bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gender Gap Amongst Doctoral Students in the Biomedical Sciences
Authors: Schaller Michael D.
Published: October 2022

Historically women have been underrepresented in STEM careers. While the number of women receiving doctorate degrees in the biological sciences has exceeded the number of men since approximately 2005, there is still a disparity between the sexes at more advanced career stages. Achieving equity is an important social goal and there is an expected benefit to science since diverse groups outperform homogeneous groups. There are many factors that contribute to the disparity between men and women in science, including a disparity in research productivity. While many studies have documented this “productivity paradox” and examined factors driving this disparity, few studies have addressed differences in productivity between men and women doctoral students. This is an important population to assess since the individuals are in the formative stages of their academic career and differences in productivity could have a significant impact on career progression. This study addresses this question and identified more than 42,000 doctoral students in the biological and biomedical sciences working with over 16,000 advisors at 235 institutions in the United States and finds a disparity in research productivity between men and women. Men produce >10% more first author papers, >15% more total papers and their first author papers receive >17% more citations. The findings establish the generality of the gender gap in research productivity among doctoral students in the biological and biomedical sciences. Redressing this gap at the formative stage of young scientists’ careers, when they are establishing their credentials to advance in their field, is important to address the disparity between the sexes in the biomedical workforce.
Rosetta’s Predictive Ability for Low-Affinity Ligand Binding in Fragment-Based Drug Discovery
Authors: Okwei Elleansar , Smith Shannon T. , Bender Brian J. , Allison Brittany , Ganguly Soumya , Geanes Alexander , Zhang Xuan , Ledwitch Kaitlyn , Meiler Jens
Published: October 2022

Fragment-based drug discovery begins with the identification of small molecules with a molecular weight of usually less than 250 Da that weakly bind to the protein of interest. This technique is challenging for computational docking methods as binding is determined by only a few specific interactions. Inaccuracies in the energy function or slight deviations in the docking pose can lead to the prediction of incorrect binding or difficulties in ranking fragments inin silicoscreening. Here we test RosettaLigand by docking a series of fragments to a cysteine-depleted variant of the TIM-barrel protein, HisF. We compare the computational results with experimental NMR spectroscopy screens. NMR spectroscopy gives details on binding affinities of individual ligands, which allows assessment of the ligand-ranking ability by RosettaLigand, and also provides feedback on the location of the binding pocket, which serves as a reliable test of RosettaLigand’s ability to identify plausible binding poses. From a library screen of 3456 fragments, we identified a set of 31 ligands with intrinsic affinities to HisF with dissociation constants as low as 400 µM. The same library of fragments was blindly screenedin silico. RosettaLigand was able to rank binders before non-binders with an area under the curve (AUC) of the receiver operating characteristics (ROC) of 0.74. The docking poses observed for binders agreed with the binding pocket identified by NMR chemical shift perturbations for all fragments. Taken together, these results provide a baseline performance of RosettaLigand in a fragment-based drug discovery setting.
A microtubule associated protein is essential for malaria parasite transmission
Authors: Wichers-Misterek Jan Stephan , Binder Annika M. , Mesén-Ramírez Paolo , Dorner Lilian Patrick , Safavi Soraya , Fuchs Gwendolin , Lenz Tobias L. , Bachmann Anna , Wilson Danny , Frischknecht Friedrich , Gilberger Tim-Wolf
Published: October 2022

Mature gametocytes ofPlasmodium(P.)falciparumdisplay a banana (falciform) shape conferred by a complex array of subpellicular microtubules (SPMT) associated to the inner membrane complex (IMC). Microtubule associated proteins (MAPs) define MT populations and modulate interaction to pellicular components. Several MAPs have been identified inToxoplasma gondiiand homologues can be found in the genome ofPlasmodiumspecies, but the function of these proteins for asexual and sexual development of malaria parasites is still unknown. Here we identified a novel subpellicular MAP, termed SPM3, that is conserved within the genusPlasmodium., especially within theLaveraniasubgenus, but absent in other Apicomplexa. Conditional knockdown and targeted gene disruption ofPfspm3inP. falciparumcause severe morphological defects during gametocytogenesis leading to round, non-falciform gametocytes with an aberrant SPMT pattern. In contrast,Pbspm3knockout inP. berghei, a species with round gametocytes, caused no defect in gametocytogenesis, but sporozoites displayed an aberrant motility and a dramatic defect in sporozoite invasion of salivary glands leading to a decreased efficiency in transmission. Electron microscopy revealed a dissociation of the SPMT from the IMC inPbspm3knockout parasites suggesting a function of SPM3 in anchoring MTs to the IMC. Overall, our results highlight SPM3 as a pellicular component with essential functions for malaria parasite transmission.

