bluuebunny/crossref_metadata_2025 huggingface dataset:
Basic helix-loop-helix pioneer factors interact with the histone octamer to invade nucleosomes and generate nucleosome depleted regions
Authors: Donovan Benjamin T. , Chen Hengye , Eek Priit , Meng Zhiyuan , Jipa Caroline , Tan Song , Bai Lu , Poirier Michael G.
Published: March 2022

Nucleosomes drastically limit transcription factor (TF) occupancy, while pioneer transcription factors (PFs) somehow circumvent this nucleosome barrier. In this study, we compare nucleosome binding of two conserved S. cerevisiae basic helix-loop-helix (bHLH) TFs, Cbf1 and Pho4. A Cryo-EM structure of Cbf1 in complex with the nucleosome reveals that the Cbf1 HLH region can electrostatically interact with exposed histone residues within a partially unwrapped nucleosome. Single molecule fluorescence studies show that the Cbf1 but not the Pho4 HLH region facilitates efficient nucleosome invasion by slowing its dissociation rate relative to DNA through interactions with histones. In vivo studies show that this enhanced binding provided by the Cbf1 HLH region enables nucleosome invasion and ensuing repositioning. These structural, single molecule, and in vivo studies reveal the mechanistic basis of dissociation rate compensation by pioneer factors and how this translates to facilitating chromatin opening inside cells.
Single-cell multiomics atlas of organoid development uncovers longitudinal molecular programs of cellular diversification of the human cerebral cortex
Authors: Uzquiano Ana , Kedaigle Amanda J. , Pigoni Martina , Paulsen Bruna , Adiconis Xian , Kim Kwanho , Faits Tyler , Nagaraja Surya , Antón-Bolaños Noelia , Gerhardinger Chiara , Tucewicz Ashley , Murray Evan , Jin Xin , Buenrostro Jason , Chen Fei , Velasco Silvia , Regev Aviv , Levin Joshua Z. , Arlotta Paola
Published: March 2022

Realizing the full utility of brain organoids as experimental systems to study human cortical development requires understanding whether organoids replicate the cellular and molecular events of this complex process precisely, reproducibly, and with fidelity to the embryo. Here we present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, spanning initial generation of neural progenitors through production of differentiated neuronal and glial subtypes. We define the lineage relationships and longitudinal molecular trajectories of cortical cell types during development in organoids, and show that developmental processes of cellular diversification in organoids correlate closely to endogenous ones, irrespective of metabolic state. Using this data, we identify genes with predicted human-specific roles in lineage establishment, and discover a developmental origin for the transcriptional diversity of human callosal projection neurons, a population that has undergone dramatic expansion and diversification during human evolution. Our work provides a comprehensive, single-cell molecular map of human corticogenesis in vitro, identifying developmental trajectories and molecular mechanisms associated with human cellular diversification.
A model for determining the length distribution of actin filaments in cells
Authors: Ueda Yuika , Matsunaga Daiki , Deguchi Shinji
Published: March 2022

Tensional homeostasis is a cellular process whereby nonmuscle cells such as fibroblasts keep a constant level of intracellular tension and signaling activities. Cells are allowed thanks to tensional homeostasis to adapt to mechanical stress, but the detailed mechanism remains unclear. Here we address from a theoretical point of view what is required for maintaining cellular tensional homeostasis. A constrained optimization problem is formulated to analytically determine the probability function of the length of individual actin filaments (AFs) responsible for sustaining cellular tension. An objective function composed of two entropic quantities measuring the extent of formation and dispersion of AFs within cells is optimized under two constraint functions dictating a constant amount of actin molecules and tension that are arguably the two most salient features of tensional homeostasis. We then derive a specific probability function of AFs that is qualitatively consistent with previous experimental observations, in which short AF populations preferably appear. Regarding the underlying mechanism, our analyses suggest that the constraint for keeping the constant tension level makes long AF populations smaller in number because long AFs have a higher chance to be involved in bearing larger forces. The specific length distribution of AFs is thus required for achieving the constrained objectives, by which individual cells are endowed with the ability to stably maintain a homeostatic tension throughout the cell, thereby potentially allowing cells to locally detect deviation in the tension, keep resulting biological functions, and hence enable subsequent adaptation to mechanical stress. Although minimal essential factors are included given the actual complexity of cells, our approach would provide a theoretical basis for understanding complicated homeostatic and adaptive behavior of the cell.
Diagnostic performance of non-invasive fibrosis markers for chronic hepatitis B in sub-Saharan Africa: a Bayesian individual patient data meta-analysis
Authors: Johannessen Asgeir , Stockdale Alexander J. , Henrion Marc Y.R. , Okeke Edith , Seydi Moussa , Wandeler Gilles , Sonderup Mark , Spearman C. Wendy , Vinikoor Michael , Sinkala Edford , Desalegn Hailemichael , Fall Fatou , Riches Nicholas , Davwar Pantong , Duguru Mary , Maponga Tongai , Taljaard Jantjie , Matthews Philippa C. , Andersson Monique , Sombie Roger , Shimakawa Yusuke , Lemoine Maud
Published: March 2022

Objective

In sub-Saharan Africa, hepatitis B is the principal cause of liver disease. Non-invasive biomarkers of liver fibrosis are needed to identify patients requiring antiviral treatment. We assessed aspartate aminotransferase-to-platelet ratio index (APRI), gamma-glutamyl transferase-to-platelet ratio (GPR) and FIB-4 to diagnose significant fibrosis and cirrhosis in an individual patient data (IPD) meta-analysis.

