bluuebunny/crossref_metadata_2025 huggingface dataset:
High-throughput screening of more than 30,000 compounds for anthelmintics against gastrointestinal nematode parasites
Authors: Elfawal Mostafa A. , Goetz Emily , Kim You-Mie , Chen Paulina , Savinov Sergey N. , Barasa Leonard , Thompson Paul R. , Aroian Raffi V.
Published: May 2024

Gastrointestinal nematodes (GINs) are amongst the most common parasites of humans, livestock, and companion animals. GIN parasites infect 1-2 billion people worldwide, significantly impacting hundreds of millions of children, pregnant women, and adult workers, thereby perpetuating poverty. Two benzimidazoles with suboptimal efficacy are currently used to treat GINs in humans as part of mass drug administrations, with many instances of lower-than-expected or poor efficacy and possible resistance. Thus, new anthelmintics are urgently needed. However, screening methods for new anthelmintics using human GINs typically have low throughput. Here, using our novel screening pipeline that starts with human hookworms, we screened 30,238 unique small molecules from a wide range of compound libraries, including ones with generic diversity, repurposed drugs, natural derivatives, known mechanisms of action, as well as multiple target-focused libraries (e.g., targeting kinases, GPCRs, and neuronal proteins). We identified 55 compounds with broad-spectrum activity against adult stages of two evolutionary divergent GINs, hookworms (Ancylostoma ceylanicum) and whipworms (Trichuris muris). Based on known databases, the targets of these 55 compounds were predicted in nematode parasites. One novel scaffold from the diversity set library, F0317-0202, showed good activity (high motility inhibition) against both GINs. To better understand this novel scaffold’s structure-activity relationships (SAR), we screened 28 analogs and created SAR models highlighting chemical and functional groups required for broad-spectrum activity. These studies validate our new and efficient screening pipeline at the level of tens of thousands of compounds and provide an important set of new GIN-active compounds for developing novel and broadly-active anthelmintics.
Homeodomain transcription factors in adipocyte thermogenesis: insights into the species-specific and conserved regulatory elements of human UCP1
Authors: B. Tóth Beáta , Hegedűs Géza , Virág Eszter , Pethő Gergely Tamás , Laczkó Levente , Fésüs László
Published: May 2024

Adipocyte thermogenesis is a promising target for treating metabolic disorders, but its regulatory mechanisms remain unclear. This study investigates transcription factors (TFs) and regulatory elements that may control the humanUCP1gene, which is essential for thermogenesis and the formation of the adipocyte phenotype. Using the Eukaryota Promoter Database, we performed computational analyses of theUCP1, UCP2andUCP3promoter sequences in humans, mice and rats to identify conserved and species-specific elements. We also used transcriptome data from human neck-derived adipocytes and databases (Contra v3, ChiPBase, TFlink, AdipoNet, ISMARA, etc.) to narrow potential regulatory TFs. Our results show that mouse and ratUCP1enhancers lack large segments, primarily due to the insertion of repetitive elements that are already lost in some clades. We identified key TFs such as PPARA, PPARG, THR, RARE, RXR, JUN, TFAP2 and SREBF1 as general regulators ofUCPs.Additionally, human-specificUCP1regulatory hotspots (e.g. 5’-TCTAATTAGA-3’) recognised by homeodomain TFs (e.g. EN1, PAX4, HOXA5 and PRRX2) and NFIL3 were detected. Phylogenetically conserved regulatory elements suggest common TFs in humanUCP1paralogues (MAX, MYCN, MNT, HES1) and cross-species (POU6F1). These results improve our understanding of thermogenic adipocyte development and provide new therapeutic targets for metabolic diseases.

Graphical Abstract
Epac activation reduces trans-endothelial migration of undifferentiated neuroblastoma cells and cellular differentiation with a CDK inhibitor further enhances Epac effect
Authors: Inuwa Rabiu , Moss Diana , Quayle John , Swadi Rasha
Published: May 2024

Abstract

Neuroblastoma (NB) is the most common solid extracranial neoplasm found in children and is derived from primitive sympathoadrenal neural precursor. The disease accounts for 15% of all cancer deaths in children. The mortality rate is high in patients presenting with a metastatic tumour even with extensive treatments. This signifies the need for further research towards the development of new additional therapies that can combat not only tumour growth but metastasis, especially amongst the high-risk groups. During metastasis, primary tumour cells become migratory and travel towards a capillary within the tumour. They then degrade the matrix surrounding the pericytes and endothelial cells traversing the endothelial barrier twice to establish a secondary. This led to the hypothesis that modulation of the endothelial cell junctional stability could have an influence on tumour metastasis. To test this hypothesis, agents that modulate endothelial permeability on NB cell line migration and invasion were assessedin vitroin a tissue culture model. The cAMP agonist and its antagonists were found to have no obvious effect on both SK-N-BE2C and SK-N-AS migration, invasion and proliferation. Next, NB cells were cocultured with HDMEC cells and live cell imaging was used to assess the effect of an Epac agonist on trans-endothelial cell migration of NB cells. Epac1 agonist remarkably reduced the trans-endothelial migration of both SK-N-BE2C and SK-N-AS cells. These results demonstrate that an Epac1 agonist may perhaps serve as an adjuvant to currently existing therapies for the high-risk NB patients.
Differences between barley and maize revealed in limitations of photosystems I and II under high temperature and low air humidity
Authors: Lysenko Eugene A.
Published: May 2024