IMPORTANCE

A key structural feature driving the transition between different life cycle stages of the malaria parasite is the unique three membrane “pellicle”, consisting of the parasite plasma membrane (PPM) and a double membrane structure underlying the PPM termed the “inner membrane complex” (IMC). Additionally, there are numerous linearly arranged intramembranous particles (IMPs) linked to the IMC, which likely link the IMC to the subpellicular microtubule cytoskeleton. Here we identify, localize and characterize a novel subpellicular microtubule associated protein unique to the genusPlasmodium(P.). The knockout of this protein in the human infectingP. falciparumspecies result in malformed gametocytes and aberrant microtubules. We confirmed the microtubule association in theP. bergheirodent malaria homologue and show that its knockout results in a perturbated microtubule architecture, aberrant sporozoite motility and decreased transmission efficiency.
Noncanonical CDK4 signaling rescues diabetes in a mouse model by promoting beta cell differentiation
Authors: Stamateris Rachel E. , Sharma Rohit B. , Landa-Galván Huguet , Darko Christine , Redmond David , Rane Sushil G. , Alonso Laura C.
Published: October 2022

Expanding beta cell mass is a critical goal in the fight against diabetes. CDK4, an extensively characterized cell cycle activator, is required to establish and maintain beta cell number. Beta cell failure in the IRS2-deletion mouse type 2 diabetes model is in part due to loss of CDK4 regulator Cyclin D2. We set out to determine whether replacement of endogenous CDK4 with the inhibitor-resistant mutant CDK4-R24C rescued the loss of beta cell mass in Irs2-deficient mice. Surprisingly, not only beta cell mass but also beta cell dedifferentiation status was effectively rescued, despite no improvement in insulin sensitivity.Ex vivostudies in primary islet cells revealed a novel mechanism in which CDK4 intervened downstream in the insulin signaling pathway to prevent FOXO1-mediated transcriptional repression of critical beta cell transcription factorPdx1. FOXO1 inhibition was not related to E2F1 activity, to FOXO1 phosphorylation, or even to FOXO1 subcellular localization, but rather was related to deacetylation of FOXO1 and reduced FOXO1 abundance. Taken together, these results demonstrate a novel differentiation-promoting activity of the classical cell cycle activator CDK4 and support the concept that beta cell mass can be expanded without compromising function.
ResFinderFG v2.0: a database of antibiotic resistance genes obtained by functional metagenomics
Authors: Gschwind Rémi , Perovic Svetlana Ugarcina , Weiss Maja , Petitjean Marie , Lao Julie , Coelho Luis Pedro , Ruppé Etienne
Published: October 2022

Metagenomics can be used to monitor the spread of antibiotic resistance genes (ARGs). ARGs found in databases such as ResFinder and CARD primarily originate from culturable and pathogenic bacteria, while ARGs from non-culturable and non-pathogenic bacteria remain understudied. Functional metagenomics is based on phenotypic gene selection and can identify ARGs from non-culturable bacteria with a potentially low identity shared with known ARGs. In 2016, the ResFinderFG v1.0 database was created to collect ARGs from functional metagenomics studies. Here, we present the second version of the database, ResFinderFG v2.0, which is available on the Center of Genomic Epidemiology web server (https://cge.food.dtu.dk/services/ResFinderFG/). It comprises 3,913 ARGs identified by functional metagenomics from 50 carefully curated datasets. We assessed its potential to detect ARGs in comparison to other popular databases in gut, soil and water (marine + freshwater) Global Microbial Gene Catalogues (https://gmgc.embl.de). ResFinderFG v2.0 allowed for the detection of ARGs that were not detected using other databases. These included ARGs conferring resistance to beta-lactams, cycline, phenicol, glycopeptide/cycloserine and trimethoprim/sulfonamide. Thus, ResFinderFG v2.0 can be used to identify ARGs differing from those found in conventional databases and therefore improve the description of resistomes.

GRAPHICAL ABSTRACT

Caption: Additional use of ResFinderFG v2.0 database (composed of antibiotic resistance genes obtained with functional metagenomics) on the Center of Genomic Epidemiology webserver (https://cge.food.dtu.dk/services/ResFinderFG/), allows for more exhaustive resistome descriptions.
RyR2 regulates store-operated Ca2+entry, phospholipase C activity, and electrical excitability in the insulinoma cell line INS-1
Authors: Harvey Kyle E. , Tang Shiqi , LaVigne Emily K. , Pratt Evan P.S. , Hockerman Gregory H.
Published: October 2022

The ER Ca2+channel ryanodine receptor 2 (RyR2) is required for maintenance of insulin content and glucose-stimulated insulin secretion, in part, via regulation of the protein IRBIT in the insulinoma cell line INS-1. Here, we examined store-operated and depolarization-dependent Ca2+entry using INS-1 cells in which either RyR2 or IRBIT were deleted. Store-operated Ca2+entry (SOCE) stimulated with thapsigargin was reduced in RyR2KOcells compared to controls, but was unchanged in IRBITKOcells. STIM1 protein levels were not different between the three cell lines. Basal and stimulated (500 μM carbachol) phospholipase C (PLC) activity was also reduced specifically in RyR2KOcells. Insulin secretion stimulated by tolbutamide was reduced in RyR2KOand IRBITKOcells compared to controls, but was potentiated by an EPAC-selective cAMP analog in all three cell lines. Cellular PIP2levels were increased and cortical f-actin levels were reduced in RyR2KOcells compared to controls. Whole-cell Cavchannel current density was increased by 65% in RyR2KOcells compared to controls, and barium current was reduced by acute activation of the lipid phosphatase pseudojanin preferentially in RyR2KOcells over control INS-1 cells. Action potentials stimulated by 18 mM glucose were more frequent in RyR2KOcells compared to controls, and insensitive to the SK channel inhibitor apamin. Taken together, these results suggest that RyR2 plays a critical role in regulating PLC activity and PIP2levels via regulation of SOCE. RyR2 also regulates β-cell electrical activity by controlling Cavcurrent density, via regulation of PIP2levels, and SK channel activation.
Cardiolipin synthesis inPseudomonas fluorescensUM270 plays a relevant role in stimulating plant growth under salt stress
Authors: Rojas-Solis Daniel , Vences-Guzman Miguel A. , Sohlenkamp Christian , Santoyo Gustavo
Published: October 2022

