bluuebunny/crossref_metadata_2025 huggingface dataset:
Niclosamide loaded Eudragit EPO nanoparticles show enhanced Candida biofilm penetration, trigger biofilm detachment and protect from mucosal candidiasis
Authors: Sutar Yogesh , Nabeela Sunna , Singh Shakti , Alqarihi Abdullah , Solis Norma , Ghebremariam Teklegiorgis , Filler Scott , Ibrahim Ashraf S. , Date Abhijit , Uppuluri Priya
Published: June 2022

Candida albicans biofilms are a complex multilayer community of cells that are resistant to almost all classes of antifungal drugs. The bottommost layers of biofilms experience nutrient limitation where C. albicans cells are required to respire. We previously reported that a protein Ndu1 is essential for Candida mitochondrial respiration; loss of NDU1 causes inability of C. albicans to grow on alternative carbon sources and triggers early biofilm detachment. Here, we screened a repurposed library of FDA approved small molecule inhibitors, to identify those that prevent NDU1-associated functions. We identified an anti-helminthic drug, Niclosamide (NCL), which not only prevented growth on acetate, C. albicans hyphenation and early biofilm growth, but also completely disengaged fully grown biofilms of drug resistant C. albicans and C. auris from their growth surface. To overcome the sub-optimal solubility and permeability of NCL that is well-known to affect its in vivo efficacy, we developed NCL encapsulated Eudragit EPO (an FDA-approved polymer) nanoparticles (NCL-EPO-NPs) with high niclosamide loading, that also provided long-term stability. The developed NCL-EPO-NPs completely penetrated mature biofilms and attained anti-biofilm activity at low microgram concentrations. NCL-EPO-NPs induced ROS activity in C. albicans, and drastically reduced oxygen consumption rate in the fungus, similar to that seen in an NDU1 mutant. NCL-EPO-NPs also significantly abrogated mucocutaneous candidiasis by fluconazole resistant strains of C. albicans, in mice models of oropharyngeal and vulvovaginal candidiasis. To our knowledge, this is the first study that targets biofilm detachment as a target to get rid of drug-resistant Candida biofilms, and uses nanoparticles of an FDA approved non-toxic drug to improve biofilm penetrability and microbial killing.
The sulfur cycle connects microbiomes and biogeochemistry in deep-sea hydrothermal plumes
Authors: Zhou Zhichao , Tran Patricia Q. , Adams Alyssa M. , Kieft Kristopher , Breier John A. , Sinha Rupesh K. , Krishnan Kottekkatu P. , Kurian P. John , Fortunato Caroline S. , Sheik Cody S. , Huber Julie A. , Li Meng , Dick Gregory J. , Anantharaman Karthik
Published: June 2022

In globally distributed deep-sea hydrothermal vent plumes, microbiomes are shaped by the redox energy landscapes created by reduced hydrothermal vent fluids mixing with oxidized seawater. Plumes can disperse over thousands of kilometers and are complex. Their characteristics are determined by geochemical sources from hydrothermal vents, e.g., hydrothermal inputs, nutrients, and trace metals. However, the impacts of plume biogeochemistry on the oceans are poorly constrained due to a lack of integrated understanding of microbiomes, population genetics, and geochemistry. Here, we use microbial genomes to understand links between biogeography, evolution, and metabolic connectivity, and elucidate their impacts on biogeochemical cycling in the deep sea. Using data from 37 diverse plumes from 8 ocean basins, we show that sulfur metabolism defines the core microbiome of plumes and drives metabolic connectivity. Amongst all microbial metabolisms, sulfur transformations had the highest MW-score, a measure of metabolic connectivity in microbial communities. Our findings provide the ecological and evolutionary basis of change in sulfur-driven microbial communities and their population genetics in adaptation to changing geochemical gradients in the oceans.
TTBK2 controls cilium stability through actin and the centrosomal compartment
Authors: Nguyen Abraham , Goetz Sarah C.
Published: June 2022

The serine-threonine kinase Tau Tubulin Kinase 2 (TTBK2) is a key regulator of the assembly of primary cilia, which are vital signaling organelles. TTBK2 is also implicated in the stability of the assembled cilium, through mechanisms that remain to be defined. Here, we use mouse embryonic fibroblasts (MEFs) derived from Ttbk2fl/fl; UBC-CreERT+ embryos (hereafter Ttbk2cmut) to dissect the role of TTBK2 in cilium stability. This system depletes TTBK2 levels after cilia formation, allowing us to assess the molecular changes to the assembled cilium over time. As a consequence of Ttbk2 deletion, the ciliary axoneme is destabilized and primary cilia are lost within 48-72 hours following recombination. Axoneme destabilization involves an increased frequency of cilia breaks and is partially driven by altered actin dynamics and a reduction in axonemal microtubule modifications. At the same time, we find that TTBK2 is required to regulate the composition of the centriolar satellites and to maintain the basal body pools of intraflagellar transport (IFT) proteins. Altogether, our results reveal parallel pathways by which TTBK2 maintains cilium stability.
Combined small molecule treatment accelerates timing of maturation in human pluripotent stem cell-derived neurons
Authors: Hergenreder Emiliano , Zorina Yana , Zhao Zeping , Munguba Hermany , Calder Elizabeth L. , Baggiolini Arianna , Minotti Andrew P. , Walsh Ryan M. , Liston Conor , Levitz Joshua , Garippa Ralph , Chen Shuibing , Ciceri Gabriele , Studer Lorenz
Published: June 2022

