bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene co-expression network reveals highly conserved, well-regulated anti-ageing mechanisms in old ant queens
Authors: Harrison Mark C. , Niño Luisa M. Jaimes , Rodrigues Marisa Almeida , Ryll Judith , Flatt Thomas , Oettler Jan , Bornberg-Bauer Erich
Published: February 2021

Evolutionary theories of ageing predict a reduction in selection efficiency with age, a so-called ‘selection shadow’, due to extrinsic mortality decreasing effective population size with age. Classic symptoms of ageing include a deterioration in transcriptional regulation and protein homeostasis. Understanding how ant queens defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory of ageing. It has often been discussed that the low extrinsic mortality of ant queens, that are generally well protected within the nest by workers and soldiers, should reduce the selection shadow acting on old queens. We tested this by comparing strength of selection acting on genes upregulated in young and old queens of the ant,Cardiocondyla obscurior. In support of a reduced selection shadow, we find old-biased genes to be under strong purifying selection. We also analysed a gene co-expression network (GCN) with the aim to detect signs of ageing in the form of deteriorating regulation and proteostasis. We find no evidence for ageing. In fact, we detect higher connectivity in old queens indicating increased transcriptional regulation with age. Within the GCN, we discover five highly correlated modules that are upregulated with age. These old-biased modules regulate several anti-ageing mechanisms such as maintenance of proteostasis, transcriptional regulation and stress response. We observe stronger purifying selection on central hub genes of these old-biased modules compared to young-biased modules. These results indicate a lack of transcriptional ageing in oldC. obscuriorqueens possibly facilitated by strong selection at old age and well-regulated anti-ageing mechanisms.

Significance Statement

Understanding the exceptional longevity of ant queens and how they defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory and molecular biology of ageing. In this study we offer several clues as to how this occurs on a molecular level inC. obscuriorqueens. Specifically, we believe a reduction in the selection shadow due to low extrinsic mortality, has allowed the evolution of well-regulated anti-ageing mechanisms. Consequently, we suggest several promising starting points for future research into the poorly understood phenomenon of extreme longevity in ant queens. Making progress in this field will not only allow us to better understand longevity and fertility in social insects but may also offer interesting research strategies for human ageing.
Multispecies site occupancy modeling and study design for spatially replicated environmental DNA metabarcoding
Authors: Fukaya Keiichi , Kondo Natsuko Ito , Matsuzaki Shin-Ichiro S. , Kadoya Taku
Published: February 2021

Environmental DNA (eDNA) metabarcoding has become widely applied to gauge biodiversity in a noninvasive and cost-efficient manner. The detection of species using eDNA metabarcoding is, however, imperfect owing to various factors that can cause false negatives in the inherent multi-stage workflow.

Imperfect detection in the multi-stage workflow of eDNA metabarcoding also raises an issue of study design: namely, how available resources should be allocated among the different stages to optimize survey efficiency.

Here, we propose a variant of the multispecies site occupancy model for eDNA metabar-coding studies where samples are collected at multiple sites within a region of interest. This model describes the variation in sequence reads, the unique output of the high-throughput sequencers, in terms of the hierarchical workflow of eDNA metabarcoding and interspecific heterogeneity, allowing the decomposition of the sources of variation in the detectability of species throughout the different stages of the workflow. We also introduced a Bayesian decision analysis framework to identify the study design that optimizes the efficiency of species detection with a limited budget.

An application of the model to freshwater fish communities in the Lake Kasumigaura watershed, in Japan, highlighted a remarkable inhomogeneity in the detectability of species, indicating a potential risk of the biased detection of specific species. Species with lower site occupancy probabilities tended to be difficult to detect as they had lower capture probabilities and lower dominance of the sequences. The expected abundance of sequence reads was predicted to vary by up to 23.5 times between species.

An analysis of the study design suggested that ensuring multiple within-site replications of the environmental samples is preferred in order to achieve better species detection efficiency, provided that a throughput of tens of thousands of sequence reads was secured.

The proposed framework makes the application of eDNA metabarcoding more error-tolerant, allowing ecologists to monitor ecological communities more efficiently.
Changes in health behaviors, mental and physical health among older adults under severe lockdown restrictions during the COVID-19 pandemic in Spain
Authors: García-Esquinas Esther , Ortolá Rosario , Gine-Vázquez Iago , Carnicero José A , Mañas Asier , Lara Elvira , Alvarez-Bustos Alejandro , Vicente-Rodriguez German , Sotos-Prieto Mercedes , Olaya Beatriz , José Garcia-Garcia Francisco , Gusi Narcis , Banegas Jose R. , Rodríguez-Gómez Irene , Struijk Ellen A. , Martínez-Gómez David , Lana Alberto , María Haro Josep , Ayuso-Mateos José L. , Rodríguez-Mañas Leocadio , Ara Ignacio , Miret Marta , Rodríguez-Artalejo F
Published: February 2021

Background

We aimed to examine main changes in health behaviors, mental and physical health among older adults under severe lockdown restrictions during the COVID-19.

