bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐efficacy as a psychological resource in the management of stress suffered by ICU nurses during the COVID‐19 pandemic: A prospective study on emotional exhaustion
Authors: Gil‐Almagro Fernanda , Carmona‐Monge F. Javier , García‐Hedrera Fernando J. , Peñacoba‐Puente Cecilia
Published: October 2024

Background

Intensive care unit (ICU) nurses have experienced a high degree of stress during the COVID‐19 pandemic. While the literature on the consequences on emotional symptomatology is abundant, studies on the protective psychosocial variables that have contributed to buffering these consequences are scarcer.

Aim

This study analyses the role of self‐efficacy as a protective personality trait in ICU nurses during the COVID‐19 pandemic, using a moderated mediation model that begins with the stress and anxiety experienced at the onset of the pandemic and concludes with the emotional exhaustion experienced 6 months later.

Study Design

Prospective longitudinal study with two data collection periods during the COVID‐19 pandemic: (1) from 5 May to 21 June 2020 and (2) a follow‐up 6 months after the state of alarm finalized (January–April 2021). These were both very stressful periods for ICU staff because of the COVID‐19 pandemic.

This study was conducted with 129 ICU nurses (a non‐probabilistic convenience sample in the Spanish health care system). Socio‐demographic, occupational and psychosocial variables (i.e. stress, anxiety, self‐efficacy and emotional exhaustion) were assessed. Descriptive analyses, Pearson correlations, covariate analyses (i.e. Student's t‐test, one‐factor ANOVA) and moderated mediation analyses were carried out (SPSS PROCESS macro, model 7). STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) reporting guidelines were followed.

Results

It shows that the higher the self‐efficacy score, the lower the effect of stress on anxiety (p < .001); likewise, the moderating role of self‐efficacy was equally valid for the whole final model (F = 8.790, p < .001), showing self‐efficacy to be a good buffer for emotional exhaustion derived from the stress suffered in the ICU.

Conclusions

Self‐efficacy (i.e. the belief of being able to do certain tasks successfully) is shown to be a highly relevant trait to enhance among ICU nurses during the COVID‐19 pandemic, allowing them to manage work stress effectively and thus buffering the development of anxiety in the short term and emotional exhaustion in the long term.

Relevance to Clinical Practice

Our results point to the need to assess and take action on self‐efficacy in ICU nurses in highly stressful situations such as the COVID‐19 pandemic. As a psychological variable, self‐efficacy refers to beliefs and therefore has to be trained by evidence‐based psychological techniques, such as cognitive behavioural therapy. In addition, previous literature has pointed out that previous experience or specific training is an influential (although not a determining) factor in self‐efficacy, so specialization for ICU nurses could also be considered.
Prone position applied to COVID‐19 patients: Systematic review–meta‐analysis
Authors: Tülüce Derya , Kaplan Serin Emine , Yıldız Karadeniz Ebru
Published: October 2024

Background

Position change and interventions to increase lung capacity should be considered in mechanically ventilated patients. The most effective of these is the prone position.

Aim

This systematic review and meta‐analysis aimed to determine the effects of the prone position on respiratory parameters and outcomes and to guide nurses working in the intensive care unit.

Study Design and Methods

This systematic review‐meta‐analysis was conducted in accordance with the Preferred Reporting in Systematic Reviews and Meta‐Analyses guideline. ScienceDirect, CINAHL, Academic Search Complete (EBSCOhost), MEDLINE, EMBASE, Web of Science, Cochrane and PubMed databases were searched between January 2022 and January 2023 to access studies related to prone position in COVID‐19 patients.

Results

Twenty‐three studies were included. This meta‐analysis shows that a prone position is feasible and can achieve improvements in gas exchange. Prone position increases PaO2/FiO2 in the majority of patients followed with a diagnosis of COVID‐19 and severe hypoxemic.

Conclusions

The study has shown that the prone position is effective in improving patients' respiratory function and oxygenation.

Relevance to Clinical Practice

The results presented in this article support the notion that the prone position can be an effective strategy in the clinical management of COVID‐19 patients.
In Vitro Comparison of Direct Attachment Shape and Size on the Orthodontic Forces and Moments Generated by Thermoplastic Aligners During Expansion
Authors: Lear Megann , Akbari Amin , Robertson Olivia , Magura Janine , Bojrab Alexandra , Eckert George , Chen Jie , Conley Richard Scott , Turkkahraman Hakan
Published: October 2024

Objective

To evaluate the effects of varying direct attachment shape and size on the forces and moments generated by thermoplastic aligners during simulated expansion.

Materials and Methods

An in vitro orthodontic force tester (OFT) was used to measure the forces and moments from a typodont where the buccal teeth were translated lingually 0.2 mm to simulate expansion. Hemi‐ellipsoid and rectangular attachments with either 0.5 or 1.0 mm thickness were added on upper right first premolar (UR4), second premolar (UR5) and first molar (UR6). Analysis of variance (ANOVA) was used to determine two‐way interactions among the factors on the outcomes.