Non-photochemical quenching and limitations of the photosystem I and photosystem II activities were studied in C3-plant barley and C4-plant maize. Plants were undergone to prolonged heat stress under high and low air humidity. Both species decreased non-photochemical quenching under tolerated heat stress (37-42°C), while increased it under nearly lethal heat stress (46°C). Usually, limitation at the acceptor side of the photosystem I was minor, while at 46°C it appeared major limiting factor. A similar decrease of photosystem II activity at 46°C by lower air humidity was achieved through different mechanisms. In barley, photosystem II downregulated by the increase of non-photochemical quenching. In maize, photosystem II downregulated by the increase of limitation at the acceptor side. Analysis of transients also revealed differences between species. One second after a light induction, limitations flashes at the acceptor sides of both photosystems. Elevating temperature reduced the size of these flashes; acceptor-side limitations of both photosystems decreased proportional to each other. In maize, the decrease was simple: the size of flashes slightly decreased at 37°C and more reduced at 42-46°C. In barley, the decrease had complex pattern: the size of flashes greatly reduced at 37°C and gradually returned to the control level under the higher temperatures. Around the photosystem II, the flash was quenched by a later burst of non-photochemical quenching. In barley, the transient peaks of acceptor-side limitation and non-photochemical quenching were very similar at any temperature. This was not observed in maize. The ratios between limitations qC/Y(NA) and qC/Y(ND) were studied.

Highlights

Light 1s induces instant limitations at acceptor-sides of PSII (qC) and PSI (Y(NA))

Temperature reduced these flashes of qC and Y(NA) proportional to each other

The pattern of reduction was different in barley and maize

Flash of qC was quenched by proportional flash of qN in barley but not in maize

Stationary PSII activity was decreased by different mechanisms in barley and maize
Genome sequencing of 'Fuji' apple clonal varieties reveals evolutionary history and genetic mechanism of the spur-type morphology
Authors: Cai Yudong , Gao Xiuhua , Mao Jiangping , Liu Yu , Tong Lu , Chen Xilong , Liu Yandong , Kou Wenyan , Chang Chuanjun , Foster Toshi , Yao Jialong , Cornille Amandine , Tahir Muhammad Mobeen , Liu Zhi , Yan Zhongye , Lin Siyi , Ma Fengwang , Ma Juanjuan , Xing Libo , An Na , Zuo Xiya , Lv Yanrong , Zhao Zhengyang , Li Wenqiang , Li Qianjin , Zhao Caiping , Hu Yanan , Liu Hangkong , Wang Chao , Shi Xueyan , Ma Doudou , Fei Zhangjun , Jiang Yu , Zhang Dong
Published: May 2024

Somatic variations arising during asexual reproduction can lead to the emergence of bud sports exhibiting advantageous traits, forming the basis for bud sport breeding in perennial plants. Here, we report a near-complete, fully phased genome assembly of 'Fuji' apple, enabling comprehensive identification of somatic variants across 74 clonally propagated 'Fuji' varieties. Phylogenetic analysis of 'Fuji' sport varieties indicates that the emergence of spur-type and early maturation traits results from multiple independent formation events. A number of putative functional somatic variants are identified, including one spur-type specific deletion located in the promoter of the TCP transcription factor gene MdTCP11. DNA methylation level of the deletion-associated miniature inverted-repeat transposable element is lower in the spur-type varieties compared to the standard-type varieties, while the expression of MdTCP11 is significantly higher. Overexpression of MdTCP11 in apple decreases the plant height, highlighting its important role in the development of spur-type apple varieties. This study sheds light on the 80-year cloning history of 'Fuji' and provides valuable candidate causative mutations for apple breeding.
State diagrams of type I collagen for the rational design of biomimetic materials
Authors: Martinier Isabelle , Deville Sylvain , Mosser Gervaise , Trichet Léa , Davidson Patrick , Fernandes Francisco M.
Published: May 2024

Ideally, designing tissue engineering grafts and 3D cell culture materials should rely on mimicking the architecture and composition of the extracellular matrix, which is predominantly comprised of type I collagen. However, while collagen molecules are assembled into fibrils by cells in vivo, well-organized fibrils rarely form spontaneously in vitro. Indeed, the physico-chemical conditions for fibrillogenesis are still poorly understood and their influence on the formation and properties of fibrillar biomimetic materials remains elusive. Here, we establish state diagrams for type I collagen over an unprecedented range of concentration and temperature, showing the collagen denaturation limits, the emergence of fibrils in acidic conditions, and a new regime of collagen molecule/fibril coexistence. We also show how the state diagrams can be used to understand the formation of biomimetic materials by classical methods, as illustrated here by collagen freeze-casting. Therefore, these state diagrams will help to optimize the production of collagen-based biomimetic materials.
Clearance of DNA damage-arrested RNAPII is selectively impaired in Cockayne syndrome cells
Authors: van der Meer Paula J. , Yakoub George , Nakazawa Yuka , Ogi Tomoo , Luijsterburg Martijn S.
Published: May 2024