The maturation of human pluripotent stem cell (hPSC)-derived neurons mimics the protracted timing of human brain development, extending over months and years to reach adult-like function. Prolonged in vitro maturation presents a major challenge to stem cell-based applications in modeling and treating neurological disease. We designed a high-content imaging assay based on morphological and functional readouts in hPSC-derived cortical neurons to reveal underlying pathways and to identify chemicals capable of accelerating neuronal maturation. Probing a library of 2688 bioactive drugs, we identified multiple compounds that drive neuronal maturation including inhibitors of LSD1 and DOT1L and activators of calcium-dependent transcription. A cocktail of 4 factors GSK-2879552, EPZ-5676, NMDA and Bay K 8644, which we collectively termed GENtoniK, triggered maturation across all assays tested including measures of synaptic density, electrophysiology and transcriptomics. Remarkably, GENtoniK was similarly effective in enhancing neuronal maturation in 3D cortical organoids and in spinal motoneurons, and improved aspects of cell maturation in non-neural lineages such as melanocytes and pancreatic beta cells. These results demonstrate that the maturation of multiple hPSC-derived cell types can be enhanced by simple pharmacological intervention and suggests that some of the mechanisms controlling the timing of human maturation are shared across lineages.
Exploring how entrepreneurial orientation improve firm resilience in digital era: findings from sequential mediation and FsQCA
Authors: Xia Qinghua , Xie Yi , Hu Shuchuan , Song Jianmin
Published: June 2022

Purpose

Under extensive pressure from normal market competition, frequent technological change and extreme exogenous shock, firms are facing severe challenge nowadays. How to withstand discontinuous crises and respond to normal risks through improving resilience (RE) is an important question worth researching. Thus, drawing on the strategic entrepreneurship theory, the purpose of this study is exploring the relationship between entrepreneurial orientation (EO) and RE, and combining digitization to discuss the role of digital business capability (DBC), digital business model innovation (DBMI) and environmental hostility (EH).

Design/methodology/approach

Based on survey data from 203 Chinese firms, using the methods of linear regression and bootstrap to test our hypothesis. Furthermore, fuzzy-set qualitative comparative analysis (FsQCA) is used to identify previously unknown combinations which lead to strong/weak RE in digital context.

Findings

First, EO positively influenced DBC and RE. Second, DBMI promoted RE, DBC and DBMI served as sequential mediators that linked EO and RE. Third, EH positively moderated the effects of EO on RE. Further the study revealed that different configuration of DBMI and dimensions of EO and DBC can explain RE.

Originality/value

The study explains mechanism of RE from perspective of digitization. The conclusion is good for further consolidating strategic entrepreneurship theory, and providing a new frame for firms to build the ability of antifragile.
An intelligent optimization technique for performance improvement in radial distribution network
Authors: Vempalle Rafi , Pradyumna Kumar Dhal
Published: June 2022

Purpose

The demand for electricity supply increases day by day due to the rapid growth in the number of industries and consumer devices. The electric power supply needs to be improved by properly arranging distributed generators (DGs). The purpose of this paper is to develop a methodology for optimum placement of DGs using novel algorithms that leads to loss minimization.

Design/methodology/approach

In this paper, a novel hybrid optimization is proposed to minimize the losses and improve the voltage profile. The hybridization of the optimization is done through the crow search (CS) algorithm and the black widow (BW) algorithm. The CS algorithm is used for finding some tie-line systems, DG locations, and the BW algorithm is used for finding the rest of the tie-line switches, DG sizes, unlike in usual hybrid optimization techniques.

Findings

The proposed technique is tested on two large-scale radial distribution networks (RDNs), like the 119-bus radial distribution system (RDS) and the 135 RDS, and compared with normal hybrid algorithms.

Originality/value

The main novelty of this hybridization is that it shares the parameters of the objective function. The losses of the RDN can be minimized by reconfiguration and incorporating compensating devices like DGs.
Fanning the flames: understanding viral content after brand transgressions
Authors: Legocki Kimberly V. , Walker Kristen L. , Eilert Meike
Published: June 2022

Purpose

This paper aims to contribute to the emerging body of research on firestorms, specifically on the inflammatory user-generated content (UGC) created in response to brand transgressions. By analyzing and segmenting UGC created and shared in the wake of three different events, the authors identify which type of inflammatory message is most likely to be widely shared; thus, contributing to a possible online firestorm.

Design/methodology/approach

Tweets were collected involving brand transgressions in the retail, fast food and technology space from varying timeframe and diverse media coverage. Then, the tweets were coded for message intention and analyzed with linguistics software to determine the message characteristics and framing. A two-step cluster analysis identified three types of UGC.

Findings

The authors found that message dimensions and the framing of tweets in the context of brand transgressions differed in characteristics, sentiment, call to action and the extent to which the messages were shared. The findings contradict traditional negative word-of-mouth studies involving idiosyncratic service and product failure. During online brand firestorms, rational activism messages with a call to action, generated in response to a firm’s transgression or “sparks,” have a higher likelihood of being shared (virality).