Results

The interactions between group and tooth were significant for all outcomes (p < 0.001). The greatest buccal forces (Fy) were observed with 1 mm rectangular attachment on the UR4 (0.78 ± 0.29 N), with 1 mm hemi‐ellipsoid attachment on UR5 (0.28 ± 0.21 N) and with 0.5 mm rectangular attachment on UR6 (1.71 ± 0.18 N). The greatest buccolingual moments (Mx) were obtained with 1 mm rectangular attachment on UR4 (5.61 ± 1.43 Nmm), without any attachments on UR5 (3.33 ± 1.73 Nmm) and with 1 mm hemi‐ellipsoid attachment on UR6 (4.18 ± 4.31).

Conclusion

Direct attachment shape and size had a significant effect on the orthodontic forces and moments generated by thermoplastic aligners during simulated expansion. Although loads varied significantly by tooth morphology and its location in the arch, best forces and moments for expansion were obtained with 1 mm rectangular attachments on UR4s, 1 mm hemi‐ellipsoid attachments on UR5s and 0.5 mm rectangular attachments on UR6s.
What Second‐Best Epistemology Could Be
Authors: Daoust Marc‐Kevin
Published: October 2024

According to the Theory of the Second Best, in non‐ideal circumstances, approximating ideals might be suboptimal (with respect to a specific interpretation of what “approximating an ideal” means). In this paper, I argue that the formal model underlying the Theory can apply to problems in epistemology. Two applications are discussed: First, in some circumstances, second‐best problems arise in Bayesian settings. Second, the division of epistemic labor can be subject to second‐best problems. These results matter. They allow us to evaluate the claim, made by many philosophers, that second‐best problems have import in epistemology (and the specific conditions under which the Theory finds applications). They also allow us to see that talk of “approximating an ideal” is ambiguous, and to clarify the conditions in which approximating an epistemic ideal might be beneficial.
Intellectual humility without limits: Magnanimous humility, disagreement and the epistemology of resistance
Authors: Yip Brandon
Published: October 2024

In this paper, I provide a characterisation of a neglected form of humility: magnanimous humility. Unlike most contemporary analyses of humility, magnanimous humility is not about limitations but instead presupposes that one possesses some entitlement in a context. I suggest that magnanimous intellectual humility (IH) consists in a disposition to appropriately refrain from exercising one's legitimate epistemic entitlements because one is appropriately motivated to pursue some epistemic good. I then shown that Magnanimous IH has an important role to play in contexts of disagreement and oppression. It calls on knowing parties to refrain from pressing their epistemic entitlements to facilitate mutual understanding. And it is a virtue that oppressed persons have good reason to cultivate in order to develop meta‐lucidity in themselves and others.
Caatinga Microbiome Initiative: disentangling the soil microbiome across areas under desertification and restoration in the Brazilian drylands
Authors: Araujo Ademir S. F. , de Medeiros Erika V. , da Costa Diogo P. , Mendes Lucas W. , Cherubin Mauricio R. , de Alcantara Neto Francisco , Beirigo Raphael M. , Lambais George R. , Melo Vania M. M. , Nobrega Gabriel N. , Barbosa Humberto A. , Mota Jaedson C. A. , Santana Rodrigo M. , Kavamura Vanessa N. , Borges Wardsson L. , Pereira Arthur P. A.
Published: October 2024

The Caatinga biome in Brazil is renowned for its rich aboveground biodiversity. However, approximately 19% of this biome has experienced desertification, severely affecting the soil microbiome. Monitoring these microbial communities is essential to understanding the impacts of desertification and the potential outcomes of restoration efforts. The Caatinga Microbiome Initiative aims to assess the soil microbiome in areas undergoing desertification and those under restoration in the Brazilian drylands. This initiative seeks to explore the core microbial communities and their functions, including overlooked groups such as protists, nematodes, and viruses across native, desertified, and restored areas. We believe that two approaches should be used simultaneously in the study of microbiomes in areas undergoing desertification. First, the use of the soil microbiome as a bioindicator of soil quality in both desertified and restored lands. Second, the manipulation of the microbiome to facilitate soil restoration. By understanding soil microbiome responses to desertification and restoration, we can develop targeted restoration strategies to enhance biodiversity and promote functional recovery in desertified areas.
Integrating grazing and food supplementation in coral restoration to enhance settler survival and growth
Authors: Lippens Christian R. A. , Banaszak Anastazia T.
Published: October 2024

