bluuebunny/crossref_metadata_2025 huggingface dataset:
DrugMechDB: A Curated Database of Drug Mechanisms
Authors: Gonzalez-Cavazos Adriana Carolina , Tanska Anna , Mayers Michael D. , Carvalho-Silva Denise , Sridharan Brindha , Rewers Patrik A. , Sankarlal Umasri , Jagannathan Lakshmanan , Su Andrew I.
Published: May 2023

Abstract

Computational drug repositioning methods have emerged as an attractive and effective solution to find new candidates for existing therapies, reducing the time and cost of drug development. Repositioning methods based on biomedical knowledge graphs typically offer useful supporting biological evidence. This evidence is based on reasoning chains or subgraphs that connect a drug to disease predictions. However, there are no databases of drug mechanisms that can be used to train and evaluate such methods. Here, we introduce the Drug Mechanism Database (DrugMechDB), a manually curated database that describes drug mechanisms as paths through a knowledge graph. DrugMechDB integrates a diverse range of authoritative free-text resources to describe 4,583 drug indications with 32,249 relationships, representing 14 major biological scales. DrugMechDB can be employed as a benchmark dataset for assessing computational drug repurposing models or as a valuable resource for training such models.
PACAP-mediated gating of anxiety-controlling circuits
Authors: Li Yan , Andero Raül , Luchkina Natalia V. , Suh Junghyup , Ross Rachel A. , Lowell Bradford B. , Carlezon William A. , Ressler Kerry J. , Bolshakov Vadim Y.
Published: May 2023

Combining the use ofex vivoandin vivooptogenetics, viral tracing, electrophysiology and behavioral testing, we show that the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) gates anxiety-controlling circuits by differentially affecting synaptic efficacy at projections from the basolateral amygdala (BLA) to two different subdivisions of the dorsal subdivision of the bed nucleus of the stria terminalis (BNST), modifying the signal flow in BLA-ovBNST-adBNST circuits in such a way that adBNST is inhibited. Inhibition of adBNST is translated into the reduced firing probability of adBNST neurons during afferent activation, explaining the anxiety-triggering actions of PACAP in BNST, as inhibition of adBNST is anxiogenic. Our results reveal how innate, fear-related behavioral mechanisms may be controlled by neuropeptides, PACAP specifically, at the level of underlying neural circuits by inducing long-lasting plastic changes in functional interactions between their different structural components.
A computational model of the DNA damage-induced IKK/ NF-κB pathway reveals a critical dependence on irradiation dose and PARP-1
Authors: Konrath Fabian , Willenbrock Michael , Busse Dorothea , Scheidereit Claus , Wolf Jana
Published: May 2023

The activation of IKK/ NF-κB by genotoxic stress is a crucial process in the DNA damage response. Due to the anti-apoptotic impact of NF-κB it can affect cell fate decisions upon DNA damage and therefore interfere with tumour therapy-induced cell death. Here, we developed a dynamical model describing IKK/ NF-κB signalling that faithfully reproduces quantitative time course data and enabled a detailed analysis of pathway regulation. The approach elucidates a pathway topology with two hubs, where the first integrates signals from two DNA damage sensors and the second forms a coherent feedforward loop. The analyses reveal a critical role of the sensor protein PARP-1 in the pathway regulation. Introducing a method for calculating the impact of individual components on pathway activity in a time-resolved manner we show how irradiation dose influences pathway activation. Our results give a mechanistic understanding relevant for the interpretation of experimental and clinical studies.
Sperm regulates locomotor activity ofC. eleganshermaphrodites
Authors: Suo Satoshi
Published: May 2023

Sex differences in sex-shared behavior are common across various species. During mating, males transfer sperm and seminal fluid to females, which can affect female behavior. Sperm can be stored in the female reproductive tract for extended periods of time. However, its role in regulating female behavior is poorly understood. In the androdioecious nematodeC. elegans, hermaphrodites produce both egg cells and sperm, enabling them to self-fertilize or mate with males. Hermaphrodites exhibit less locomotor activity compared to males, indicating sex difference in behavioral regulation. In this study, sperm-deficient mutants were examined to investigate the role of sperm in the regulation of locomotor behavior. The results suggest that sperm plays a significant role in regulating sex-shared behavior inC. elegans, as sperm-deficient mutants exhibited increased locomotor activity. Additionally, females of closely related gonochoristic species,C. remaneiandC. brenneri, exhibited reduced locomotor activity after mating. The regulation of locomotion by sperm may be an adaptive mechanism that enables sperm-less hermaphrodites to search for mates and allow females to cease their search for mates after mating.
Duplications of human longevity-associated genes across placental mammals
Authors: Huang Zixia , Jiang Chongyi , Gu Jiayun , Uvizl Marek , Power Sarahjane , Douglas Declan , Kacprzyk Joanna
Published: May 2023