Arrest of elongating RNA polymerase II (RNAPII) at DNA lesions initiates transcription-coupled repair (TCR), involving the concerted action of specific TCR factors, followed by downstream nucleotide excision repair steps. Remarkedly, only congenital defects in the CSA or CSB genes cause the neurodegenerative disorder Cockayne syndrome, which is not observed with other TCR genes, despite their equal importance in TCR. An explanation for this discrepancy has been lacking. In this study, we developed an assay to track the fate of elongating RNAPII at sites of UV-induced DNA lesions. Employing this method on an isogenic collection of TCR knockout cells reveals a selective RNAPII clearance defect in cells defective in CSA or CSB, in contrast to knockouts of other TCR genes. Our findings provide evidence that a deficiency in RNAPII processing and prolonged transcription arrests in response to DNA damage, rather than compromised DNA repair, may underlie the Cockayne syndrome-like neurodegenerative phenotype.
Tagless LysoIP method for molecular profiling of lysosomal content in clinical samples
Authors: Saarela Daniel , Lis Pawel , Gomes Sara , Nirujogi Raja S. , Dong Wentao , Rawat Eshaan , Glendinning Sophie , Zeneviciute Karolina , Bagnoli Enrico , Fasimoye Rotimi , Lin Cindy , Nyame Kwamina , Boros Fanni A. , Zunke Friederike , Lamoliatte Frederic , Elshani Sadik , Jaconelli Matthew , Jans Judith J. M. , Huisman Margriet A. , Posern Christian , Westermann Lena M. , Schulz Angela , van Hasselt Peter M. , Alessi Dario R. , Abu-Remaileh Monther , Sammler Esther M.
Published: May 2024

Lysosomes are implicated in a wide spectrum of human diseases including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models allowed major discoveries in the field, however studying lysosomal dysfunction in human patients remains challenging. Here, we report the development of the “tagless LysoIP method” to enable rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.g. induced Pluripotent Stem Cell (iPSCs) derived neurons). Isolated lysosomes are intact and suitable for subsequent multimodal omics analyses. To validate our approach, we employed the tagless LysoIP to enrich lysosomes from peripheral blood mononuclear cells (PBMCs) derived from fresh blood from patients with CLN3 disease, a neurodegenerative LSD. Metabolic profiling of isolated lysosomes showed massive accumulation of glycerophosphodiesters (GPDs) in patients’ lysosomes. Interestingly, a patient with a milder phenotype and genotype displayed lower accumulation of lysosomal GPDs, consistent with their potential role as disease biomarkers. Altogether, the tagless LysoIP provides a framework to study native lysosomes from patient samples, identify novel biomarkers and discover human-relevant disease mechanisms.
Transcriptomic analysis identifies injury-responsive fibroblast populations as potential mediators of Wnt-dependent spinal cord regeneration
Authors: Alper Samuel R. , Vasudevan Deeptha , Wheeler Maya K. , Panahi Samin , Dorsky Richard I.
Published: May 2024

Background

In humans and other mammals, spinal cord injury (SCI) can lead to a permanent loss of sensory and motor function, due to the inability of damaged neurons and axons to regenerate. However, other vertebrate species including zebrafish exhibit complete spinal cord regeneration and functional recovery after SCI. Wnt signaling is required for neurogenesis and axon regrowth in a larval zebrafish SCI model, but the genes regulated by this pathway and the cell types that express them remain largely unknown.

Results

In this study, we used bulk RNA-sequencing (RNAseq) to identify candidate genes regulated by Wnt signaling that are expressed after SCI. Using this unbiased screen, we identified multiple genes previously unassociated with SCI in larval zebrafish, and confirmed by in situ hybridization that their expression is injury-responsive, Wnt-dependent, and localized to fibroblast-like cells surrounding the spinal cord.

Conclusions

Together, our data reveal potential novel gene targets and cell populations that may play important roles in spinal cord regeneration.
Massively parallel free energy calculations forin silicoaffinity maturation of designed miniproteins
Authors: Novack Dylan , Zhang Si , Voelz Vincent A
Published: May 2024

Computational protein design efforts continue to make remarkable advances, yet the discovery of high-affinity binders typically requires large-scale experimental screening of site-saturated mutant (SSM) libraries. Here, we explore how massively parallel free energy methods can be used forin silicoaffinity maturation ofde novodesigned binding proteins. Using an expanded ensemble (EE) approach, we perform exhaustive relative binding free energy calculations for SSM variants of three miniproteins designed to bind influenza A H1 hemagglutinin by Chevalier et al. (2017). We compare our predictions to experimental ΔΔGvalues inferred from a Bayesian analysis of the high-throughput sequencing data, and to state-of-the-art predictions made using the Flex ddG Rosetta protocol. A systematic comparison reveals prediction accuracies around 2 kcal/mol, and identifies net charge changes, large numbers of alchemical atoms, and slow side chain conformational dynamics as key contributors to the uncertainty of the EE predictions. Flex ddG predictions are more accurate on average, but highly conservative. In contrast, EE predictions can better classify stabilizing and destabilizing mutations. We also explored the ability of SSM scans to rationalize known affinity-matured variants containing multiple mutations, which are non-additive due to epistatic effects. Simple electrostatic models fail to explain non-additivity, but observed mutations are found at positions with higher Shannon entropies. Overall, this work suggests that simulation-based free energy methods can provide predictive information forin silicoaffinity maturation of designed miniproteins, with many feasible improvements to the efficiency and accuracy within reach.
The chlamydial transcriptional regulator Euo is a key switch in cell form developmental progression but is not involved in the committed step to the formation of the infectious form
Authors: Appa Cody R. , Grieshaber Nicole A. , Yang Hong , Omsland Anders , McCormick Sean , Chiarelli Travis J. , Grieshaber Scott S.
Published: May 2024