Originality/value

This research provides novel insights into UGC created after brand transgressions. Different types of messages created after these events vary in the extent that they “fan the flames” of the transgression. A message typology and flowchart are provided to assist managers in identifying and responding to three message types: ash, sparks and embers.
Does size matter? Is there an optimal size for tenant–owner associations?
Authors: Karpestam Peter , Palm Peter
Published: June 2022

Purpose

The authors investigate how prices of condominiums are affected by the size of the tenant-owner associations that they belong to.

Design/methodology/approach

The authors use data of sold apartments in the Swedish municipality Malmö 2013–2018 and estimate hedonic price regressions. The authors also perform semi-structured interviews with three senior professionals in real estate companies.

Findings

The authors find significantly negative relationships between the prices of condominiums and the size of tenant-owner associations. Also, regression results indicate that associations should be no smaller than 6–10 apartments. The interviews support that associations should not be too small or too big. The lower and upper limit was suggested by the respondents to 40–50 and 80–150 apartments, respectively. In these ranges, economies of scale can be achieved, and residents will not lose the sense of community and responsibility.

Research limitations/implications

The authors do not prove causality. Smaller associations may have relatively exclusive common amenities, about which we lack data. The same relationships may not exist in different market conditions.

Originality/value

The authors are not aware of previous studies with the same research question. The size of tenant-owner associations may affect the price through different channels. First, several of the banks in Sweden do not always grant mortgages for condominiums that belong to small associations. Second, larger associations may have better economies of scale and more efficient property management. Third, homeowners may prefer smaller tenant-owned associations, because they may feel less anonymous and provide more influence on common amenities.
A systematic review on forensic accounting and its contribution towards fraud detection and prevention
Authors: Kaur Baljinder , Sood Kiran , Grima Simon
Published: June 2022

Purpose

This paper aims to determine how forensic accounting contributes to fraud detection and prevention and answer the following research questions: What are the standard techniques for fraud detection and prevention; and What are the significant challenges that hinder the application of forensic accounting in fraud prevention and detection?

Design/methodology/approach

The authors use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to carry out a systematic literature review (SLR) to identify and assess the existing literature on forensic accounting.

Findings

There exists a positive correlation between forensic accounting and fraud detection and prevention. Moreover, in both the empirical and non-empirical findings, the authors note that fraud is complex, and in carrying out fraud investigations, one must be aware of its complexity.

Practical implications

Although drug counterfeiting is a sector where forensic accountants have paid less attention, it is a rapidly expanding fraud area. This paper finds that to detect fraud at an early stage, one must increase consumer understanding of basic forensic accounting techniques by implementing accurate supply chain monitoring systems and inventory management controls and conducting adequate and effective regulatory, honest and legitimate customs inspections.

Social implications

The major factors that restrict forensic accounting are a lack of awareness and education. Hence, it is essential to incorporate forensic accounting in undergraduate and post-graduate courses.

Originality/value

From the existing literature, it has been observed that very few studies have been conducted in this field using the PRISMA and SLR techniques. Also, the authors carried out a holistic study that focuses on three different areas – fraud detection, fraud prevention and the challenges in forensic accounting.
A scale for measuring healthcare service quality incorporating patient-centred care and using a psychometric analytics framework
Authors: Rave Jorge Iván Pérez , Sánchez Figueroa Génesis Angélica , González Echavarría Favián
Published: June 2022

Purpose

Recent developments in healthcare contexts increasingly emphasize patient-centred approaches to service quality measures; however, few studies consider this dimension explicitly. The present study develops and psychometrically validates a scale of healthcare service quality explicitly incorporating a patient-centred care dimension from a communicational perspective. The paper also enriches the traditional content of service quality by including equity items and presents the underlying structure of service quality in an emerging country.

Design/methodology/approach

The final sample consisted of 869 healthcare users (complete cases in the service quality items derived from 917 surveys received) from Colombia. The authors used a psychometric analytics framework comprising seven processes incorporating exploratory factor analysis, structural equation modelling, and machine learning methods to examine construct plausibility, reliability, construct validity, equity, and criterion/predictive validity (e.g. explaining/predicting subjective well-being and behavioural intentions).

Findings

The final scale consists of 17 items and satisfies all psychometric properties. Its validation allows for the discovery and psychometrical confirmation of two essential dimensions: patient-centred communication (eight items) and process quality (nine items).

Practical implications

The authors illustrate three practical uses of the scale: the possibility for diagnoses; hypothesis contrast based on confidence intervals; and estimation of the capacity of the service to satisfy specifications.

Originality/value

Both dimensions reveal users' relevant needs and complement previous studies that have focused on process aspects of healthcare service quality.
Design and development of digital information product and service using colour QR codes for smartphone user's of academic libraries
Authors: Kharat Santosh Abaji , Nagarkar Shubhada , Panage Bhausaheb Murlidhar
Published: June 2022

Purpose

The objectives of the study include the following: (1) to design and develop digital information products by using Quick Response (QR) codes (2) to make an awareness of QR codes in library users; (3) to study user preferences for black and green QR codes in the library services of management institutes and (4) to raise awareness of the product layer among the library profession.