Design

In total, 3,549 patients from 12 cohorts of HBsAg positive individuals in 8 sub-Saharan African countries were included. Transient elastography was used as a reference test for cirrhosis (>12.2 kPa), excluding patients who were pregnant, had hepatitis C, D, or HIV co-infection, were on hepatitis B therapy, or had acute hepatitis. A bivariate Bayesian IPD model was fitted with patient-level covariates and study-level random effects.

Results

APRI and GPR had the best discriminant performance (area under receiver operating curve 0.81 and 0.82) relative to FIB-4 (0.77) for cirrhosis. The World Health Organization (WHO) recommended APRI threshold of ≥2.0 was associated with a sensitivity and specificity (95% credible interval) of 16.5% (12.5-20.5) and 99.5% (99.2-99.7) for cirrhosis. For APRI, we identified an optimised rule-in threshold for cirrhosis (cut-off 0.65) with a sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (cut-off 0.36) with a sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8).

Conclusions

The WHO recommended APRI threshold of 2.0 is too high to diagnose cirrhosis in sub-Saharan Africa. We identified new and optimised rule-in and rule-out thresholds for cirrhosis, with direct consequences for treatment guidelines in this setting.
The SUMO activating enzyme subunit, SAE2, contributes SUMO protein bias for mitotic fidelity
Authors: Walker Alexandra K. , Lanz Alexander J. , Jamshad Mohammed , Garvin Alexander J. , Wotherspoon Peter , Cooper Benjamin F. , Knowles Timothy J. , Morris Joanna R.
Published: March 2022

Mammalian cells possess three conjugatable SUMO variants: SUMO1 and the largely indistinguishable SUMO2 and SUMO3 (designated SUMO2/3). Some SUMOylated substrates are modified by both SUMO1 and SUMO2/3, while others show biased modifications towards SUMO1 or SUMO2/3. How preferential SUMO protein conjugation is coordinated is poorly understood.

Here, we examine a modification of the catalytic component of the human SUMO Activation Enzyme, SAE2. We observe that lysine 164 of SAE2 is deacetylated during mitosis in an HDAC6-dependent manner. We find that an acetyl-analogue mutant, SAE2-K164Q, biases the activation and conjugation of SUMO2>SUMO1 and discriminates SUMO1 and SUMO2/3 through their C-terminal tails.

Complementation of SAE2-depleted or inhibited cells with SAE2-K164Q restricts mitotic SUMO1-conjugates and increases multipolar spindle formation. We confirm the SUMO E1-dependent modification of the nuclear mitotic apparatus, NuMA, and find that the mitotic defects of both SAE2-K164Q complemented cells and HDAC6-inhibitor-treated cells are corrected by either over-expression of SUMO1 or by expression of a GFP-SUMO1-NuMA-K1766R fusion protein.

Our observations suggest a model in which the SAE1:SAE2 enzyme is deacetylated on early mitosis to encourage the conjugation of SUMO1 to support mitotic fidelity. These surprising data reveal that the SUMO-activating enzyme can bias SUMO variant conjugation.
COVID-19 patients have increased levels of membrane-associated and soluble CD48
Authors: Pahima Hadas , Zaffran Ilan , Ben-Chetrit Eli , Jarjoui Amir , Gaur Pratibha , Manca Maria Laura , Reichmann Dana , Orenbuch-Harroch Efrat , Puxeddu Ilaria , Zinner Carl , Tzankov Alexandar , Levi-Schaffer Francesca
Published: March 2022

COVID-19 is a respiratory-centered systemic disorder caused by SARS-CoV-2. The disease can progress into a severe form causing acute lung injury.

CD48 is a co-signaling receptor, existing as both membrane-bound and soluble forms reported to be dysregulated in several inflammatory conditions. Therefore, we reasoned that CD48 could be deregulated in COVID-19 as well.

Here we analyzed CD48 expression in autoptic sections and peripheral blood leukocytes and sera of COVID-19 patients by gene expression profiling (HTG® autoimmune panel), immunohistochemistry, flow cytometry and ELISA.

