological and molecular diagnoses of early cancer with bile and pancreatic juice
Authors: Kuwatani Masaki , Sakamoto Naoya
Published: May 2022

The dismal prognosis of pancreaticobiliary malignancies is mainly attributed to the extremely difficult detection of early‐stage lesions, including intraepithelial neoplasia. To improve prognosis, several studies on the early detection of cancer have been conducted using bile and pancreatic juices for pathological or molecular analyses. One approach is liquid biopsy that includes information about the tumor, such as circulating tumor cells, circulating tumor DNA, microRNAs, and exosomes released by the tumor. Another approach is proteomics/metabolomics that reflects specific conditions in the tumor. These two approaches lead to artificial intelligence‐based multiomics analyses that comprises genomics, proteomics/metabolomics, and transcriptomics. Based on the findings of molecular analysis, pathological analysis using immunohistochemical staining/fluorescence in situ hybridization has also been developed. Moreover, there have been reports of new methods/ingenuities for obtaining appropriate samples for the diagnosis of early‐stage cancer. Here we review the knowledge on cutting‐edge pathological and molecular analyses of bile and pancreatic juices, introduce some ingenuities in sampling and sample processing to promote effective clinical practice, and provide a basis for future studies.
Sticky wages in a world of ideas
Authors: Huang Kevin X. D. , Katayama Munechika , Shintani Mototsugu , Tsuruga Takayuki
Published: May 2022

This paper examines the implications of idea production and knowledge capital for monetary business cycles. We construct a sticky‐wage model where workers produce goods based on firm‐specific knowledge capital and researchers develop new ideas aided by economywide knowledge. As a quantitatively small group in the economy, researchers are inconsequential for the real effects of monetary shocks when the returns to research are low. However, when the returns to research are high, the result can be overturned. Monetary shocks can have significant real effects, even if wages are perfectly flexible for workers, who are quantitatively dominant in the economy.
NMDA receptor antagonists engender neuroprotection against gp120‐induced cognitive dysfunction in rats through modulation of PKR activation, oxidative stress, ER stress and IRE1α signal pathway
Authors: Zeng Yirong , Wang Lixuan , Zhou Yijun , Liang Mei , Yu Jiajia , Wu Sisi , Zhou Yan
Published: May 2022

It is widely accepted that the surface glycoprotein (gp120) of human immunodeficiency virus‐1 (HIV‐1) plays an important role in HIV‐1‐induced nerve damage and pathogenesis of HIV‐associated neurocognitive disorders (HAND). Our previous work has demonstrated that gp120 enhanced excitatory postsynaptic currents (EPSCs) mediated by N‐methyl‐d‐aspartate receptors (NMDARs) and caused neural injury. However, the relationship between gp120, NMDARs and HAND is still unclear. Several lines of evidence indicate that double‐stranded RNA‐activated protein kinase (PKR) is involved in NMDA‐induced cerebral ischaemia and retinal damage, but because its role in neuropathology is still debated, we examined whether PKR links oxidative stress and endoplasmic reticulum (ER) stress to exert a deleterious role in the rat model with gp120‐induced dementia. In this study, we found that NMDAR antagonist memantine or PKR inhibitor C16 improved gp120‐induced learning and memory impairment and inhibited gp120‐induced PKR activity. Furthermore, memantine or C16 was found to attenuate gp120‐induced neuroinflammation, oxidative stress, ER stress and its downstream IRE1α/JNK pathway. Additionally, memantine or C16 evidently inhibited apoptotic pathways by reducing the Bax and caspase‐3, ‐8, ‐9 expressions and increasing Bcl‐2 expression. So the NMDA receptor antagonists could alleviate HIV/gp120‐induced dementia in the rat model by altering PKR level. In conclusion, this study demonstrates that NMDARs play a key role in HIV/gp120‐induced hippocampal damage and cognitive dysfunction through PKR‐mediated oxidative stress, ER stress, and IRE1α/JNK signalling pathway in rats, and implicating PKR inhibitors could provide a novel neuroprotective strategy for HAND via inhibiting ER stress and its downstream IRE1α signalling pathway.
Biodiversity and yield trade‐offs for organic farming
Authors: Gong Shanxing , Hodgson Jenny A. , Tscharntke Teja , Liu Yunhui , van der Werf Wopke , Batáry Péter , Knops Johannes M. H. , Zou Yi
Published: May 2022