Methods

We used prospective data from 3041 participants in four cohorts of community-dwelling individuals aged ≥65 years in Spain. Data were obtained using validated questionnaires through a pre-pandemic face-to-face interview and a telephone interview conducted between weeks 7 to 15 after the beginning the COVID-19 lockdown. Lineal or multinomial, as appropriate, regression models with adjustment for the main confounders were used to assess changes in the outcome variables from the pre-pandemic to the confinement period, and to identify their associated factors.

Results

On average, the confinement was not associated with a deterioration in lifestyle risk factors (smoking, alcohol intake, diet or weight), except for a decreased physical activity and increased sedentary time, which reversed with the end of confinement. However, chronic pain worsened, and moderate declines in mental health, that did not seem to reverse after restrictions were lifted, were observed. Several subgroups of individuals were at increased risk of developing unhealthier lifestyles or mental health decline with confinement: (i)-males (for physical activity and sedentariness), (ii)-those with greater social isolation (for diet, physical activity, mental health), (iii)-feelings of loneliness (for diet, sleep quality, mental health), (iv)-poor housing conditions (for diet, physical activity, TV viewing time), (v)-unhealthy sleep duration (for physical activity and sedentariness), and (vi-worse overall health or chronic morbidities (for physical activity, screen time, mental health). On the other hand, previously having a greater adherence to the Mediterranean diet and doing more physical activity protected older adults from developing unhealthier lifestyles with confinement.

Conclusions

The lockdown during the first wave of the COVID-19 in Spain, which was one of the most restrictive in Europe, only led to minor average changes in health behaviors among older adults. However, mental health was moderately affected. If another lockdown were imposed on this or future pandemics, public health programs should specially address the needs of older individuals with male sex, greater social isolation, poor housing conditions and chronic morbidities, because of their greater vulnerability to the enacted movement restrictions
Dorsal CA1 Hippocampal Place Cells Form a Multi-Scale Representation of Megaspace
Authors: Harland B.C. , Contreras M. , Souder M. , Fellous J.M.
Published: February 2021

Spatially firing “place cells” within the hippocampal CA1 region form internal maps of the environment necessary for navigation and memory. In rodents, these neurons have been almost exclusively studied in small environments (<4 m2). It remains unclear how place cells encode a very large open 2D environment, which is more analogous to the natural environments experienced by rodents and other mammals. Such an ethologically realistic environment would require a more complex spatial representation, capable of simultaneously representing space at overlapping multiple fine to coarse informational scales. Here we show that in a ‘megaspace’ (18.6 m2), the majority of dorsal CA1 place cells exhibited multiple place subfields of different sizes, akin to those observed along the septo-temporal axis. Furthermore, the total area covered by the subfields of each cell was not correlated with the number of subfields, and this total area increased with the scale of the environment. The multiple different-sized subfields exhibited by place cells in the megaspace suggest that the ensemble population of subfields form a multi-scale representation of space within the dorsal hippocampus. Our findings point to a new dorsal hippocampus ensemble coding scheme that simultaneously supports navigational processes at both fine- and coarse-grained resolutions.
Assessment of the suitability of marker fragments DNA sequences of the internal transcribed spacer region (ITS), beta-tubulin gene (TUB) and elongation factor (EF1) genes for diagnostics ofFusarium tricinctumspecies complex in Russian in grain products
Authors: Shchukovskaya A.
Published: February 2021

By results of laboratory researches from plant samples of grain crops speciesFusarium avenaceum, Fusarium tricinctumandFusarium acuminatumrelated toFusarium tricinctumspecies complex were isolated and identified, based on cultural and morphological characteristics, molecular-genetic analysis of 3 DNA fragments was performed: internal transcribed spacer (ITS) site, beta-tubulin gene site (TUB), elongation factor gene site (EF1) showed insignificant intraspecific and interspecific variability at ITS and EF1 sites, which may negatively affect the reliability of target species identification, TUB site was more effective for distinguishing and identifying the studied species, due to significant intraspecific and interspecific variability
Microbial tryptophan catabolism affects the vector competence ofAnopheles
Authors: Feng Yuebiao , Peng Yeqing , Wen Han , Song Xiumei , An Yanpeng , Tang Huiru , Wang Jingwen
Published: February 2021

The influence of microbiota on mosquito physiology and vector competence is becoming increasingly clear but our understanding of interactions between microbiota and mosquitoes still remains incomplete. Here we show that gut microbiota ofAnopheles stephensi, a competent malaria vector, participates mosquito tryptophan metabolism. Elimination of microbiota by antibiotics treatment leads to the accumulation of tryptophan (Trp) and its metabolites, kynurenine (Kyn), 3‐hydroxykynurenine (3‐HK) and xanthurenic acid (XA). Of these, 3‐HK impairs the structure of peritrophic matrix (PM), thereby promotingPlasmodium bergheiinfection. Among the major gut microbiota inAn. stephensi, Pseudomonas alcaligenesplays a role in catabolizing 3‐HK as revealed by whole genome sequencing and LC‐MS metabolic analysis. The genome ofP. alcaligenesencodes kynureninase (KynU) that is responsible for the conversion of 3‐HK to 3‐Hydroxyanthranilic acid (3‐HAA). Mutation of this gene abrogates the ability ofP. alcaligenesto metabolize 3‐HK, which in turn abolishes its role on PM protection. Colonization ofAn. stephensiwith KynU mutatedP. alcaligenesfails to protect mosquitoes against parasite infection as effectively as those with wild type bacterium. In summary, we identify an unexpected function of gut microbiota in controlling mosquito tryptophan metabolism with the major consequences on vector competence.
Cerebral cortical communication overshadows computational energy-use, but these combine to predict synapse number
Authors: Levy William B , Calvert Victoria G.
Published: February 2021

