bluuebunny/crossref_metadata_2025 huggingface dataset:
Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture
Authors: Delben Priscilla Barros , Zomer Helena Debiazi , da Silva Camila Acordi , Gomes Rogério Schutzler , Melo Fernanda Rosene , Dillenburg-Pilla Patricia , Trentin Andrea Gonçalves
Published: April 2021

Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies.In vitroamplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization, but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-β-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γ-H2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability.
Single-cell analysis of localized low- and high-grade prostate cancers
Authors: Eksi Sebnem Ece , Chitsazan Alex , Sayar Zeynep , Thomas George V. , Fields Andrew , Kopp Ryan P. , Spellman Paul T. , Adey Andrew
Published: April 2021

Approximately, 30% of early-stage localized prostate cancer cases reoccur within 5 to 10 years [1, 2]. However, identifying precise molecular subtypes attributable to specific stages of prostate cancer has proven difficult due to high heterogeneity within localized tumors [3–5]. Bulk assays represent a population average, which is a result of the heterogeneity that exists at the individual prostate cancer cell level [6]. Here, we sequenced the accessible chromatin regions of 14,424 single-cells collected from 18 fresh-frozen prostate tumors using sci-ATAC-seq [7, 8]. We observed that shared chromatin features among low-grade prostate cancer epithelial cells were lost in high-grade tumors. Despite this loss, all high-grade tumors exhibited an enrichment for FOXA1, HOXB13 and CDX2 transcription factor binding sites within their accessible chromatin regions, indicating a shared trans-regulatory program. Single-cell analysis of the differentially accessible regions in high- versus low-grade prostate tumors identified two unique genes encoding neuronal adhesion molecules, NRXN1 and NLGN1. We found that NRXN1 and NLGN1 are expressed in the epithelial luminal, basal and neuroendocrine cells, as well as the immune, endothelial and neuronal cell types in all prostate tumors. Overall, these results provide a deeper understanding of the active gene regulatory networks in low- and high-grade prostate tumors at a striking resolution and provide critical insights for molecular stratification of the disease.
Protein visualization and manipulation inDrosophilathrough the use of epitope tags recognized by nanobodies
Authors: Xu Jun , Kim Ah-Ram , Cheloha Ross W. , Fischer Fabian A. , Shun Li Joshua Shing , Feng Yuan , Stoneburner Emily , Binari Richard , Mohr Stephanie E. , Zirin Jonathan , Ploegh Hidde , Perrimon Norbert
Published: April 2021

Expansion of the available repertoire of reagents for visualization and manipulation of proteins will help understand their function. Short epitope tags linked to proteins of interest and recognized by existing binders such as nanobodies facilitate protein studies by obviating the need to isolate new antibodies directed against them. Nanobodies have several advantages over conventional antibodies, as they can be expressed and used as tools for visualization and manipulation of proteinsin vivo. Here, we characterize two short (<15 aa) NanoTag epitopes, 127D01 and VHH05) and their corresponding high-affinity nanobodies. We demonstrate their use inDrosophilaforin vivoprotein detection and re-localization, direct and indirect immunofluorescence, immunoblotting, and immunoprecipitation. We further show that CRISPR-mediated gene targeting provides a straightforward approach to tagging endogenous proteins with the NanoTags. Single copies of the NanoTags, regardless of their location, suffice for detection. This versatile and validated toolbox of tags and nanobodies will serve as a resource for a wide array of applications, including functional studies inDrosophilaand beyond.
A genome-scale antibiotic screen inSerratia marcescensidentifies YdgH as a conserved modifier of cephalosporin and detergent susceptibility
Authors: Lazarus Jacob E. , Warr Alyson R. , Westervelt Kathleen A. , Hooper David C. , Waldor Matthew K.
Published: April 2021

Serratia marcescens,a member of the order Enterobacterales, is adept at colonizing healthcare environments and an important cause of invasive infections. Antibiotic resistance is a daunting problem inS. marcescensbecause in addition to plasmid-mediated mechanisms, most isolates have considerable intrinsic resistance to multiple antibiotic classes. To discover endogenous modifiers of antibiotic susceptibility inS. marcescens,a high-density transposon insertion library was subjected to sub-minimal inhibitory concentrations of two cephalosporins, cefoxitin and cefepime, as well as the fluoroquinolone ciprofloxacin. Comparisons of transposon insertion abundance before and after antibiotic exposure identified hundreds of potential modifiers of susceptibility to these agents. Using single gene deletions, we validated several candidate modifiers of cefoxitin susceptibility and choseydgH, a gene of unknown function, for further characterization. In addition to cefoxitin, deletion of ydgHinS. marcescensresulted in decreased susceptibility to multiple 3rdgeneration cephalosporins, and in contrast, to increased susceptibility to both cationic and anionic detergents. YdgH is highly conserved throughout the Enterobacterales, and we observed similar phenotypes inEscherichia coliO157:H7 andEnterobacter cloacaemutants. YdgH is predicted to localize to the periplasm and we speculate that it may be involved there in cell envelope homeostasis. Collectively, our findings provide insight into chromosomal mediators of antibiotic resistance inS. marcescensand will serve as a resource for further investigations of this important pathogen.
Phytophthora capsici sterol reductase PcDHCR7 has a role in mycelium development and pathogenicity
Authors: Wang Weizhen , Zhang Fan , Zhang Sicong , Xue Zhaolin , Xie Linfang , Govers Francine , Liu Xili
Published: April 2021