Organic farming supports higher biodiversity than conventional farming, but at the cost of lower yields. We conducted a meta‐analysis quantifying the trade‐off between biodiversity and yield, comparing conventional and organic farming. We developed a compatibility index to assess whether biodiversity gains from organic farming exceed yield losses, and a substitution index to assess whether organic farming would increase biodiversity in an area if maintaining total production under organic farming would require cultivating more land at the expense of nature. Overall, organic farming had 23% gain in biodiversity with a similar cost of yield decline. Biodiversity gain is negatively correlated to yield loss for microbes and plants, but no correlation was found for other taxa. The biodiversity and yield trade‐off varies under different contexts of organic farming. The overall compatibility index value was close to zero, with negative values for cereal crops, positive for non‐cereal crops, and varies across taxa. Our results indicate that, on average, the proportion of biodiversity gain is similar to the proportion of yield loss for paired field studies. For some taxa in non‐cereal crops, switching to organic farming can lead to a biodiversity gain without yield loss. We calculated the overall value of substitution index and further discussed the application of this index to evaluate when the biodiversity of less intensified farming system is advantageous.
The European Academy of Neurology Brain Health Strategy: One brain, one life, one approach
Authors: Bassetti Claudio L. A. , Endres Mathias , Sander Anja , Crean Michael , Subramaniam Sumathi , Carvalho Vanessa , Di Liberto Giovanni , Franco Oscar H. , Pijnenburg Yolande , Leonardi Matilde , Boon Paul
Published: May 2022

Background and purpose

Brain health is essential for health, well‐being, productivity and creativity across the entire life. Its definition goes beyond the absence of disease embracing all cognitive, emotional, behavioural and social functions which are necessary to cope with life situations.

Methods

The European Academy of Neurology (EAN) Brain Health Strategy responds to the high and increasing burden of neurological disorders. It aims to develop a non‐disease‐, non‐age‐centred holistic and positive approach (‘one brain, one life, one approach’) to prevent neurological disorders (e.g., Alzheimer's disease and other dementias, stroke, epilepsy, headache/migraine, Parkinson's disease, multiple sclerosis, sleep disorders, brain cancer) but also to preserve brain health and promote recovery after brain damage.

Results

The pillars of the EAN Brain Health Strategy are (1) to contribute to a global and international brain health approach (together with national and subspecialty societies, other medical societies, the World Health Organization, the World Federation of Neurology, patients' organizations, industry and other stakeholders); (2) to support the 47 European national neurological societies, healthcare and policymakers in the implementation of integrated and people‐centred campaigns; (3) to foster research (e.g., on prevention of neurological disorders, determinants and assessments of brain health); (4) to promote education of students, neurologists, general practitioners, other medical specialists and health professionals, patients, caregivers and the general public; (5) to raise public awareness of neurological disorders and brain health.

Conclusions

By adopting this ‘one brain, one life, one approach’ strategy in cooperation with partner societies, international organizations and policymakers, a significant number of neurological disorders may be prevented whilst the overall well‐being of individuals is enhanced by maintaining brain health through the life course.
Earthworms as catalysts in the formation and stabilization of soil microbial necromass
Authors: Angst Gerrit , Frouz Jan , van Groenigen Jan Willem , Scheu Stefan , Kögel‐Knabner Ingrid , Eisenhauer Nico
Published: May 2022

Microbial necromass is a central component of soil organic matter (SOM), whose management may be essential in mitigating atmospheric CO2 concentrations and climate change. Current consensus regards the magnitude of microbial necromass production to be heavily dependent on the carbon use efficiency of microorganisms, which is strongly influenced by the quality of the organic matter inputs these organisms feed on. However, recent concepts neglect agents relevant in many soils: earthworms. We argue that the activity of earthworms accelerates the formation of microbial necromass stabilized in aggregates and organo‐mineral associations and reduces the relevance of the quality of pre‐existing organic matter in this process. Earthworms achieve this through the creation of transient hotspots (casts) characterized by elevated contents of bioavailable substrate and the efficient build‐up and quick turnover of microbial biomass, thus converting SOM not mineralized in this process into a state more resistant against external disturbances, such as climate change. Promoting the abundance of earthworms may, therefore, be considered a central component of management strategies that aim to accelerate the formation of stabilized microbial necromass in wide locations of the soil commonly not considered hotspots of microbial SOM formation.
A demographic framework for understanding fire‐driven reptile declines in the ‘land of the lizards'
Authors: Santos Julianna L. , Sitters Holly , Keith David A. , Geary William L. , Tingley Reid , Kelly Luke T.
Published: May 2022