Design/methodology/approach

This study uses a participatory action research approach. The researcher implemented QR codes in the library, and participants scanned QR codes through their smartphones. All data analyses were performed using IBM SPSS and Microsoft Excel 2016.

Findings

The researcher found that both QR codes will be popular in the future; however, users will prefer to scan the green QR code multiple times due to the code's increased benefits and advantages (which have been discussed in this report).

Research limitations/implications

This study implemented QR codes in MBA libraries affiliated with Savitribai Phule Pune University in the Pune and Pimpri Chinchwad areas.

Originality/value

The current study implemented a QR code in the library service with green and black colours. This study examined which QR code will be popular in the future owing to QR code's advanced features and specifications. This, in turn, will assist the library in designing such a collection and developing more QR codes that will be recommended to users. This will assist in the creation of good digital information products for smartphone users.
Women on boards, firms’ competitive advantage and its effect on ESG disclosure in Malaysia
Authors: Wan Mohammad Wan Masliza , Zaini Rapiah , Md Kassim Aza Azlina
Published: June 2022

Purpose

The purpose of this paper is to investigate the effects of women on board moderated by firms’ competitive advantage on firms’ environmental, social and governance (ESG) disclosures.

Design/methodology/approach

The sample consists of 332 firm-year observations from the year 2012 to 2017 of 65 firms listed in Bursa Malaysia. To improve the robustness of this analysis, the authors adopt clustering techniques in the regression analysis. Sensitivity analysis is also conducted using two-stage least square regression and robust standard errors for panel regression with a cross-sectional dependence approach.

Findings

The findings of this research indicate that women on board encourage ESG and environmental disclosures. Nonetheless, in competitively advantaged firms, the authors find that the interaction between WOMENPER and COMADVANTAGE is negatively influencing ESG scores. However, no evidence is found to indicate that women on board in a competitively advantaged firm have an effect on the environmental scores of a firm.

Research limitations/implications

The findings urge regulators to ensure the appointment of qualified and competent women on board, particularly in competitively advantage firms.

Practical implications

Though firms with more women on board are associated with better ESG disclosures and environmental disclosures, the author’s additional analysis found that this is less pronounced in competitively advantage firms. Since a number of the competitive firms are owned by family firms as well as government-linked firms, the appointment of women should not be based on directors’ affiliation, network and family relationships.

Originality/value

To the best of authors’ knowledge, this is one of the few studies which seek to investigate women’s appointment in competitive advantage firms.
A practical guide for generating unsupervised, spectrogram‐based latent space representations of animal vocalizations
Authors: Thomas Mara , Jensen Frants H. , Averly Baptiste , Demartsev Vlad , Manser Marta B. , Sainburg Tim , Roch Marie A. , Strandburg‐Peshkin Ariana
Published: June 2022

Background: The manual detection, analysis and classification of animal vocalizations in acoustic recordings is laborious and requires expert knowledge. Hence, there is a need for objective, generalizable methods that detect underlying patterns in these data, categorize sounds into distinct groups and quantify similarities between them. Among all computational methods that have been proposed to accomplish this, neighbourhood‐based dimensionality reduction of spectrograms to produce a latent space representation of calls stands out for its conceptual simplicity and effectiveness.

Goal of the study/what was done: Using a dataset of manually annotated meerkatSuricata suricattavocalizations, we demonstrate how this method can be used to obtain meaningful latent space representations that reflect the established taxonomy of call types. We analyse strengths and weaknesses of the proposed approach, give recommendations for its usage and show application examples, such as the classification of ambiguous calls and the detection of mislabelled calls.

What this means: All analyses are accompanied by example code to help researchers realize the potential of this method for the study of animal vocalizations.
Home is where the heat is: Thermoregulation of European bats inhabiting artificial roosts and the threat of heat waves
Authors: Czenze Zenon J. , Noakes Matthew J. , Wojciechowski Michał S.
Published: June 2022

Anthropogenic land use changes, such as deforestation and commercial forestry, have substantially reduced natural roost sites for European bats. A common conservation solution is to provide artificial roosts (i.e. bat boxes), but there are concerns that these can become hotter than natural roosts in summer and could be death traps during heat waves. Nevertheless, females of several bat species form maternity colonies in these boxes, thus occupying hotter and more humid microclimates than solitarily roosting males. We tested if cooling efficiency and heat tolerance differ between sexes in European bats, and estimated the evaporative water requirements for bats living in bat boxes during hot summer days.

We used indirect calorimetry and thermometry to quantify thermoregulation at high air temperatures (Ta) in four species of verspitilionid bats that regularly occupy artificial roosts. We measured resting metabolic heat production, evaporative water loss rates (EWL) and body temperature (Tb) at Ta between 28°C and 48°C during summer. We predicted that females have higher evaporative cooling efficiency (evaporative heat loss/metabolic heat production) than males, allowing them to reach their heat tolerance limit at higher Ta.

We found no sex differences in maximum evaporative cooling efficiency, maximum Tb, and maximum Ta tolerated. However, the patterns of increasing EWL with Ta differed between sexes. Females tolerated higher Ta before increasing EWL than males and then rapidly increased EWL to higher values than males at the maximum Ta tolerated. These sex differences in heat dissipation strategies may reflect varying ecological and physiological constraints associated with different summer roosting habits.