The de novo biosynthesis of sterols is critical for eukaryotes, however, some organisms lack this pathway including most oomycetes. Phytophthora spp. are sterol auxotroph but remarkably, have retained a few genes encoding enzymes in the sterol biosynthesis pathway. Here we investigated the function of PcDHCR7, a gene in Phytophthora capsici predicted to encode the △7-sterol reductase. When expressed in Saccharomyces cerevisiae, PcDHCR7 showed a △7-sterol reductase activity. Knocking out PcDHCR7 in P. capsici resulted in loss of the capacity to transform ergosterol into brassicasterol, which means PcDHCR7 has a △7-sterol reductase activity in P. capsici itself. This enables P. capsici to transform sterols recruited from the environment for better use. Biological characteristics were compared between wild-type isolate and PcDHCR7 knock-out transformants. The results indicated that PcDHCR7 plays a key role in mycelium development and pathogenicity of zoospores in P. capsici.
Time-resolved single-cell sequencing identifies multiple waves of mRNA decay during mitotic exit
Authors: Krenning Lenno , Sonneveld Stijn , Tanenbaum Marvin E.
Published: April 2021

Accurate control of the cell cycle is critical for development and tissue homeostasis and requires precisely-timed expression of many genes. Cell cycle gene expression is regulated through transcriptional and translational control, as well as through regulated protein degradation. Here, we show that widespread and temporally-controlled mRNA decay acts as an additional mechanism for gene expression regulation during the cell cycle. We find that two waves of mRNA decay occur sequentially during the mitosis-to-G1 phase transition, and identify the deadenylase CNOT1 as a factor that contributes to mRNA decay during this cell cycle transition. Collectively, our data show that, akin to protein degradation, scheduled mRNA decay helps to reshape cell cycle gene expression as cells move from mitosis into G1 phase.
A Landlord's Certainty: The Taxation of Property Investment
Authors: Furfine Craig
Published: April 2021

32-year-old Heather Wilson was about to become a property investor. After years of painstaking savings, she had finally reached agreement to purchase her first buy-to-let property, a 1 bedroom flat in London's sought-after Kensington and Chelsea neighborhood. She looked forward to a lifetime of building wealth through property investments. Of course, some of the income the property would generate would be owed to Her Majesty's Revenue and Customs (HMRC). But such was the nature of life. Unfortunately, the tax laws had only recently become less favorable for property investors, but Wilson expected to negotiate a lower purchase price as a result and so she felt confident that her investment remained solid.
Tulaberry Plaza: Leasing Decisions in Commercial Real Estate
Authors: Furfine Craig
Published: April 2021

In January 2019, Benedict Clarke needed to address the vacancies at retail shopping center Tulaberry Plaza. The rise in online shopping forced Tulaberry's anchor tenant into bankruptcy and weakened the outlook for retail more generally. Clarke must devise a plan that presents the most logical and profitable way forward for the shopping center. The case asks students to make leasing decisions from the perspective of the property owner, Clarke, giving them an appreciation for both the quantitative and qualitative factors that influence optimal leasing decisions.
Responsible research and innovation key performance indicators in industry
Authors: Yaghmaei Emad
Published: April 2021

Purpose

Responsible research and innovation (RRI) is taking a role in assisting all types of stakeholders, including industry members, in moving their research and innovation (R&I) initiatives to tackle grand challenges. The literature on RRI, however, focuses little on how industry can implement RRI principles. To solve this gap, the purpose of this study is to construct a conceptual framework for managing and assessing RRI principles in the industry.

Design/methodology/approach

Qualitative research was used to build the RRI key performance indicator list; 30 interviews were conducted to design a framework which was pilot tested in a company to identify how to align technology outcomes to the values, needs and expectations of the society.

Findings

This study depicts five successive RRI implementation levels and exhibits RRI key performance indicators. Drawing on extant models, this study develops RRI levels and indicators to discuss why industry should become engaged in RRI, how it can embed RRI principles into R&I processes and how RRI indicators can be managed systematically.

Originality/value

The connection between RRI key performance indicators and RRI levels determines how industry can integrate principles and methodologies of RRI into R&I processes. The model in the study shows how companies move from one RRI stage to another and this study aims to exhibit an ideal stage of RRI for industry.
Competitive drivers of interspecific deviations of crown morphology from theoretical predictions measured with Terrestrial Laser Scanning
Authors: Owen Harry J. F. , Flynn William R. M. , Lines Emily R.
Published: April 2021

Tree crown morphology is a key driver of forest dynamics, determining not only the competitiveness of an individual but also the competitive effect exerted on neighbouring trees. Multiple ecological theories, including metabolic scaling theory (MST), predict crown morphology from first principles, but typically lack consideration of competition. The accurate quantification of crown morphology to test theoretical predictions, and the canopy interactions that could alter them, has historically been limited by the simplicity and associated error of traditional crown measurements.