Lung tissue of COVID-19 patients showed increased CD48 mRNA expression and infiltration of CD48+ lymphocytes. In the peripheral blood, mCD48 was considerably increased on all evaluated cells, and additionally, sCD48 levels were significantly higher in COVID-19 patients independently of disease severity. Considering the alterations of mCD48 and sCD48, a specific role for CD48 in COVID-19 can be assumed, suggesting it as a potential target for therapy.
Hsp multichaperone complex buffers pathologically modified Tau
Authors: Moll Antonia , Ramirez Lisa Marie , Ninov Momchil , Schwarz Juliane , Urlaub Henning , Zweckstetter Markus
Published: March 2022

Alzheimer’s disease is a neurodegenerative disorder in which misfolding and aggregation of pathologically modified Tau is critical for neuronal dysfunction and degeneration. The two central chaperones Hsp70 and Hsp90 coordinate protein homeostasis, but the nature of the interaction of Tau with the Hsp70/Hsp90 machinery has remained enigmatic. Here we show that Tau is a high-affinity substrate of the human Hsp70/Hsp90 machinery. Complex formation involves extensive intermolecular contacts, blocks Tau aggregation and depends on Tau’s aggregation-prone repeat region. The Hsp90 co-chaperone p23 directly binds Tau and stabilizes the multichaperone/substrate complex, whereas the E3 ubiquitin-protein ligase CHIP efficiently disassembles the machinery targeting Tau to proteasomal degradation. Because phosphorylated Tau binds the Hsp70/Hsp90 machinery but is not recognized by Hsp90 alone, the data establish the Hsp70/Hsp90 multichaperone complex as a critical regulator of Tau in neurodegenerative diseases.
Loop extrusion driven volume phase transition of entangled chromosomes
Authors: Yamamoto Tetsuya , Schiessel Helmut
Published: March 2022

Mitotic chromosomes without nucleosomes have been reconstituted in recent experiments. When topo II is depleted from the reconstituted chromosomes, these chromosomes are entangled and form ‘sparklers’, where DNA is condensed in the core with linker histone H1.8 and condensin is localized at the periphery. To understand the mechanism of the assembly of sparklers, we here take into account the loop extrusion by condensin in an extension of the theory of entangled polymer gels. The loop extrusion stiffens an entangled DNA network because DNA segments in the elastically effective chains are translocated to loops, which are elastically ineffective. Our theory predicts that the loop extrusion by condensin drives the volume phase transition that collapses a swollen entangled DNA gel as the stiffening of the network destabilizes the swollen phase. This is an important element to understand the mechanism of the assembly of the reconstituted chromosomes.
Per-Pathogen Virulence of HIV-1 subtypes A, C and D
Authors: Bouman Judith A , Venner Colin M , Walker Courtney , Arts Eric J , Regoes Roland R
Published: March 2022

HIV-1 subtypes differ, among other things, in their clinical manifestations and the speed in which they spread. In particular, the frequency of subtype C is increasing relative to subtype A and D. We aim to investigate whether HIV-1 subtype A, C and D differ in their per-pathogen virulence and to what extend this can explain the difference in spread between these subtypes.

We use data from the Hormonal Contraception and HIV-1 Genital Shedding and Disease Progression among Women with Primary HIV Infection (GS) Study. For each study participant, we determine the set-point viral load value, CD4+ T cell level after primary infection and CD4+ T cell decline. Based on both the CD4+ T cell count after primary infection and CD4+ T cell decline, we estimate the time until AIDS for each individual. We then obtain our newly introduced measure of virulence as the inverse of the estimated time until AIDS. This new measure of virulence has an improved correlation with the set-point viral load compared to the decline of CD4+ T cells alone. After fitting a model to the measured virulence and set-point viral load values, we tested if this relation varies per subtype. We found that subtype C has a significantly higher per-pathogen virulence than subtype A. Based on an evolutionary model, we then hypothesize that differences in the primary length of infection period cause the observed variation in the speed of spread of the subtypes.

Author summary

HIV-1 subtype C is currently spreading relatively fast in various parts of the world. Data from a study that followed many women infected with different HIV-1 subtypes (A, C and D) before they started treatment shows that neither their viral load nor the disease duration are increased for subtype C compared to subtype A and D. Thus, it seems that subtype C does not have a transmission advantage, neither per contact nor due to longer infection, making the observed relative rise in subtype C a puzzle. We used the same data to test if subtype C has optimized its potential to spread by decreasing the disease duration per unit of viral load (per-pathogen virulence) compared to subtype A and D. However, we find that subtype C has a significantly higher per-pathogen virulence than subtype A and D. This result makes the rise of subtype C even more counter-intuitive.

In a last step, we develop an evolutionary model, in which we synthesize all our empirical results. With this model we can show that the most likely explanation for the global spread of subtype C is a difference in the duration of primary infection between the subtypes.
The RNA-binding protein EIF4A3 promotes axon development by direct control of the cytoskeleton
Authors: Alsina Fernando C. , Lupan Bianca M. , Lin Lydia J. , Musso Camila M. , Mosti Federica , Newman Carly R. , Wood Lisa M. , Agostino Mark , Moore Jeffrey K. , Silver Debra L.
Published: March 2022

The exon junction complex (EJC), nucleated by EIF4A3, is indispensable for mRNA fate and function throughout eukaryotes. Unexpectedly, we discover that EIF4A3 directly controls microtubules independent of RNA, and this is critical for neural wiring. While neuronal survival in the developing mouse cerebral cortex depends upon an intact EJC, axonal tract formation requires only Eif4a3. Using human cortical organoids, we demonstrate that EIF4A3 disease mutations also impair neuronal maturation, highlighting conserved functions relevant for neurodevelopmental pathology. Employing biochemistry and molecular modeling we discover that EIF4A3 directly binds to microtubules, mutually exclusive of the RNA-binding complex. In growing neurons, EIF4A3 is essential for microtubule dynamics, and sufficient to promote microtubule polymerization and stability in vitro. Together, our data show that tubulin-bound EIF4A3 orchestrates microtubule dynamics, underlying key events of neuronal development. This reveals a new mechanism by which neurons re-utilize core gene expression machinery to rapidly and directly control the cytoskeleton.