Natural selection has shaped a wide range of lifespans across mammals, with a few long-lived species showing negligible signs of ageing. Approaches used to elucidate the genetic mechanisms underlying mammalian longevity usually involve phylogenetic selection tests on candidate genes, analyses of differential gene expression between age cohorts or species, and measuring age-related epigenetic changes. However, the link between gene duplication and evolution of mammalian longevity has not been widely investigated. Here, we explored the association between gene duplication and mammalian lifespan by analysing 287 human longevity-associated genes across 37 placental mammals. We estimated that the expansion rate of these genes is eight times higher than their contraction rate across these 37 species. Using phylogenetic approaches, we identified 43 genes whose duplication levels are significantly correlated with longevity quotients (FDR < 0.05). In particular, strong correlation observed for four genes (CREBBP,PIK3R1,HELLS,FOXM1) appears to be driven mainly by their high duplication levels in two ageing extremists, the naked mole rat (Heterocephalus glaber) and the greater mouse-eared bat (Myotis myotis). Further sequence and expression analyses suggest that the genePIK3R1may have undergone a convergent duplication event, whereby the similar region of its coding sequence was independently duplicated multiple times in both of these long-lived species. Collectively, this study identified several candidate genes whose duplications may underlie the extreme longevity in mammals, and highlighted the potential role of gene duplication in the evolution of mammalian long lifespans.
Strong breeding colony fidelity in northern gannets following High Pathogenicity Avian Influenza Virus (HPAIV) outbreak
Authors: Grémillet David , Ponchon Aurore , Provost Pascal , Gamble Amandine , Abed-Zahar Mouna , Bernard Alice , Courbin Nicolas , Delavaud Grégoire , Deniau Armel , Fort Jérôme , Hamer Keith C. , Jeavons Ruth , Lane Jude V. , Langley Liam , Matthiopoulos Jason , Poupart Timothée , Prudor Aurélien , Stephens Nia , Trevail Alice , Wanless Sarah , Votier Stephen C. , Jeglinski Jana W.E.
Published: May 2023

High pathogenicity avian influenza virus (HPAIV) caused the worst seabird mass-mortalities on record in Europe across 2021-2022. The northern gannet (Morus bassanus) was one of the most affected species, with tens of thousands of casualties in the northeast Atlantic between April-September 2022. Disease outbreaks can drastically modify the movement ecology of animals and diminish spatial consistency, thereby increasing the potential for disease transmission. To detect potential changes in movement behaviour, we GPS-tracked breeding adults following the initial HPAIV outbreak, at three of the largest gannet breeding colonies where major mortality of adults and chicks occurred (Bass Rock, Scotland, UK; Grassholm, Wales, UK; Rouzic island, Brittany, France). Crucially, GPS-tracked birds remained faithful to their breeding sites and did not prospect other breeding colonies. They performed regular foraging trips at sea, similar to their behaviour before the outbreak. Gannet foraging effort was nonetheless lower than in 2019, thus surviving birds may have benefited from reduced intra- and interspecific food competition. Breeding colony fidelity of adult northern gannets following HPAIV mass-mortalities suggests limited long-term capacity to virus spread, which may contrast with the behaviour of adults during the disease outbreak, or with that of younger individuals.
The stage- and sex-specific transcriptome of the human parasiteSchistosoma mansoni
Authors: Buddenborg Sarah K. , Lu Zhigang , Sankaranarayan Geetha , Doyle Stephen R. , Berriman Matthew
Published: May 2023

The flatwormSchistosoma mansoniis an important but neglected pathogen that causes the disease schistosomiasis in millions of people worldwide. The parasite has a complex life cycle, undergoing sexual reproduction in a mammalian host and asexual replication in a snail host. Understanding the molecular mechanisms the parasite uses to transition between hosts and develop into dimorphic reproductively competent adults may reveal new strategies for control. We present the first comprehensive transcriptomic analysis ofS. mansoni, from eggs to juvenile worms. Focusing on eight life stages spanning free-living water-borne and parasitic stages from both intermediate and definitive hosts, we have generated deep RNA-seq data for five replicates per group for a total of 75 data sets. The data were produced using a single approach to increase the accuracy of stage-to-stage comparisons and made accessible via a user-friendly tool to visualise and explore gene expression (https://lifecycle.schisto.xyz/). These data are valuable for understanding the biology and sex-specific development of schistosomes and the interpretation of complementary genomic and functional genetics studies.
Simulation of 69 microbial communities indicates sequencing depth and false positives are major drivers of bias in Prokaryotic metagenome-assembled genome recovery
Authors: Nunes da Rocha Ulisses , Kasmanas Jonas Coelho , Toscan Rodolfo , Sanches Danilo S. , Magnusdottir Stefania , Saraiva Joao Pedro
Published: May 2023

We hypothesize that sample evenness, sequencing depth and taxonomic relatedness influence the recovery of metagenome-assembled genomes (MAGs). To test this hypothesis, we assessed MAG recovery in three in silico microbial communities composed of 42 species with the same richness but different sample evenness, sequencing depth and taxonomic distribution profiles using three different pipelines for MAG recovery.

The pipeline developed by Parks and colleagues (8K) generated the highest number of MAGs and the lowest number of true positives per community profile. The pipeline by Karst and colleagues (DT) showed the most accurate results (∼ 92%), outperforming the 8K and Multi-Metagenome pipeline (MM) developed by Albertsen and collaborators. Sequencing depth influenced the accurate recovery of genomes when using the 8K and MM, even with contrasting patterns: the MM pipeline recovered more MAGs found in the original communities when employing sequencing depths up to 60 million reads, whilst the 8K recovered more true positives in communities sequenced above 60 million reads. DT showed the best species recovery from the same genus, even though close-related species have a low recovery rate in all pipelines.