Background

Fire creates habitats for many animals but changes in fire activity threaten species worldwide. While conservation assessments routinely identify fire as a threat to lizards and snakes, the processes underlying fire‐driven population declines have received less attention. Assessing the effects of fire on demographic processes – survival, reproduction and movement – provides a means to identify mechanisms of population declines and forecast population changes. Here, we synthesize how inappropriate fire regimes contribute to declines of animal populations, using threatened Australian squamates as a case study.

Methods

We applied a demographic framework in a systematic review to identify fire characteristics and interacting threats associated with population declines in imperilled Australian squamates (n = 88). We reviewed primary literature and conservation assessments on these species and classified fire‐related threats according to seven key mechanisms of population decline, five fire‐regime characteristics, and eight interacting threats.

Results

Inappropriate fire regimes threaten 43% of Australian squamates of conservation concern, including geckos, skinks and snakes. Our analysis indicates that high fire intensity and severity, high fire frequency, and large fires are the main causes of fire‐related population declines, particularly via their impacts on survival. Low fire frequency also contributes to declines of some species through reduced survival or reproductive success. Weed invasion and predation are observed or predicted to interact with fire to amplify reptile declines. Our results also reveal a dearth of robust empirical studies on squamates of conservation concern.

Main conclusions

The demographic framework applied here will help forecast population changes in a new era of fire. By focusing on processes that are relevant to squamate populations globally, we anticipate that the framework will help diagnose causes of population declines in ecosystems that experience fire, and quantify the consequences of alternative management actions, including urgent conservation interventions after megafires.
Working in the gig economy is boring: Non‐encounters and the politics of detachment in platform capitalism
Authors: Straughan Elizabeth R. , Bissell David
Published: May 2022

This paper develops the concept of the non‐encounter for geography in the context of the changing experience of gig economy work during COVID‐19. Supplementing political economy insights with a cultural geographic sensitivity to embodiment, we explore the fluctuating bodily capacities of food delivery drivers during the first year of the COVID‐19 pandemic in Melbourne, Australia. We reflect on fieldwork with gig workers which drew our attention to how the practice of doorstep food delivery became ‘contact‐free’ during the pandemic. In dialogue with cultural geographical literatures on boredom and interruptions, our paper highlights the deleterious impacts of repetition without interruption on workers' bodies. We argue that the felt absences of previously enjoyed light‐touch interactions with customers and other delivery drivers has created a strange kind of ‘non‐encounter’ for gig workers, intensifying feelings of boredom and a sense of detachment. We speculate on what this means for the future of gig work and for cultural geographers.
National heroes, disposable workers. How collective action in the health and social care sector during the pandemic negotiated with the self‐sacrificing worker ideal
Authors: Galanti Costanza
Published: May 2022

During the pandemic, the ideal of the self‐sacrificing health and social care worker became both more powerful and more unsustainable than ever. This article explores the manner and extent to which health and social care workers collectively challenged this ideal. Drawing on ethnographic fieldwork in Italy, this paper discusses mobilizations organized within three occupations: doctors in training, nurses, and social care workers. The study finds that collective action partially rejected and partially reproduced the self‐sacrificing worker ideal. Moreover, it shows how inequality regimes, imposing this ideal through classist, gendered, ageist, and racist‐nationalist processes in a pattern specific to each occupation, fundamentally shape the ways in which the ideal is challenged, as does the political culture of the groups organizing the mobilizations.
Histologic characterization of paediatric mesenchymal neoplasms treated with kinase‐targeted therapy
Authors: Baranov Esther , Winsnes Katrina , O'Brien Matthew , Voss Stephan D , Church Alanna J , Janeway Katherine A , DuBois Steven G , Davis Jessica L , Al‐Ibraheemi Alyaa
Published: May 2022

Aims

Recurrent alterations involving receptor tyrosine or cytoplasmic kinase genes have been described in soft‐tissue neoplasms such as infantile fibrosarcoma (IFS) and inflammatory myofibroblastic tumour (IMT). Recent trials and regulatory approvals for targeted inhibitors against the kinase domains of these oncoproteins have allowed for increased use of targeted therapies. We aimed to characterize the histologic features of paediatric mesenchymal neoplasms with kinase alterations treated with targeted inhibitors.