Synthesis and applications. Our study revealed that some small European bat species are already at risk of succumbing to lethal dehydration during present‐day heat waves, with daytime evaporative water requirements equivalent to ~30% of body mass in sun‐exposed boxes. For conservation managers working with common European bat species, particularly those in monoculture forests with woodcrete bat‐boxes, our physiologically informed recommendations include positioning boxes in diverse locations varying in aspect and sun exposure. This will ensure thermal heterogeneity of roost sites and provide a wide gradient of microclimate conditions, allowing for roost switching when necessary.
Connections between Evaporite Deposition and Glacial Periods since the Middle Pleistocene in Salt Lakes in the Western Qaidam Basin, China
Authors: GU Jiani , CHEN Andong , LIU Jiajun , HAN Guang , WANG Xuefeng
Published: June 2022

The Quaternary was the main evaporite deposition period in the Qaidam Basin (QB), but the correlation between the evaporite deposition period and the glacial period is still unclear. In this study, the research objects are primarily evaporite‐bearing strata in a 461.58 m‐long drill core in the QB. X‐ray powder diffraction (XRD) and scanning electron microscopy (SEM) were applied to study the evaporite minerals, U‐Th dating being applied to construct the 230Th geochronological framework. Evaporite deposition from Marine Isotope Stage (MIS) 15 to MIS 4 in the borehole was reconstructed via mineralogical and geochronological data. The evaporite minerals are mainly halite (NaCl), mirabilite (Na2SO4·10H2O), thenardite (Na2SO4) and gypsum (CaSO4·2H2O). A total of 9 effective 230Th data points, ranging from 492.5 ± 43.0 ka to 62.0 ± 11.9 ka, were obtained. The depositional age of the earliest halite layer in the borehole is 592.5–563.0 ka. There were mirabilite deposits in the QB during the cold glacial environment of MIS 6. During MIS 4, the study area desiccated, with mirabilite and halite being deposited. This study suggests that mirabilite is an indicator mineral for the glacial environment in the QB, while halite deposition does not correspond well to glaciation.
Engaged Egalitarianism: Why the Australian Recovery Must Prioritise Openness*
Authors: Leigh Andrew
Published: June 2022

Australian living standards, relative to the rest of the world, have been highest in eras of economic openness. Openness can also increase equality. Tariffs tend to be regressive, so poor households benefit most from trade liberalisation. In the case of immigration, skilled permanent migrants tend to earn considerably more than the Australian‐born population, so any wage pressures are felt at the upper end of the distribution. Foreign investment can also have an equalising effect, by raising wages and lowering the rate of return on domestic capital. An approach of engaged egalitarianism – ensuring that the gains from globalisation are broadly shared – will benefit the most disadvantaged Australians.
New Zealand divaricate plant species: Tensile strength and Remote Island occurrence
Authors: Howard Jarden , Cameron Ewen , Bellve Andre , Baba Yumiko , Wright Shane
Published: June 2022

Divaricate plant species account for more than 10% of New Zealand/Aotearoa's woody flora, a higher proportion for that life form than anywhere else on earth. Two main hypotheses have been proposed to account for the prevalence of this phenotype. The first suggests herbivorous birds, particularly large flightless moa, exerted selective pressure on many plants to adopt the form. The second proposes climate as the main driver since insular New Zealand has many exposed habitats and, historically, experienced stressing conditions during the Pleistocene. Our study investigated two questions to shed further light on the evolution of divaricates, in particular related to the potential influence of browsing by large avian herbivores. First, divaricate plants have been posited to have a higher tensile strength than non‐divaricates as a defence mechanism against moa browsing. We tested the great majority of New Zealand plant genera within which divaricates occur, contrasting the stem tensile strength of these plants against their closest non‐divaricate counterparts using accurate testing technology. The results indicate divaricate species have tensile strength that approaches twice that of non‐divaricates across a broad and disparate phylogenetic range that includes gymnosperms and many clades of angiosperms. Second, we tested the species level distributions of widely dispersed woody plant genera across the New Zealand archipelago on islands where moa had been present or always absent. We found that no endemic divaricate species occurred on any islands from which moa had been permanently absent. In contrast, their non‐divaricate counterparts were commonly endemic to those same islands.
Distribution of intraepithelial lymphocytes, mast cells, and goblet cells in the intestine of alpaca
Authors: Ma Meng , Bai Xue , Wang Zixu , Dong Yulan , Chen Yaoxing , Cao Jing
Published: June 2022

Intestinal diseases in ruminants are frequent and susceptible to invasion by exogenous substances, and the intestinal mucosal barrier is the first line of defence of the body's immune defence. At present, the study on the structure of intestinal mucosal immune barrier in alpaca is incomplete. Therefore, the alpaca intestines were studied to show the distribution characteristics of intestinal mucosal barrier structure and cells associated with immune system using histology, histochemistry, and immunohistochemistry. The results showed that the intestinal tract of alpaca was composed of mucosa, submucosa, muscularis, and serosa. Intraepithelial lymphocytes were distributed in mucosal epithelium and glands of the large intestine. Mast cells were distributed in each segment of the intestine, mainly in the intestinal lamina propria, intestinal glands, and duodenal glands around, as well as in the muscularis, and the particles of cytoplasm were obvious. Acidic goblet cells were mainly distributed in the ileal mucosal epithelium and ileal intestinal glands, while sialomucins were mainly expressed in the colon. The cells associated with the immune system in the intestinal mucosa of alpaca play an important role in protecting against foreign microbial invasion and infection, and this result provides a theoretical basis for revealing the occurrence of gastrointestinal diseases in alpaca.
Mutation of KRAS in colorectal adenocarcinoma in Greenland
Authors: Mousavi Nabi , Truelsen Sarah Line Bring , Bernth‐Andersen Simon , Koch Anders , Heegaard Steffen
Published: June 2022