Highlights

The Exon Junction Complex controls neuronal survival but only EIF4A3 directs axonal growth

EIF4A3 controls axonal tract formation in vivo.

Human EIF4A3 deficient iPSC-derived cortical organoids recapitulate neuronal defects.

EIF4A3 directly binds to microtubules to control their growth and stability in neurons.
Technology applications in bovine gait analysis: a scoping review
Authors: Nejati Amir , Bradtmueller Anna , Shepley Elise , Vasseur Elsa
Published: March 2022

Quantitative bovine gait analysis using technology has evolved significantly over the last two decades. However, subjective methods of gait assessment using visual locomotion scoring remain the primary on-farm and experimental approach. The objective of this review is to map research trends in quantitative bovine gait analysis and to explore the technologies that have been utilized to measure biomechanical parameters of gait. A scoping literature review was conducted according to PRISMA guidelines. A search algorithm based on PICO framework generated three components – bovine, gait, and technology – to address our objectives. Three online databases were searched for original work published from January 2000 to June 2020. A two-step screening process was then conducted, starting with the review of article titles and abstracts based on inclusion criteria. A remaining 125 articles then underwent a full-text assessment, resulting in 82 final articles. Thematic analysis of research aims resulted in four major themes among the studies: gait/claw biomechanics, lameness detection, intervention/comparison, and system development. Lameness detection (55 % of studies) was the most common reason for technology use. Studies in the field of bovine gait analysis used three main technologies: force and pressure platforms (FPP), vision-based systems (VB), and accelerometers. FPP were the first and most popular technologies to evaluate bovine gait and were used in 58.5 % of studies. They include force platforms, pressure mapping systems, and weight distribution platforms. The second most applied technology was VB (34.1 % of studies), which predominately consists of video analysis and image processing systems. Accelerometers, another technological method to measure gait characteristics, were used in 14.6 % of studies. A strong demand for automatic lameness detection influences the path of development for quantitative gait analysis technologies. Although progress has been made, more research is needed to achieve more accurate, practical, and user-friendly technologies.
Synapses and Ca2+activity in oligodendrocyte precursor cells can predict where myelin sheaths form
Authors: Li Jiaxing , Miramontes Tania , Czopka Tim , Monk Kelly R.
Published: March 2022

In the nervous system, only one type of neuron-glial synapse is known to exist: that between neurons and oligodendrocyte precursor cells (OPCs). Neuron-OPC synapses are thought to bridge neuronal activity to OPCs. However, their composition, assembly, downstream signaling, andin vivofunctions remain largely unclear. Here, we use zebrafish to address these questions and identify postsynaptic molecules PSD-95 and Gephyrin in OPCs. They increase during early development and decrease upon OPC differentiation. PSD-95 and Gephyrin in OPCs are highly dynamic and frequently assemble at “hotspots.” Gephyrin hotspots and synapse-associated Ca2+activity in OPCs predict where a subset of myelin sheaths form in oligodendrocytes. Further analyses reveal that spontaneous synaptic release is integral to OPC Ca2+activity, while evoked synaptic release contributes only in early development. Finally, disruption of the synaptic genesdlg4a&b,gephyrinb, andnlgn3bimpairs OPC differentiation and myelination. Together, we propose that neuron-OPC synapses are dynamically assembled and can predetermine myelination patterns through Ca2+signaling.
Cross-cultural differences in consumers' attention to food labels
Authors: Ho Kenneth Fu Xian , Liu Fang , Tarabashkina Liudmila , Volery Thierry
Published: March 2022

Purpose

Extended from Hofstede’s cultural framework, this study investigated the differences between the Australian (representing the Western culture) and Chinese (representing the Eastern Culture) consumers in regard to their attention paid to product attribute cues presented on food labels and the degree of such attention controlling for an individual-level moderator of product involvement.

Design/methodology/approach

Data were collected using face-to-face interviews with semi-structured questionnaires for both Australian and Chinese samples. The questionnaire data were analysed using factorial between-groups analysis of variance (ANOVA) to investigate the influence of culture and product involvement on the attention paid/degree of attention to product nature-related (e.g. brand name), product assurance-related (e.g. country-of-origin) and health-related attribute (e.g. nutritional panel) cues.