Bacteria in the genusChlamydiaare a significant health burden world wide. They infect a wide range of vertebrate animals including humans and domesticated animals. In humans,C. psittacican cause zoonotic pneumonia whileC. pneumoniaecauses a variety of respiratory infections. Infections withC. trachomatiscause ocular or genital infections. All chlamydial species are obligate intracellular parasites of eukaryotic cells and are dependent on a complex infection cycle that depends on transitions between specific cell forms. This cycle consists of cell forms specialized for host cell invasion, the Elementary Body (EB), and a form specialized for intracellular replication, the Reticulate Body (RB). In addition to the EB and RB there is a transitionary cell form that mediates the transformation between the RB and the EB, the Intermediate Body (IB). In this study we ectopically expressed the regulatory protein Euo and showed that high levels of expression resulted in reversible arrest of the development cycle. The arrested chlamydial cells were trapped phenotypically at an early IB stage of the cycle. These cells had exited the cell cycle but had not shifted gene expression from RB-like to IB/EB-like. This arrested state was dependent on continued expression of Euo. When ectopic expression was reversed, Euo levels dropped in the arrested cells which led to the repression of native Euo expression and the resumption of the developmental cycle. Our data are consistent with a model where Euo expression levels impact IB maturation to the infectious EB but not the production of the IB form.

Importance

Bacterial species in the Chlamydiales order infect a variety of vertebrate animals and are a global health concern. They cause various diseases in humans, including genitital and respiratory infections. The bacteria are obligate intracellular parasites that rely on a complex infectious cycle involving multiple cell forms. All species share the same life cycle, transitioning through different states to form the infectious elementary body (EB) to spread infections to new hosts. The Euo gene, encoding a DNA binding protein, is involved in regulating this cycle. This study showed that ectopic expression of Euo halted the cycle at an early stage. This arrest depended on continued Euo expression. When Euo expression was reversed, the developmental cycle resumed. Additionally, this study suggests that high levels of Euo expression affects the formation of the infectious EB, but not the production of the cell form committed to EB formation.
Mapping the Cerebrovascular Abnormality in Transgenic Alzheimer’s Disease (AD) Mice with deep-learning-based super-resolution cerebral blood volume (CBV)-MRI
Authors: Zhou Xiaoqing Alice , Liu Xiaochen , Li Hongwei Bran , Hike David , Jiang Yuanyuan , Rosen Matthew S. , Iglesias Juan Eugenio , Yu Xin
Published: May 2024

To measure the brain-wide vascular density (VD) alteration in degenerated brains with Alzheimer’s Disease (AD), deep learning-based super-resolution approach was developed to assist the segmentation of micro-vessels from the Monocrystalline Iron Oxide Nanoparticle (MION)-based CBV MRI images of transgenic mouse brains. Iron-induced T2* amplification effect well separated micro-vessels with tens of microns from capillary-enriched parenchyma voxels, enabling vascular compartment-specific VD differential analysis between AD and wildtype control mice. The differential maps based on segmented micro-vessels identified decreased VD in the anterior cingulate cortex (ACC) and medial entorhinal cortex (mEC) and increased VD in several highlighted brain regions, including dentate gyrus (DG) of the hippocampus, central and geniculate thalamus, medial septal area (MS), ventral tegmental area (VTA), and lateral entorhinal cortex (lEC). In contrast, the T2*-weighted capillary density mapping from parenchyma voxels showed increased VD in several cortical regions, including somatosensory and visual cortex, retrosplenial cortex, as well as piriform area and lEC in AD brains. However, dramatic capillary VD decrease was observed in the subcortical areas including hippocampus, thalamus, hypothalamus, and pontine areas. These high-resolution MION-based CBV MRI elucidates altered vascular compartments in degenerated AD brains, reconciling the various region-specific vascular impairment and angiogenesis in functional areas critical for cognitive decline of AD.
Bursts from the past: Intrinsic properties link a network model to zebra finch song
Authors: Medina Nelson D. , Margoliash Daniel
Published: May 2024

Neuronal intrinsic excitability is a mechanism implicated in learning and memory that is distinct from synaptic plasticity. Prior work in songbirds established that intrinsic properties (IPs) of premotor basal-ganglia-projecting neurons (HVCX) relate to learned song. Here we find that temporal song structure is related to specific HVCXIPs: HVCXfrom birds who sang longer songs including longer invariant vocalizations (harmonic stacks) had IPs that reflected increased post-inhibitory rebound. This suggests a rebound excitation mechanism underlying the ability of HVCXneurons to integrate over long periods of time and represent sequence information. To explore this, we constructed a network model of realistic neurons showing how in-vivo HVC bursting properties link rebound excitation to network structure and behavior. These results demonstrate an explicit link between neuronal IPs and learned behavior. We propose that sequential behaviors exhibiting temporal regularity require IPs to be included in realistic network-level descriptions.
Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids
Authors: Scuderi Soraya , Kang Tae-Yun , Jourdon Alexandre , Yang Liang , Wu Feinan , Nelson Alex , Anderson George M. , Mariani Jessica , Sarangi Vivekananda , Abyzov Alexej , Levchenko Andre , Vaccarino Flora M.
Published: May 2024