Methods and results

Eight patients with tyrosine kinase‐altered mesenchymal neoplasms with pre‐ and posttreatment samples were identified. Tumours occurred in five females and three males with a median age at presentation of 6.5 years. Tumour sites were bone/somatic soft‐tissue (n = 5) and viscera (n = 3). Pretreatment diagnoses were: IMT (n = 3), epithelioid inflammatory myofibroblastic sarcoma (n = 1), and descriptive diagnoses (n = 4) such as “kinase‐driven spindle cell tumor.” Fusions identified were ETV6::NTRK3 (n = 2), TPM3::NTRK1, SEPT7::BRAF, TFG::ROS1, KLC1::ALK, RANBP2::ALK, and MAP4::RAF1. Patients were treated with larotrectinib (n = 3), ALK or ALK/ROS1 inhibitors (n = 3), and MEK inhibitors (n = 2). Posttreatment tumours exhibited a striking decrease in cellularity (7/8) and the presence of collagenous stroma (7/8) with extensive glassy hyalinization (5/8). In two cases, abundant coarse or psammomatous calcifications were seen and in one case prominent perivascular hyalinization was noted. Residual viable tumour was seen in 3/8 cases (<5% in one case, and >75% in 2/8 cases).

Conclusion

Mesenchymal neoplasms with tyrosine kinase alterations treated with targeted inhibitors show a pathologic response, which includes decreased cellularity and stromal hyalinization. The presence of these features may be helpful in assessing tumour response after targeted therapy.
How to streamline the low and negligible research ethics and governance review process from 80 to 10 days: submission to decision
Authors: Milosavljevic Marianna , Hewitt Lyndel , Fish Janaye , Cuenca Jose , Ashford Bruce
Published: May 2022

Most clinicians find research ethics and governance difficult and time consuming. This study aimed to develop a better local review process for low‐risk research. We used real‐time processing, leveraged local expertise and streamlined paperwork. As a result, turnaround times decreased from more than 80 days to 10 days, creating an efficient review process for low‐risk projects.
Dielectric relaxations of lead zirconate titanate films up to millimeter‐wave frequencies
Authors: Manikandan Suraj , Aruchamy Naveen , Allirol Lucas , Girod Stéphanie , Glinsek Sebastjan , Defay Emmanuel , Granzow Torsten
Published: May 2022

Modern high‐frequency applications critically depend on the availability of data on the dielectric properties of functional materials in the microwave and millimeter‐wave range. This paper investigates the dielectric response of polycrystalline lead zirconate titanate (PZT) thin films prepared by solution deposition at frequencies between 10 MHz and 70 GHz and temperatures of 305–395 K by measuring the S‐parameters of coplanar waveguides (CPW). The real and imaginary parts of the permittivity of the PZT film are de‐coupled from the electrical properties of both the fused silica substrate and the copper electrodes. Two dielectric relaxations are identified: one around 850 MHz, with room‐temperature permittivity dropping from 1080 to 560, and one around 36 GHz, with permittivity dropping below 100, respectively. The low‐frequency relaxation shows a shift to lower frequencies with increasing temperature; it is explained by the conventional Arlt model of mechanical shear mode resonance across the film thickness. The high‐frequency relaxation, which is practically independent of temperature, is attributed to the response of ferroelectric domain walls.
Degradation of oxalic acid by Trichoderma afroharzianum and its correlation with cell wall degrading enzymes in antagonizing Botrytis cinerea
Authors: Wu Xiaoqing , Lyu Yuping , Ren He , Zhou Fangyuan , Zhang Xinjian , Zhao Xiaoyan , Zhang Guangzhi , Yang Hetong
Published: May 2022

Aim

Oxalic acid (OA) is one of the pathogenic factors of Botrytis cinerea. Trichoderma afroharzianum exerts both antagonistic and oxalate-degrading effects on B. cinerea. This study aimed to investigate the relationship between the elimination of OA by T. afroharzianum and its antagonistic effects on B. cinerea.