Membrane cardiolipin (CL) phospholipids play a fundamental role in the adaptation of bacteria to various environmental conditions, including saline stress. Here, we constructed deletion mutants of two CL synthetase genes,clsAandclsB, in the rhizobacteriumPseudomonas fluorescensUM270, and evaluated their role in plant growth promotion under salt stress.P. fluorescensUM270 ΔclsAand ΔclsBmutants showed a significant reduction in CL synthesis compared to the UM270 wild-type strain (58% ΔclsAand 53% ΔclsB), and their growth rate was not affected, except when grown at 100 and 200 mM NaCl. Additionally, the root colonization capacity of both mutant strains was impaired compared with that of the wild type. Concomitant with the deletion ofclsAandclsB, some physiological changes were observed in the UM270 ΔclsAand ΔclsBmutants, such as a reduction in indole acetic acid and biofilm production. By contrast, an increase in siderophore biosynthesis was observed. Further, inoculation of the UM270 wild-type strain in tomato plants (Lycopersicon esculentumSaladette) grown under salt stress conditions (100 and 200 mM NaCl) resulted in an increase in root and shoot length, chlorophyll content, and dry weight. On the contrary, when each of the mutants(ΔclsAand ΔclsB) were inoculated in tomato plants, a reduction in root length was observed when grown at 200 mM NaCl, but the shoot length, chlorophyll content, and total plant dry weight parameters were significantly reduced under normal or saline conditions (100 and 200 mM NaCl), compared to UM270 wild-type-inoculated plants. In conclusion, these results suggest that CL synthesis inP. fluorescensUM270 plays an important role in the promotion of tomato plant growth under normal conditions, but to a greater extent, under salt-stress conditions.
Timing and magnitude of the type-I interferon response are determinants of disease tolerance in arbovirus infection
Authors: Hardy Alexandra , Bakshi Siddharth , Furnon Wilhelm , MacLean Oscar , Gu Quan , Varjak Margus , Varela Mariana , Aziz Muhamad A , Shaw Andrew , Pinto Rute Maria , Ruiz Natalia Cameron , Mullan Catrina , Taggart Aislynn , Filipe Ana , Randall Richard E. , Wilson Sam , Stewart Meredith E. , Palmarini Massimo
Published: October 2022

Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: (i) “resistance”, directed to abrogate virus replication, or (ii) “disease tolerance”, aimed to avoid organ and tissue damage without overly controlling viral burden. The overall principles governing pathogen resistance are well understood, while less is known about those involved in disease tolerance. Here, we studied bluetongue virus (BTV), the cause of a major disease of ruminants, bluetongue, as a model system to investigate the mechanisms of disease tolerance. BTV induces clinical disease mainly in sheep, while cattle are considered reservoirs of infection, rarely exhibiting clinical symptoms despite sustained viremia. Here, we show that BTV consistently reaches higher titres in ovine primary cells, compared to cells derived from cattle. The variable replication kinetics of BTV in sheep and cattle cells were mostly abolished by abrogating the cell type-I interferon (IFN) response. By screening a library of bovine interferon stimulated genes (ISGs), we identified restriction factors blocking BTV replication, however both sheep and cattle orthologues of these antiviral genes possess anti-BTV properties. Importantly, we demonstrate that BTV induces a faster host cell protein synthesis shutoff in primary sheep cells, compared to cattle cells, which results in an earlier downregulation of antiviral proteins. Moreover, by RNAseq we also show a more pronounced expression of ISGs in BTV infected cattle cells compared to sheep cells. Our data provide a new perspective on how the type-I IFN response in reservoir species can have overall positive effects on both virus and host evolution.
L-Aspartate oxidase provides new insights into fumarate reduction in anaerobic darkness inSynechocystissp. PCC6803
Authors: Kukil Kateryna , Hawkes Jeffrey A. , Blikstad Cecilia , Lindberg Pia
Published: October 2022

Cyanobacteria are promising microbial hosts for production of various industrially relevant compounds, such as succinate, a central metabolite of the tricarboxylic acid cycle (TCA). Cyanobacteria have been engineered to produce succinate during photoautotrophic growth, and are also able to secrete it during anoxic fermentation conditions. It has been assumed that under anoxic darkness, succinate can be formed by reduction of fumarate catalyzed by the succinate dehydrogenase complex (SDH), however, no characterization of SDH regarding this activity has been performed. In this study, we address this issue by generating strains of the unicellular cyanobacteriumSynechocystisPCC 6803 (Synechocystis) deficient in one or several subunits of SDH, and investigating succinate accumulation in these strains during dark anaerobic fermentation. The results showed higher succinate accumulation in SDH deletion strains than in the wild type, indicating a succinate dehydrogenase activity of SDH rather than fumarate reduction under these conditions. We further explored the possibility of another potential route for succinate formation from fumarate via L-aspartate oxidase (Laspo). The gene encoding Laspo inSynechocystiscould not be inactivated, indicating an essential function for this enzyme. Using purifiedSynLaspo, we could demonstratein vitrothat in addition to L-aspartate oxidation the enzyme exhibits an L-aspartate-fumarate oxidoreductase activity. We therefore suggest that reduction of fumarate to succinate during anoxic darkness can be a byproduct of the Laspo reaction, which is the first step in biosynthesis of NAD cofactors. This work contributes to the understanding of cyanobacterial TCA cycle for future engineering and sustainable production of dicarboxylic acids.
ATP modulates self-perpetuating conformational conversion generating structurally distinct yeast prion amyloids that limit autocatalytic amplification
Authors: Mahapatra Sayanta , Sarbahi Anusha , Punia Neha , Joshi Ashish , Avni Anamika , Walimbe Anuja , Mukhopadhyay Samrat
Published: October 2022