Our results highlight that more bins do not translate to the actual community composition and that sequencing depth plays a role in MAG recovery and increased community resolution. Even low MAG recovery error rates can significantly impact biological inferences. Our data indicates the scientific community should their findings from MAG recovery, especially when asserting novel species or metabolic traits.
An image segmentation method based on the spatial correlation coefficient of Local Moran's I - identification of A-type potassium channel clusters in the thalamus.
Authors: David Csaba , Giber Kristof , Kerti-Szigeti Katalin , Kollo Mihaly , Nusser Zoltan , Acsady Laszlo
Published: May 2023

Unsupervised segmentation in biological and non-biological images is only partially resolved. Segmentation either requires arbitrary thresholds or large teaching datasets. Here we propose a spatial autocorrelation method based on Local Moran's I coefficient to differentiate signal, background and noise in any type of image. The method, originally described for geoinformatics, does not require a predefined intensity threshold or teaching algorithm for image segmentation and allows quantitative comparison of samples obtained in different conditions. It utilizes relative intensity as well as spatial information of neighboring elements to select spatially contiguous groups of pixels. We demonstrate that Moran's method outperforms threshold-based method (TBM) in both artificially generated as well as in natural images especially when background noise is substantial. This superior performance can be attributed to the exclusion of false positive pixels resulting from isolated, high intensity pixels in high noise conditions. To test the method's power in real situation we used high power confocal images of the somatosensory thalamus immunostained for Kv4.2 and Kv4.3 (A-type) voltage gated potassium channels. Moran's method identified high intensity Kv4.2 and Kv4.3 ion channel clusters in the thalamic neuropil. Spatial distribution of these clusters displayed strong correlation with large sensory axon terminals of subcortical origin. The unique association of the special presynaptic terminals and a postsynaptic voltage gated ion channel cluster was confirmed with electron microscopy. These data demonstrate that Moran's method is a rapid, simple image segmentation method optimal for variable and high nose conditions.
Role of the inner membrane cytochrome ImcH inGeobacterextracellular electron transfer and energy conservation
Authors: Pimenta Andreia I. , Paquete Catarina M. , Morgado Leonor , Edwards Marcus J. , Clarke Thomas , Salgueiro Carlos A. , Pereira Inês A.C. , Duarte Américo G.
Published: May 2023

Electroactive bacteria combine the oxidation of carbon substrates with an extracellular electron transfer (EET) process that discharges electrons to an electron acceptor outside the cell. This process involves electron transfer through consecutive redox proteins that efficiently connect the inner membrane to the cell exterior. In this study, we isolated and characterized the quinone-interacting membrane cytochromecImcH fromGeobacter sulfurreducens, which is involved in the EET process to high redox potential acceptors. Our work provides evidence that ImcH is electroneutral, as it transfers electrons and protons to the same side of the membrane, contributing to the maintenance of a proton motive force, and plays a central role in recycling the menaquinone pool.

Importance

Geobacter sulfurreducensis a model electroactive bacterium, widespread in the environment and of significant interest for biotechnological applications. Its ability to form thick and conductive biofilms on top of conducting surfaces makes this microbe very useful in bioelectrochemical systems for the production of energy or added value products. To exploreGeobacterspp. as a biocatalyst it is essential to understand its metabolism, particularly the molecular mechanisms for extracellular electron transfer and energy conservation. Our results reveal the importance of ImcH in both processes, identifying this protein as a major player onGeobactermetabolism.
Production and characterization of GNPs-reinforced Al-based composite material by mechanical alloying
Authors: Behret Göksel , Sahin Oguzhan , Erturun Veysel
Published: May 2023

Purpose

The purpose of this study is to investigate the effects of graphene nanoplates (GNPs), and alloying time on aluminum matrix composite. After mixing the powdered materials in the alloying device, solid samples were formed by sintering. It is thought that the effect of using such a mechanical mixer on GNPs will be investigated and this study will give a perspective on the composites that GNPs will make with Al and its alloys.

Design/methodology/approach

Mechanical alloying (MA) device capable of high-speed shaking (Spex) movement was used and alloying was performed by adding other metal powders into aluminum, which is the matrix material, with the addition of GNPs at three different rates and times. The crystal size and lattice stress parameters were calculated by obtaining the X-ray diffraction (XRD) graphics of the obtained powder mixtures.

Findings

The XRD graphs of the obtained powder mixtures showed that the Al peaks decreased when the MA time increased. When the scanning electron microscopy images of the powder mixtures were examined, it was observed that agglomeration occurred especially in 1 and 1.5 Wt.% graphene reinforced mixtures that were MA for 90 min. The increase in the amount of graphene had a negative effect on the homogeneous distribution. When the Vickers microhardness values of the samples were examined, the hardness value of all samples increased up to the MA time of 45 min, and decreased in the times over 45 min.

Originality/value

The use of GNPs in the mechanical alloying technique and the fact that this technique was performed on the Retsch MM 400 device, which is a Spex type mixer, shows the originality of the study in terms of time and material content.
The impacts of supply visibility and demand visibility on product innovation: the mediating role of supply chain integration
Authors: Hu Miao , Jiang Shenyang , Huo Baofeng
Published: May 2023

Purpose

Drawing on absorptive capacity theory, this study explores the impacts of supply visibility and demand visibility on product innovation (i.e. exploratory and exploitative innovation), and it examines how supplier integration, customer integration and internal integration mediate these impacts.