The repertory of neurons generated by progenitor cells depends on their location along antero-posterior and dorso-ventral axes of the neural tube. To understand if recreating those axes was sufficient to specify human brain neuronal diversity, we designed a mesofluidic device termed Duo-MAPS to expose induced pluripotent stem cells (iPSC) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison of single cell transcriptomes with fetal human brain revealed that Duo-MAPS-patterned organoids generated the major neuronal lineages of the forebrain, midbrain, and hindbrain. Morphogens crosstalk translated into early patterns of gene expression programs predicting the generation of specific brain lineages. Human iPSC lines from six different genetic backgrounds showed substantial differences in response to morphogens, suggesting that interindividual genomic and epigenomic variations could impact brain lineages formation. Morphogen gradients promise to be a key approach to model the brain in its entirety.
KAT3 mutations impair neural crest migration through EMT regulatorssnai1b andsnai2in Rubinstein Taybi Syndrome
Authors: Verma Shweta , Dalabehera Sujit , Gowda Subhash , Chandrasekaran Koushika , Singh Dayanidhi , Prasher Bhavana , Bapat Sharmila , Ramalingam Sivaprakash , Sachidanandan Chetana
Published: May 2024

Rubinstein Taybi syndrome, a rare congenital disease is caused by mutation in KAT3 genes,EP300andCREBBP. A subset of tissues affected in RSTS have their origin in neural crest cells, prompting our exploration into the role of KAT3 in neural crest development. Our zebrafish RSTS models generated by knocking down or mutatingep300aandcbpagenes, reveal defects in neural crest migration and its derived tissues when KAT3 genes are perturbed. We also demonstrate that the effects on neural crest can be reversed by HDAC inhibition in in morphant embryos. KAT3 knockdown causes downregulation of EMT regulators,snai1bandsnai2. Snai2 is known to represscdh6bin neural crest cells facilitating their delamination from neural tube and migration. We generated RSTS patient-derived iPSC line and differentiated them into neural crest cells in vitro. We show that role of KAT3 proteins in neural crest migration is conserved in human iPSC derived neural crest cells. Our findings make a case for classifying RSTS as a neurocristopathy.

Highlights

Perturbation of KAT3 gene expression in zebrafish recapitulates the Rubinstein Taybi patient defects

The zebrafish model of Rubinstein Taybi model reveals defects in neural crest cell migration

KAT3 proteins regulatesnai2, snai1band cdh6, genes important for neural crest migration

The neural crest migration defects in the zebrafish model can be partially rescued by modulating the global acetylation levels

Study of RSTS patient-derived neural crest cells reveals that the role of KAT3 in neural crest migration is conserved across vertebrates

Graphical Abstract
Wall modes and the transition to bulk convection in rotating Rayleigh-Bénard convection
Authors: Zhang Xuan , Reiter Philipp , Shishkina Olga , Ecke Robert E.
Published: May 2024

We investigate states of rapidly rotating Rayleigh-Bénard convection in a cylindrical cell over a range of Rayleigh numbers 3×105≤Ra≤5×109 and Ekman numbers 10−6≤Ek≤10−4 for Prandtl number Pr=0.8 and aspect ratios 1/5≤Γ≤5 using direct numerical simulations. We characterize, for perfectly insulating sidewall boundary conditions, the first transition to convection via wall mode instability and the nonlinear growth and instability of the resulting wall mode states, including a secondary transition to time dependence. We show how the radial structure of the vertical velocity uz and the temperature T is captured well by the linear eigenfunctions of the wall mode instability where the radial width of uz is δuz∼Ek1/3r/H whereas δT∼e−kr (k is the wave number of a laterally infinite wall mode state). The disparity in spatial scales for Ek=10−6 means that the heat transport is dominated by the radial structure of uz since T varies slowly over the radial scale δuz. We further describe how the transition to a state of bulk convection is influenced by the presence of the wall mode states. We use temporal and spatial scales as measures of the local state of convection and the Nusselt number

Nu

as representative of global transport. Our results elucidate the evolution of the wall state of rotating convection and confirm that wall modes are strongly linked with the boundary zonal flow being the robust remnant of nonlinear wall mode states. We also show how the heat transport (Nu) contributions of wall modes and bulk modes are related and discuss approaches to disentangling their relative contributions.

Published by the American Physical Society
2024
Ethical leadership in the Netherlands: testing the broader conceptualization and measurement scale
Authors: Shakeel Fahad , Kruyen Peter Mathieu , Van Thiel Sandra
Published: May 2024

Purpose

This paper aims to validate a broader conceptualization of ethical leadership and a matching measurement scale (BELS) using survey data from 909 public servants in leadership positions in the Netherlands.

Design/methodology/approach

The confirmatory factor analysis (CFA) (using AMOS) and exploratory factor analysis were carried out with repeated CFA. A social desirability scale was used to check for model fitness.

Findings

Our findings support the notion that ethical leadership is broader in conceptualization and hence reject the theories that limit the role of ethical leaders within the confines of organizations. This study confirms that attributes like sustainability, leadership learning, ethical competency, diversity and resilience are part of ethical leadership. Such characteristics could not be measured with previous scales for ethical leadership. Also, ethical leadership is not separate from associated leadership styles.