Prion-like self-perpetuating conformational conversion of proteins into amyloid aggregates is associated with both transmissible neurodegenerative diseases and non-Mendelian inheritance. Here, we demonstrate that ATP modulates the formation and dissolution of amyloids from a yeast prion domain (NM domain ofSaccharomyces cerevisiaeSup35) and restricts autocatalytic amplification by controlling the amount of fragmentable and seeding-competent aggregates. ATP, at (high) physiological concentrations in the presence of Mg2+, kinetically accelerates NM aggregation. Interestingly, ATP also promotes phase-separation-mediated aggregation of a human protein harboring a yeast prion-like domain. We also show that ATP dose independently disaggregates preformed NM fibrils. Furthermore, high concentrations of ATP delimited the number of seeds by generating compact, ATP-bound NM fibrils that exhibited nominal fragmentation by either free ATP or Hsp104 disaggregase. Additionally, (low) pathological ATP concentrations restricted autocatalytic amplification by forming structurally distinct seeding-inefficient amyloids. Our results provide mechanistic underpinnings of concentration-dependent chemical chaperoning by ATP against prion-like transmissions.
PP2A-B55α controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus
Authors: Perl Abbey L , Koetsier Jennifer L , Green Kathleen J
Published: October 2022

Critical for the maintenance of epidermal integrity and function are attachments between intermediate filaments (IF) and intercellular junctions called desmosomes. The desmosomal cytoplasmic plaque protein desmoplakin (DP) is essential for anchoring IF to the junction. DP-IF interactions are regulated by a phospho-regulatory motif within the DP C-terminus controlling keratinocyte intercellular adhesion. Here we identify the protein phosphatase 2A (PP2A)-B55α holoenzyme as the major serine/threonine phosphatase regulating DP’s C-terminus and consequent intercellular adhesion. Using a combination of chemical and genetic approaches, we show that the PP2A-B55α holoenzyme interacts with DP at intercellular membranes in 2D- and 3D- epidermal models and human skin samples. Our experiments demonstrate that PP2A-B55α regulates the phosphorylation status of junctional DP and is required for maintaining strong desmosome-mediated intercellular adhesion. These data identify PP2A-B55α as part of a regulatory module capable of tuning intercellular adhesion strength and a candidate disease target in desmosome-related disorders of the skin and heart.
Patterning of phase-separated condensates by Dnd1 controls cell fate
Authors: Westerich Kim Joana , Tarbashevich Katsiaryna , Gupta Antra , Zhu Mingzhao , Hull Kenneth , Romo Daniel , Gross-Thebing Theresa , Raz Erez
Published: October 2022

Germ granules, condensates of phase-separated RNA and protein, are essential for germline development, but how these molecules are organized within the granules and whether such an organization is relevant for germ cell fate is unclear. Combining three-dimensionalin vivostructural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the vertebrate-specific Dead end protein is essential for positioningnanos3RNA at the condensates’ periphery, where ribosomes are located. Without Dead end, or when translation is inhibited,nanos3RNA translocates into granule interiors, far from the ribosomes’ location. These findings reveal the molecular mechanisms controlling the spatial organization of RNA within the phase-separated organelle and the importance of subgranule RNA localization for preserving germ cell totipotency.
Extracellular matrix stiffness regulates fibroblast differentiation by influencing DNA methyltransferase 1 expression through microtubule polymerization
Authors: Zhao Zhihan , Huang Guotao , He Yong , Zuo Xiaohu , Han Wuyue , Li Hong
Published: October 2022

Cells sense physical cues, such as changes in extracellular matrix (ECM) stiffness, and translate these stimuli into biochemical signals that control various aspects of cellular behavior, thereby facilitating physiological and pathological processes in various organs. Evidence from multiple studies suggests that the anterior vaginal wall stiffness is higher in POP patients than in non-POP patients. Our experiments found that the expression of α-smooth muscle actin (α-SMA) in the anterior vaginal wall of patients with POP was increased, and the expression of DNMT1 was decreased. We used polyacrylamide gel to simulate matrix stiffening in vitro, and substrate stiffening induced the high expression of myofibroblast markers α-SMA and CTGF in L929 cells. Inhibition of DNMT1 promotes fibroblast differentiation into myofibroblasts in vitro. The results of bioinformatics analysis showed that the expression of DNMT1 was significantly correlated with microtubule polymerization-related proteins. The experiment showed that the microtubule polymerization inhibitor nocodazole could eliminate the decrease of DNMT1 expression in fibroblasts induced by high stiffness. We conclude that fibroblasts sense an increase in the stiffness of the surrounding matrix and regulate fibroblast differentiation by regulating the expression of DNA methyltransferase 1 (DNMT1) through the regulation of microtubule polymerization. This study may help to elucidate the complex crosstalk between vaginal fibroblasts and their surrounding matrix in both healthy and pathological conditions, and provide new insights into the implications of potentially targeted phenotypic regulation mechanisms in material-related therapeutic applications.
Multi-crystal native-SAD phasing at 5 keV with a helium environment
Authors: Karasawa Akira , Andi Babak , Fuchs Martin R. , Shi Wuxian , McSweeney Sean , Hendrickson Wayne A. , Liu Qun
Published: October 2022