Design/methodology/approach

The authors employ empirical survey data from 200 Chinese manufacturers and use structural equation modeling to test the proposed relationships.

Findings

The results show that supply visibility is positively related to supplier integration and internal integration and that demand visibility is positively related to customer integration. Furthermore, only customer integration and internal integration positively relate to exploratory and exploitative innovation.

Originality/value

First, this study emphasizes that supply visibility and demand visibility are important sources of a firm's innovation performance and that supply chain integration increases focal firms' capability of exploiting information and facilitates product innovation. Second, the study shows that supply visibility and demand visibility have distinct effects on three dimensions of supply chain integration and exploratory and exploitative innovation. The study also provides significant managerial guidelines for effectively leveraging supply chain visibility and integration in the promotion of product innovation.
Do refugee inflows contribute to the host countries’ entrepreneurial rates? A dynamic panel data analysis, 2000–2019
Authors: Noorbakhsh Sajad , Teixeira Aurora A.C.
Published: May 2023

Purpose

This study aims to estimate the impact of refugee inflows on host countries’ entrepreneurial rates. The refugee crisis led to an increased scientific and public policy interest in the impact of refugee inflows on host countries. One important perspective of such an impact, which is still underexplored, is the impact of refugee inflows on host countries entrepreneurial rates. Given the high number of refugees that flow to some countries, it would be valuable to assess the extent to which such countries are likely to reap the benefits from increasing refugee inflows in terms of (native and non-native) entrepreneurial talent enhancement.

Design/methodology/approach

Resorting to dynamic (two-step system generalized method of moments) panel data estimations, based on 186 countries over the period between 2000 and 2019, this study estimates the impact of refugee inflows on host countries’ entrepreneurial rates, measured by the total early-stage entrepreneurial activity (TEA) rate and the self-employment rate.

Findings

In general, higher refugee inflows are associated with lower host countries’ TEA rates. However, refugee inflows significantly foster self-employment rates of “medium-high” and “high” income host countries and host countries located in Africa. These results suggest that refugee inflows tend to enhance “necessity” related new ventures and/ or new ventures (from native and non-native population) operating in low value-added, low profit sectors.

Originality/value

This study constitutes a novel empirical contribution by providing a macroeconomic, quantitative assessment of the impact of refugee from distinct nationalities on a diverse set of host countries' entrepreneurship rates in the past two decades resorting to dynamic panel data models, which enable to address the heterogeneity of the countries and deal with the endogeneity of the variables of the model.
Impact of artificial intelligence text generators (AITGs) on libraries
Authors: Inamdar Saba
Published: May 2023

Purpose

The purpose of studying the impact of artificial intelligence text generators (AITGs) on libraries is to examine the effect of AITGs on the library landscape, including the services offered, the resources provided and the roles of library staff.

Design/methodology/approach

The current study examined how AITGs impact libraries. The researcher was able to comprehend the problem by critically analyzing and reviewing the pertinent published works, such as books, journals and articles.

Findings

This study concludes AITGs can assist libraries in streamlining operations, enhancing services and making collections more accessible. It is vital to highlight that AITGs are not intended to dissuade its users from visiting physical libraries or to replace them with virtual ones. Instead, they are a tool that can improve and supplement the services and resources provided by virtual libraries.

Originality/value

The study’s observations add to the corpus of information on AITGs in libraries and help users comprehend their technological foundations. Further empirical research is recommended on the effects of AITGs and their impact on libraries.
Are emergency department nurse practitioners homeless?
Authors: Pankevich Volha , Maclaine Christopher
Published: May 2023

The professional body for nurses working in emergency medicine is the College of Emergency Nursing Australasia. The professional body for doctors working in emergency medicine is the Australasian College for Emergency Medicine (ACEM). There is no professional body for nurse practitioners working in emergency medicine. The clinical role of nurse practitioners in emergency medicine more closely resembles that of doctors rather than nurses. Associate membership in ACEM would recognise their role in treating patients and would enhance their access to relevant continued professional development as has been endorsed by ACEM. It would also facilitate their further integration into the body of those who autonomously treat patients in the ED.
Molecular‐defined clonal evolution in patients with classical myeloproliferative neoplasms
Authors: Hinze Anna , Rinke Jenny , Crodel Carl C. , Möbius Susanne , Schäfer Vivien , Heidel Florian H. , Hochhaus Andreas , Ernst Thomas
Published: May 2023

Classical myeloproliferative neoplasms (MPNs) are characterized by distinct clinical phenotypes. The discovery of driver mutations in JAK2, CALR and MPL genes provided new insights into their pathogenesis. Next‐generation sequencing (NGS) identified additional somatic mutations, most frequently in epigenetic modulator genes. In this study, a cohort of 95 MPN patients was genetically characterized using targeted NGS. Clonal hierarchies of detected mutations were subsequently analysed using colony forming progenitor assays derived from single cells to study mutation acquisition. Further, the hierarchy of mutations within distinct cell lineages was evaluated. NGS revealed mutations in three epigenetic modulator genes (TET2, DNMT3A, ASXL1) as most common co‐mutations to the classical driver mutations. JAK2V617F as well as DNMT3A and TET2 mutations were detected as primary events in disease formation and most cases presented with a linear mutation pattern. Mutations appear mostly in the myeloid lineages but can also appear in lymphoid subpopulations. In one case with a double mutant MPL gene, mutations exclusively appeared in the monocyte lineage. Overall, this study confirms the mutational heterogeneity of classical MPNs and highlights the role of JAK2V617F and epigenetic modifier genes as early events in hematologic disease formation.
Supporting living together: Group work on animal rights for children
Authors: Kara Yunus
Published: May 2023