Darwinian evolution tends to produce energy-efficient outcomes. On the other hand, energy limits computation, be it neural and probabilistic or digital and logical. Taking a particular energy-efficient viewpoint, we define neural computation and make use of an energy-constrained, computational function. This function can be optimized over a variable that is proportional to the number of synapses per neuron. This function also implies a specific distinction between ATP-consuming processes, especially computationper sevs the communication processes including action potentials and transmitter release. Thus to apply this mathematical function requires an energy audit with a partitioning of energy consumption that differs from earlier work. The audit points out that, rather than the oft-quoted 20 watts of glucose available to the brain (1, 2), the fraction partitioned to cortical computation is only 0.1 watts of ATP. On the other hand at 3.5 watts, long-distance communication costs are 35-fold greater. Other novel quantifications include (i) a finding that the biological vs ideal values of neural computational efficiency differ by a factor of 108and (ii) two predictions ofN, the number of synaptic transmissions needed to fire a neuron (2500 vs 2000).

Significance Statement

Engineers hold up the human brain as a low energy form of computation. However from the simplest physical viewpoint, a neuron’s computation cost is remarkably larger than the best possible bits/J – off by a factor of 108. Here we explicate, in the context of energy consumption, a definition of neural computation that is optimal given explicit constraints. The plausibility of this definition as Nature’s perspective is supported by an energy-audit of the human brain. The audit itself requires certain novel perspectives and calculations revealing that communication costs are 35-fold computational costs.
Deletion of Small Ubiquitin-like Modifier-1 Attenuates Behavioral and Anatomical Deficits by Enhancing Functional Autophagic Activities in Huntington Disease
Authors: Ramírez-Jarquín Uri Nimrod , Sharma Manish , Shahani Neelam , Subramaniam Srinivasa
Published: February 2021

Mutant HTT (mHTT) associated with Huntington disease (HD) affects the central nervous system by prominent atrophy in the striatum and promotes psychiatric, cognitive, and choreiform movements, although the exact mechanism remains obscure. Previous studies have shown that SUMO1 (Small Ubiquitin-like Modifier-1) modification of mHTT promotes cellular toxicity, but the in vivo role and functions of SUMO1 in HD pathogenesis are unclear. Here, we report that SUMO1 deletion in Q175DN HD-het knock-in mice (HD mice) prevented age-dependent HD-like motor and neurological impairments and suppressed the striatal atrophy and inflammatory response. SUMO1 deletion caused a drastic reduction in soluble mHtt levels and nuclear and extracellular mHtt inclusions, while increasing cytoplasmic inclusions in the striatum of HD mice. SUMO1 deletion also enhanced autophagic activity, characterized by augmented interactions between mHTT inclusions and a lysosomal marker (LAMP1), increased LC3B/LAMP1 interaction, and decreased sequestosome-1 (p62) and mHTT and diminished p62/LAMP1 interactions in DARPP-32–positive medium spiny neurons (MSNs) in HD mice. Depletion of SUMO1 in an HD cell model also diminished the mHtt levels and enhanced autophagy flux. In addition, the SUMOylation inhibitor ginkgolic acid strongly enhanced autophagy and diminished mHTT levels in human HD fibroblasts. These results indicate that SUMO is a critical therapeutic target in HD and that blocking SUMO may ameliorate HD pathogenesis by improving autophagy activities.
Di-μ-chlorido-bis(chlorido{8-[2-(dimethylamino)ethylamino]quinoline}cadmium) ethanol monosolvate
Authors: Al-Sudani Abdul-Razak H. , Abdulridha Myasim Qasim , Kariuki Benson M.
Published: February 2021

The title solvated bimetallic complex, [Cd2Cl4(C13H17N3)2]·C2H5OH, comprises two Cd2+ metal ions linked by a pair of μ2 Cl− ions. The coordination sphere around each Cd2+ ion is completed by three N atoms of a tridentate 8-[2-(dimethylamino)ethylamino]quinoline ligand and another chloride ion to form a distorted fac-CdN3Cl3 octahedron. The ethanol molecule is both an acceptor of an N—H...O and a donor of an O—H...Cl hydrogen bonds to its adjacent complex unit. In the crystal, weak aromatic π–π stacking is observed.
How companies can learn to operate as co-creational, adaptive, “living” enterprises
Authors: Ramaswamy Venkat , Pieters Maarten K.
Published: February 2021

Purpose

The authors anticipate that in a post-COVID, hyper-connected and interdependent world, all businesses will inevitably have to become co-creational “living” enterprises -- organizations that purposefully learn and adapt through experiential interactions with all stakeholders.