De novo structure determination from single-wavelength anomalous diffraction using native sulfur or phosphorus in biomolecules (native-SAD) is an appealing method to mitigate the labor-intensive production of heavy-atom derivatives and selenomethionyl substitutions. The native-SAD method is particularly attractive for membrane proteins, which are difficult to produce and often recalcitrant to grow into decent-sized crystals. Native-SAD uses lower-energy X-rays to enhance anomalous signals from sulfur or phosphorus. However, at lower energies, the scattering and absorption of air contribute to the background noise, reduce the signals and are thus adverse to native-SAD phasing. We have previously demonstrated native-SAD phasing at an energy of 5 keV in air at the NSLS-II FMX beamline. Here, the use of a helium path developed to reduce both the noise from background scattering and the air absorption of the diffracted X-ray beam are described. The helium path was used for collection of anomalous diffraction data at 5 keV for two proteins: thaumatin and the membrane protein TehA. Although anomalous signals from each individual crystal are very weak, robust anomalous signals are obtained from data assembled from micrometre-sized crystals. The thaumatin structure was determined from 15 microcrystals and the TehA structure from 18 microcrystals. These results demonstrate the usefulness of a helium environment in support of native-SAD phasing at 5 keV.
Subcritical fluid extraction of antioxidant compounds from soybean seed coats (Glycine max (L.) Merr.)
Authors: Bergesse Antonella Estefania , Velez Alexis Rafael , Ryan Liliana Cecilia , Nepote Valeria
Published: October 2022

Purpose

The aim of this work was to evaluate the efficiency of subcritical conditions using different water–ethanol mixtures to recover antioxidant compounds from soybean seed coats (SSCs).

Design/methodology/approach

SSCs were subjected to high temperature and pressure conditions, using ethanol–water mixtures as extractive solvent, to obtain phenolic and flavonoid compounds with antioxidant activity. A mathematical model, namely one-site desorption kinetic model, was used to describe the extraction kinetics.

Findings

Temperature, solvent mass flow rate and solvent composition were studied, and the best extraction conditions were defined by a screening design. The maximum concentration of phenolics was obtained at 220 °C, 50% of ethanol and 2.5 g/min of solvent mass flow rate and a high antioxidant capacity toward different techniques was achieved. The one-site desorption kinetic model showed that before 30 min under optimal conditions, more than 90% of phenolics and flavonoids were recovered, a shorter extraction time than the commonly used at normal pressure and room temperature.

Originality/value

The seed coat is a major by-product of soybean processing, and it only markets as a low value ruminant feed. To date, there are no reports on the extract phenolics from SSCs by means of this methodology. The extraction technique described in this study provides a potential alternative for extraction of bioactive compounds from SSCs. This study contributes to adding value to this industrial waste and, ultimately, to optimize the postharvest production chain of soybean grains.
Numerical simulation of drop deformation under simple shear flow of Giesekus fluids by SPH
Authors: Moinfar Zahra , Vahabi Shahed , Vahabi Mohammad
Published: October 2022

Purpose

The purpose of this study is to investigate the effects of the shear-thinning viscoelastic behavior of the surrounding matrix on droplet deformation by weakly compressible smoothed particle hydrodynamics (WC-SPH). Also, the effect of the presence of another droplet is examined.

Design/methodology/approach

A modified consistent weakly compressible SPH method is proposed. After code verification, a complete parameter study is performed for a drop under the simple shear flow of a Giesekus liquid. The investigated parameters are 0.048≤Ca ≤ 14.4, 0.1≤c ≤ 10, 0.04≤De ≤ 10, 0≤α ≤ 1 and 0.12≤Re ≤ 12.

Findings

It is demonstrated that the rheological behavior of the surrounding fluid could dramatically affect the droplet deformation. It is shown that the droplet deformation is increased by increasing Re and Ca. In contrast, the droplet deformation is decreased by increasing a, De and polymer content. Also, it is indicated the presence of another droplet could drastically affect the flow field, and the primary stress difference (N1) is resonated between two droplets.