Methods and Results

Reversed-phase high performance liquid chromatogram (RP-HPLC) analysis showed that T. afroharzianum LTR-2 eliminated 10- or 20-mmol/L OA within 120 h, with the degradation being particularly efficient at the concentration of 20 mmol/L. RNA-seq analysis showed that the oxalate decarboxylase (OXDC) gene Toxdc, β-1,3-exoglucanase gene Tglu and aspartic protease gene Tpro of LTR-2 were significantly upregulated after treatment with 20-mmol/L OA. RT-qPCR analysis showed that under the conditions of confrontation, Toxdc and three cell wall degrading enzyme (CWDE) genes were upregulated before physical contact with B. cinerea. In addition, RT-qPCR analysis showed that OA synthesis in B. cinerea was not significantly affected by LTR-2.

Conclusions

The results revealed a correlation between OA degradation and mycoparasitism in T. afroharzianum when antagonising B. cinerea at the transcriptional level.

Significance and Impact of the Study

The relationship between OA degradation by T. afroharzianum and its effects against B. cinerea provide a new perspective on the antagonism of T. afroharzianum against B. cinerea. In addition, this study provides theoretical data for the scientific application of T. afroharzianum in the field of biocontrol.
Low molecular weight chitooligosaccharide inhibits infection of SARS-CoV-2 in vitro
Authors: Jang Donghwan , Lee Dagyum , Shin Young Chul , Lee Joong Su , Jung Jihee , Ryoo Sungweon
Published: May 2022

Aims

The discovery of antiviral substances to respond to COVID-19 is a global issue, including the field of drug development based on natural materials. Here, we showed that chitosan-based substances have natural antiviral properties against SARS-CoV-2 in vitro.

Methods and Results

The molecular weight of chitosan-based substances was measured by the gel permeation chromatography analysis. In MTT assay, the chitosan-based substances have low cytotoxicity to Vero cells. The antiviral effect of these substances was confirmed by quantitative viral RNA targeting the RdRp and E genes and plaque assay. Among the substances tested, low molecular weight chitooligosaccharide decreased the fluorescence intensity of SARS-CoV-2 nucleocapsid protein of the virus-infected cells in a dose-dependent manner.

Conclusions

In conclusion, the chitooligosaccharide, a candidate for natural treatment, has antiviral effects against the SARS-CoV-2 virus in vitro.

Significance and Impact of Study

In this study, it was suggested for the first time that chitosan-based substances such as chitooligosaccharide can have an antiviral effect on SARS-CoV-2 in vitro.
Dual species dry surface biofilms; Bacillus species impact on Staphylococcus aureus survival and surface disinfection
Authors: Centeleghe Isabella , Norville Phillip , Hughes Louise , Maillard Jean-Yves
Published: May 2022

Aims

Dry surface biofilms (DSB) survive on environmental surfaces throughout hospitals, able to resist cleaning and disinfection interventions. This study aimed to produce a dual species DSB and explore the ability of commercially available wipe products to eliminate pathogens within a dual species DSB and prevent their transfer.

Methods and Results

Staphylococcus aureus was grown with two different species of Bacillus on stainless steel discs, over 12 days using sequential hydration and dehydration phases. A modified version of ASTM 2967–15 was used to test six wipe products including one water control with the Fitaflex Wiperator. Staphylococcus aureus growth was inhibited when combined with Bacillus subtilis. Recovery of S. aureus on agar from a dual DSB was not always consistent. Our results did not provide evidence that Bacillus licheniformis protected S. aureus from wipe action. There was no significant difference of S. aureus elimination by antimicrobial wipes between single and dual species DSB. B. licheniformis was easily transferred by the wipe itself and to new surfaces both in a single and dual species DSB, whilst several wipe products inhibited the transfer of S. aureus from wipe. However, S. aureus direct transfer to new surfaces was not inhibited post-wiping.