Design/methodology/approach

Maps out how enterprises will need to develop “Platformized Impact Ecosystems of Engagements of Experiences” (PIEEE). These are digital platforms that bring together five key facets of the current fourth industrial revolution -- digital technology platforms, impacts of activities, experience personalization, service ecosystems and flows of engagements

Findings

Industry 4.0 enterprises now manage a software-based value chain that must constantly learn and adapt its offerings to meet the rising expectations of individuals as they navigate through a multitude of interactive experiences.

Practical implications

Microsoft's Health Care in the Cloud and Signify's platforms transform value for stakeholding individuals’ experiences in ways that were never possible before.

Originality/value

This article imagines a not-too-distant future in which the most successful companies conduct business with customers, partners and a variety of stakeholders on digital platforms that are so interactive, adaptive and responsive that it’s not hyperbole to describe them as co-creative “living” systems.
Matching customers’ preferences for tariff reform with managers’ appetite for change: The case of volumetric‐only tariffs in Australia
Authors: Khosroshahi Saeideh , Crase Lin , Cooper Bethany , Burton Michael
Published: February 2021

At the height of the Millennium Drought in Australia, there was unprecedented interest in the role of demand‐side management in the urban water sector. Conservation tariffs, where water users pay significantly less by reducing consumption, were mooted in some policy circles, although they were never seriously trialled. The easing of the drought was also accompanied by a new era of economic regulation, where monopoly water suppliers are increasingly encouraged to deliver services valued by customers. This trend has been embraced in Victoria, where the Essential Services Commission effectively rewards water businesses that match their services against customer expectations. This article explores whether customers and business managers hold similar priorities for water services by using a Best‐Worst Scaling experiment. The experiment includes a conservation tariff, and findings suggest that customers enjoy relatively higher utility from these tariffs, sustainability, water restrictions and small‐scale projects compared to the services emphasised by managers. The study exposes the general difficulty of water businesses matching their customers’ preferences, especially if there is heterogeneity in preferences and given businesses must simultaneously deliver on many other fronts.
Early exposure of pregnant women to non‐steroidal anti‐inflammatory drugs delivered outside hospitals and preterm birth risk: nationwide cohort study
Authors: Quantin C , Yamdjieu Ngadeu C , Cottenet J , Escolano S , Bechraoui‐Quantin S , Rozenberg P , Tubert‐Bitter P , Gouyon J‐B
Published: February 2021

Objective

To assess the risk of preterm birth associated with nonsteroidal anti‐inflammatory drugs (NSAIDs), focusing on early exposure in the period from conception to 22 weeks of gestation (WG).

Design

National population‐based retrospective cohort study.

Setting

The French National Health Insurance Database that includes hospital discharge data and health claims data.

Population

Singleton pregnancies (2012–2014) with a live birth occurring after 22WG from women between 15 and 45 years old and insured the year before the first day of gestation and during pregnancy were included. We excluded pregnancies for which anti‐inflammatory medications were dispensed after 22WG.

Methods

The association between exposure and risk of preterm birth was evaluated with GEE models, adjusting on a large number of covariables, socio‐demographic variables, maternal comorbidities, prescription drugs and pregnancy complications.

Main outcome measures

Prematurity, defined as a birth that occurred before 37WG.

Results

Among our 1 598 330 singleton pregnancies, early exposure to non‐selective NSAIDs was associated with a significantly increased risk of preterm birth, regardless of the severity of prematurity: adjusted odds ratio (aOR) = 1.76 (95% CI 1.54–2.00) for extreme prematurity (95% CI 22–27WG), 1.28 (95% CI 1.17–1.40) for moderate prematurity (28–31WG) and 1.08 (95% CI 1.05–1.11) for late prematurity (32–36WG), with non‐overlapping confidence intervals. We identified five NSAIDs for which the risk of premature birth was significantly increased: ketoprofen, flurbiprofen, nabumetone, etodolac and indomethacin: for the latter, aOR = 1.92 (95% CI 1.37–2.70) with aOR = 9.33 (95% CI 3.75–23.22) for extreme prematurity.

Conclusion

Overall, non‐selective NSAID use (delivered outside hospitals) during the first 22WG was found to be associated with an increased risk of prematurity. However, the association differs among NSAIDs.

Tweetable abstract

French study for which early exposure to non‐selective NSAIDs was associated with increased risk of prematurity.
TaxonTableTools: A comprehensive, platform‐independent graphical user interface software to explore and visualise DNA metabarcoding data
Authors: Macher Till‐Hendrik , Beermann Arne J. , Leese Florian
Published: February 2021