Sexual coral propagation faces a significant bottleneck due to high post‐settlement mortality, impeding large‐scale reef restoration. This study assessed the effectiveness of co‐culturing Diploria labyrinthiformis settlers with the herbivorous gastropod Cerithium lutosum and supplementing their diet with a commercially available food source, Reef‐Roids, to enhance settler survival and growth. Settlers were reared for 10 weeks under controlled conditions in one of four treatments: Control (C), Feeding with Reef‐Roids (F), Grazing by C. lutosum (G), and combined Feeding + Grazing (FG). Settlers in the Grazing treatment exhibited the highest survival at 87% after 10 weeks, significantly outperforming those in the Control (43%) and Feeding (48%) treatments. The combined feeding and grazing treatment improved survival rates to 74% and resulted in the highest growth rates, with settlers in this group averaging 11.98 ± 2.38 mm2, approximately 3.4‐fold larger than the control and 2.6‐fold larger than the feeding group. The feeding treatment alone did not significantly enhance survival or growth, underscoring the critical role of grazing in mitigating algal competition and promoting settler development. The results highlight the efficacy of grazing by C. lutosum (G and FG) in improving both survival and growth of coral settlers, substantially surpassing the outcomes of ungrazed treatments (F and C). This study highlights the potential of integrating microherbivores, such as C. lutosum, in ex situ coral nurseries. By regulating algal growth, these grazers minimize the need for labor‐intensive maintenance, offering a scalable and cost‐effective strategy to mitigate the high mortality rates of coral settlers.
Core funding and the performance of international organizations: Evidence from UNDP projects
Authors: Heinzel Mirko , Reinsberg Bernhard , Zaccaria Giuseppe
Published: October 2024

Scholarship on the administration of international organizations (IOs) has extensively discussed how autonomy influences their performance. While some argue that autonomy increases performance through greater adaptability, others warn that it may increase the risk of agency slack. Authors typically distinguish between three types of performance: output, outcome, and impact performance. We focus on core funding as a key source of IO autonomy and argue that projects with more core funding show decreased output performance but an increased outcome and impact performance. Our empirical analysis relies on results from data on up to 3590 development projects run by the United Nations Development Program (UNDP) in 128 recipient countries between 2004 and 2020. Subsequently, we test the impact of more core funding on project volumes (output performance), objectives achieved in individual projects (outcome performance), and their effects on sub‐national human development in project regions (impact performance). Our findings suggest that, although reliance on core resources is associated with lower output performance (less funding), it may result in stronger outcome and impact performance, as reflected by more objectives achieved and a higher sub‐national HDI where UNDP projects are implemented. Our findings have important implications for debates on the effectiveness of global governance.
Dynamic modeling of human error in industrial maintenance through structural analysis and system dynamics
Authors: Bafandegan Emroozi Vahideh , Kazemi Mostafa , Pooya Alireza , Doostparast Mahdi
Published: October 2024

Human error constitutes a significant cause of accidents across diverse industries, leading to adverse consequences and heightened disruptions in maintenance operations. Organizations can enhance their decision‐making process by quantifying human errors and identifying the underlying influencing factors, thereby mitigating their repercussions. Consequently, it becomes crucial to examine the value of human error probability (HEP) during these activities. The objective of this paper is to determine and simulate HEP in maintenance tasks at a cement factory, utilizing performance shaping factors (PSFs). The research employs the cross‐impact matrix multiplication applied to classification (MICMAC) analysis method to evaluate the dependencies, impacts, and relationships among the factors influencing human error. This approach classifies and assesses the dependencies and impacts of different factors on HEP, occupational accidents, and related costs. The study also underscores that PSFs can dynamically change under the influence of other variables, emphasizing the necessity to forecast the behavior of human error over time. Therefore, this paper utilizes the MICMAC method to analyze the interdependencies, relationships, and impact levels among different variables. These relationships are then utilized to optimize the implementation of the system dynamics (SD) method. An SD model is employed to forecast the system's behavior, and multiple scenarios are presented. By considering the HEP value, managers can adjust organizational conditions and personnel to ensure acceptability. The paper also presents various scenarios related to HEP to assist managers in making informed decisions.
Risk communication and public response to potential radiation emergencies in New York City
Authors: Gupta Kuhika , Ripberger Joseph , Fox Andrew , Maiello Mark , Peach Katie , Jenkins‐Smith Hank
Published: October 2024

Public knowledge and awareness about radiation (both natural and manmade) tend to be low, while perceived risk of radiation tends to be high. High perceptions of risk associated with radiation have been linked to the affect heuristic and general feelings of dread, which are often not proportionate to actual risk. For example, studies routinely show that members of the public rate the risk of radiation from nuclear power plants as significantly higher (and riskier) than radiation from medical X‐rays. This disconnect can have implications for adoption of protective actions during a potential radiation emergency and the perceived efficacy of these actions. This study explores how risk communication efforts influence public risk perceptions, intended protective action, and perceived efficacy of those actions. Using unique data from a survey of New York City adults, we analyze how information provision using different formats—no information, an infographic, an informational video—impact perceptions and response to a hypothetical radiation emergency. We hypothesize that respondents who receive some information, either through the infographic or the video, will have higher perceived efficacy and are more likely to take protective action. Findings suggest that providing information about what to do during a radiation emergency has a statistically significant impact on both perceived efficacy and adoption of protective action. Respondents who saw the informational video were most likely to say that they would take the correct protective actions and had the highest perceived efficacy, followed by those who saw the infographic.
A simple activity to introduce matched pairs and learning effect
Authors: Davidson Allison
Published: October 2024