KRAS mutation is one of the most frequent driver mutations in colorectal cancer (CRC) and is also a prognostic biomarker. The aim of the present study was to determine the frequency of KRAS mutations over time in the Greenlandic population diagnosed with CRC. In total, 578 patients with the diagnosis of adenocarcinoma between 1988 and 2017 were identified. The status of KRAS and the mutational subtypes of KRAS mutations were determined in 102 representative samples by the Idylla™ platform in the time periods 1988–1990, 2002–2004, and 2015–2017. The results showed that the frequency of the KRAS mutations increased significantly, from 27% in 1988–1990 to 43% in 2015–2017 (p < 0.001). Furthermore, the most frequent subtypes of KRAS mutations in Greenland were G12D (c.35G > A) with 14%, G12V (c.35G > T) with 7%, and G13D (c.38G > A) with 6%. In conclusion, this study showed that the frequency of KRAS mutations in CRC has been increasing in recent decades in the specific population of Greenland. The results of this study may be used in initiatives related to targeted therapy of CRC in specific ethnicities and in investigations focusing on the environmental factors of cancer‐related somatic mutations.
Open habitats in a tropical biodiversity hotspot support pollinator diversity in both protected and unprotected areas
Authors: Balogun Ibukun , Eluyeba Olumayowa , Adedoja Opeyemi , Samways Michael J. , Polašek Ozren , Kehinde Temitope
Published: June 2022

Protected areas (PAs) are vital in the global effort to preserve biodiversity, particularly for disturbance‐intolerant pollinator species in the tropics. As there is little information on the potential of PAs for pollinator conservation in sensitive tropical ecosystems, we assessed here insect pollinator diversity in protected vs. unprotected areas in two vegetation zones in Nigeria, within the West African Guinea Biodiversity Hotspot. We selected two land‐use types based on predominant canopy cover type (open and tree‐shaded habitats) and these were sampled in both protected and unprotected areas of tropical rain forest and savanna vegetation zones. Pollinator composition varied significantly between protected vs. unprotected areas in each vegetation zone, signifying both areas support unique assemblages of insect pollinators. However, pollinator diversity varied according to land‐use type (open vs. shaded habitats) rather than protected area per se, such that pollinators were more abundant and species‐rich in open habitat than shaded habitat. These findings emphasize that beyond the protection of ecosystems, fine scale habitat management promoting the availability of adequate floral resources in natural areas is critical for ensuring conservation of these pollinators in tropical ecosystems.
Automation of dry eye disease quantitative assessment: A review
Authors: Brahim Ikram , Lamard Mathieu , Benyoussef Anas‐Alexis , Quellec Gwenolé
Published: June 2022

Dry eye disease (DED) is a common eye condition worldwide and a primary reason for visits to the ophthalmologist. DED diagnosis is performed through a combination of tests, some of which are unfortunately invasive, non‐reproducible and lack accuracy. The following review describes methods that diagnose and measure the extent of eye dryness, enabling clinicians to quantify its severity. Our aim with this paper is to review classical methods as well as those that incorporate automation. For only four ways of quantifying DED, we take a deeper look into what main elements can benefit from automation and the different ways studies have incorporated it. Like numerous medical fields, Artificial Intelligence (AI) appears to be the path towards quality DED diagnosis. This review categorises diagnostic methods into the following: classical, semi‐automated and promising AI‐based automated methods.
UVB‐induced SFRP1 methylation potentiates skin damage by promoting cell apoptosis and DNA damage
Authors: Liang Junqin , Liu Lina , Tang Hongbo , Ma Qingyu , Sang Yingbing , Kang Xiaojing
Published: June 2022