DNA metabarcoding is increasingly used as a tool to assess biodiversity in research and environmental management. Powerful analysis software exists to process raw data. However, the translation of sequence read data into biological information and downstream analyses may be difficult for end users with limited expertise in bioinformatics. Thus, there is a growing need for easy‐to‐use, graphical user interface (GUI) software to analyse and visualise DNA metabarcoding data. Here, we present TaxonTableTools (TTT), a new platform‐independent GUI that aims to fill this gap by providing simple, reproducible analysis and visualisation workflows. At its base, TTT uses a "TaXon table", which is a data format that can be generated easily within TTT from two input files: a read table and a taxonomy table obtained using various published metabarcoding pipelines. TTT analysis and visualisation modules include Venn diagrams to compare taxon overlap among replicates, samples, or analysis methods. TTT analyses and visualises basic statistics, such as read proportion per taxon, as well as more sophisticated visualisations, such as interactive Krona charts for taxonomic data exploration. Various ecological analyses can be produced directly, including alpha or beta diversity estimates, and rarefaction analysis ordination plots. Metabarcoding data can be converted into formats required for traditional, taxonomy‐based analyses performed by regulatory bioassessment programs. In addition, TTT is able to produce html‐based interactive graphics that can be analysed in any web browser. The software comes with a manual and tutorial, is free and publicly available through GitHub (https://github.com/TillMacher/TaxonTableTools) or the Python package index (https://pypi.org/project/taxontabletools/).
Sleep‐wake rhythms determined by actigraphy during in‐hospital stay following discharge from an intensive care unit
Authors: Okutan Betül , Kjer Cilia Klara W. , Poulsen Lone M. , Gögenur Ismail , Mathiesen Ole , Estrup Stine , Madsen Michael Tvilling
Published: February 2021

Background

Sleep and circadian disturbances play a major role in recovery after critical illness. Ample research has shown sleep to be disturbed during the stay at the intensive care unit (ICU); however, the trajectory of sleep after ICU discharge is sparsely described.

The current study aimed to describe the development of the sleep‐wake rhythm in subjects discharged from ICU to a hospital ward.

Methods

Following discharge from the ICU to a general hospital ward, the participants were monitored with an ActiGraph for sleep assessment for 7 days or until hospital discharge or death. Data were analysed for day‐to‐day change with t‐tests and for the whole period with repeated measures analysis.

Results

For the 38 included patients, repeated measures analysis showed no significant improvement in total sleep time and wake time. However, for secondary outcomes, improvements for wake after sleep onset (P = .02) and reduction in the number of naps (P = .03) both in the day‐to‐day and overall trend analysis were observed.

Conclusion

The duration of sleep and wake time did not improve during ward stay. However, sleep became less fragmented and naps during the day declined. Due to the small sample size further, larger trials are needed.
Western Australian Peritonectomy Service: a review of the first 6 years of operation of a low‐volume peritonectomy centre
Authors: McEntee Phillip , Keelan Simon , Salama Paul , Moroz Paul
Published: February 2021

Background

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal early chemotherapy has gained acceptance as the standard of care for peritoneal surface malignancy over the past decade. This study reports the results of the first 6 years of activity of the Western Australian Peritonectomy Service to compare outcomes of a low‐volume centre with world standards.

Methods

An audit of all patients who received CRS ± hyperthermic intraperitoneal early chemotherapy treatment at the Western Australian Peritonectomy Service in its first 6 years of operation was performed and results were compared to the recent world literature.

Results

A total of 130 patients were treated with 150 CRS procedures, including 50 pseudomyxoma peritonei (PMP), 53 colorectal cancers (CRCs), 27 appendix adenocarcinomas (AAs) and 20 other cancers. The median operating time was 12 h with median length of hospital stay of 15 days. Perioperative mortality was 0.67% and Clavien‐Dindo III/IV morbidity was 20%. The mean packed red cell transfusion requirement was 0.34 units/case. Post‐discharge readmission rate was 25% and the return to theatre rate was 13%. The 4‐year overall survival rates for PMP, CRC and AA were 97%, 49% and 81%, respectively. The 3‐year disease‐free survival rates for PMP, CRC and AA were 74%, 26% and 36%, respectively.

Conclusion

A CRS centre averaging 25 cases per year can achieve strong outcomes in line with high‐volume world centres.
Investigation of red blood cell partitioning in an in vitro microvascular bifurcation
Authors: Pskowski Andrew , Bagchi Prosenjit , Zahn Jeffrey D.
Published: February 2021

There is a long history of research examining red blood cell (RBC) partitioning in microvasculature bifurcations. These studies commonly report results describing partitioning that exists as either regular partitioning, which occurs when the RBC flux ratio is greater than the bulk fluid flowrate ratio, or reverse partitioning when the RBC flux ratio is less than or equal to that of the bulk fluid flowrate. This paper presents a study of RBC partitioning in a single bifurcating microchannel with dimensions of 6 to 16 μm, investigating the effects of hematocrit, channel width, daughter channel flowrate ratio, and bifurcation angle. The erythrocyte flux ratio, N*, manifests itself as either regular or reverse partitioning, and time‐dependent partitioning is much more dynamic, occurring as both regular and reverse partitioning. We report a significant reduction in the well‐known sigmoidal variation of the erythrocyte flux ratio (N*) versus the volumetric flowrate ratio (Q*), partitioning behavior with increasing hematocrit in microchannels when the channel dimensions are comparable with cell size. RBCs “lingering” or jamming at the bifurcation were also observed and quantified in vitro. Results from trajectory analyses suggest that the RBC position in the feeder channel strongly affects both partitioning and lingering frequency of RBCs, with both being significantly reduced when RBCs flow on streamlines near the edge of the channel as opposed to the center of the channel. Furthermore, our experiments suggest that even at low Reynolds number, partitioning is affected by the bifurcation angle by increasing cell–cell interactions. The presented results provide further insight into RBC partitioning as well as perfusion throughout the microvasculature.
Scythian Culture burial complexes of the Dnipro Left‐bank forest steppe: A multivariate analysis
Authors: Korokhina A. V. , Grechko D. S.
Published: February 2021