Findings

The findings revealed that Chinese consumers, as compared to Australian consumers, paid attention to more product-assurance cues (i.e. country of origin) and health-related cues (i.e. bioactivity indicators). The degrees of attention to these cues were also greater among Chinese consumers than for Australian consumers. Product involvement moderated the relationship between culture and attention towards product nature and product assurance-related cues.

Practical implications

Results from this study enable exporters to customize their labelling design by strategically including label information that is more salient to certain export markets.

Originality/value

This study offers a novel insight into the impact of culture on consumers’ attention to food product attributes and the interaction effects of product involvement on these relationships, hitherto underexplored.
Comparative impacts of long‐term trends in snowmelt and species interactions on plant population dynamics
Authors: Campbell Diane R. , Price Mary V. , Waser Nickolas M. , Irwin Rebecca E. , Brody Alison K.
Published: March 2022

Climate change can impact plant fitness and population persistence directly through changing abiotic conditions and indirectly through its effects on species interactions. Pollination and seed predation are important biotic interactions that can impact plant fitness, but their impact on population growth rates relative to the role of direct climatic effects is unknown.

We combined 13 years of experiments on pollen limitation of seed set and pre‐dispersal seed predation in Ipomopsis aggregata, a subalpine wildflower, with a long‐term demographic study that has documented declining population growth with earlier spring snowmelt date. We determined how pollen limitation and seed predation changed with snowmelt date over 21 years and incorporated those effects into an integral projection model to assess relative impacts of biotic factors on population growth.

Both pollen limitation and the difference in stigma pollen load between pollen‐supplemented and control plants declined over years. Neither pollen limitation nor seed predation changed detectably with snowmelt date, suggesting an absence of indirect effects of that specific abiotic factor on these indices of biotic interactions. The projected biotic impacts of pollen limitation and seed predation on population growth rate were small compared to factors associated with snowmelt date. Providing full pollination would delay the projected date when earlier snowmelt will cause populations to fall below replacement by only 14 years.

Synthesis. Full pollination and elimination of seed predation would not compensate for the strong detrimental effects of early snowmelt on population growth rate, which in I. aggregata appears driven largely by abiotic environmental factors. The reduction over two decades in pollen limitation also suggests that natural selection on floral traits may weaken with continued climate change. These results highlight the value of studying both abiotic factors and biotic interactions to understand how climate change will influence plant populations.
The use of photos to investigate ecological change
Authors: Depauw Leen , Blondeel Haben , De Lombaerde Emiel , De Pauw Karen , Landuyt Dries , Lorer Eline , Vangansbeke Pieter , Vanneste Thomas , Verheyen Kris , De Frenne Pieter
Published: March 2022

Global change is causing ecosystems to change at unprecedented rates and the urgency to quantify ecological change is high. We therefore need all possible sources of ecological data to address key knowledge gaps.

Ground‐based photos are a form of remote sensing and an unconventional data source with a high potential to improve our understanding of ecological change. They can provide invaluable information on ecological conditions in the past and present at relevant spatiotemporal scales that is very difficult to obtain with other approaches.

Here we review the use of ground‐based photos in a set of relevant ecological research topics, such as biodiversity and community ecology, phenology, global change ecology and landscape ecology. We highlight three main photo‐based methods in ecological research (repeat photography, time‐lapse photography and public archives), alongside which we discuss three case studies to demonstrate novel applications of these methods, to answer fundamental ecological questions.

Synthesis. Photos can significantly support ecological research to improve our understanding of biotic responses in a rapidly changing world. Photos cover relatively large temporal and spatial scales, and can provide large amounts of information with limited time investment. To exploit their full potential, we need to invest not only in technological advances to compile, process and analyse images but also in proper data management.
Dialectal Layers in West Iranian: A Hierarchical Dirichlet Process Approach to Linguistic Relationships1
Authors: Cathcart Chundra A.
Published: March 2022

This paper addresses a series of complex and unresolved issues in the historical phonology of West Iranian languages, (Persian, Kurdish, Balochi, and other languages), which display a high degree of irregular, non‐Lautgesetzlich behaviour. Most of this irregularity is undoubtedly due to language contact; I argue, however, that an oversimplified view of the processes at work has prevailed in the literature on West Iranian dialectology, with specialists assuming that deviations from an expected outcome in a given non‐Persian language are due to lexical borrowing from some chronological stage of Persian. It is demonstrated that this qualitative approach yields at times problematic conclusions stemming from the lack of explicit probabilistic inferences regarding the distribution of the data: Persian may not be the sole donor language; additionally, borrowing at the lexical level is not always the mechanism that introduces irregularity. In many cases, the possibility that West Iranian languages show different reflexes in different conditioning environments remains under‐explored. I employ a novel Bayesian approach designed to overcome these problems and tease apart the different determinants of irregularity in patterns of West Iranian sound change. This methodology helps to provisionally resolve a number of outstanding questions in the literature on West Iranian dialectology concerning the dialectal affiliation of certain sound changes. I outline future directions for work of this sort.
Are we paying enough attention to uterine contractions?
Authors: Tarvonen Mikko
Published: March 2022

Linked article: This is a mini commentary on Tuija Hautakangas et al. pp. 1790–1797 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17128
Screening for late‐onset gestational diabetes: Are there any clinical benefits?
Authors: Cauldwell Matthew , Chmielewska Basia , Kaur Kiran , van‐de‐l'Isle Yolande , Sherry Anneka , Watt Coote Ingrid , Steer Philip J.
Published: March 2022

Objective

To determine whether screening for gestational diabetes mellitus (GDM) in the third trimester and managing those who are screen positive on a diabetes pathway affects obstetric and neonatal outcomes.