In this study, we calculate high‐resolution two‐ and three‐dimensional crown metrics from Terrestrial Laser Scanning data for 1,441 Pinus sylvestris, P. nigra, Quercus faginea and Q. ilex trees from a water‐limited forest community in central Spain and test height‐crown metric scaling relationships. We demonstrate new TLS methods to define symmetric and asymmetric neighbourhood metrics based on tree height, crown size and neighbour projected crown area, and test the importance of neighbourhood genus diversity on crown morphology by separating competition from congeneric and heterogeneric neighbours.

Competition negatively impacted all crown metrics except crown depth where only P. nigra showed sensitivity. Asymmetric competition was the strongest driver of pine crown morphology, but oaks were more sensitive to symmetric competition, in line with shade tolerance expectations. Congeneric competition reduced Q. faginea crown size and changed its shape, but we found no significant effects of heterogeneric neighbours. Most species and crown dimensions had height‐crown scaling exponents below those predicted by MST, which may be due to water limitation effects. Pines and oaks showed large differences in crown depth to height scaling, with the former shallower and the latter deeper, in contrast to theoretical predictions.

Synthesis. Our study is the first to demonstrate the ability of TLS to characterise crown morphology from leaf‐wood separated clouds and competitive neighbour effects in a water‐limited forest community, and to use TLS metrics to test ecological crown scaling theory. Most crown metrics scaled below theoretical predictions. Pines were more sensitive to competition by larger neighbours and oaks to crowding from all neighbours, with competition from neighbours of the same genus having a consistent negative effect.
Taxonomic, phylogenetic and functional diversity of understorey plants respond differently to environmental conditions in European forest edges
Authors: De Pauw Karen , Meeussen Camille , Govaert Sanne , Sanczuk Pieter , Vanneste Thomas , Bernhardt‐Römermann Markus , Bollmann Kurt , Brunet Jörg , Calders Kim , Cousins Sara A. O. , Diekmann Martin , Hedwall Per‐Ola , Iacopetti Giovanni , Lenoir Jonathan , Lindmo Sigrid , Orczewska Anna , Ponette Quentin , Plue Jan , Selvi Federico , Spicher Fabien , Verbeeck Hans , Vermeir Pieter , Zellweger Florian , Verheyen Kris , Vangansbeke Pieter , De Frenne Pieter
Published: April 2021

Forest biodiversity world‐wide is affected by climate change, habitat loss and fragmentation, and today 20% of the forest area is located within 100 m of a forest edge. Still, forest edges harbour a substantial amount of terrestrial biodiversity, especially in the understorey. The functional and phylogenetic diversity of forest edges have never been studied simultaneously at a continental scale, in spite of their importance for the forests' functioning and for communities' resilience to future change.

We assessed nine metrics of taxonomic, phylogenetic and functional diversity of understorey plant communities in 225 plots spread along edge‐to‐interior gradients in deciduous forests across Europe. We then derived the relative effects and importance of edaphic, stand and landscape conditions on the diversity metrics.

Here, we show that taxonomic, phylogenetic and functional diversity metrics respond differently to environmental conditions. We report an increase in functional diversity in plots with stronger microclimatic buffering, in spite of their lower taxonomic species richness. Additionally, we found increased taxonomic species richness at the forest edge, but in forests with intermediate and high openness, these communities had decreased phylogenetic diversity.

Functional and phylogenetic diversity revealed complementary and important insights in community assembly mechanisms. Several environmental filters were identified as potential drivers of the patterns, such as a colder macroclimate and less buffered microclimate for functional diversity. For phylogenetic diversity, edaphic conditions were more important. Interestingly, plots with lower soil pH had decreased taxonomic species richness, but led to increased phylogenetic diversity, challenging the phylogenetic niche conservatism concept.

Synthesis. Taxonomic, phylogenetic and functional diversity of understorey communities in forest edges respond differently to environmental conditions, providing insight into different community assembly mechanisms and their interactions. Therefore, it is important to look beyond species richness with phylogenetic and functional diversity approaches when focusing on forest understorey biodiversity.
Professional development training preferences of occupational therapists working with older adults in Australia: A discrete choice experiment
Authors: Day Sally D. , Nguyen Kim‐Huong , Comans Tracy , Clemson Lindy , Laver Kate
Published: April 2021

Introduction

Members of the public expect occupational therapists to provide evidence‐based practice. Participation in professional development activities is essential to update knowledge and acquire skills to enable delivery of evidence‐based assessment and intervention. Therapists commonly choose to participate in professional development through attending training workshops. Little is known about occupational therapists’ preference of how continuing professional development training programmes should be designed and delivered.

Methods

An online quantitative survey of occupational therapists working with older people in Australia, conducted June to September 2018, incorporated a discrete choice experiment to elicit and estimate preferences for professional development training when acquiring skills in delivering an evidence‐based intervention. A series of questions asked participants to choose one of two options for training, each differing in terms of attributes (level of recognition, mode of learning, follow‐up post‐training and cost to establish willingness to pay). Statistical analyses were conducted according to recommended practice in the field of choice‐modelling.

Results

A total of 108 responses were received from occupational therapists practicing around Australia. Therapists reported a strong preference for receiving post‐training support to implement their new skills in practice and would be willing to pay an additional A$200 for training that included this option. They also highly regarded achieving ‘certification’ in their new skill (willing to pay an additional A$100) and having the opportunity to become a ‘Master Trainer’ in the future (willing to pay an additional A$200).