Conclusions

Although we observed that the dual DSB did not confer protection of S. aureus, we demonstrated that environmental species can persist on surfaces after disinfection treatment. Industries should test DSB against future products and hospitals should consider carefully the products they choose.

Significance and Impact of the Study

To our knowledge, this is the first study reporting on the production of a dual species DSB. Multispecies DSB have been identified throughout the world on hospital surfaces, but many studies focus on single species biofilms. This study has shown that DSB behave differently to hydrated biofilms.
L-norvaline affects the proliferation of breast cancer cells based on the microbiome and metabolome analysis
Authors: Zhu Qin , Zai Hongyan , Zhang Kejing , Zhang Xian , Luo Na , Li Xin , Hu Yu , Wu Yuhui
Published: May 2022

Aims

The altered faecal metabolites and microbiota might be involved in the development of breast cancer. We aimed to investigate the effect of differential metabolites on the proliferative activity of breast cancer cells.

Methods and Results

We collected faecal samples from 14 breast cancer patients and 14 healthy subjects. Untargeted metabolomics analysis, short-chain fatty acid (SCFA) targeted analysis, and 16S rDNA sequencing was performed. The gut metabolite composition of patients changed significantly. Levels of norvaline, glucuronate and galacturonate were lower in the cancer group than in the Control (p < 0.05). 4-Methylcatechol and guaiacol increased (p < 0.05). Acetic acid and butyric acid were lower in the cancer group than in the control group (p < 0.05). Isobutyric acid and pentanoic acid were higher in the cancer group than in the control (p < 0.05). In the genus, the abundance of Rothia and Actinomyces increased in the cancer group, compared with the control group (p < 0.05). The differential microbiotas were clearly associated with differential metabolites but weakly with SCFAs. The abundance of Rothia and Actinomyces was markedly positively correlated with 4-methylcatechol and guaiacol (p < 0.05) and negatively correlated with norvaline (p < 0.05). L-norvaline inhibited the content of Arg-1 in a concentration-dependent manner. Compared with the L-norvaline or doxorubicin hydrochloride (DOX) group, the proliferation abilities of 4 T1 cells were the lowest in the L-norvaline combined with DOX (p < 0.05). The apoptosis rate increased (p < 0.05).

Conclusions

Faecal metabolites and microbiota were significantly altered in breast cancer. Levels of differential metabolites (i.e. Norvaline) were significantly correlated with the abundance of differential microbiota. L-norvaline combined with DOX could clearly inhibit the proliferation activity of breast cancer cells.

Significance and Impact of Study

This might provide clues to uncover potential biomarkers for breast cancer diagnosis and treatment.
Body mass index is superior to other body adiposity indexes in predicting incident hypertension in a highly admixed sample after 10‐year follow‐up: The Baependi Heart Study
Authors: Maciel de Oliveira Camila , França da Rosa Francielle , de Oliveira Alvim Rafael , Mourão Junior Carlos Alberto , Bacells Mercedes , Liu Chunyu , Pavani Jessica , Capasso Robson , Lavezzo Dias Fernando Augusto , Eduardo Krieger José , Costa Pereira Alexandre
Published: May 2022

Hypertension is the leading cause of overall mortality in low‐ and middle‐income countries. In Brazil, there is paucity of data on the determinants of incident hypertension and related risk factors. We aimed to determine the incidence of hypertension in a sample from the Brazilian population and investigate possible relationships with body adiposity indexes. We assessed risk factors associated with cardiovascular disease, including adiposity body indexes and biochemical analysis, in a sample from the Baependi Heart Study before and after a 10‐year follow‐up. Hypertension was defined by the presence of systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or the use of antihypertensive drugs. From an initial sample of 1693 participants, 498 (56% women; mean age 38 ± 13 years) were eligible to be included. The overall hypertension incidence was 24.3% (22.3% in men and 25.6% in women). Persons who developed hypertension had higher prevalence of obesity, higher levels for blood pressure, higher frequency of dyslipidemia, and higher body adiposity indexes at baseline. The best prediction model for incident hypertension includes age, sex, HDL‐c, SBP, and Body Mass Index (BMI) [AUC = 0.823, OR = 1.58 (95% CI 1.23‐2.04)]. BMI was superior in its predictive capacity when compared to Body Adiposity Index (BAI), Body Roundness Index (BRI), and Visceral Adiposity Index (VAI). Incident hypertension in a sample from the Brazilian population was 24.3% after 10‐year follow‐up and BMI, albeit the simpler index to be calculated, is the best anthropometric index to predict incident hypertension.
Single‐nucleus transcriptome analysis reveals disease‐ and regeneration‐associated endothelial cells in white matter vascular dementia
Authors: Mitroi Daniel N. , Tian Min , Kawaguchi Riki , Lowry William E. , Carmichael S. Thomas
Published: May 2022