In response to the accumulation of genetic mutations and cellular changes, ultraviolet radiation B (UVB) skin lesions undergo dysplasia and transform into a cutaneous squamous cell carcinoma (CSCC). Consistent with our previous findings that secreted frizzled‐related protein 1 (SFRP1), a member of the SFRP gene family, was downregulated in human CSCC tissue samples, we found a significant downregulation of SFRP1 in HaCaT, A431, and SCL‐1 cells after UVB irradiation. DNA methyltransferase 1 (DNMT1) was significantly increased in CSCC tissues as well as UVB‐exposed A431 and SCL‐1 cells. Bisulfite genomic sequencing analysis showed that the downregulation of SFRP1 was mainly due to methylation of the SFRP1 promoter, as indicated by increased methylation rate of SFRP1 after UVB irradiation in HaCaT cells. Moreover, demethylation treatment with 5‐aza′‐deoxycytidine (5‐AzaC) increased SFRP1 expression and reduced the methylation rate of SFRP1 in HaCaT cells. Flow cytometry analyses demonstrated that 5‐AzaC treatment or overexpression of SFRP1 ameliorated UVB‐induced apoptosis, while knockdown of SFRP1 promoted UVB‐induced apoptosis in HaCaT cells. In addition, a comet assay confirmed that 5‐AzaC treatment reduced DNA damage following UVB irradiation, while knockdown of SFRP1 enhanced DNA damage following UVB irradiation. In conclusion, our study identified DNA methylation of SFRP1 as a key mediator in the UVB‐induced apoptosis of keratinocytes. These findings indicate that reinforcing SFRP1 defences by 5‐AzaC may help prevent UVB‐induced skin damage.
HETEROGENEOUS TREATMENT EFFECTS OF NUDGE AND REBATE: CAUSAL MACHINE LEARNING IN A FIELD EXPERIMENT ON ELECTRICITY CONSERVATION
Authors: Murakami Kayo , Shimada Hideki , Ushifusa Yoshiaki , Ida Takanori
Published: June 2022

This study investigates the different impacts of monetary and nonmonetary incentives on energy‐saving behaviors using a field experiment conducted in Japan. We find that the average reduction in electricity consumption from the rebate is 4%, whereas that from the nudge is not significantly different from zero. Applying a novel machine learning method for causal inference (causal forest) to estimate heterogeneous treatment effects at the household level, we demonstrate that the nudge intervention's treatment effects generate greater heterogeneity among households. These findings suggest that selective targeting for treatment increases the policy efficiency of monetary and nonmonetary interventions.
Characterization of cation disorder and oxygen vacancies in Li‐rich Li2TiO3
Authors: Guo Hao , Shi Yanli , Wang Hailiang , Chen Ruichong , Ye Diyin , Shi Qiwu , Qi Jianqi , Liao Zhijun , Lu Tiecheng
Published: June 2022

Li2TiO3 has a broad stoichiometric range and wide application prospects such as cathode, tritium breeder, and microwave dielectric materials. Particularly, Li2TiO3 shows a faster tritium release performance and exceptional chemical and radiation stabilities, making it one of the most promising solid breeder materials. Li‐rich Li2TiO3 has been developed for years as an advanced breeder material due to its enhanced tritium production and better stability in hydrogen atmosphere. However, the defect chemistry responsible for accommodating excess Li and how the non‐stoichiometry improves the material's performance is still unclear. In this work, the crystal structure and non‐stoichiometry‐induced defects in Li‐rich Li2TiO3 were investigated by means of X‐ray diffraction, electron spin resonance, and X‐ray photoelectron spectroscopy. Results show that oxygen vacancies and cation disorder both play a major role in the incorporation of excess Li. The sintering atmosphere (air/vacuum) has a negligible effect on the formation of the non‐stoichiometry‐induced defects but will influence the concentration of the oxygen vacancies. The better stability in the reduction atmosphere may be ascribed to the oxygen vacancies inside the Li‐rich Li2TiO3 crystals.
Precipitation of cesium lead halide perovskite nanocrystals in glasses based on liquid phase separation
Authors: Ye Ying , Li Kai , Zhang Wenchao , Liu Chao
Published: June 2022

Incorporation of cesium lead halide perovskite nanocrystals (CsPbX3 PNCs, X = Cl, Br, I) into glasses can significantly improve their stabilities and extend their application areas. Precipitation of CsPbX3 PNCs in glasses is mainly based on thermal treatment; however, the formation of mechanism is not clarified. Here, several in situ methods are employed to illustrate the precipitation mechanism of CsPbX3 PNCs. It is found that precipitation of CsPbX3 PNCs in glasses is based on the liquid phase separation in solid amorphous matrix, followed by crystallization in the supercooled state. Liquid phase separation process determines the composition of CsPbX3 PNCs, and cooling process has strong effect on the crystallinity and quality of CsPbX3 PNCs. These results clarify the precipitation mechanism of CsPbX3 PNCs in glasses and provide important guideline for the development of CsPbX3 PNCs embedded glasses for opto‐electronic applications.
FOXM1 regulates glycolysis in nasopharyngeal carcinoma cells through PDK1
Authors: Yang Qing , Wu Fang , Zhang Yong , Wang Rensheng
Published: June 2022

The transcription factor forkhead box M1 (FOXM1) is a well‐known proto‐oncogene that plays a significant role in the pathogenesis of various human cancers. However, the regulatory role and underlying mechanisms of FOXM1 in nasopharyngeal carcinoma (NPC) metabolism remain unclear. We demonstrated that FOXM1 could positively regulate glycolysis in NPC cells. Functional studies have shown that pyruvate dehydrogenase kinase 1 (PDK1) is involved in FOXM1‐regulated lactate production, ATP generation and glycolysis. FOXM1 binds directly to the PDK1 promoter region and increases the expression of PDK1 at the transcriptional level, leading to the phosphorylation of pyruvate dehydrogenase (PDH) at serine 293, inhibiting its activity. Knocking down FOXM1 using specific short hairpin RNAs (shRNAs) can significantly decrease glycolysis and the expression of PDK1 in NPC cells. Furthermore, microenvironmental factors can increase the expression of FOXM1 by regulating hypoxia‐inducible factor 1α (HIF‐1α) expression. Clinical data and in vivo studies confirmed the positive roles of FOXM1/PDK1 in NPC proliferation and progression. In conclusion, our findings revealed that FOXM1 regulates glycolysis and proliferation of NPC through PDK1‐mediated PDH phosphorylation. Therefore, targeting the FOXM1‐PDK1 axis may be a potential therapeutic strategy for NPC.
A Not Merely Charitable Alliance: Anti‐Poverty Workers Within and Against the State
Authors: Anastasi Andrew
Published: June 2022