Discussion

This study generates new knowledge about aspects of a professional development training programme that occupational therapists’ value and aspects that they are willing to compromise on when acquiring new skills that they intend to use in their practice. These findings can influence the training programme design utilised by those working in implementation research and providers of continuing professional development for health professionals.
‘Our Point of Departure is Feminist’: Féminin Masculin Avenir and the Intersectional Origins of Women's Liberation in France, 1967–1970
Authors: Leffingwell Hannah
Published: April 2021

This paper examines the intersectional origins of the Mouvement de libération des femmes (MLF) in France through analysis of one of its founding groups: Féminin, Masculin, Avenir (FMA). Complicating historiographical perceptions that the feminist revival of 1970 largely resulted from the revolutionary activity of May 1968 in France, this article argues that Women's Liberation also sprung from a transnational, multi‐issue activist network that predated the events of that year. FMA, though statistically insignificant in the vast arena of late‐1960s activism, boasted a disproportionately influential share of MLF activists who would go on to shape the principle theories of Women's Liberation in France. Their engagement with anti‐colonialism, Black liberation and Marxism facilitated their feminist activism, sharpened their theories of oppression and provided them with models of successful identity‐based social movements. FMA explored the intersections of race, class and gender before eventually abandoning these intersections in the name of ‘women’ as a class. This turn away from solidarity with anti‐racist and anti‐colonial movements in the name of feminism shaped the priorities of Women's Liberation for years to come.
Valorization of byproducts from tropical fruits: A review, Part 2: Applications, economic, and environmental aspects of biorefinery via supercritical fluid extraction
Authors: Villacís‐Chiriboga José , Vera Edwin , Van Camp John , Ruales Jenny , Elst Kathy
Published: April 2021

The global trade of tropical fruits is expected to increase significantly in the coming years. In 2018, the production was approximately 100 million tones, an increase of 3.3% compared to the previous year. Nevertheless, according to the Food and Agricultural Organization, every year one‐third of the food produced in the world for human consumption is lost or wasted. More specifically, around 45% of the fruits, constituted mainly by peels, seeds, and pulps after juice extraction, are discarded mainly in the agricultural and processing steps. Therefore, decreasing and/or using these byproducts, which are often rich in bioactive components, have become an important focus for both the scientific community and the fruit processing industry. In this line, supercritical fluid extraction (SFE) technology is expected to play a significant role in the valorization of these byproducts. This review presents the concepts of a tropical fruit biorefinery using supercritical CO2 extraction and the potential applications of the isolated fractions. There is a specific focus on the extraction of bioactive compounds, that is, carotenoids and phenolics, but also oils and other valuable molecules. Moreover, the techno‐economic and environmental performance is assessed. Overall, the biorefinery of tropical fruits via SFE provides new opportunities for development of food and pharmaceutical products with improved economic and environmental performance.
Soyasaponin ameliorates obesity and reduces hepatic triacylglycerol accumulation by suppressing lipogenesis in high‐fat diet‐fed mice
Authors: Tsai Wei‐Ting , Nakamura Yuki , Akasaka Taiki , Katakura Yoshinori , Tanaka Yasutake , Shirouchi Bungo , Jiang Zhe , Yuan Xingyu , Sato Masao
Published: April 2021

Soyasaponins are triterpenoid glycosides found in soybean. We investigated whether soyasaponin ameliorates lipid metabolism and its possible mechanisms. In C57BL/6J mice fed a high‐fat diet (HFD), soyasaponin (SAP) was orally administered for 9 weeks. Additionally, we evaluated the effect of soyasapogenols on 3T3‐L1 adipocytes. In HFD‐fed mice, the SAP significantly reduced body weight by 7% and relative adipose tissue weight by 35%. X‐ray computed tomography demonstrated that the SAP reduced visceral and subcutaneous adipose tissue weights during week 3 of feeding. The SAP reduced sterol regulatory element‐binding protein‐1c (SREBP‐1c) mRNA levels by 32% in the epididymal adipose tissue, significantly decreasing the triacylglycerol (TAG) content by 37% and SREBP‐1c and fatty acid synthase mRNA levels by 52% and 61%, respectively, in the liver. In 3T3‐L1 adipocytes, soyasapogenol B significantly decreased lipid droplets. The SAP containing soyasaponin A and B as conjugates demonstrate anti‐obesity effects by suppressing adipocyte differentiation and lipogenesis, with a preventive effect on hepatic TAG accumulation by suppressing lipogenesis.