Background

Vascular dementia (VaD) is the accumulation of vascular lesions in the subcortical white matter of the brain. These lesions progress and there is no direct medical therapy.

Aims

To determine the specific cellular responses in VaD so as to provide molecular targets for therapeutic development.

Materials and Methods

Single‐nucleus transcriptome analysis was performed in human periventricular white matter (PVWM) samples of VaD and normal control (NC) subjects.

Results

Differential analysis shows that cell type‐specific transcriptomic changes in VaD are associated with the disruption of specific biological processes, including angiogenesis, immune activation, axonal injury and myelination. Each cell type in the neurovascular unit within white matter has a specific alteration in gene expression in VaD. In a central cell type for this disease, subcluster analysis of endothelial cells (EC) indicates that VaD contains a disease‐associated EC subcluster that expresses genes associated with programmed cell death and a response to protein folding. Two other subpopulations of EC in VaD express molecular systems associated with regenerative processes in angiogenesis, and in axonal sprouting and oligodendrocyte progenitor cell maturation.

Conclusion

This comprehensive molecular profiling of brain samples from patients with VaD reveals previously unknown molecular changes in cells of the neurovascular niche, and an attempt at regeneration in injured white matter.
Effects of wearing personal protective equipment during COVID‐19 pandemic on composition and diversity of skin bacteria and fungi of medical workers
Authors: Lin X. , Li Y.Z. , Chen T. , Min S.H. , Wang D.F. , Ding M.M. , Jiang G.
Published: May 2022

Background

During the COVID‐19 pandemic, wearing PPE can induce skin damage such as erythema, pruritus, erosion, and ulceration among others. Although the skin microbiome is considered important for skin health, the change of the skin microbiome after wearing PPE remains unknown.

Objective

The present study aimed to characterize the diversity and structure of bacterial and fungal flora on skin surfaces of healthcare workers wearing personal protective equipment (PPE) during the COVID‐19 pandemic using metagenomic next‐generation sequencing (mNGS).

Methods

A total of 10 Chinese volunteers were recruited and the microbiome of their face, hand, and back were analysed before and after wearing PPE. Moreover, VISIA was used to analyse skin features.

Results

Results of alpha bacterial diversity showed that there was statistically significant decrease in alpha diversity indice in the skin samples from face, hand, and three sites after wearing PPE as compared with the indice in the skin samples before wearing PPE. Further, the results of evaluated alpha fungal diversity show that there was a statistically significant decrease in alpha diversity indices in the skin samples from hand after wearing PPE as compared with the indices in the skin samples before wearing PPE (P < 0.05). Results of the current study found that the main bacteria on the face, hand, and back skin samples before wearing the PPE were Propionibacterium spp. (34.04%), Corynebacterium spp. (13.12%), and Staphylococcus spp. (38.07%). The main bacteria found on the skin samples after wearing the PPE were Staphylococcus spp. (31.23%), Xanthomonas spp. (26.21%), and Cutibacterium spp. (42.59%). The fungal community composition was similar in three skin sites before and after wearing PPE.