This essay explores the insurgent practices of members of the Volunteers in Service to America (VISTA) program from 1965–1973. VISTA is situated historically in relation to New Left community organizing projects and the War on Poverty. Testimonials of VISTA workers demonstrate that many developed political perspectives critical of the “war” in which they had enlisted. Records of collective mobilization chart how VISTA workers attempted to form a labor union and bring the program under community control. Their largest organization, the National VISTA Alliance, represented a form of social justice unionism ante litteram within and against the U.S. state.
Risk‐sharing rules and their properties, with applications to peer‐to‐peer insurance
Authors: Denuit Michel , Dhaene Jan , Robert Christian Y.
Published: June 2022

This paper offers a systematic treatment of risk‐sharing rules for insurance losses, based on a list of relevant properties. A number of candidate risk‐sharing rules are considered, including the conditional mean risk‐sharing rule proposed in Denuit and Dhaene and the newly introduced quantile risk‐sharing rule. Their compliance with the proposed properties is established. Then, methods for building new risk‐sharing rules are discussed. The results derived in this paper are helpful in the development of peer‐to‐peer insurance (or crowdsurance), as well as to manage contingent risk funds where a given budget is distributed among claimants.
From one year to the next: Video gaming life‐style predicts subsequent psychosocial risk in adolescent boys and girls
Authors: Pagani Linda S , Jalbert Mégane , Derevensky Jeffrey L
Published: June 2022

Aim

The ubiquitous societal presence of screens and gaming software is ever growing in popularity. However, can this recreational life‐style pose risks for children's psychosocial adjustment? We thus examine associations between gaming life‐style and later psychosocial development.

Methods

The study sample originates from the 2120 boys and girls from the Quebec Longitudinal Study of Child Development birth cohort. At age 12, 625 boys and 702 girls from the original sample self‐reported the number of hours engaged in video gaming per week and 1 year later, they self‐reported psychosocial outcomes.

Results

Among boys, higher weekly video gaming frequency at age 12 forecasted increases in subsequent reactive aggression, emotional distress and ADHD symptoms at age 13. For girls, higher weekly video gaming frequency at age 12 predicted increases in subsequent reactive aggression and ADHD symptoms at age 13. No association between video game use and emotional distress was found for girls.

Conclusion

In both boys and girls, a more intense video gaming life‐style predicted subsequent risks for reactive aggression and ADHD symptoms, compared with their same sex counterparts reporting less intensity. For boys only, video gaming was associated with subsequent reactive emotional distress, likely due to the gender differences in violent content. Our data were collected at a time when there were less versatile screen‐based technologies; therefore, our findings can be interpreted as very conservative compared to current estimates. Paediatric professionals and allied disciplines must take preventive measures to ensure that parents are aware of the risks associated with excessive use by their sons and daughters.
Radiographic evidence of metaphyseal sclerosis secondary to canine distemper virus: 4 cases in juvenile dogs
Authors: Johnson Kryssa L. , Craig Linden E. , Wilson Sabrina , McLarty Ehren , Hespel Adrien‐Maxence
Published: June 2022

Background

Metaphyseal sclerosis secondary to canine distemper virus has been described histopathologically, but its radiographic appearance has not been described.

Objectives

Describe the radiographic appearance of metaphyseal sclerosis secondary to canine distemper virus in juvenile dogs as distinct from metaphyseal osteopathy (formerly called hypertrophic osteodystrophy).

Animals

Four dogs (2 intact females and 2 intact males) between 2.5 and 4 months of age presented to 2 different veterinary teaching hospitals.

Methods

Retrospective case series in which definitive diagnosis of canine distemper virus based on antemortem positive reverse transcription‐polymerase chain reaction (RT‐PCR) result or necropsy was required.

Results

All 4 dogs were presented for evaluation of neurologic abnormalities, respiratory signs, and lethargy; 2 dogs had gastrointestinal signs and ocular abnormalities. Radiographs on all patients featured multifocal, symmetric, metaphyseal sclerosis, with no evidence of lysis or changes to the adjacent growth plate. The metaphyseal sclerosis was most apparent at the proximal humeral diaphyses and other included long bones. Diagnosis of distemper was confirmed by necropsy (2 of 4 dogs) or positive RT‐PCR results (2 of 4 dogs). Three dogs were euthanized because of progressive illness, and 1 dog was lost to follow‐up.

Conclusion and Clinical Importance

Identification of metaphyseal sclerosis on radiographs during diagnostic evaluation of young dogs should lead to a clinical suspicion of canine distemper virus infection. Sclerosis identified secondary to canine distemper virus is distinct from the necrosis and inflammation of metaphyseal osteopathy.