This paper describes an in‐class activity to introduce random assignment, paired data, and learning effect. The activity requires minimal materials, can be completed in a single class period, and is suitable for those using technology to conduct data exploration but can also be adapted for use in a technology‐free classroom. The activity consists of students filling in two lines of circles, one using their dominant and the other using their nondominant hand. The difference in time to fill in the circles is compared. Results typically show a significant difference in time to fill in circles with the nondominant hand taking significantly longer, a significant learning effect, and a difference in time to fill in circles using a pencil compared to pen.
Special applets for elucidating the difference between prediction intervals and confidence intervals—Why are arising ovals actually ellipses?
Authors: Humenberger Hans
Published: October 2024

In the last years special “ovals” appear increasingly often in diagrams and applets for discussing crucial items of statistical inference (when dealing with confidence intervals for an unknown probability p; approximation of the binomial distribution by the normal distribution; especially in German literature, see e.g. [Meyer, Stochastik in der Schule 2011; 31:18–22] or [Riemer, Statistik unterrichten. Eine handlungsorientierte Didaktik der Stochastik; 2023, p. 69ff]). These applets concerning confidence intervals aim at illustrating vividly the crucial differences (as we know, often vague for students) and connections between confidence intervals and prediction intervals. In English literature such applets seem to be not so well known, thus at the beginning, we describe how they work and highlight their high potential for teaching and learning. The fact that the mentioned ovals are, actually, ellipses is not important for stochastic purposes which is probably the reason why one can hardly find related explanations in the literature. Another aim of this paper is to explain the ellipse shape in a preferably elementary manner involving geometry, even spatial geometry.
Physics-informed neural networks in support of modal wavenumber estimation
Authors: Yoon Seunghyun , Park Yongsung , Lee Keunhwa , Seong Woojae
Published: October 2024

A physics-informed neural network (PINN) enables the estimation of horizontal modal wavenumbers using ocean pressure data measured at multiple ranges. Mode representations for the ocean acoustic pressure field are derived from the Hankel transform relationship between the depth-dependent Green's function in the horizontal wavenumber domain and the field in the range domain. We obtain wavenumbers by transforming the range samples to the wavenumber domain, and maintaining range coherence of the data is crucial for accurate wavenumber estimation. In the ocean environment, the sensitivity of phase variations in range often leads to degradation in range coherence. To address this, we propose using OceanPINN [Yoon, Park, Gerstoft, and Seong, J. Acoust. Soc. Am. 155(3), 2037–2049 (2024)] to manage spatially non-coherent data. OceanPINN is trained using the magnitude of the data and predicts phase-refined data. Modal wavenumber estimation methods are then applied to this refined data, where the enhanced range coherence results in improved accuracy. Additionally, sparse Bayesian learning, with its high-resolution capability, further improves the modal wavenumber estimation. The effectiveness of the proposed approach is validated through its application to both simulated and SWellEx-96 experimental data.
High variability phonetic training facilitates perception-to-production transfer in Mandarin-speaking children with cochlear implants: An acoustic investigation
Authors: Zhang Hao , Xu Lele , Ma Wen , Han Junning , Wang Yanxiang , Ding Hongwei , Zhang Yang
Published: October 2024

This study primarily aimed to evaluate the effectiveness of high variability phonetic training (HVPT) for children with cochlear implants (CIs) via the cross-modal transfer of perceptual learning to lexical tone production, a scope that has been largely neglected by previous training research. Sixteen CI participants received a five-session HVPT within a period of three weeks, whereas another 16 CI children were recruited without receiving any formal training. Lexical tone production was assessed with a picture naming task before the provision (pretest) and immediately after (posttest) and ten weeks after (follow-up test) the completion of the training protocol. The production samples were coded and analyzed acoustically. Despite considerable distinctions from the typical baselines of normal-hearing peers, the trained CI children exhibited significant improvements in Mandarin tone production from pretest to posttest in pitch height of T1, pitch slope of T2, and pitch curvature of T3. Moreover, the training-induced acoustic changes in the concave characteristic of the T3 contour was retained ten weeks after training termination. This study represents an initial acoustic investigation on HVPT-induced benefits in lexical tone production for the pediatric CI population, which provides valuable insights into applying this perceptual training technique as a viable tool in clinical practices.
Loss of atrial natriuretic peptide signaling causes insulin resistance, mitochondrial dysfunction, and low endurance capacity
Authors: Carper Deborah , Lac Marlène , Coue Marine , Labour Axel , Märtens Andre , Banda Jorge Alberto Ayala , Mazeyrie Laurène , Mechta Mie , Ingerslev Lars Roed , Elhadad Mohamed , Petit Justine Vily , Maslo Claire , Monbrun Laurent , Del Carmine Peggy , Sainte-Marie Yannis , Bourlier Virginie , Laurens Claire , Mithieux Gilles , Joanisse Denis R. , Coudray Charles , Feillet-Coudray Christine , Montastier Emilie , Viguerie Nathalie , Tavernier Geneviève , Waldenberger Melanie , Peters Annette , Wang-Sattler Rui , Adamski Jerzy , Suhre Karsten , Gieger Christian , Kastenmüller Gabi , Illig Thomas , Lichtinghagen Ralf , Seissler Jochen , Mounier Remy , Hiller Karsten , Jordan Jens , Barrès Romain , Kuhn Michaela , Pesta Dominik , Moro Cedric
Published: October 2024