Practical Application

Soyasaponin is one of the oleanane triterpenoids in soybeans. We have demonstrated that soyasaponin potently reduces body weight and white adipose tissue weight, and hepatic triacylglycerol accumulation in high‐fat diet‐fed mice. Thus, soyasaponin is a beneficial compound to prevent obesity and fatty liver.
Variations in natural polyphenols determine the anti‐inflammatory potential of virgin coconut oils
Authors: Illam Soorya Parathodi , Narayanankutty Arunaksharan , Kandiyil Sruthi Panniyan , Raghavamenon Achuthan Chathrattil
Published: April 2021

Virgin coconut oil (VCO), an edible oil prepared from fresh coconut kernel by natural or mechanical means without undergoing chemical refining, has been in the limelight of research as functional food oil. The phenolic components in VCO have been accredited with these pharmacological benefits. The present study compared the phenolic constituents of freshly prepared fermentation processed (FVCO) and hot‐pressed VCO (HVCO) and their anti‐inflammatory efficacies. The biochemical analysis documented quantitative variation in the phenolic content, being higher in HVCO than FVCO (40.03 ± 5.8 µg and 25.55 ± 5.8 µg/mL of oil, respectively). In vitro studies observed nitric oxide radical scavenging efficacy (IC50 value of 14.84 ± 0.81 µg/mL) for HVCO polyphenols, which shows higher inhibition efficacy than FVCO (29.41 ± 1.7 µg/mL). In dextran and formalin mediated acute and chronic inflammation in mice, HVCO displayed more protective efficacy (40.5 and 46.4% inhibition) than FVCO (33.3 and 43.8% inhibition), which is similar to the standard diclofenac (55.6 and 59.8% inhibition). The study, thus, concludes that compared to FVCO, HVCO is a more active anti‐inflammatory agent.

Practical Application

Virgin coconut oil, a widely used edible oil in South Asian countries, has been shown to have health benefits possibly exerted by the natural phenolics it contains. However, different modes of preparations of VCO determine the phenolic combinations and efficacy as well. Our study compared two different VCO preparations and suggests that the VCO prepared by the traditional way (HVCO) is pharmacologically potent than that prepared by simple fermentation process (FVCO) in reducing inflammation. The efficacy is attributed to the variations in phenolic profile revealed by LC‐MS analysis. Hence, the current study suggests HVCO as a potential food supplement that can reduce the incidence of degenerative diseases.
Bioactive compounds in Apis mellifera monofloral honeys
Authors: Viteri Rafael , Zacconi Flavia , Montenegro Gloria , Giordano Ady
Published: April 2021

Honey is a natural product with a sweet flavor. Honey is made by the honeybee (Apis mellifera L.) from the nectar of flowers or other plant secretions that are collected near the hive. These products are mixed with bee saliva and stored. Several studies have demonstrated that honey exhibits antioxidant, antimicrobial, nematicidal, antifungal, anticancer, and anti‐inflammatory activities. These properties are influenced by the plants from which the secretions are harvested, from the naturally occurring compounds present in the nectar. Studies of the properties and applications of honey have distinguished honey from other natural products due to the presence of certain compounds and due its bioactive properties. The focus of this review is to discuss the identified and isolated compounds from monofloral honey produced by A. mellifera, with specific emphasis on antioxidant and antimicrobial properties of honey and its therapeutic health benefits.
New‐onset atrial fibrillation in the intensive care unit: Protocol for an international inception cohort study (AFIB‐ICU)
Authors: Wetterslev Mik , Møller Morten Hylander , Granholm Anders , Haase Nicolai , Hassager Christian , Lange Theis , Hästbacka Johanna , Wilkman Erika , Myatra Sheila Nainan , Shen Jiawei , An Youzhong , Siegemund Martin , Young Paul J , Aslam Tayyba N. , Szczeklik Wojciech , Aneman Anders , Arabi Yaseen M. , Cronhjort Maria , Keus Frederik , Perner Anders
Published: April 2021

Introduction

New‐onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be associated with prolonged hospital stay and increased mortality. Considerable variation exists in the reported frequencies of NOAF due to the lack of a standardised definition and detection method. Importantly, there are limited data on NOAF in the intensive care unit (ICU). Thus, we aim to provide contemporary epidemiological data on NOAF in the ICU.

Methods and Analysis

We have designed an international inception cohort study including at least 1,000 consecutive adult patients acutely admitted to the ICU without prior history of persistent or permanent AF. We will present data on the incidence, risk factors, used management strategies and outcomes of NOAF. We will register data daily during stay in the ICU for a maximum of 90 days after admission. The incidence of NOAF and management strategies used will be presented descriptively, and we will use Cox regression analyses including competing risk analyses to assess risk factors for NOAF and any association with 90‐day mortality.

Conclusion

The outlined international AFIB‐ICU inception cohort study will provide contemporary data on the incidence, risk factors, used management strategies and outcomes of NOAF in adult ICU patients.

Ethics and dissemination

This observational study poses no risk to the included patients. All participating sites will obtain relevant approvals according to national laws before patient enrollment. Funding sources will have no influence on data handling, analyses or writing of the manuscript. The study report(s) will be submitted to an international peer‐reviewed journal.
The effects of adding quinolones to beta‐lactam antibiotics for sepsis
Authors: Korang Steven K. , Maagaard Mathias , Feinberg Joshua B. , Perner Anders , Gluud Christian , Jakobsen Janus C
Published: April 2021

Background

Sepsis is common, deadly, and a major challenge to treat. Quinolones added to beta‐lactam antibiotics are currently recommended as a second‐line empiric regimen in sepsis, but the evidence regarding their benefits and harms is unclear.

Objective

To assess the benefits and harms of adding quinolones to standard care for sepsis.