Research limitations/implications

A self-assessment scale for leaders was used for this study. Although there is no indication of social desirability bias, future research can also focus on follower assessments of their leaders. This study only focuses on the public sector context only.

Practical implications

Our results suggest that ethical leadership contains more subvalues than in the seminal definition. This study has, therefore, corroborated a broader definition of ethical leadership.

Originality/value

This study indicates the need for ethical leadership to be studied and assessed using a broader conceptualization and measurement scale.
The pursuit of splendour: a recipe of psychological motivations driving conspicuous luxury consumption
Authors: Zhang Xiaoyu , Aw Eugene Cheng-Xi , Wei-Han Tan Garry , Ooi Keng-Boon
Published: May 2024

Purpose

The purpose of the present study is to examine and validate a research model encompassing power distance belief, need for uniqueness, self-monitoring, self-construal, social adjustive attitude, and value-expressive attitude as the causal antecedents for conspicuous luxury consumption.

Design/methodology/approach

Survey data was collected from a large consumer panel. The study applied a combinatory partial least squares structural equation modelling (PLS-SEM) and fuzzy-set qualitative comparative analysis (fsQCA) approach in examining the research hypotheses and proposition.

Findings

The results indicated the effects of power distance belief, need for uniqueness, self-monitoring, and self-construal on social adjustive attitude and value-expressive attitude, which in turn determine conspicuous luxury consumption. In addition, the fsQCA findings revealed three configurations that articulate the complex interactions of the causal antecedents.

Originality/value

This study enriches the literature by providing a comprehensive understanding of the psychological motivation factors that drive conspicuous luxury consumption and assists luxury retailers in developing targeted strategies to appeal to consumers.
Ensemble-based deep learning techniques for customer churn prediction model
Authors: Subramanian R. Siva , Yamini B. , Sudha Kothandapani , Sivakumar S.
Published: May 2024

Purpose

The new customer churn prediction (CCP) utilizing deep learning is developed in this work. Initially, the data are collected from the WSDM-KKBox’s churn prediction challenge dataset. Here, the time-varying data and the static data are aggregated, and then the statistic features and deep features with the aid of statistical measures and “Visual Geometry Group 16 (VGG16)”, accordingly, and the features are considered as feature 1 and feature 2. Further, both features are forwarded to the weighted feature fusion phase, where the modified exploration of driving training-based optimization (ME-DTBO) is used for attaining the fused features. It is then given to the optimized and ensemble-based dilated deep learning (OEDDL) model, which is “Temporal Context Networks (DTCN), Recurrent Neural Networks (RNN), and Long-Short Term Memory (LSTM)”, where the optimization is performed with the aid of ME-DTBO model. Finally, the predicted outcomes are attained and assimilated over other classical models.

Design/methodology/approach

The features are forwarded to the weighted feature fusion phase, where the ME-DTBO is used for attaining the fused features. It is then given to the OEDDL model, which is “DTCN, RNN, and LSTM”, where the optimization is performed with the aid of the ME-DTBO model.

Findings

The accuracy of the implemented CCP system was raised by 54.5% of RNN, 56.3% of deep neural network (DNN), 58.1% of LSTM and 60% of RNN + DTCN + LSTM correspondingly when the learning percentage is 55.

Originality/value

The proposed CCP framework using the proposed ME-DTBO and OEDDL is accurate and enhances the prediction performance.
The future of academic librarianship: the imperatives of embedded librarianship practice and implementation
Authors: Munshi Shamim Aktar , Koner Souvik , Barsha Sayantoni
Published: May 2024

Purpose

The present study discusses the future of academic librarianship, emphasizing the essential aspects of embedded librarianship practice and implementation. In addition, it also explores the changing role of academic librarians, addressing challenges and opportunities in various contexts and highlighting the significance of embedded librarianship practice.

Design/methodology/approach

The study employs a literature review to understand the significance of embedded librarianship and its implementation in academic libraries. The researchers searched a range of electronic data sources, including Emerald Insight, Taylor and Francis, Science Direct, Web of Science, EBSCOhost, Scopus, Information Science and Technology Abstracts (LISTA), Library and Information Science Abstracts (LISA), etc. Moreover, only peer-reviewed articles were considered for the review.

Findings

The study identified five major competencies, i.e. communication and interpersonal skills, teaching, research, collaboration and coordination and technological expertise, that are essential for implementing embedded librarianship in the academic library. However, in developing countries, there are various challenges faced by academic librarians such as inadequate ICT infrastructure, resource accessibility, cooperations, cultural diversity and a lack of financial support from the authority were major barriers to the successful implementation of embedded librarianship.

Practical implications

The study findings are of considerable value to academic librarians, providing them with the opportunity to assess and evaluate their competencies and acquire the essential skills for implementing embedded librarianship. Further, the study also recommended some practical implications of embedded librarianship practices in the academic environment.