With this group work, which includes activities for animal rights, it is aimed that children can raise awareness about animal rights and interact with animals. The research was carried out as a pretest‐posttest experimental study in order to evaluate the effect of group work on children receiving counselling and training from a Guidance and Research Center in Istanbul. The study group of the research between May 2022 and June 2022 consists of 20 children (10 in the experimental group, 10 in the control group) between the ages of 11–12 and continuing their education in Istanbul. In addition to the Personal Information Form, which included questions such as gender, age, education status, number of siblings, socio‐economic levels, and status of living with pets, the Oney Animal Love Scale and Scale of Behaviour for Animals were administered to the study group as pretest‐posttest. The group work was held on Saturdays at 13:00, consisted of six sessions, and in each session, activities for socialization, animal rights and child–animal interaction were carried out. The collected data were analysed in the SPSS 22.0 package program. At the end of the group work, it was observed that there was a positive significant difference in the total scores of the Oney Animal Love and Scale of Behaviour for Animals of the children in the experimental group.
Preventing acute liver injury via hepatocyte‐targeting nano‐antioxidants
Authors: Yuan Xuejiao , Zhou Yanfeng , Sun Jinli , Wang Shanshan , Hu Xingjie , Li Jiyu , Huang Jing , Chen Nan
Published: May 2023

Acute liver injury (ALI) is a severe liver disease that is characterized by sudden and massive hepatocyte necrosis and deterioration of liver functions. Oxidative stress is increasingly recognized as a key factor in the induction and progression of ALI. Scavenging excessive reactive oxygen species (ROS) with antioxidants has become a promising therapeutic option, but intrinsically hepatocyte‐targeting antioxidants with excellent bioavailability and biocompatibility are yet to be developed. Herein, self‐assembling nanoparticles (NPs) composed of amphiphilic polymers are introduced to encapsulate organic Selenium compound L‐Se‐methylselenocysteine (SeMC) and form SeMC NPs, which protect the viabilities and functions of cultured hepatocytes in drug‐ or chemical‐induced acute hepatotoxicity models via efficient ROS removal. After further functionalization with the hepatocyte‐targeting ligand glycyrrhetinic acid (GA), the resultant GA‐SeMC NPs exhibit enhanced hepatocyte uptake and liver accumulation. In mouse models of ALI induced by acetaminophen (APAP) or carbon tetrachloride (CCl4), treatment with GA‐SeMC NPs significantly decrease the levels of hepatic lipid peroxidation, tissue vacuolization and serum liver transaminases, while prominently increase that of endogenous antioxidant enzymes. Our study therefore presents a liver‐targeting drug delivery strategy for the prevention and treatment of hepatic diseases.
Longitudinal assessment of undergraduate dental students: Building evidence for validity
Authors: Dickie Jamie , Sherriff Andrea , McEwan Michael , Bell Aileen , Naudi Kurt
Published: May 2023

Purpose

To investigate the content and criterion validity, and reliability of longitudinal clinical assessment of undergraduate dental student clinical competence by determining patterns of clinical performance and comparing them with validated standalone undergraduate examinations.

Methods

Group‐based trajectory models tracking students' clinical performance over time were produced from LIFTUPP© data for three dental student cohorts (2017–19; n = 235) using threshold models based on the Bayesian information criterion. Content validity was investigated using LIFTUPP© performance indicator 4 as the threshold for competence. Criterion validity was investigated using performance indicator 5 to create distinct trajectories of performance before linking and cross‐tabulating trajectory group memberships with a ‘top 20%’ performance in the final Bachelor of Dental Surgery (BDS) examinations. Reliability was calculated using Cronbach's alpha.

Results

Threshold 4 models showed all students followed a single upward trajectory in all three cohorts, showing clear progression in competence over three clinical BDS years. A threshold 5 model produced two distinct trajectories, and in each cohort a ‘better performing’ trajectory was identified. Students allocated to the ‘better performing’ trajectories scored higher on average in the final examinations for cohort 2 (29% vs 18% (BDS4); 33% vs. 15% (BDS5)) and cohort 3 (19% vs. 16% (BDS4); 21% vs. 16% (BDS5)). Reliability for the undergraduate examinations was high for all three cohorts (≥0.8815) and did not change appreciably when longitudinal assessment was included.