Type 2 diabetes (T2D) and obesity are strongly associated with low natriuretic peptide (NP) plasma levels and a down-regulation of NP guanylyl cyclase receptor-A (GCA) in skeletal muscle and adipose tissue. However, no study has so far provided evidence for a causal link between atrial NP (ANP)/GCA deficiency and T2D pathogenesis. Here, we show that both systemic and skeletal muscle ANP/GCA deficiencies in mice promote metabolic disturbances and prediabetes. Skeletal muscle insulin resistance is further associated with altered mitochondrial function and impaired endurance running capacity. ANP/GCA-deficient mice exhibit increased proton leak and reduced content of mitochondrial oxidative phosphorylation proteins. We further show that GCA is related to several metabolic traits in T2D and positively correlates with markers of oxidative capacity in human skeletal muscle. Together, these results indicate that ANP/GCA signaling controls muscle mitochondrial integrity and oxidative capacity in vivo and plays a causal role in the development of prediabetes.
SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac
Authors: Lee Hyun Jae , Fenollar-Ferrer Cristina , Isgrig Kevin , Wang Ya-Xian , Valente Kerstin , Eide Juleh , Honda Keiji , Chien Wade W. , Petralia Ronald S. , Dong Lijin , Friedman Thomas B. , Bonifacino Juan S. , Griffith Andrew J. , Roux Isabelle
Published: October 2024

Decreased presence or activity of human SLC26A4 at the plasma membrane is a common cause of hearing loss. SLC26A4 (Pendrin) is necessary for normal reabsorption of endolymph, the fluid bathing the inner ear. We identified the μ2 subunit of adaptor protein 2 (AP-2) complex required for clathrin-mediated endocytosis as a protein-partner of SLC26A4 involved in regulating its plasma membrane abundance. We showed that, in the endolymphatic sac, where fluid reabsorption occurs, SLC26A4 is localized along the apical microvilli of mitochondria-rich cells, in contact with the endolymph, and associated with clathrin-coated pits where μ2 and AP-2 are present. Based on SLC26A4 structure, the elements involved in SLC26A4-μ2 interaction were identified and validated experimentally, allowing modeling of this interaction at the atomic level. Pharmacological inhibition of clathrin-mediated endocytosis led to an increased plasma membrane abundance of hemagglutinin-tagged SLC26A4 virally or endogenously expressed in mitochondria-rich cells. These results indicate that the SLC26A4-μ2 interaction regulates SLC26A4 abundance at the apical surface of mitochondria-rich cells.
The massive 2016 marine heatwave in the Southwest Pacific: An “El Niño–Madden-Julian Oscillation” compound event
Authors: Dutheil Cyril , Lal Shilpa , Lengaigne Matthieu , Cravatte Sophie , Menkès Christophe , Receveur Aurore , Börgel Florian , Gröger Matthias , Houlbreque Fanny , Le Gendre Romain , Mangolte Inès , Peltier Alexandre , Meier H. E. Markus
Published: October 2024

El Niño typically induces cooling in the Southwest Pacific Ocean during austral summers, usually leading to decreased marine heatwave frequency and severity. However, the 2016 extreme El Niño unexpectedly coincided with the longest and most extensive marine heatwave ever recorded in the region. This heatwave, spanning over 1.7 million square kilometers, persisting for 24 days with a peak intensity of 1.5°C, resulted in massive coral bleaching and fish mortality. This exceptional warming resulted from anomalously strong shortwave radiation and reduced heat loss via latent heat fluxes, owing to low wind speed and increased air humidity. These anomalies are attributed to a rare combined event “Madden-Julian Oscillation and extreme El Niño.” Following 10 February, the rapid dissipation of this marine heatwave results from the most intense cyclone ever recorded in the South Pacific. The hazardous ecological impacts of this extreme event highlight the needs for improving our understanding of marine heatwave–driving mechanisms that may result in better seasonal predictions.
Asymmetric one-carbon ring expansion of diverse N-heterocycles via copper-catalyzed diyne cyclization
Authors: Li Fu-Shuai , Zou Xiu-Yuan , Hu Tian-Qi , Sun Qing , Xu Zhou , Zhou Bo , Ye Long-Wu
Published: October 2024