This paper deals with the application of multivariate analysis to the classification of Scythian Culture burials of the Dnipro Left‐bank forest‐steppe region. Six types of burial complexes have been distinguished based on the analysis of a burial chamber, its orientation and grave goods set composition. In order to reveal probable trends, the impact of spatial, chronological and ethnic–social factors on the distribution of the analysed parameters was investigated.
Comparison of the injection‐site experience of the starting doses with semaglutide and dulaglutide: A randomized, double‐blind trial in healthy subjects
Authors: Snitker Søren , Andersen Andreas , Berg Birgitte , van Marle Sjoerd , Sparre Thomas
Published: February 2021

This double‐blind, randomized, single‐site, crossover trial compared the injection‐site experience with the starting doses of semaglutide and dulaglutide. Healthy subjects (aged 18–75 years; body mass index ≥ 25 kg/m2; n = 104) were randomized 1:1, using a pregenerated list, to semaglutide 0.25 mg as the first injection and dulaglutide 0.75 mg as the second injection or vice versa; each was administered using their proprietary pen‐injectors, according to instructions for use. The primary endpoint was intensity of injection‐site pain, measured using a visual analogue scale (VAS; 0 mm = no pain, 100 mm = unbearable pain). Exploratory endpoints included intensity category, duration and quality of injection‐site pain, and comparative assessment of injection‐site pain with the two injections. The point estimate of the VAS score for injection‐site pain intensity was 11.5 mm with dulaglutide versus 5.6 mm with semaglutide; mean (95% confidence interval) estimated treatment difference 5.9 (3.6; 8.2) mm; p < .0001. Other endpoints corroborated a less painful injection experience with semaglutide versus dulaglutide. Safety was consistent with reported data for the drugs. In conclusion, the injection‐site experience with semaglutide was rated as less painful than that with dulaglutide.
Pathogenic characteristics and infection‐related genes of Metarhizium anisopliae FM‐03 infecting Planococcus lilacinus
Authors: Huang Peng , Yao Jinai , Lin Yongwen , Yu Deyi
Published: February 2021

Planococcus lilacinus (Cockerell) (Hemiptera: Pseudococcidae) is a global flower and fruit pest, and a severe infestation is currently seen in the sugar apple (Annona squamosa L., Annonaceae) orchards of Zhangzhou, Fujian Province, China. Biological control with entomopathogenic fungi is safe, effective, and long‐lasting, and has potential for the control of mealybugs. In this study, we analyzed the pathogenic characteristics and infection‐related genes of Metarhizium anisopliae (Metschn.) Sorokīn FM‐03, a strain discovered in the sugar apple orchards, against P. lilacinus, to evaluate its biocontrol potential and application prospects against mealybugs. The results showed that M. anisopliae FM‐03 was highly pathogenic against P. lilacinus. At 10 days after infection, the median lethal concentration (LC50) of strain FM‐03 was 1.45 × 105 spores ml−1 and the cumulative corrected mortality was 93%, whereas the median lethal time (LT50) was 5.27 days for treatment with the highest spore concentration (108 spores ml−1). Planococcus lilacinus was primarily infected from the legs, abdominal segments, and body edges, which are sites with less wax. Infection became clearly visible 72 h post inoculation. Substantial changes occurred in activity of fungal enzymes, with peak values of 26 U ml−1 for proteases and 17 U ml−1 for lipases on day 5 post inoculation to enzyme inducing culture media. The activity of chitinases was relatively stable, with a peak value of 8 U ml−1 on day 6 post inoculation. At 3 days post P. lilacinus infection, a total of 1 069 genes were differentially expressed, of which 137 were annotated as infection‐related. Among the 136 upregulated genes, 10 were identified as potentially crucial for infection regulation. These 10 genes could be targeted for subsequent construction of genetically engineered FM‐03 strains, driving the research and development of effective biocontrol agents for P. lilacinus.
Cardiovascular health and chronic axonal polyneuropathy: A population‐based study
Authors: Taams Noor E. , Ahmadizar Fariba , Hanewinckel Rens , Drenthen Judith , Voortman Trudy , Ikram M. Arfan , Kavousi Maryam , van Doorn Pieter A.
Published: February 2021

Background and purpose

Chronic axonal polyneuropathy is a common, usually multifactorial, disease for which there is no treatment yet available. We investigated the association between cardiovascular health, defined by the health score of the American Heart Association, and chronic axonal polyneuropathy.

Methods

Between June 2013 and January 2017, we investigated participants of the Rotterdam Study, a population‐based cohort study. Participants were screened for polyneuropathy and categorized as having no, possible, probable or definite polyneuropathy. The cardiovascular health score (range 0–14; higher score reflecting better health) consisted of four health behaviours (diet, physical activity, smoking and body mass index) and three health factors (blood pressure, serum cholesterol and fasting glucose level).