Data sources

We conducted a systematic review of randomized clinical trials with meta‐analysis and Trial Sequential Analysis. We searched CENTRAL, MEDLINE, Embase, LILACS, SCI‐Expanded, and BIOSIS.

Study selection

Randomized clinical trials assessing the effects of adding any quinolone to standard care for children and adults with sepsis.

Data extraction and synthesis

Two independent reviewers screened studies and extracted data. The certainty of the evidence was assessed by GRADE.

Results

We included three trials randomizing 995 adults. All trials were at overall “high risk of bias.” All trials compared a quinolone (moxifloxacin, levofloxacin, or ciprofloxacin) and a beta‐lactam antibiotic versus the same beta‐lactam antibiotic. We found no evidence of an effect of adding quinolones to beta‐lactam antibiotics when assessing all‐cause mortality (RR 1.07, 95% CI 0.86 to 1.33; 2 trials; 915 participants; very low certainty of evidence) and serious adverse events (RR 1.00, 95% CI 0.67 to 1.50; 977 participants; two trials; very low certainty of evidence). No trials reported on quality of life.

Conclusions

The effects of adding quinolones to beta‐lactam antibiotics for the treatment of sepsis were unclear for all outcomes. Additional trial data are warranted to support the recommendation of empirical use of quinolones for sepsis.
Alcohol subjective responses in heavy drinkers: Measuring acute effects in the natural environment versus the controlled laboratory setting
Authors: Fridberg Daniel J. , Cao Dingcai , King Andrea C.
Published: April 2021

Background

For decades, laboratory alcohol challenges have been the “gold standard” for measuring individual differences in alcohol's subjective effects. However, these approaches are expensive and labor‐intensive, making them impractical for large‐scale use. This study examined the reliability and validity of a new high‐resolution EMA (HR‐EMA) ambulatory approach to assessing alcohol use and subjective responses in drinkers’ natural environments.

Methods

Participants were 83 young adult heavy social drinkers (58% male; mean ± SD age = 25.4 ± 2.6 years) who completed up to two smartphone‐based, 3‐h HR‐EMA assessments of alcohol use and related subjective responses in their typical drinking environments. Reported alcohol consumption during the HR‐EMA periods was used to calculate estimated blood alcohol concentration (eBAC). Subjective effects were measured using the Brief Biphasic Alcohol Effects Scale (B‐BAES) and Drug Effects Questionnaire (DEQ). All participants also completed identical measures during a separate, 4 to 5‐h laboratory session in which they received a 0.8 g/kg alcohol challenge.

Results

Most natural environment drinking episodes (87%) met or exceeded the threshold for binge drinking (final mean eBAC = 0.12 g/dl). Associations between reported alcohol use and subjective responses on the B‐BAES and DEQ were strongest earlier in the drinking events, with fair reliability of reported subjective effects across two HR‐EMA episodes (intraclass correlation [ICC] range = 0.46−0.49). There was fair‐to‐good correspondence between HR‐EMA‐ and laboratory‐derived subjective responses (ICC range = 0.49−0.74), even after accounting for differences in alcohol consumption and drinking context. Reported stimulating and rewarding alcohol effects were higher in the ambulatory than laboratory setting, and vice versa for sedating effects.

Conclusions

This study supports the reliability and validity of smartphone‐based HR‐EMA to measure alcohol use and subjective responses in heavy drinkers’ natural environments. These findings lend support to the use of ambulatory HR‐EMA as a measure of alcohol subjective responses in risky drinkers when a laboratory protocol is not practical, feasible, or safe.
Cocaine experience induces functional adaptations in astrocytes: Implications for synaptic plasticity in the nucleus accumbens shell
Authors: O'Donovan Bernadette , Neugornet Austin , Neogi Richik , Xia Mengfan , Ortinski Pavel
Published: April 2021

Astrocytes have become established as an important regulator of neuronal activity in the brain. Accumulating literature demonstrates that cocaine self‐administration in rodent models induces structural changes within astrocytes that may influence their interaction with the surrounding neurons. Here, we provide evidence that cocaine impacts astrocytes at the functional level and alters neuronal sensitivity to astrocyte‐derived glutamate. We report that a 14‐day period of short access to cocaine (2 h/day) decreases spontaneous astrocytic Ca2+ transients and precipitates changes in astrocyte network activity in the nucleus accumbens shell. This is accompanied by increased prevalence of slow inward currents, a physiological marker of neuronal activation by astrocytic glutamate, in a subset of medium spiny neurons. Within, but not outside, of this subset, we observe an increase in duration and frequency of N‐methyl‐D‐aspartate (NMDA) receptor‐mediated synaptic events. Additionally, we find that the link between synaptic NMDA receptor plasticity and neuron sensitivity to astrocytic glutamate is maintained independent of drug exposure and is observed in both cocaine and saline control animals. Imaging analyses of neuronal Ca2+ activity show no effect of cocaine self‐administration on individual cells or on neuronal network activity in brain slices. Therefore, our data indicate that cocaine self‐administration promotes astrocyte‐specific functional changes that can be linked to increased glutamate‐mediated coupling with principal neurons in the nucleus accumbens. Such coupling may be spatially restricted as it does not result in a broad impact on network structure of local neuronal circuits.
The validity of the state–trait anxiety inventory and the brief scale for anxiety in an inpatient sample with alcohol use disorder
Authors: Shah Navan N. , Schwandt Melanie L. , Hobden Breanne , Baldwin David S. , Sinclair Julia , Agabio Roberta , Leggio Lorenzo
Published: April 2021