Originality/value

The main originality of this paper is to introduce a new consistent WC-SPH algorithm. The proposed method is very versatile for tackling the shear-thinning viscoelastic multiphase problems. Furthermore, a complete parameter study is performed for a drop under the simple shear flow of Giesekus liquid. Another novelty of the current paper is studying the effect of the presence of a second droplet. To the best of the authors’ knowledge, this is performed for the first time.
A novel trussed fin-and-elliptical tube heat exchanger with periodic cellular lattice structures
Authors: Lotfi Babak , Sunden Bengt Ake
Published: October 2022

Purpose

This study aims to computational numerical simulations to clarify and explore the influences of periodic cellular lattice (PCL) morphological parameters – such as lattice structure topology (simple cubic, body-centered cubic, z-reinforced body-centered cubic [BCCZ], face-centered cubic and z-reinforced face-centered cubic [FCCZ] lattice structures) and porosity value ( ) – on the thermal-hydraulic characteristics of the novel trussed fin-and-elliptical tube heat exchanger (FETHX), which has led to a deeper understanding of the superior heat transfer enhancement ability of the PCL structure.

Design/methodology/approach

A three-dimensional computational fluid dynamics (CFD) model is proposed in this paper to provide better understanding of the fluid flow and heat transfer behavior of the PCL structures in the trussed FETHXs associated with different structure topologies and high-porosities. The flow governing equations of the trussed FETHX are solved by the CFD software ANSYS CFX® and use the Menter SST turbulence model to accurately predict flow characteristics in the fluid flow region.

Findings

The thermal-hydraulic performance benchmarks analysis – such as field synergy performance and performance evaluation criteria – conducted during this research successfully identified demonstrates that if the high porosity of all PCL structures decrease to 92%, the best thermal-hydraulic performance is provided. Overall, according to the obtained outcomes, the trussed FETHX with the advantages of using BCCZ lattice structure at 92% porosity presents good thermal-hydraulic performance enhancement among all the investigated PCL structures.

Originality/value

To the best of the authors’ knowledge, this paper is one of the first in the literature that provides thorough thermal-hydraulic characteristics of a novel trussed FETHX with high-porosity PCL structures.
A contextual understanding of diaspora entrepreneurship: identity, opportunity and resources in the Sri Lankan Tamil and Kurdish diasporas
Authors: Syrett Stephen , Keles Janroj Yilmaz
Published: October 2022

Purpose

Within the growing study of transnational entrepreneurial practice, existing conceptualisation of diaspora entrepreneurship has often lacked engagement with the particularities of the diaspora condition. This paper seeks to advance theoretical understanding and empirical study of diaspora entrepreneurship through identifying the processes that generate diaspora entrepreneurship across economic, social and political spheres.

Design/methodology/approach

To analyse the relationship between the development of venture activity and diaspora (re)production, in depth, qualitative biographical analysis was undertaken with UK-based diaspora entrepreneurs embedded within the particular contexts of the Sri Lankan Tamil and Kurdish diasporas. Skilled and active diaspora entrepreneurs were purposively selected from these extreme case contexts to explore their entrepreneurial agency within and across the business, social and political realms.

Findings

Results identified key dimensions shaping the development of diaspora entrepreneurship. These comprised the role of diaspora context in shaping opportunity frameworks and the mobilisation of available resources, and how venture activity served to sustain collective diaspora identity and address diaspora interests. These findings are used to produce an analytical model of the generation of diaspora entrepreneurship to serve as a basis for discussing how heterogeneous and hybrid entrepreneurial strategies emerge from and shape the evolving diaspora context.

Originality/value

By placing the reproduction of social collectivity centre-stage, this paper identifies the particularities of diaspora entrepreneurship as a form of transnational entrepreneurship. This recognizes the significance of a contextualised understanding of entrepreneurial diversity within wider processes of diaspora development, which has important implications for policy and practice development in homeland and settlement areas.
Construing travelers’ choice on peer-to-peer accommodation-sharing platform: an investigation into cultural identity and accommodation type
Authors: Hou Tingting , Fu Shixuan , Cao Yichen , Zheng Xiaojiang , Yu Jianhua (Jordan)
Published: October 2022

Purpose

This research is motivated by the increasing need for international interactions during the gradual recovery of the tourism industry. By recognizing the paucity of research on cultural closeness and accommodation categories, this research aims to illuminate the influencing mechanisms of psychological closeness and travelers’ willingness to book an accommodation-sharing property while booking an accommodation.

Design/methodology/approach

The authors employ a mixed-methods approach, including an experiment and semistructured interviews.

Findings

Results show that hosts’ higher cultural identity congruence leads to travelers’ higher willingness to book an accommodation-sharing property. Psychological closeness mediates the positive effect of cultural identity congruence on travelers’ willingness to book. The authors further explore the moderating role of room types (entire room vs. private room) and find that the mediation effect is stronger for booking an entire room.

Originality/value

The current research underlines the importance of cultural identity congruence and accommodation type on travelers’ willingness to book an accommodation-sharing property and psychological closeness.
How can the subjective well-being of nurses be predicted? Understanding the mediating effect of psychological distress, psychological resilience and emotional exhaustion
Authors: Anasori Elham , Kucukergin Kemal Gurkan , Soliman Mohammad , Tulucu Fadime , Altinay Levent
Published: October 2022

Purpose

This paper aims to examine the relationships among work–family conflict (WFC), cognitive regulation, psychological resilience (PR), psychological distress (PD), emotional exhaustion (EE) and subjective well-being (SWB) in a very complex model based on job demands–resources. Also, mediator roles of PD, PR and EE are analyzed.

Design/methodology/approach

Data for the study were collected from 158 full-time nurses working in two hospitals in North Cyprus. Partial Least Squares-Structural Equation Modelling (PLS-SEM) was used to test the model.