One-carbon ring expansion reaction of N-heterocycles has gained particular attention in the past decade because this method allows for the conversion of readily available N-heterocycles into potentially useful complex ring-expanded N-heterocycles, which are inaccessible by traditional methods. However, the catalytic asymmetric variant of this reaction has been rarely reported to date. Herein, we disclose an enantioselective one-carbon ring expansion reaction through chiral copper-catalyzed diyne cyclization, leading to the practical, atom-economic and divergent assembly of an array of valuable chiral N-heterocycles bearing a quaternary stereocenter in generally good to excellent yields with excellent enantioselectivities (up to >99% ee). This protocol represents the first example of asymmetric one-carbon ring expansion reaction of N-heterocycles based on alkynes.
Decreased mitochondrial creatine kinase 2 impairs skeletal muscle mitochondrial function independently of insulin in type 2 diabetes
Authors: Rizo-Roca David , Guimarães Dimitrius Santiago P. S. F. , Pendergrast Logan A. , Di Leo Nicolas , Chibalin Alexander V. , Maqdasy Salwan , Rydén Mikael , Näslund Erik , Zierath Juleen R. , Krook Anna
Published: October 2024

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (
CKMT2
). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog β-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing
Ckmt2
using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of
Ckmt2
in skeletal muscle of high-fat diet–fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of
Ckmt2
improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes.
An altered natural killer cell immunophenotype characterizes clinically severe pediatric RSV infection
Authors: Reilly Roisin B. , Ramdour Saïsha K. , Fuhlbrigge Mary E. , Tavares Luciana P. , Staffa Steven J. , Booth Jocelyn M. , Krishnamoorthy Nandini , Levy Bruce D. , Duvall Melody G.
Published: October 2024

Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV
+
children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense. In this study of 47 critically ill RSV
+
children, we coupled NK cell immunophenotype and cytotoxic function with clinical parameters to identify an NK cell immune signature of severe pediatric RSV disease. Airway NK cells were increased in intubated RSV
+
children with severe hypoxemia and prolonged duration of mechanical ventilation and were correlated with clinical severity scores. Peripheral blood NK cells were decreased in RSV
+
patients and had altered activating receptor expression, with increased expression of CD69 and decreased expression of NKG2D. Ex vivo, circulating NK cells from RSV
+
patients exhibited functional impairment characterized by decreased cytotoxicity as well as aberrant immune synapse assembly and lytic granule trafficking. NK cell frequency and phenotype correlated with clinical measures that defined disease severity. These findings implicate a role for NK cells in mediating RSV immunopathology and suggest that an altered NK cell immunophenotype is associated with severe RSV disease in young children.
A multispecific antibody against SARS-CoV-2 prevents immune escape in vitro and confers prophylactic protection in vivo
Authors: Misasi John , Wei Ronnie R. , Wang Lingshu , Pegu Amarendra , Wei Chih-Jen , Oloniniyi Olamide K. , Zhou Tongqing , Moliva Juan I. , Zhao Bingchun , Choe Misook , Yang Eun Sung , Zhang Yi , Boruszczak Marika , Chen Man , Leung Kwanyee , Li Juan , Yang Zhi-Yong , Andersen Hanne , Carlton Kevin , Godbole Sucheta , Harris Darcy R. , Henry Amy R. , Ivleva Vera B. , Lei Q. Paula , Liu Cuiping , Longobardi Lindsay , Merriam Jonah S. , Nase Danielle , Olia Adam S. , Pessaint Laurent , Porto Maciel , Shi Wei , Wallace Shannon M. , Wolff Jeremy J. , Douek Daniel C. , Suthar Mehul S. , Gall Jason G. , Koup Richard A. , Kwong Peter D. , Mascola John R. , Nabel Gary J. , Sullivan Nancy J.
Published: October 2024

Despite effective countermeasures, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists worldwide because of its ability to diversify and evade human immunity. This evasion stems from amino acid substitutions, particularly in the receptor binding domain (RBD) of the spike protein that confers resistance to vaccine-induced antibodies and antibody therapeutics. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different RBD sites into multispecific antibodies. Here, we describe multispecific antibodies, including a trivalent trispecific antibody that potently neutralized diverse SARS-CoV-2 variants and prevented virus escape more effectively than single antibodies or mixtures of the parental antibodies. Despite being generated before the appearance of Omicron, this trispecific antibody neutralized all major Omicron variants through BA.4/BA.5 at nanomolar concentrations. Negative stain electron microscopy suggested that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated binding across more than one spike protein. Moreover, a tetravalent trispecific antibody containing the same variable regions as the trivalent trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2, and BA.5 challenge, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. These results demonstrated that multispecific antibodies have the potential to provide broad SARS-CoV-2 coverage, decrease the likelihood of escape, simplify treatment, and provide a strategy for antibody therapies that could help eliminate pandemic spread for this and other pathogens.
Antimicrobial activity of novel symmetrical antimicrobial peptides centered on a hydrophilic motif against resistant clinical isolates:
in vitro
and
in vivo
analyses
Authors: Zhang Chaoqun , Fu Le , Zhu Yuan , Chen Qigui , Chen Zetong , Chang Yung-Fu , Li Yide , Yao Mengjing , Huang Xinyi , Jin Li , Gao Xue , Zhang Yiyu , Jin Biao , Chou Shuli , Luo Liang
Published: October 2024

Antibiotic resistance poses a significant public health threat worldwide. The rise in antibiotic resistance and the sharp decline in effective antibiotics necessitate the development of innovative antibacterial agents. Based on the central symmetric structure of glycine–serine–glycine, combined with tryptophan and arginine, we designed a range of antimicrobial peptides (AMPs) that exhibited broad-spectrum antibacterial activity. Notably, AMP W
5
demonstrated a rapid and effective sterilization against methicillin-resistant
Staphylococcus aureus
(MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W
5
killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W
5
also exhibited excellent biocompatibility in both
in vitro
and
in vivo
safety evaluations. AMP W
5
treatment significantly reduced skin bacterial load in our murine skin infection model. In conclusion, we designed a novel centrosymmetric AMP representing a promising medical alternative to conventional antibiotics for treating MRSA infections.