Background and Aims

The Brief Scale for Anxiety (BSA) and the State–Trait Anxiety Inventory Form Y‐2 (STAI‐Y‐2) are self‐report scales used to gauge anxiety symptoms in clinical settings. Co‐occuring anxiety is common in alcohol use disorder (AUD); however, no studies have assessed the validity of the BSA and STAI‐Y‐2 compared with a clinical diagnostic tool of anxiety in alcohol treatment programs. We aimed to examine the validity of the BSA and STAI‐Y‐2 to predict a clinical diagnosis of an anxiety disorder (via the Structured Clinical Interview for DSM [SCID]) in AUD patients.

Design

Participants were administered the BSA (n = 1005) on day 2 and the STAI‐Y‐2 (n = 483) between days 2 and 10 of the detoxification program. SCID‐based clinical diagnoses of AUD and anxiety were made approximately on day 10.

Setting and participants

Individuals seeking treatment for AUD admitted to an inpatient unit at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, USA (n = 1010).

Measurements

Inclusion criteria included a current diagnosis of alcohol dependence (AD) according to DSM‐IV‐TR or moderate to severe AUD according to DSM‐5‐RV, as well as available baseline BSA and/or STAI Y‐2 data. Empirical receiver operating characteristic (ROC) curves were generated using estimates of sensitivity, 1‐specificity and positive and negative predictive values for each cut‐point to determine the accuracy of scale outcomes in relation to SCID diagnoses.

Findings

The BSA demonstrated low accuracy relative to a clinical diagnosis of anxiety with an area under the curve (AUC) of 0.67 at the optimal cut‐point of ≥ 10. The STAI‐Y‐2 had moderate accuracy relative to a clinical diagnosis of anxiety with an AUC of 0.70 at the optimal cut‐point of ≥ 51. The accuracy of the STAI‐Y‐2 increased (AUC = 0.74) when excluding post‐traumatic stress disorder and obsessive–compulsive disorder from anxiety disorder classification.

Conclusions

Use of the Brief Scale for Anxiety (BSA) and/or State–Trait Anxiety Inventory Form Y‐2 (STAI‐Y‐2) does not appear to be a reliable substitute for clinical diagnoses of anxiety disorder among inpatients with alcohol use disorder. The BSA and STAI‐Y‐2 could serve as a screening tool to reject the presence of anxiety disorders rather than for detecting an anxiety disorder.
Reward‐related decision‐making deficits in internet gaming disorder: a systematic review and meta‐analysis
Authors: Yao Yuan‐Wei , Zhang Jin‐Tao , Fang Xiao‐Yi , Liu Lu , Potenza Marc N.
Published: April 2021

Aims

To estimate the aggregated effect sizes of reward‐related decision‐making deficits in internet gaming disorder (IGD) and to explore potential moderators on the variability of effect sizes across studies.

Design

Review of peer‐reviewed studies comparing reward‐related decision‐making performance between IGD and control participants identified via PubMed, Web of Science and ProQuest databases. Random‐effects modeling was conducted using Hedge‘s g as the effect size (ES). The effects of decision‐making situation, valence, sample type, testing environment, IGD severity and self‐reported impulsivity on decision‐making differences were examined by moderator analyses.

Setting

No restrictions on location.

Participants

Twenty‐four studies (20 independent samples) were included in the meta‐analysis, resulting in 604 IGD and 641 control participants and 35 ESs.

Measures

Reward‐related decision‐making differences between IGD and control groups.

Findings

The overall ES for decision‐making deficits in IGD was small (g = −0.45, P < 0.01). The effects were comparable across risky, ambiguous and inter‐temporal decision‐making. Larger aggregate ESs were identified for pure‐gain and mixed compared with pure‐loss decision‐making. Studies based on clinical and community samples showed similar effects. No significant difference between behavioral studies and those with extra measurements was observed. Decision‐making alterations were not closely associated with IGD severity or self‐reported impulsivity differences at the study level.

Conclusions

Internet gaming disorder appears to be consistently associated with reward‐related decision‐making deficits.
Abnormal expression of the costimulatory molecule B7‐H4 in placental chorionic villous and decidual basalis tissues of patients with preeclampsia and HELLP syndrome
Authors: Duan Liyan , Reisch Beatrix , Iannaccone Antonella , Hadrovic Elina , Wu Yuqing , Vogtmann Rebekka , Winterhager Elke , Kimmig Rainer , Köninger Angela , Mach Pawel , Gellhaus Alexandra
Published: April 2021

Background

B7‐H4, a checkpoint molecule of the B7 family, regulates a broad spectrum such as T‐cell activation, cytokine secretion, tumour progression, and invasion capacities. Our previous data revealed that soluble B7‐H4 (sB7‐H4) blood serum levels are elevated in women at high risk for the hypertensive pregnancy disorder preeclampsia (PE) in the first trimester, as well as in patients with confirmed early/late‐onset PE.