Results

We included 1919 participants, of whom 120 (6.3%) had definite polyneuropathy. The median (interquartile range [IQR]) age was 69.0 (58.6–73.7) years and 53.4% were women. A higher cardiovascular health score was associated with a lower prevalence of definite polyneuropathy (per point increase: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.84–0.96). Optimal cardiovascular health (score≥10) was strongly associated with a lower prevalence of definite polyneuropathy (OR 0.55, 95% CI 0.32–0.90). An increase in health factors and health behaviour scores separately was associated with a lower prevalence of polyneuropathy (per point increase: OR 0.82, 95% CI 0.71–0.95 and OR 0.86, 95% CI 0.78–0.96, respectively). The association between a lower cardiovascular health score and lower sural nerve amplitude was not significant after correction for covariates (difference 0.07µV, 95% CI −0.02–0.17).

Conclusions

Better cardiovascular health, consisting of both modifiable health behaviours and health factors, is associated with a lower prevalence of chronic axonal polyneuropathy.
An integrative approach uncovers transcriptome‐wide determinants of mRNA stability regulation in Saccharomyces cerevisiae
Authors: Tomecki Rafal , Drazkowska Karolina
Published: February 2021

mRNA degradation rate is one of the key stages of gene expression regulation in eukaryotic cells. To date, intertwined processes of post‐transcriptional control have been widely investigated, but focused rather on the examination of mechanisms controlling stability of particular protein‐coding transcripts. Currently, a wealth of information from structural, biochemical, and high‐throughput studies makes it tempting to define general rules governing mRNA stability that could be considered as versatile and valid on a genome‐wide scale. Basu et al. analyzed multiple experimental and computational data on Saccharomyces cerevisiae mRNA half‐lives as well as on secondary structures and protein‐binding sites within transcripts, and collated it with available structures of ribonucleases, that is, enzymes responsible for mRNA degradation. This approach allowed to conclude how particular mRNA features such as lengths of unstructured terminal or internal regions or sequestration into ribonucleoprotein complexes impact half‐lives of protein‐coding transcripts and to define genome‐scale principles of mRNA stability control in yeast.
Hallmarks of the aging T‐cell system
Authors: Zhang Huimin , Weyand Cornelia M. , Goronzy Jörg J.
Published: February 2021

The adaptive immune system has the enormous challenge to protect the host through the generation and differentiation of pathogen‐specific short‐lived effector T cells while in parallel developing long‐lived memory cells to control future encounters with the same pathogen. A complex regulatory network is needed to preserve a population of naïve cells over lifetime that exhibit sufficient diversity of antigen receptors to respond to new antigens, while also sustaining immune memory. In parallel, cells need to maintain their proliferative potential and the plasticity to differentiate into different functional lineages. Initial signs of waning immune competence emerge after 50 years of age, with increasing clinical relevance in the 7th–10th decade of life. Morbidity and mortality from infections increase, as drastically exemplified by the current COVID‐19 pandemic. Many vaccines, such as for the influenza virus, are poorly effective to generate protective immunity in older individuals. Age‐associated changes occur at the level of the T‐cell population as well as the functionality of its cellular constituents. The system highly relies on the self‐renewal of naïve and memory T cells, which is robust but eventually fails. Genetic and epigenetic modifications contribute to functional differences in responsiveness and differentiation potential. To some extent, these changes arise from defective maintenance; to some, they represent successful, but not universally beneficial adaptations to the aging host. Interventions that can compensate for the age‐related defects and improve immune responses in older adults are increasingly within reach.
Development and initial validation of a deep learning algorithm to quantify histological features in colorectal carcinoma including tumour budding/poorly differentiated clusters
Authors: Pai Reetesh K , Hartman Douglas , Schaeffer David F , Rosty Christophe , Shivji Sameer , Kirsch Richard , Pai Rish K
Published: February 2021

Aims

To develop and validate a deep learning algorithm to quantify a broad spectrum of histological features in colorectal carcinoma.

Methods and results

A deep learning algorithm was trained on haematoxylin and eosin‐stained slides from tissue microarrays of colorectal carcinomas (N = 230) to segment colorectal carcinoma digitised images into 13 regions and one object. The segmentation algorithm demonstrated moderate to almost perfect agreement with interpretations by gastrointestinal pathologists, and was applied to an independent test cohort of digitised whole slides of colorectal carcinoma (N = 136). The algorithm correctly classified mucinous and high‐grade tumours, and identified significant differences between mismatch repair‐proficient and mismatch repair‐deficient (MMRD) tumours with regard to mucin, inflammatory stroma, and tumour‐infiltrating lymphocytes (TILs). A cutoff of >44.4 TILs per mm2 carcinoma gave a sensitivity of 88% and a specificity of 73% in classifying MMRD carcinomas. Algorithm measures of tumour budding (TB) and poorly differentiated clusters (PDCs) outperformed TB grade derived from routine sign‐out, and compared favourably with manual counts of TB/PDCs with regard to lymphatic, venous and perineural invasion. Comparable associations were seen between algorithm measures of TB/PDCs and manual counts of TB/PDCs for lymph node metastasis (all P < 0.001); however, stronger correlations were seen between the proportion of positive lymph nodes and algorithm measures of TB/PDCs. Stronger associations were also seen between distant metastasis and algorithm measures of TB/PDCs (P = 0.004) than between distant metastasis and TB (P = 0.04) and TB/PDC counts (P = 0.06).