Originality/value

The findings and insights from this investigation provide a valuable perspective on the future of academic librarianship, shedding light on the critical role that embedded librarianship plays in shaping its direction.
The significance of Syndecan 1, a new marker for endothelial dysfunction, in cases of fetal growth retardation
Authors: Oğuz Yüksel , Ağaoğlu Recep Taha , Ulusoy Can Ozan , Kurt Dilara , Özgürlük İzzet , Soysal Çağanay , Yılmaz Vural Zehra , Yakut Yücel Kadriye
Published: May 2024

Problem

In the current study we aimed to investigate Syndecan 1 (SDC1) levels in pregnant women diagnosed with fetal growth restriction (FGR) and the relationship between SDC1 levels and clinical and doppler parameters in FGR cases associated with endothelial dysfunction, angiogenesis and uteroplacental insufficiency

Method of Study

A total of 90 pregnant women included in the study, (45 with FGR, 45 healthy control) matched by week of gestation and maternal age. Venous blood samples were collected and plasma concentrations of SDC1 were determined by a specific immunoassay. Doppler examination was performed to evaluate the relationship between the SDC1 levels and placental blood supply.

Results

Doppler parameters; mean UtA‐PI (p < .001), CPR (p = .002) and CPUR (p < .001) were different between the groups, however MCA PI, umbilical artery PI and umbilical artery S/D were not (p > .05). While gestational age at delivery, birth weight, APGAR score at 1 and 5 min were significantly lower (all, p < .001) in the study group, non‐reassure fetal heart rate tracing (p = .09) and NICU admission (p = .02) were significantly higher. SDC 1 level was 2,00 ± 1,47 ng/mL and 2,34 ± 1,12 ng/mL in the FGR and control groups, respectively (p = .008). In the study group SDC 1 level was 1,69 ± 2,00 in those with gestational age below 32 weeks and 2,13 ± 1,18 in those with gestational age above 32 weeks and there was a statistically significant difference between the groups (p = .015). Plasma SDC 1 concentration of 2,1850 ng/mL or less had a sensitivity of 70%, a specificity of 72%, area under the ROC curve .65 (p < .005).

Conclusions

Low maternal plasma SDC1 level may be associated with placental insufficiency and FGR. Low levels of SDC1 may be helpful as a predictor for the development of FGR during gestation.
Postoperative cognitive dysfunction in heart transplantation recipients
Authors: Qin Qian , Lei Yu , Sun Xiaojie , Fu Xiaona , Fan Wenliang , Zhu Dongyong , Lei Ziqiao , Liu Jia , Wang Jing
Published: May 2024

Objective

This study aimed to investigate the occurrence and risk factors of postoperative neurocognitive disorder (NCD) in patients who underwent heart transplantation.

Methods

Seventy‐six heart transplant patients were analyzed for clinical data including gender, age, height, weight, education level, left ventricular ejection fraction (LVEF), stroke volume (SV), transplantation duration, and pretransplant medical history. Cognitive function was assessed using the mini‐mental status examination (MMSE) and Montreal cognitive assessment (MoCA) scales. Patients were categorized into cognitively normal and impaired groups based on the presence or absence of cognitive dysfunction, and their cognitive function scores were compared. Multivariate logistic regression was used to identify independent risk factors for cognitive impairment in postoperative cardiac transplant patients.

Results

Cognitive dysfunction was observed in 48 out of 76 heart transplant patients, representing an incidence of 63.2%. Cognitive impairment in heart transplant recipients predominantly affected multiple cognitive domains. Logistic regression analysis identified age (OR = 1.057, 95% CI 1.002–1.115), gender (OR = .200, 95% CI .044–.919), education level (OR = .728, 95% CI .600–.883), LVEF (OR = .891, 95% CI .820–.969), and history of diabetes (OR = 7.674, 95% CI 1.317–44.733) as independent risk factors for postoperative NCD in heart transplant recipients (P < .05).

Conclusion

The study found a high incidence of postoperative NCD in heart transplant patients, with gender, age, education level, LVEF, and diabetes history being significant risk factors. Early identification and intervention targeting these risk factors may help prevent NCD in postheart transplant patients and improve long‐term outcomes.
Niche structure and habitat shifts for coastal sharks of the US Southeast Atlantic and Gulf of Mexico
Authors: O'Brien Kaitlyn A. , Cortés Enric , Driggers William B. , Frazier Bryan S. , Latour Robert J.
Published: May 2024

Understanding spatial ecology and predicting animal movements in response to environmental changes, such as anthropogenic climate change and multidecadal variability, is critical for effective conservation strategies. Niche structuring is key to some coastal shark species and size classes coexisting in the US Atlantic and Gulf of Mexico to limit interspecific and intraspecific interaction. Data from four fishery‐independent bottom longline surveys were used to evaluate the abiotic ecological niches of eight species of small and large coastal sharks. Gaussian mixture models separated length composition data into 14 size categories for ecological niche analysis. Generalized additive mixed effect models were fit and coupled with output from dynamic high‐resolution ocean models to predict suitable abiotic habitats, evaluate potential shifts in distribution, and explore the impacts of large‐scale climatological trends on abiotic habitats from 1994 to 2019. The abiotic niche for small coastal sharks generally tended toward warmer, high salinity, shallow bottom waters close to shore. No overarching niche was found for large coastal sharks, but appreciable ontogenetic differences were seen. Most taxa analyzed exhibited declining annual trends in higher quality habitats, particularly during fall months. The analysis provided evidence of shifts north along the Atlantic, to deeper offshore waters in the Atlantic and Gulf of Mexico, and the potential to redistribute in response to multidecadal climate variability for multiple species. The analytical framework described could aid in developing various spatiotemporal management measures, and results provide insight into the habitat characteristics of several species over broad spatiotemporal ranges and through ontogeny.
Ontogenetic diet shifts and temporal separations in gonad development of two icefish species in Hongze Lake, China
Authors: Cheng Fei , Zhao Lishuang , Cao Juan , Jia Meixiang , Li Yacheng , Chen Yushun , Xie Songguang
Published: May 2024

Resource partitioning through temporal, spatial and/or trophic dimensions is suggested as a mechanism for long‐term coexistence among sympatric species. However, how the combined effects of the different dimensions contribute to the partitioning during the ontogenetic process is unclear.