IMPORTANCE

Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant
Staphylococcus aureus
(MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimicrobial peptides (AMPs) exhibit significant potential as alternatives to traditional antibiotics. This study designed a novel series of AMPs, characterized by a glycine–serine–glycine-centered symmetrical structure, and our results indicated that AMP W5 exhibited a rapid and effective bactericidal effect against MRSA. AMP W5 also demonstrated excellent biocompatibility and a bactericidal mechanism that disrupted membrane integrity, leading to leakage of cellular contents. The notable reduction in skin bacterial load observed in mouse models reinforced the clinical applicability of AMP W5. This study provides a promising solution for addressing the increasing threat of antibiotic-resistant bacteria and heralds new prospects for clinical applications.
Altitudinal variation in rhizosphere microbial communities of the endangered plant
Lilium tsingtauense
and the environmental factors driving this variation
Authors: Liu Boda , Yang Jinming , Lu Wanpei , Wang Hai , Song Xuebin , Yu Shaobo , Liu Qingchao , Sun Yingkun , Jiang Xinqiang
Published: October 2024

The rhizosphere soil properties and microbial communities of
Lilium tsingtauense
, an endangered wild plant, have not been examined in previous studies. Here, we characterized spatial variation in soil properties and microbial communities in the rhizosphere of
L. tsingtauense
. We measured the abundance of
L. tsingtauense
at different altitudes and collected rhizosphere and bulk soils at three representative altitudes. The results showed that
L. tsingtauense
was more abundant, and the rhizosphere soil was richer in nitrogen, phosphorus, potassium, water content, and organic matter and more acidic at high altitudes than at lower altitudes. The diversity and richness of rhizosphere bacteria and fungi increased with altitude and were higher in rhizosphere soil than in bulk soil. In addition, ectomycorrhizal fungi, endophytic fungi, and nitrogen-fixing bacteria were more abundant, and plant-pathogenic fungi were less abundant at high altitudes. Co-occurrence network analysis identified four key phyla (Bacteroidota, Proteobacteria, Ascomycota, and Basidiomycota) in the microbial communities. We identified a series of microbial taxa (Acidobacteriales, Xanthobacteraceae, and Chaetomiaceae) and rhizosphere soil metabolites (phosphatidylcholine and phosphatidylserine) that are crucial for the survival of
L. tsingtauense
. Correlation analysis and random forest analysis showed that some environmental factors were closely related to the rhizosphere soil microbial community and played an important role in predicting the distribution and growth status of
L. tsingtauense
. In sum, the results of this study revealed altitudinal variation in the rhizosphere microbial communities of
L. tsingtauense
and the factors driving this variation. Our findings also have implications for habitat restoration and the conservation of this species.

IMPORTANCE

Our study highlighted the importance of the rhizosphere microbial community of the endangered plant
L. tsingtauense
. We found that soil pH plays an important role in the survival of
L. tsingtauense
. Our results demonstrated that a series of microbial taxa (Acidobacteriales, Xanthobacteraceae, Aspergillaceae, and Chaetomiaceae) and soil metabolites (phosphatidylcholine and phosphatidylserine) could be essential indicators for
L. tsingtauense
habitat. We also found that some environmental factors play an important role in shaping rhizosphere microbial community structure. Collectively, these results provided new insights into the altitudinal distribution of
L. tsingtauense
and highlight the importance of microbial communities in their growth.
Understanding the barriers and facilitators related to never treatment during mass drug administration among mobile and migrant populations in Mali: a qualitative exploratory study
Authors: Sangare Moussa , Diabate Abdoul Fatao , Coulibaly Yaya Ibrahim , Tanapo Diadje , Thera Sekou Oumarou , Dolo Housseini , Dicko Ilo , Coulibaly Oumar , Sall Binta , Traore Fatoumata , Doumbia Seydou , Kulkarni Manisha A , Nutman Thomas B , Krentel Alison
Published: October 2024

Introduction

Five of the neglected tropical diseases use a strategy of preventative chemotherapy distributed via mass drug administration (MDA) for all eligible people living in endemic areas. To be successful, high coverage must be sustained over multiple rounds. Therefore, it will be difficult to reach elimination as a public health problem using MDA if there remain clusters of people who have never been treated. The study aims to explore the reasons why people with high mobility report being never treated during MDA and to provide evidence to support the development of standardised questions for data collection using qualitative research tools.