Design

Retrospective study of prospectively collected data.

Setting

London Teaching Hospital.

Population or sample

A total of 14 366 women delivering between 1 January 2018 and 31 December 2020.

Methods

Retrospective chart analysis.

Main outcome measures

Diagnosis of late‐onset GDM, obstetric and neonatal outcomes.

Results

Five hundred and thirty‐one women were tested by home glucose monitoring for late‐onset GDM from 33 weeks of gestation. In all, 244 were diagnosed as having GDM (group 1) and managed accordingly, and 287 (group 2) were returned to normal care. A total of 1415 women had GDM diagnosed by oral glucose tolerance test before 33 weeks of gestation (group 3). Of the women in group 2, 49.5% had a spontaneous onset of labour compared with only 25.8% and 27% in groups 1 and 3. However, women in group 2 were significantly more likely to have a macrosomic baby (≥4000 g, 25.4%) than groups 1 (16.0%) or 3 (7.2%), and their babies were more likely to be admitted to special care (5.2% versus 2% in group 1). Macrosomic babies were associated with significantly higher rates of shoulder dystocia, third‐ and fourth‐degree tears and postpartum haemorrhage.

Conclusions

Apparent late‐onset GDM affects a significant proportion of women, and targeted intervention was associated with better obstetric and neonatal outcomes. These results suggest that all pregnancies with risk factors for late‐onset GDM might benefit from active GDM management irrespective of specific glucose thresholds.

Tweetable abstract

Women with risk factors for GDM in the third trimester, and their babies, would probably benefit from active management of their blood sugars irrespective of threshold values.
Speeding up the detection of invasive bivalve species using environmental DNA: A Nanopore and Illumina sequencing comparison
Authors: Egeter Bastian , Veríssimo Joana , Lopes‐Lima Manuel , Chaves Cátia , Pinto Joana , Riccardi Nicoletta , Beja Pedro , Fonseca Nuno A.
Published: March 2022

Traditional detection of aquatic invasive species via morphological identification is often time‐consuming and can require a high level of taxonomic expertise, leading to delayed mitigation responses. Environmental DNA (eDNA) detection approaches of multiple species using Illumina‐based sequencing technology have been used to overcome these hindrances, but sample processing is often lengthy. More recently, portable nanopore sequencing technology has become available, which has the potential to make molecular detection of invasive species more widely accessible and substantially decrease sample turnaround times. However, nanopore‐sequenced reads have a much higher error rate than those produced by Illumina platforms, which has so far hindered the adoption of this technology. We provide a detailed laboratory protocol and bioinformatic tools (msi package) to increase the reliability of nanopore sequencing to detect invasive species, and we test its application using invasive bivalves while comparing it with Illumina‐based sequencing. We sampled water from sites with pre‐existing bivalve occurrence and abundance data, and contrasting bivalve communities, in Italy and Portugal. Samples were extracted, amplified, and sequenced by the two platforms. The mean agreement between sequencing methods was 69% and the difference between methods was nonsignificant. The lack of detections of some species at some sites could be explained by their known low abundances. This is the first reported use of MinION to detect aquatic invasive species from eDNA samples.
Taking Systems Thinking to the Global Level: Using the WHO Building Blocks to Describe and Appraise the Global Health System in Relation to COVID‐19
Authors: Borghi Josephine , Brown Garrett W.
Published: March 2022

Adequately preparing for and containing global shocks, such as COVID‐19, is a key challenge facing health systems globally. COVID‐19 highlights that health systems are multilevel systems, a continuum from local to global. Goals and monitoring indicators have been key to strengthening national health systems but are missing at the supranational level. A framework to strengthen the global system—the global health actors and the governance, finance, and delivery arrangements within which they operate—is urgently needed. In this article, we illustrate how the World Health Organization Building Blocks framework, which has been used to monitor the performance of national health systems, can be applied to describe and appraise the global health system and its response to COVID‐19, and identify potential reforms. Key weaknesses in the global response included: fragmented and voluntary financing; non‐transparent pricing of medicines and supplies, poor quality standards, and inequities in procurement and distribution; and weak leadership and governance. We also identify positive achievements and identify potential reforms of the global health system for greater resilience to future shocks. We discuss the limitations of the Building Blocks framework and future research directions and reflect on political economy challenges to reform.
Drivers of professional fulfillment and burnout among emergency medicine faculty: A national wellness survey by the Society for Academic Emergency Medicine
Authors: Lu Dave W. , Lee Justin , Alvarez Alai , Sakamoto Jeffrey T. , Bird Steven B. , Sundaram Vandana , Lall Michelle D. , Nordenholz Kristen E. , Manfredi Rita A. , Blomkalns Andra L.
Published: March 2022

Background

Professional fulfillment and the mitigation of burnout can enhance clinician well‐being and the resiliency of the health care organization. This study examined the extent to which specific individual and workplace factors are associated with professional fulfillment and burnout among a national sample of academic emergency physicians.