Conclusions

There is some evidence to support that longitudinal data have a degree of content and criterion validity for assessing the development of clinical competence in undergraduate dental students, which should increase confidence in decisions based on these data. The findings also provide a good foundation for subsequent research.
Salivary fluoride levels after daily brushing with 5000 ppm fluoride toothpaste: A randomised, controlled clinical trial
Authors: Staun Larsen L. , Nyvad B. , Baelum V.
Published: May 2023

This study explored salivary fluoride levels following toothbrushing with 5000 and 1450 ppm fluoride toothpaste and determined the decline in salivary fluoride levels following the return from 5000 to 1450 ppm fluoride toothpaste. The study was a randomised, controlled double‐blind parallel clinical trial (n = 24/group) measuring salivary fluoride five times during a 3‐week trial phase involving 2×/day use of 5000 or 1450 ppm fluoride toothpaste, and five times during an ensuing 2‐week wash‐out phase where all participants used 1450 ppm toothpaste. Salivary fluoride was measured using a fluoride electrode and data were analysed using multilevel mixed‐effects linear regression. Baseline salivary fluoride geometric means were 0.014 and 0.016 ppm for the 1450 and 5000 ppm groups, while the values at the end of the trial phase were 0.023 and 0.044 ppm, respectively. During the trial phase, except at baseline, differences between groups were statistically significant. The salivary fluoride levels for the 5000 ppm group remained statistically significantly higher than for the 1450 ppm group only at the first measurement in the wash‐out phase (≈30 h after the last 5000 ppm brushing), indicating that higher salivary fluoride levels resulting from use of 5000 ppm are sustained only as long as the brushing habit continues.
Drone sensing volumes
Authors: Jackman Anna
Published: May 2023

We are in the midst of a global turn to the drone. Following their establishment as icons of contemporary warfare, drones are increasingly deployed in a range of more‐than‐military applications. Interrogating this diverse ecosystem of platforms, scholars have examined the ways in which drones see, sense and manoeuvre, asserting that they enable distinct perspectives and the rendering visible of expanded and extended sensory terrains. In parallel, scholars from across and beyond the social sciences are increasingly mobilising the concept of volume to (re)consider conceptions of space in three‐, rather than two‐dimensional terms, with complex heights and depths. Thinking at the intersection of these discussions has explored drones as at once acting in, enacting, capturing and comprising volume. This paper extends these discussions by foregrounding drone sensing volumes and the diverse visualities, practices and relations they compose and comprise. Through the lens of drone sensing volumes in the context of emergency—and specifically through the snapshot example of sensing for signs of death following a homicide—the paper understands the sensor‐laden drone as a volumetric project both demonstrative of diverse sensing sensibilities and prompting a thinking otherwise of volume. While existing scholarship importantly attends to the conflict, control and calculative dimensions of volume, this paper mobilises the snapshot of drone sensing as an invitation for further attention to diverse forms of techno‐instrumentalisation, and the accommodation of more diverse drone sensing sensibilities that seek to resolve, rather than to perpetrate, volumetric violence.
Bile duct adenoma and small‐sized small duct type intrahepatic cholangiocarcinoma show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components
Authors: Sasaki Motoko , Sato Yasunori , Nakanuma Yasuni
Published: May 2023

Aims

Given that bile duct adenoma was significantly more prevalent in the liver with small duct type intrahepatic cholangiocarcinoma (small duct iCCA), compared to other primary liver carcinomas, we examined the possibility of bile duct adenoma as a precursor of small duct iCCA by analysing genetic alterations and other features in bile duct adenomas.

Methods and results

Subjects included 33 bile duct adenomas and 17 small‐sized (up to 2 cm in diameter) small duct iCCAs. Genetic alterations were examined by direct sequencing for hot‐spot regions and immunohistochemical staining. The expression of p16INK4a, EZH2 and IMP3 and stromal and inflammatory components were also examined. Genetic alterations examined including BRAF were not detected in bile duct adenomas, whereas genetic alterations of p53 (47%), ARID1A (41%), PBRM1 (12%), MTAP (12%), IDH1 (6%), KRAS (6%) and TERT promoter (6%) were detected in 16 small‐sized small duct iCCA (94%) (P < 0.01). The expression of IMP3 and EZH2 was not detected in bile duct adenomas, whereas it was detected in most small duct iCCA (94%) (P < 0.01). Immature stroma and neutrophilic infiltration were significantly more prevalent in small duct iCCA, compared to bile duct adenoma (P < 0.01).

Conclusion

Bile duct adenomas and small‐sized small duct iCCAs show distinct differences in genetic alterations, expression of IMP3 and EZH2 and stromal and inflammatory components. There was no evidence suggesting that bile duct adenoma is a precursor of small duct iCCA. Immunohistochemical staining for IMP3, EZH2, p53, ARID1A and MTAP may be useful for differential diagnosis between bile duct adenomas and small duct iCCAs.
Intergenerational sex and early sexual debut are associated with HIV infection among transgender women in Paraguay
Authors: Morel Zoilo , Aguilar Gloria , Samudio Tania , López Gladys , Rios‐González Carlos Miguel , Giménez Liliana , Schaerer Christian , Gómez Santiago , Báez Teresita , Estigarribia Gladys , Méndez Julieta , Muñoz Sergio , McFarland Willi
Published: May 2023

Introduction

HIV prevalence among transgender women is high worldwide. The objectives of the present study were to estimate the current prevalence of HIV and identify factors associated with high HIV burden among transgender women in Paraguay.

Methods

Transgender women aged ≥15 years in four regions of Paraguay were recruited by Starfish sampling between February and March 2021.