Conclusions

Our results highlight the potential of deep learning to identify and quantify a broad spectrum of histological features in colorectal carcinoma.
Artificial intelligence grading of breast cancer: a promising method to refine prognostic classification for management precision
Authors: Elsharawy Khloud A , Gerds Thomas A , Rakha Emad A , Dalton Leslie W
Published: February 2021

Aim

Artificial intelligence (AI)‐based breast cancer grading may help to overcome perceived limitations of human assessment. Here, the potential value of AI grade was evaluated at the molecular level and in predicting patient outcome.

Methods and results

A supervised convolutional neural network (CNN) model was trained on images of 612 breast cancers from The Cancer Genome Atlas (TCGA). The test set, obtained from the Cooperative Human Tissue Network (CHTN), comprised 1058 cancers with corresponding survival data. Upon reversal, a CNN was trained from images of 1537 CHTN cancers and tested on 397 TCGA cancers. In TCGA, mRNA models were trained using AI grade and Nottingham grade (NG) as labels. Performance of mRNA models in predicting patient outcome was evaluated using data from 1807 cancers from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. In selecting images for training, nucleolar prominence determined high‐ versus low‐grade cancer cells. In CHTN, NG corresponded to significant survival stratification in stages 1, 2 and 3 cancers, while AI grade showed significance in stages 1 and 2 and borderline in stage 3 tumours. In METABRIC, the mRNA model trained from AI grade was not significantly different to the NG‐based model. The gene which best described AI grade was TRIP13, a gene involved with mitotic spindle assembly.

Conclusion

An AI grade trained from the morphologically distinctive feature of nucleolar prominence could transmit significant patient outcome information across three independent patient cohorts. AI grade shows promise in gene discovery and for second opinions.
A second cryoballoon system—New and improved?
Authors: Su Wilber W.
Published: February 2021

Generations of cryoballoon transformed the atrial fibrillation ablation landscape. New advancements continue to make cryoballoon more successful and safer treatment. A new cryoballoon PolaRx from Boston Scientific has unique features compared to that of the Medtronic Arctic Front Advance system. Comparison of the two available cryoballoons will require ongoing larger trial and clinical experience.
Evaluating a digital life story app in a nursing home context – A qualitative study
Authors: Thoft Diana S. , Møller Anders K. , Møller Ann K. K.
Published: February 2021

Aims and objectives

To evaluate how digital life stories can be used to support person‐centred care focusing on benefits and challenges experienced by the staff and the management team in a nursing home context.

Background

Life story work can be used to support person‐centred care and help people with dementia maintain their identity. The use of digital life stories provides opportunities to easily share the content between staff and relatives and combine different types of multimedia, for example pictures, videos, text and sound.

Design

Six healthcare professionals and two members of the management team at a nursing home were recruited. Participant observations with informal interviews of the formal health career were conducted in two day shifts and two night shifts. Field notes were taken during the observations. Also, individual semi‐structured interviews were held with four of the recruited participants. This article adheres to the Standards for Reporting Qualitative Research (SRQR).

Results

Themes revealed were (1) person‐centred care and life story work as interrelated approaches; (2) Pros and cons related to the My Life Story app; and how (3) Time and information and communication technology (ICT) can restrict life story work.

Conclusion

Digital life stories can be used to support a person‐centred care approach. However, a number of challenges exist related to digital life story work. When using digital life stories, it is important to ensure the staff time and competences needed to work with, for example an app and that visible support and encouragement are provided by the management team.

Relevance to clinical practice

Challenges are revealed when life story work is embedded in the culture and everyday work of a nursing home. It is of great importance to clinical practice to be aware of and address these challenges in order to succeed with digital life story work.
The effect of vibration stimulation on intramuscular injection pain and patient satisfaction: Single–blind, randomised controlled study
Authors: Dincer Berna , Yildirim Dilek
Published: February 2021

Aims and objectives

The aim of this study was to assess the effect of vibration stimulation application in ventrogluteal region on intramuscular injection pain and patient satisfaction.

Background

Intramuscular injection pain caused distress for the patients and affected their compliance with the treatment.

Design

This was a prospective, single‐blind, cross‐over study. The study complied with the guidelines of Consolidated Standards of Reporting Trials (CONSORT).

Methods

Eighty‐four patients who applied to the adult emergency department received an intramuscular injection of amoxicillin\ cefuroxime sodium to the ventrogluteal site with and without vibration in a random order following a standard procedure by the same investigator. Pain and satisfaction were assessed immediately after the injection with Visual Analogue Scale (VAS), by a researcher blinded to the study. The data were evaluated using mean, standard deviation, percentage, Student's t‐test, paired sample t‐test, linear regression analysis and generalised linear mixed model.

Results

A total of 174 injections were analysed. The result of the study revealed that vibration decreased the severity of pain and increased the patient satisfaction.

Conclusions

Vibration is a non‐pharmacologic approach, which can be effective in decreasing the injection pain and increasing patient satisfaction.

Relevance to clinical practice

Intramuscular injection is the most frequently used nursing practice in the clinic. The use of vibration in decreasing pain due to intramuscular applications can help increase the self‐confidence of nurses and the quality of the care they provide.