Methods

This was a cross‐sectional survey of faculty members of the Society for Academic Emergency Medicine. Primary outcomes were professional fulfillment and burnout. The survey also examined individual and workplace factors as well as faculty's thoughts of attrition from academic and clinical medicine. Logistic regression was performed to determine the relationships between each outcome and each factor, respectively.

Results

A total of 771 of 3130 faculty completed the survey (response rate 24.6%). A total of 38.7% reported professional fulfillment and 39.1% reported burnout. Meaningfulness of work (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.9–2.5), perceived appreciation (OR 1.9, 95% CI 1.7–2.1), and the academic work environment (OR 1.7, 95% CI 1.5–1.9) had the highest odds of being associated with professional fulfillment. In contrast, low score responses for meaningfulness of work (OR 0.6, 95% CI 0.5–0.6), self‐compassion (0.6, 95% CI 0.5–0.6), and control over schedule (OR 0.6, 95% CI 0.6–0.7) were most associated with burnout. Faculty with professional fulfillment were less likely to report plans for attrition from academics (OR 0.1, 95% CI 0.1–0.2) and from clinical medicine (OR 0.2, 95% CI 0.1–0.4). Faculty with burnout were more likely to report plans for attrition from academics (OR 7, 95% CI 4.8–10.4) and clinical medicine (OR 5.7, 95% CI 3.9–8.6).

Conclusions

Individual and workplace factors that contributed to professional fulfillment and burnout were identified, with meaningfulness of clinical work demonstrating the strongest association with both occupational phenomena. Knowledge of which factors are most impactful in promoting professional fulfillment and mitigating burnout may be useful in guiding efforts to enhance clinician well‐being.
Microsite abiotic conditions and juvenile response under three early successional shrub/tree species in a SEMI‐ARID region
Authors: Sales Lucas Diego , Pereira de Oliveira Dayana Maria , Soares Arlete Aparecida , Churka Blum Susana , Sgobaro Zanette Lorenzo Roberto , Boscaini Zandavalli Roberta
Published: March 2022

In environments with water and nutrient constraints, some early successional shrub/tree species may promote facilitation by ameliorating the microclimate and increasing resource availability. We ask whether early successional semi‐arid shrub/tree species have facilitation effects for other woody species and if they do, which mechanisms are involved and how they affect the water status of juvenile plants. Three early successional woody species; Combretum leprosum, Cenostigma bracteosum and Mimosa tenuiflora, were chosen for investigation. The richness of regenerating woody species and their leaf water potential were used as response variables, while air and soil temperature, leaf area index, humidity and soil attributes were used as explanatory environmental variables. Species growing under the canopy of C. leprosum had better water status and growth at higher soil moisture and lower thermal and solar radiation stress, receiving a facilitative effect. The lower leaf area index, higher radiation and more negative soil water content under the canopy of C. bracteosum in comparison to C. leprosum may have a small negative effect on species richness. M. tenuiflora did not reduce environmental stress, and the species associated with it had low water potential, thus no increase in species richness was detected under its canopy. C. leprosum and C. bracteosum improve the environmental conditions under their canopies and provide favourable microsites for the establishment of other species. The positive effects may be generated by functional traits that modify microclimatic characteristics under the nurse species' canopy and lead to a higher water status of the juveniles growing under it.
Shorebirds adjust resting orientation in response to solar radiation and wind speed
Authors: Cestari César , de Melo Celine
Published: March 2022

Animals may signal behavioural responses to climate stressors. To date, there has been no study investigating the altered behaviour of birds due to the synergetic effects of wind, solar radiation and ambient temperature in natural environments. We analysed the body orientation of three close‐related Charadriiformes species with different body masses in response to wind speed, wind direction, sun position and ambient temperature on beaches in south‐eastern Brazil. We expected these birds to adjust their postures according to the intensity of climate stressors and their different body masses. We found that regardless of body mass, resting birds faced the wind according to its speed and reduced their surface area exposed to airflow. They also exhibited a perpendicular orientation to the sun in lower ambient temperatures, which correlated with higher wind speeds. The behavioural adjustments of resting birds to concomitant climate stressors may prevent body destabilization and promote thermoregulation and energy savings.
Phosphoglycerate mutase 5 promotes necroptosis in trophoblast cells through activation of dynamin‐related protein 1 in early‐onset preeclampsia
Authors: Zhang Jiejie , Huang Jingrui , Lin Xinxiu , Fei Kuilin , Xie Yingming , Peng Qiaozhen , Li Xun , Xie Liangqun , Dai Lei , Zhang Weishe
Published: March 2022

Objectives

Placentae from patients with preeclampsia have increased susceptibility to necroptosis and phosphoglycerate mutase 5 (PGAM5) plays a role in many necrosis pathways. We determined whether PGAM5 promotes necroptosis of trophoblast cells and the underlying mechanisms in this study.