Findings

The authors’ findings reveal that cognitive emotion regulation reduces employees' WFC. WFC also has a negative effect on employees' SWB directly and through the mediating role of EE. However, the role of PR in the relationship between cognitive emotion regulation and PD was not significant.

Originality/value

The study adds the original views for hospitals and service providers to recognize the factors which exert detrimental effects on employees' mental health and also the factors which help them to tackle the harsh situation specifically in the time of crisis. Theoretical and practical implications are provided in the study.
G-code generation in a NURBS workflow for precise additive manufacturing
Authors: Chacón Jesús Miguel , Sánchez-Reyes Javier , Vallejo Javier , Núñez Pedro José
Published: October 2022

Purpose

Non-uniform rational B-splines (NURBSs) are the de facto standard for representing objects in computer-aided design (CAD). The purpose of this paper is to discuss how to stick to this standard in all phases of the additive manufacturing (AM) workflow, from the CAD object to the final G-code, bypassing unnecessary polygonal approximations.

Design/methodology/approach

The authors use a commercial CAD system (Rhino3D along with its programming environment Grasshopper) for direct slicing of the model, offset generation and trimming. Circular arcs are represented as quadratic NURBSs and free-form geometry as quadratic or cubic polynomial B-splines. Therefore, circular arcs are directly expressible as G2/G3 G-code commands, whereas free-form paths are rewritten as a succession of cubic Bézier curves, thereby admitting exact translation into G5 commands, available in firmware for AM controllers, such as Marlin.

Findings

Experimental results of this paper confirm a considerable improvement in quality over the standard AM workflow, consisting of an initial polygonization of the object (e.g. via standard tessellation language), slicing this polygonal approximation, offsetting the polygonal sections and, finally, generating G-code made up of polyline trajectories (G1 commands).

Originality/value

A streamlined AM workflow is obtained, with a seamless transfer from the initial CAD description to the final G-code. By adhering to the NURBS standard at all steps, the authors avoid multiple representations and associated errors resulting from approximations.
Are families supported to come to terms with an autism diagnosis? A service evaluation of referrals to family therapy for young people with autism in one NHS trust
Authors: Burton Lauren , Fox Claudine
Published: October 2022

Young people with autism are increasingly being referred for family therapy (FT) owing to impaired family functioning, but few studies have investigated the support families receive following a diagnosis through specific NHS Trusts. This study examined (1) the proportion of autism cases referred for FT in one Trust and (2) the post‐diagnostic support families received. Participants (n = 144; 9.5–19.3 years) were FT referrals between 2019–2020. Autism diagnostic status and the support families received from FT, from the neurodevelopmental (ND) service which specialises in autism, and for co‐occurring conditions [e.g., cognitive behavioural therapy (CBT)] was extracted retrospectively from routine data. Forty FT referrals met autism criteria: several families did not receive FT; few were provided with support from the ND service; and if CBT was offered, no adaptations for autism were noted. Families received insufficient support following a diagnosis through this Trust. Implications include improving post‐diagnostic support for families in practice.
Construction and comprehensive analysis of the biological network related to rheumatoid arthritis‐related interstitial lung disease
Authors: Zhou Wei , Ma Xianghui , Jia Xiaodong , Zheng Juan , Yan Lili , Fu Yanfa
Published: October 2022

Objective

Interstitial lung disease (ILD) is a severe manifestation of rheumatoid arthritis (RA), which is characterized by low survival time post‐diagnosis. Thus, it is important to explore the role of gene regulation related with ILD.

Method

Constructed a RA‐ILD‐related long chain noncoding RNA – messenger RNA (lncRNA‐mRNA) network (ILD‐LMN), based on ILD‐ and RA‐related genes. We analyzed the topological properties of the resulting network.

Result

The results for network modularization and functional analysis showed that ILD‐LMN performed basic and specific functions in ILD pathology. Furthermore, differential expression and correlation analysis of hub nodes revealed highly correlated competitive endogenous RNA regulatory relationships with important roles in pathological regulation. Following this, statistical analysis of disease‐related single nucleotide polymorphisms (SNPs) in hub lncRNAs revealed that some of transcription factor‐related SNPs were significantly associated with the expression of lncRNA. In fact, these SNPs exhibited significant differential expression in disease and normal samples.

Conclusion

These results suggest that ILD‐LMN has important implications in the study of disease. Altogether, the study of RA‐ and ILD‐related lncRNA and genes on the basis of biological network would assist in providing better treatment opportunities for ILD patients. Additionally, it would promote further research on treatment of the disease.
Thromboembolic and bleeding events in ICU patients with COVID‐19: A nationwide, observational study
Authors: Russell Lene , Weihe Sarah , Madsen Emilie Kabel , Hvas Christine Lodberg , Leistner Jens Wolfgang , Michelsen Jens , Brøchner Anne Craveiro , Bastiansen Anders , Nielsen Frederik Mølgaard , Meier Nick , Andreasen Anne Sofie , Ribergaard Niels‐Erik , Rasmussen Bodil Steen , Sølling Christoffer Grant , Buck David Levarett , Bundgaard Helle , Pedersen Helle Scharling , Darfelt Iben Strøm , Poulsen Lone Musaeus , Ibsen Michael , Plovsing Ronni R. , Sigurdsson Sigurdur T. , Iversen Susanne , Hildebrandt Thomas , Mohr Thomas , Espelund Ulrick Skipper , Jørgensen Vibeke , Haase Nicolai , Perner Anders
Published: October 2022

Background

Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID‐19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID‐19 in Denmark during the first and second waves of the pandemic.