Results

In total, 322 transgender women were included. Mean age was 31 years (range 15–67), and 102 had positive HIV test results (31.7%, 95% confidence interval [CI] 26.6–37.1). In multivariable analysis, factors associated with HIV infection were age at first intercourse ≤17 years (adjusted odds ratio [aOR] 5.47; 95% CI 1.05–28.42), >10 years difference in age with the last sexual partner (aOR 1.60; 95% CI 1.04–2.46), substance use (mostly cocaine) (aOR 3.00; 95% CI 1.47–6.12), higher risk perception (aOR 3.08; 95% CI 1.53–6.17), not testing for HIV (aOR 1.23; 95% CI 1.09–1.39), and accessed by a peer educator (aOR 3.86; 95% CI 1.77–8.38).

Conclusions

Sexual debut as a minor and a large age difference with sexual partners are associated with high burden of HIV among transgender women in Paraguay. Our study corroborates the finding of cocaine use during sex as a risk factor for HIV. Prevention programmes must address structural and social vulnerabilities to stem the tragically high burden of HIV among transgender women.
Camelthorn and blackthorn trees provide important resources for Southern Pied Babblers (Turdoides bicolor) in the Kalahari
Authors: Hunt Kim , Marais Liamé , Cunningham Susan J. , Ridley Amanda R. , Moagi Lesedi , Rose Sanjo , Mckechnie Andrew E. , Bourne Amanda R.
Published: May 2023

In the southern Kalahari Desert, cooperatively breeding Southern Pied Babblers Turdoides bicolor frequently build their nests and forage in camelthorn trees Vachellia erioloba, a keystone species in the region, and blackthorn trees Senegalia mellifera, a widespread early successional shrub. Using Ivlev's electivity indices (Ei), we show that Southern Pied Babblers preferentially nest in camelthorn trees and preferentially forage in or under camelthorn and blackthorn trees. Southern Pied Babblers primarily forage on the ground; however, they will make use of arboreal resources when these are available. We observed the birds spending the highest proportion of foraging time off the ground during October, when breeding is also most common, compared with all other months within the austral summer breeding season. They are most likely to be observed foraging in camelthorn trees earlier in the breeding season and blackthorn trees later in the breeding season. We demonstrate that Southern Pied Babblers have a strong relationship with camelthorn trees, in which they prefer to both nest and forage. We highlight the importance of protecting camelthorn trees, a keystone species in the region, as part of the conservation and management of endemic Kalahari fauna such as the Southern Pied Babbler. In addition to contributing to the literature on keystone species, our observations raise questions about the ways in which avian reproduction in the arid zone could be decoupled from rainfall via the phenology of deep‐rooted tree species.
Designing slurry conditions to control size distribution of spray‐dried dense YSZ granules
Authors: Cha Hyun‐Ae , Shin Kyung‐Chan , Son Hee‐Jin , Hahn Byung‐Dong , Ahn Cheol‐Woo , Choi Jong‐Jin , Kim Do Kyung
Published: May 2023

This study suggests approaches to achieve the desired size and size distribution of highly dense spherical granules by investigating the effect of slurry conditions on size distribution. Highly dense spherical granules were prepared with a solid content of over 77 wt% by spray‐drying the slurry. A prolonged deagglomeration time of 64 h provided adequate flowing ability by breaking up almost all aggregates and improved dispersibility, resulting in reduced granule sizes and narrow size distributions. The optimum slurry conditions for maintaining dispersibility were 1 wt% of the dispersant and a strong basic pH, which had the greatest effect on size distribution. Based on these considerations, the 10.6 µm sized 3 mol% yttria‐stabilized zirconia granules were synthesized with 99.83% density, 97.17% sphericity, and uniform size with fraction yield of 80.01% at 10–20 µm. These dense granules have significantly higher hardness and modulus values of 19.19 and 206.68 GPa, respectively, than that of pellet and film types. To the best of our knowledge, the relationship between the slurries and the span of the size distribution of ceramic granules during spray‐drying has been demonstrated for the first time.
Immigrant voter turnout and time: Does period of arrival matter more than length of stay?
Authors: White Stephen E.
Published: May 2023

Research shows that the longer immigrants have been in their settlement country, the more likely they are to vote. This study examines whether when immigrants arrived, rather than how long they have resided, is the critical determinant of their electoral participation. Using Canadian data covering a 45‐year time span, this study demonstrates that the apparent relationship between immigrants' length of residence and their propensity to vote in elections is a result of the enduring influence of the historical period in which immigrants arrived in Canada. The results have implications for how researchers interpret immigrant adaptation to new political settings.
Dapagliflozin's effect on serum homocysteine in patients with hypertension complicated with insulin resistance
Authors: Yu Xiaoqian , Wen Cong , Xu Rui , Huang Wen
Published: May 2023