Aim

We here aim to investigate the expression pattern of B7‐H4 in placental tissues of PE and HELLP Syndrome versus control group.

Methods

B7‐H4 protein expression and localization were investigated by immunoblotting and co‐immunohistochemistry in placental chorionic villous and decidual basalis tissues.

Results

B7‐H4 protein was prominently expressed at the cell membrane, in the cytoplasm of the syncytiotrophoblast (STB) and interstitial extravillous trophoblast (EVT). B7‐H4 protein levels in placental chorionic villous tissue were significantly higher in women with early‐onset/late‐onset PE and HELLP, while it was decreased in decidual basalis tissues of early‐onset PE and HELLP compared with controls.

Conclusion

B7‐H4 was inversely expressed in placental chorionic villous and decidual basalis tissues of PE and HELLP patients. The increase in B7‐H4 in the STB in PE and HELLP may lead to excessive apical expression and release of soluble B7‐H4 in the maternal circulation. In contrast, the decrease in B7‐H4 in decidual basalis tissues could be related to the decrease in invasion ability of the EVT in PE. Thus, the current results strongly suggest that B7‐H4 is involved in the pathogenesis of PE and HELLP.
No longer recommended for cervical screening: How women aged 18–24 feel about the renewed National Cervical Screening Program
Authors: Jegathees Sharuja , Mac Olivia A. , Dodd Rachael H.
Published: April 2021

Background

Since December 2017, the Australian National Cervical Screening Program no longer recommends screening for women under 25 years of age.

Aim

To explore the attitudes of women under 25 years toward the changes.

Methods

In December 2019, women aged 18–24, residing in Australia, were recruited via the social media platform Instagram and Facebook. Descriptive analysis, t‐tests, χ2 tests and multivariable regressions were used to analyse the data.

Results

Five hundred and twelve women completed a cross‐sectional web‐based survey. Women who were older (22–24: 3.1 vs 18–21: 2.8, P < 0.001), sexually active (3.1 vs 2.7, P = 0.003), vaccinated against human papillomavirus (mean = 3.2 vs 2.7, P = 0.005) or who had screened previously (mean = 3.5 vs 2.8, P < 0.001) had significantly greater knowledge about the current cervical screening practices. Older women (odds ratio (OR) = 0.85, 95% CI 0.80–0.95) or those who had screened previously (OR = 0.51, 95% CI 0.31–0.83) were less positive about the delayed start age of screening and five‐yearly screening (OR = 0.54, 95% CI 0.35–0.85). A significant association was determined between being sexually active (χ2(4) = 32.71, P < 0.001) and women who had screened previously (χ2(4) = 34.43, P < 0.001), with a greater intention to screen in the future. Regarding health information, 64.6% of women had never heard of the ‘National Cervical Screening Program’ website and 38.9% of the sample (n = 199/512) reported they had ‘rarely’ noticed any health information regarding cervical screening in the past 12 months.

Conclusion

Further work is required to rectify women’s knowledge of cervical screening to ensure women under 25 are aware of the screening guidelines and reduce the potential for over‐testing and overtreatment in this age group.
Dynamic Policy Sabotage
Authors: Gieczewski Germán , Li Christopher
Published: April 2021

A common feature of democratic politics is that the opposition may sabotage the implementation of policies put forth by the incumbent party. This paper presents a theoretical analysis of the opposition's optimal use of sabotage and of how the prospect of sabotage conditions the incumbent's agenda. We show that, when a proposed policy enjoys moderate public support, the incumbent will attempt to pass it as early as possible, and the opposition will exert increasing effort to sabotage it as the next election approaches. In contrast, the incumbent delays the passage of highly popular policies until near the end of her term, and these are not subject to sabotage. Finally, the threat of sabotage persuades the incumbent to abandon unpopular proposals. In extensions, we show how our results compare under different electoral institutions, and how legislative obstruction can be used as an alternative or complement to sabotage.
Paratesticular lesions: Aetiology and appearances on ultrasound
Authors: Rafailidis Vasileios , Huang Dean Y. , Sidhu Paul S.
Published: April 2021

Background

Ultrasound (US) is the primary modality for the investigation of scrotal pathology, including both intra‐ and paratesticular abnormalities.

Objective

To describe the abnormalities of the paratesticular space.

Materials/Methods

The paratesticular space contains the epididymis, spermatic cord and the tunica vaginalis cavity and is affected by a variety of inflammatory or tumoral entities. Differential diagnosis based on US criteria is frequently problematic, as the findings are non‐specific.

Results

Some general rules apply: (i) unlike testicular lesions, extra‐testicular entities are usually benign in the adult, (ii) the first steps to accurate diagnosis include careful localization of the lesion and assessment of its consistency (solid or cystic) and (iii) magnetic resonance imaging can be useful for further tissue characterization of lesions suspected to contain fat, but surgical biopsy will often provide the definite diagnosis. Contrast‐enhanced ultrasound (CEUS) has been applied with limited experience indicating a narrow role, primarily for the differential diagnosis of echogenic cystic entities and the delineation of a necrotic abscess from a solid neoplasm.

Discussion

The various abnormalities are discussed and illustrated.

Conclusion

This manuscript summarizes the literature on paratesticular lesions and the value of US in diagnosis.