Methods

This was a sub‐study of the Danish Intensive Care Covid database, in which all patients with SARS‐CoV‐2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included. We registered coagulation variables at admission, and all thromboembolic and bleeding events, and the use of heparins during ICU stay. Variables associated with thrombosis and bleeding and any association with 90‐day mortality were estimated using Cox regression analyses.

Results

We included 1369 patients in this sub‐study; 158 (12%, 95% confidence interval 10–13) had a thromboembolic event in ICU and 309 (23%, 20–25) had a bleeding event, among whom 81 patients (6%, 4.8–7.3) had major bleeding. We found that mechanical ventilation and increased D‐dimer were associated with thrombosis and mechanical ventilation, low platelet count and presence of haematological malignancy were associated with bleeding. Most patients (76%) received increased doses of thromboprophylaxis during their ICU stay. Thromboembolic events were not associated with mortality in adjusted analysis (hazard ratio 1.35 [0.91–2.01, p = .14], whereas bleeding events were 1.55 [1.18–2.05, p = .002]).

Conclusions

Both thromboembolic and bleeding events frequently occurred in ICU patients with COVID‐19. Based on these data, it is not apparent that increased doses of thromboprophylaxis were beneficial.
Glycemic control and blood gas sampling frequency during continuous glucose monitoring in the intensive care unit: A before‐and‐after study
Authors: Mårtensson Johan , Cutuli Salvatore , Yanase Fumitaka , Ancona Paolo , Toh Lisa , Osawa Eduardo , Bellomo Rinaldo
Published: October 2022

Background

Whether subcutaneous continuous glucose monitoring (CGM) can safely replace intermittent arterial blood gas glucose analyses in intensive care unit (ICU) patients remains uncertain. We aimed to compare CGM to blood gas glucose values and assess whether CGM use reduces blood gas sampling frequency and glucose variability in ICU patients with type 2 diabetes managed with liberal glucose control.

Methods

We used the FreeStyle Libre CGM in 15 ICU patients and compared their blood glucose metrics with a pre‐CGM control population of 105 ICU patients with type 2 diabetes. Both groups received insulin to target glucose range of 10–14 mmol/L. We used linear regression analysis adjusted for illness severity to assess the association of CGM use with blood gas sampling frequency and glucose variability. We used mean absolute relative difference (MARD) and Clarke error grid analysis to assess accuracy of matched CGM‐blood glucose values overall, across glucose stata (<10, 10–14, >14 mmol/L), and over time (≤48, 48–96, >96 h).

Results

We analyzed 483 matched glucose values. Overall MARD was 11.5 (95% CI, 10.7–12.3)% with 99% of readings in Clarke zones A and B. MARD was 15.5% for glucose values <10 mmol/L, 11.1% at 10–14 mmol/L, and 11.4% >14 mmol/L. MARD was 13.8% in the first 48 h, 10.9% at 48–96 h, and 8.9% beyond 96 h. CGM use was associated with 30% reduction in blood gas sampling frequency. CGM use was not associated with glucose variability as determined by glycemic lability index or standard deviation of blood glucose.

Conclusions

In our cohort of ICU patients with type 2 diabetes receiving liberal glycemic control, CGM showed acceptable accuracy and was associated with a reduction in blood gas sampling frequency without compromising glucose control. Lowest accuracy was observed at glucose values below 10 mmol/L and during the first 48 h of CGM use.
Who are the patients who deny suicidal intent? Exploring patients' characteristics associated with self‐disclosure and denial of suicidal intent
Authors: Bloch‐Elkouby Sarah , Zilcha‐Mano Sigal , Rogers Megan L. , Park Ji Yoon , Manlongat Katherine , Krumerman Mia , Galynker Igor
Published: October 2022

Background

Patients' non‐disclosure of suicidal ideation and intent concealment represent a major obstacle to the effective assessment of suicide risk and to the delivery of suicide prevention treatments. The present study aimed to investigate this phenomenon and to assess (1) if outpatient psychiatric patients are more or less likely to disclose intent to mental health clinicians in the context of psychiatric/psychological treatment than they are to in the context of research interviews with non‐clinicians; and (2) if certain demographic, trait‐like, and state‐like characteristics may predict such disclosure differences.

Methods

A total of 780 psychiatric outpatient participants aged 18 to 84 and 193 clinician participants aged 25 to 54 were included in the study. The proportion of patients who disclosed to clinicians only, to research assistants (RAs) only, to both, and to none, was compared using a z‐test. Univariate analyses were used to compare the participants' variables across disclosure groups, and significant individual predictors were included in multilevel regression analyses.

Results

Participants were more significantly more likely to disclose to RAs (10.4%) than to clinicians (5.6%), p < 0.001. Neuroticism and trait anxiety predicted disclosure to RAs vs no disclosure; low extraversion predicted disclosure to clinician versus no disclosure; and extraversion and trait anxiety predicted disclosure to RAs versus to clinicians.

Discussion

Patients' disclosure patterns, the personality variables predicting them, and their clinical implications were discussed in the context of the extant literature on patients' reasons for concealing suicidal ideation and intent.