Methods

The injury model was established by treating JEG3 cells with hypoxia for 24 h. The functional measurements were assessed by the cell counting kit‐8, propidium iodide (PI)/Annexin V staining, JC‐1 staining and firefly luciferase ATP assay. The expression of proteins in human placentae and JEG3 cells was measured Western blot. PGAM5 was knocked down to study its role in hypoxia‐induced necroptosis.

Results

The placentae from patients with preeclampsia showed up‐regulation of PGAM5 and decreased levels of p‐Drp1‐S637, accompanied by increased necroptosis‐relevant proteins expression. The expression of PGAM5 in JEG3 cells was up‐regulated under hypoxia, which promoted dephosphorylation of Drp1 at Serine 637 residue, mitochondrial dysfunction (elevated ROS level and reduced mitochondrial membrane potential and ATP content) and cellular necroptosis (increased PI+/Annexin V+ cells and decreased cell viability), accompanied by increased expression of necroptosis‐relevant proteins; knockdown of PGAM5 attenuated these phenomena.

Conclusions

Our results indicate that PGAM5 can promote necroptosis in trophoblast cells through, at least in part, activation of Drp1. It may be used as a new therapeutic target to prevent trophoblast dysfunction in preeclampsia.
Is “thank you” effective even in Japan where “sorry” may be preferred? Toward extending the Find‐Remind‐and‐Bind theory
Authors: Imai Tatsuya
Published: March 2022

The core idea of the find‐remind‐and‐bind theory articulated by (Algoe, 2012, Social and Personality Psychology Compass, 6, 455) is that receiving expressed gratitude facilitates positive attitudes toward the expressor such as increased prosocial behaviour. The current study tries to observe the phenomena in Japan where apologies are sometimes used when people express gratitude. In this experimental study, 671 Japanese participants received expressions of gratitude, apologies, both, or neither (control condition) in exchange for their help. The results showed that expressed gratitude had the most positive effect compared to the control, apology and both conditions; that is, expressed gratitude most strongly facilitated the message receiver's prosocial behaviour, self‐disclosure, predicted outcome values, and social worth. Expressed apologies showed a limited positive effect. A structural equation model further indicated that predicted outcome values and social worth functioned in unique ways to mediate the link between expressed gratitude and prosocial behaviour as well as self‐disclosure.
Adamgammadex in patients to reverse a moderate rocuronium‐induced neuromuscular block
Authors: Jiang Ying Ying , Zhang Yu Jun , Zhu Zhao Qiong , Huang Yi Dan , Zhou Da Chun , Liu Jing Chen , Li Chao Yu , Liu Jin , Liu Bin , Zhang Wen Sheng
Published: March 2022

Aims

The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients.

Methods

Forty‐eight patients aged 18–64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg−1) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg−1 rocuronium‐induced neuromuscular block. Neuromuscular function was monitored by TOF‐Watch® SX. When the T2 of train‐of‐four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo.

Results

The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg−1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post‐operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose‐dependent manner. The 24‐hour cumulative fraction of adamgammadex in urine was 65–83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25–30%.

Conclusion

Adamgammadex was found to be effective for reversal of rocuronium‐induced neuromuscular block, and it was safe and well tolerated in patients.
Resilience, science, technology, engineering, and mathematics (STEM), and anger: A linguistic inquiry into the psychological processes associated with resilience in secondary school STEM learning
Authors: Hall Sophie S. , McGill Ross Morrison , Puttick Steven , Maltby John
Published: March 2022

Aim

To examine resilience in Science, Technology, Engineering, and Mathematics (STEM) learning within an ecological model, identifying the psychological processes associated with resilient, and non‐resilient learning to develop a framework for promoting STEM resilience.

Sample and method

From a sample of secondary‐school students (n = 4,936), 1,577 students who found their STEM lesson difficult were identified. Students were assessed on three resilience capabilities and asked to write a commentary on how they responded to the lesson.

Results

Factor analysis revealed that resilience in STEM learning could be positioned within the ecological systems model, with students’ resilience being comprised of three capabilities; the ability to quickly and easily recover (Recovery), remain focussed on goals (Ecological), and naturally adjust (Adaptive capacity). Using a linguistic analysis programme, we identified the prevalence of words within the student commentaries which related to seven psychological processes. Greater ability to recover was negatively related to negative emotional processes. To increase the specificity of this relationship, we identified high and low resilient students and compared their commentaries. Low resilient students used significantly more anger words. Qualitative analysis revealed interpersonal sources of anger (anger at teacher due to lack of support) and intrapersonal sources of anger (including rumination, expression and control, and seeking distraction).

Conclusions

Anger is a key process that distinguishes students who struggle to recover from a difficult STEM lesson. An ecological systems model may prove useful for understanding STEM resilience and developing intervention pathways. Implications for teacher education include the importance of students’ perceptions of teacher support.