Methods

We conducted an exploratory study using qualitative methods among displaced people, nomads/transhumants and economic migrants who self-reported that they had never been treated during MDA in the health districts of Tominian and Kalabancoro in Mali. Data were collected through in-depth individual interviews and focus group discussions. Nvivo V.14 software was used for data management and analysis.

Results

The main reasons reported for never treatment included: geographical mobility, lack of awareness/information, negative rumours, fear of side effects, conflict and insecurity and logistical difficulties faced in reaching these populations. Proposed solutions included involving communities in the MDA, increasing awareness and information campaigns, effectively managing side effects, and designing and implementing flexible and effective interventions.

Conclusion

This study highlights that there are people with high mobility who may never have been treated during any round of MDA. The reasons for never treatment highlight the challenges faced when reaching particular groups during MDA activities/interventions. Suggested remedies will require programmes to implement more flexible and tailored interventions. Customised approaches based on the context are essential to guarantee fair access to preventive chemotherapy. Effective interventions must consider the supply and demand side in crafting interventions. This research adds to the evidence base to understand never treatment, particularly among highly mobile population groups and in schistosomiasis elimination programmes.
Efficacy of 100% autologous platelet-rich plasma and 100% autologous serum in dry eye disease: a randomised controlled trial
Authors: Jongkhajornpong Passara , Lekhanont Kaevalin , Rattanasiri Sasivimol , Numthavaj Pawin , McKay Gareth , Attia John , Thakkinstian Ammarin
Published: October 2024

Objective

The 0bjective is to compare treatment effects between undiluted autologous platelet-rich plasma (APRP) and autologous serum (AS) in patients with moderate-to-severe dry eye disease (DED).

Methods and analysis

A single-centre, randomised, double-masked, non-inferiority clinical trial was conducted. 96 adult DED patients with an Ocular Surface Disease Index (OSDI) Score of ≥23 and/or Oxford staining grade of ≥2 were randomised to receive either 100% APRP (n=48) or 100% AS (n=48) for 4 weeks. Primary outcomes included OSDI Score and ocular surface staining measured by Oxford grading scale at 4 weeks. Secondary outcomes included fluorescein tear break-up time, Schirmer’s test, meibum quality and expressibility, and adverse events. The 95% CI for the mean difference in OSDI scores between groups was estimated to assess non-inferiority of the OSDI score at a prespecified margin of 4.18 points.

Results

At week 4, there was no significant difference in decreased OSDI scores between groups, with the mean difference (100% APRP−100% AS) of 1.41 (95% CI −1.26, 4.08, p=0.299). The upper limit was less than the prespecified margin, indicating non-inferiority of 100% APRP vs 100% AS. The probabilities of achieving an Oxford grade 0–1 after treatment were not significantly different between groups, with an OR of 0.61 (95% CI 0.25, 1.52, p=0.288). No significant differences in secondary outcomes were observed between groups.

Conclusion

In the short-term, 100% APRP was not inferior to 100% AS in reducing dry eye symptoms and ocular surface staining in moderate-to-severe DED.

Trial registration number

NCT04683796.
Maternal perceived safety and parenting practices with young children: a cross-sectional analysis from 15 low-income and middle-income countries
Authors: Ramos de Oliveira Clariana Vitória , Neves Paulo , Coll Carolina V N , Palombo Cláudia Nery Teixeira , Jeong Joshua
Published: October 2024

Introduction

Social environments can influence parents’ caregiving capacities and the quality of nurturing care provided to children. These links, in turn, can shape children’s developmental outcomes over the life course. We aimed to examine the relationship between maternal perceived safety at home and in the neighbourhood and maternal parenting practices in low-income and middle-income countries (LMICs).

Method

We combined cross-sectional data from the Multiple Indicator Cluster Surveys in 15 LMICs (2018–2019). Mothers of children aged 36–59 months were included in the sample. We assessed maternal perceived safety at home and in the neighbourhood and two parenting outcomes of maternal stimulation and discipline. We used multiple logistic regression models to estimate the associations while adjusting for sociodemographic characteristics and maternal well-being in the pooled sample. Also, analyses were performed for each country separately.

Results

After adjusting for covariates, maternal perceived safety at home was associated with increased odds of high maternal stimulation (OR: 1.15, 95% CI: 1.01; 1.32) and lower odds of aggressive psychological discipline (OR: 0.87, 95% CI: 0.77; 0.98). Maternal perception of safety in the neighbourhood was associated with lower odds of aggressive psychological discipline (OR: 0.79, 95% CI: 0.71; 0.88), aggressive physical discipline (OR: 0.87, 95% CI: 0.77; 0.98) and non-violent discipline (OR: 0.78, 95% CI: 0.63; 0.95).

Conclusion

Maternal perceived safety at home and in the neighbourhood was positively associated with improved parenting behaviours with young children in LMICs. Interventions that address safety and security at home and across communities may have the potential to enhance maternal well-being and parenting practices to promote integral child development.