Most patients with hypertension are complicated with insulin resistance (IR), which is one of the risk factors of hypertension and can increase the level of serum homocysteine (Hcy) by affecting Hcy's metabolic enzyme and insulin level. Investigations in recent years have shown that Hcy is an independent risk factor for cardiovascular diseases. At present, folic acid is the prominent medicine used to reduce Hcy, but its effection for Hcy has an obvious individual difference, which is closely related to individual genes. Moreover, folic acid is chiefly used in patients with Hcy ≥15 μmol/L, but Hcy ≥10 μmol/L has had an adverse effect on the cardiovascular system. Randomized clinical trials have shown that dapagliflozin can improve IR. Therefore, whether it can reduce Hcy has become a new direction. This study was a retrospective case–control study. Patients with high serum Hcy and hypertension complicated with IR were divided into two groups: the dapagliflozin group (n = 166) and the control group (n = 198). Before and after 12 weeks of treatment, the changes in serum Hcy and IR index were measured and compared. We found that dapagliflozin could reduce the serum Hcy level of patients with hypertension and IR to a certain extent. Dapagliflozin could be a viable option for hypertension complicated with IR and hyperhomocysteinemia. However, these findings need to be further confirmed in future randomized clinical trials with a large number of samples.
Socially optimal dosing for scarce vaccines: Ethical analysis through the principlism framework
Authors: Armitage Richard C.
Published: May 2023

Rationale, Aims, and Objectives

Under conditions of vaccine scarcity, the socially optimal dosing (SOD) strategy administers a lower dose of vaccine to a larger number of people than the individually optimal dosing (IOD) strategy, which administers a higher dose of vaccine to a smaller number of people. In the context of vaccines that generate diminishing returns of effectiveness with each additional dose beyond the first, SOD therefore generates a greater total amount of vaccine‐induced protection than IOD and, as such, constitutes the socially optimal strategy. While the clinical and public health arguments in favour of SOD have previously been outlined, this article conducts an ethical analysis of SOD for scarce vaccines through the ethical framework of principlism.

Methods

SOD is examined with regard to each principle within the principlism framework—nonmaleficence, beneficence, autonomy, and justice.

Results

SOD is found to satisfy each of the ethical requirements under examination. Regarding nonmaleficence, SOD induces less iatrogenic harm than IOD since the dose of vaccine administered to each individual is lower in the former than the latter. Furthermore, both the good and bad effects of SOD are foreseen while only the good effects are intended, meaning this strategy simultaneously satisfies the doctrine of double effect. Regarding autonomy, SOD makes vaccine‐induced protection available to a greater number of individuals who wish to receive it, thereby respecting their capacity for self‐determination and to make independent decisions. Regarding beneficence, SOD renders the good—namely the protection of health—more widely available to the individuals that constitute the population in question. Finally, SOD promotes theories of justice that treat individuals equally and is unlikely to reduce the effectiveness of other distribution policies that allocate scarce vaccines in a just manner.

Conclusion

In conditions of vaccine scarcity, SOD favourably satisfies the ethical framework of principlism.
Dermatoses in overweight and obese children and their relationship with insulin and skin color
Authors: Kus Mine Mujde , Mulayim Mehmet Kamil , Kus Celal , Doganer Adem , Ozturk Perihan , Temiz Fatih , Nazik Hulya
Published: May 2023

Background/Aim

The aim of the present study was to investigate the prevalence of obesity‐related dermatoses in obese children, and the association between these dermatoses and insulin resistance as well as skin color.

Methods

Obese, overweight, and normal weight children according to body mass index who were followed up and treated in the outpatient clinics were included in the study. Dermatological examinations of the participants were performed, and fasting insulin and glucose levels were checked.

Results

The obese and overweight children were evaluated as the patient group (70 girls, 41 boys, mean age: 12.37 ± 3.14 years). One hundred one healthy children with normal weight were determined as the control group (59 girls, 42 boys, mean age: 12.15 ± 2.43). The first five common dermatoses in the patient group when compared with the control group were keratosis pilaris (KP), striae distensae, hyperhidrosis, acanthosis nigricans (AN), and plantar hyperkeratosis. The first five dermatoses which were positively correlated with formation and insulin resistance were KP, striae distensae, AN, hyperhidrosis, and plantar hyperkeratosis. According to the Fitzpatrick skin scale, we found that the darker the skin color, the higher the probability of AN and KP (OR, 0.298; 95% CI, 0.106–0.834, p = 0.021; OR, 0.306; 95% CI, 0.117–0.796, p = 0.015, respectively).

Conclusion

Some dermatoses associated with obesity and insulin resistance were not found in obese children, or there was no significant association. These results indicate that many skin morbidities may be prevented by preventing and treating obesity and insulin resistance in the early period.
Long‐Term RCT outcomes for adolescent alcohol and cannabis use within a predominantly Hispanic sample
Authors: Dash Genevieve F. , Bryan Angela D. , Montanaro Erika , Feldstein Ewing Sarah W.
Published: May 2023

Because adolescents are unlikely to seek, receive, or complete treatment for alcohol and/or cannabis misuse, it is important to enhance the lasting impact of clinical contacts when they do occur. Adolescents (N = 506; 72.5% Hispanic) were randomized to motivational interviewing (MI) versus alcohol and cannabis education (ACE). Latent growth models estimated change over time. Significant reductions in alcohol use were observed, with slightly greater reductions by 12‐month follow‐up for MI. Both interventions significantly reduced cannabis use, with no treatment group differences. When outcomes were examined comparing Hispanic to non‐Hispanic participants, there were no significant differences in intervention efficacy by group. MI's inherently client‐centered and culturally adaptive approach may contribute to its equitable degree of behavior change for youth across race/ethnic backgrounds.