Conclusion

It was evident that wearing PPE may affect the skin microbiota, especially bacteria. Therefore, it was evident that the symbiotic microbiota may reflect the skin health of medical workers during the COVID‐19 pandemic.
Niche availability and habitat affinities of the red porgy Pagrus pagrus (Linnaeus, 1758): An important ecological player on the world's largest rhodolith beds
Authors: Anderson Antônio B. , Bernardes Manuela B. , Pinheiro Hudson T. , Guabiroba Helder C. , Pimentel Caio R. , Vilar Ciro C. , Gomes Luiz E. O. , Bernardino Angelo F. , Delfino Stephanie D. T. , Giarrizzo Tommaso , Ferreira Carlos E. L. , Joyeux Jean‐Christophe
Published: May 2022

The red porgy (Pagrus pagrus) is a carnivore bottom dweller sparid, inhabiting flat sandy bottoms, rhodolith and seagrass beds of the Mediterranean Sea, the Western Atlantic (from Florida to Argentina) and the Eastern Atlantic (from Britain to Gabon). Along its native range, the red porgy is highly targeted by commercial and artisanal fisheries. In the past 40 years, the population decline of the species has been widely reported. In many locations, such as the Brazilian coast, stocks have collapsed. The central portion of the Brazilian coast harbours the largest rhodolith beds in the world and the highest levels of nektonic and benthic biodiversity. Along the rhodolith megahabitat, P. pagrus density is disproportionately higher (by 480%) than that of conspicuous benthic fishes inhabiting the same environment. Despite the ecological and economic importance of such an important species along its native range, little is known regarding its habitat use, niche availability and population responses to global warming. Here we present habitat affinities based on data sampled using baited remote stereo‐video systems, and modelled niche availability and global warming populational responses. Our findings reveal that the red porgy is a species highly associated with rhodolith beds along the central portion of the Brazilian coast. The presence of a disproportional density and biomass of the red porgy, compared to other marine fish species, indicates that the species plays a key ecological role as a carnivore, mesoconsumer and prey/predator tolerant species, maintaining essential ecological functions in the habitat. In a global warming scenario, the model predicted populational niche shifts poleward and a severe niche erosion at lower latitudes as expected. Conservation initiatives (implementation of Maine Protected Areas, trawling exclusion zones, mining exclusion zones, fisheries management policies) are urgent to secure future stocks of the red porgy and also preserve the fragile rhodolith beds they inhabit.
Release behavior of vitamin C nanoliposomes from starch–vitamin C active packaging films
Authors: Khuntia Anjali , Kumar Rahul , Premjit Yashaswini , Mitra Jayeeta
Published: May 2022

Ascorbic acid (Vitamin C) is an essential nutrient that cannot be synthesized by the human body. It is highly susceptible to degradation in presence of air, light, and moisture. Hence, encapsulation techniques are employed to provide better stability under adverse conditions. The present study used the nanoliposome technique because of its biocompatibility and controlled release efficiency. Nanoliposomes containing vitamin C (VC) were prepared by the thin‐layer dispersion technique followed by sonication at different phosphatidylcholine (PC) to stearic acid (SA) ratio, that is, 100:0, 90:10, 80:20, 70:30, 60:40, and 50:50 of PC:SA. The effect of sonication and varying ratios of wall materials on liposomes were explored. The nanoliposomes were characterized based on the particle size, zeta potential, encapsulation efficiency (EE) and storage stability. The optimal VC‐loaded nanoliposomes were incorporated in starch films for studying the release profiles at different storage temperatures. The kinetics modeling was done for specific food samples (apple and beans) to simulate different pH effects. It was observed that sonication had a significant effect on the liposomal particle size. Nanoliposomes prepared without SA showed the highest EE (94.18 ± 1.5%) and storage stability. The storage study represents that VC loss was lowest in lyophilized SA‐free nanoliposomes for the analysis period. The release study showed notable differences in VC release profile for different pH conditions. A significant release was observed at 37°C and neutral pH. It was concluded that vitamin‐loaded SA‐free liposomes could effectively replace sterol‐based liposome preparation for food packaging applications.

Practical applications

The activity of biodegradable film can be effectively modified incorporating encapsulated ascorbic acid rather than the unencapsulated form that is more susceptible to degradation. Liposomal technique was used to encapsulate the vitamin. As well, the packaging material must be examined for the possibility of nutrient release into the product. But, this release behavior is typically investigated in the presence of food simulants. On the contrary, any living system upon exposure to the active packaging will respond in a different way than the food simulant as a result of complex stimulation where several processes function simultaneously. So, this study was carried out for real food applications with the packaging of the cut fruits and vegetables being considered rather than food simulants. The goal of these methods is to increase the vitamin C content of the cut products deploying at room temperature and without the use of energy‐intensive cooling.