We sampled two sympatric icefish species [Protosalanx hyalocranius (Abbott, 1901) and Neosalanx taihuensis (Chen, 1956)] monthly from July 2015 to June 2016 in Hongze Lake, China. We evaluated the hypothesis that combined effects of separation in gonad development dynamics and ontogenetic diet shifts facilitate resource partitioning in temporal and trophic dimensions during the entire life cycle process of the two icefish species.

Increased gonadosomatic index (GSI) of female P. hyalocranius occurred during October 2015 to January 2016, and that of female N. taihuensis occurred during January to March 2016. Thus, energy and nutrition investments in gonad development separated seasonally between the two species. Consequently, temporal separations in gonad development between P. hyalocranius (GSI peaked in January) and N. taihuensis (GSI peaked in March) indicated potential segregations in spawning time and consequent larval abundance peaks, suggesting reduced overlap of prey consumption during the early life stages.

The dominant diet of P. hyalocranius shifted from cladocerans to copepods, and then shrimp, and finally to fish during its ontogeny, whereas the dominant diet of N. taihuensis changed gradually from cladocerans to copepods during its ontogeny. The diet overlap in cladocerans during May was high between the two species.

Our findings support the hypothesis of an associative strategy, combining temporal (separations in gonad development and subsequently spawning time) and trophic (ontogenetic diet shifts) dimensions, for the resource partitioning between P. hyalocranius and N. taihuensis, which may be an important mechanism for long‐term coexistence among sympatric short‐lived fishes.
An exploration of barriers to access to healthcare in Hancock County, Tennessee: A qualitative study
Authors: Blackburn Christine Crudo , Nuzhath Tasmiah
Published: May 2024

Objective

Explore barriers to healthcare access in Hancock County, Tennessee using a conceptual framework for access to healthcare.

Methods

We collected data from 30 participants in Hancock County during 1 week in April 2023 using a combination of network and purposive sampling. We analyzed the data using thematic analysis and the conceptual framework of healthcare access.

Results

All dimensions of the conceptual framework of healthcare access presented barriers to healthcare access for participants of the study. A lack of acceptability of local healthcare among participants manifested in a perceived lack of availability of healthcare. This resulted in participants travelling or considering it necessary to travel long distances for care, even in a life‐threatening emergency, despite the local availability of a hospital with an emergency department.

Conclusions

A lack of acceptability can create healthcare access barriers similar to a lack of availability of healthcare facilities.

Patient or Public Contribution

The research team met several times with the leader of a local community organization to discuss this research in Hancock County. These conversations helped to inform the study design and provided necessary background to conduct in‐depth interviews. Members of the community organization helped identify individuals to interview and provide access to Remote Area Medical clinic patients. The research team discussed the final themes with the primary community collaborator.
Factors influencing nurse manager retention, intent to stay or leave and turnover: A systematic review update
Authors: Penconek Tatiana , Tate Kaitlyn , Lartey Sarah A. , Polat Dilsah , Bernardes Andrea , Moreno Dias Bruna , Nuspl Megan , Cummings Greta G.
Published: May 2024

Aims

To understand factors influencing nurse manager retention or intention to leave, develop a preliminary theoretical model and identify strategies and interventions for workforce planning.

Design

Systematic review update of literature with integrated design of mixed research synthesis.

Methods

We included peer‐reviewed articles examining factors influencing retention or intention to leave for front‐line, middle or patient care nurse managers. Authors independently screened articles for inclusion and assessed included articles for quality. We adhered to a convergent synthesis approach.

Data Sources

Nine databases included MEDLINE, EMBASE, PsychINFO, CINAHL Plus with Full Text, ERIC, Health Source Nursing/Academic Edition, Scopus, ProQuest Dissertations and Theses and LILACS in January 2023.

Results

Thirty‐five studies published between 1990 and 2022, 22 quantitative and 13 qualitative or mixed methods, were included. 155 factors influencing nurse manager retention, intention to stay, or turnover were reported. Job satisfaction was most frequently examined (n = 7), followed by factors such as empowerment (n = 3), decision‐making (n = 3) and resilience (n = 2). We developed a preliminary theoretical model demonstrating staff relations and leadership, organizational and job characteristics, socio‐demographics, personal characteristics, well‐being and nurse manager relationship with work influence managers' intention to stay or to leave.

Conclusions

Nurse managers who were empowered, satisfied with their work, received constructive feedback and found meaning in their roles showed greater intent to stay.

Implications for the Profession and/or Patient Care

Nurse administrators can ensure managers are provided with authority to make decisions that promote autonomy. Work cultures that allow for regular meaningful constructive feedback from staff and leaders may contribute to nurse managers feeling valued.

Impact

Understanding factors that influence job retention or intention to leave may help nurse managers and their supervisors identify areas for strategy and intervention design to ensure sustainability of this workforce.

Reporting Method

PRISMA 2020 Guidelines.

Patient or Public Contribution

No patient or public contribution.