bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental noise and phenotypic plasticity are correlated in Drosophila simulans
Authors: Saito Keita , Tsuboi Masahito , Takahashi Yuma 
Published: January 2024

Abstract
Non-genetic variation is the phenotypic variation induced by the differential expression of a genotype in response to varying environmental cues and is broadly categorized into two types: phenotypic plasticity and developmental noise. These aspects of variation have been suggested to play an important role in adaptive evolution. However, the mechanisms by which these two types of non-genetic variations influence the evolutionary process are currently poorly understood. Using a machine-learning-based phenotyping tool, we independently quantified phenotypic plasticity and developmental noise in the wing morphological traits of the fruit fly Drosophila simulans. Utilizing a rearing experiment, we demonstrated plastic responses in both wing size and shape as well as non-zero heritability of both phenotypic plasticity and developmental noise, which suggests that adaptive phenotypic plasticity can evolve via genetic accommodation in the wing morphology of D. simulans. We found a positive correlation between phenotypic plasticity and developmental noise, while the correlation between the plastic response to three kinds of environmental factors that were examined (nutrient condition, temperature, and light–dark cycle) was poor. These results suggest that phenotypic plasticity and developmental noise contribute to evolvability in a similar manner, however, the mechanisms that underlie the correspondence between these two types of variation remain to be elucidated.
Does cycle commuting reduce the risk of mental ill-health? An instrumental variable analysis using distance to nearest cycle path
Authors: Berrie Laurie , Feng Zhiqiang , Rice David , Clemens Tom , Williamson Lee , Dibben Chris 
Published: January 2024

Abstract

Background
Previous studies have linked cycling with improved mental wellbeing but these studies tend to use cross-sectional survey data that have small sample sizes and self-reported health measures, and are potentially susceptible to omitted-variable bias and reverse causation. We use an instrumental variable approach and an objective measure of mental ill-health taken from linked administrative data to ask: ‘Does cycle commuting reduce the risk of mental ill-health?’

Methods
Our study links data on commuting in Edinburgh and Glasgow from the Scottish population census with mental health prescriptions from the National Health Service Prescribing Information System records. We use road distance from home to nearest cycle path as an instrumental variable for cycle commuting.

Results
In total, 378 253 people aged 16–74 years living and working in the City of Edinburgh and Glasgow City council areas at the 2011 census were included in our study; 1.85% of commuters in Glasgow and 4.8% of commuters in Edinburgh cycled to work. Amongst cyclists, 9% had a prescription for mental health compared with 14% amongst non-cyclists. Using a bivariate probit model, we estimate a mean average reduction in prescriptions for antidepressants and/or anxiolytics in the 5 years following the census of –15.1% (95% CI: –15.3% to –15.0%) amongst cycle commuters compared with those who use any other mode to commute.

Conclusions
This work suggests that cycle commuting is causally related to reduced mental ill-health and provides further evidence in support of the promotion of active travel to encourage commuters travelling shorter distances to shift to cycle commutes.
Dimension reduction based on approximate gramians via Laguerre polynomials for coupled systems
Authors: Qi Zhen-Zhong , Xiao Zhi-Hua , Yuan Jia-Wei 
Published: January 2024

Abstract
In this paper, we focus on the topic of model order reduction (MOR) for coupled systems. At first, an approximation via Laguerre polynomials expansions to controllability and observability gramians for such systems are presented, which provides a low-rank decomposition form whose factors are constructed from a recurrence formula instead of Lyapunov equations. Then, in combination of balanced truncation and dominant subspace projection method, a series of MOR algorithms are proposed that preserve the coupled structures. What’s more, some main properties of reduced-order models, such as stability preservation, are well discussed. Finally, three numerical simulations are provided to illustrate the effectiveness of our algorithms.
Bureaucracy and Cyber Coercion
Authors: Demarest Heidi , Jost Tyler , Schub Robert 
Published: January 2024

Abstract
States are increasingly incorporating militarized cyber technologies, or cyber weapons, into their defense arsenals, but there is vigorous debate about their coercive utility. Existing scholarship often adjudicates the debate by parsing technical differences between cyber and conventional weapons. This technical approach overlooks a critical consideration: bureaucrats who inform state assessments may hold unique perspectives on coercion due to their organizational affiliation. We make an empirical intervention by fielding a survey experiment on bureaucrats inside US Cyber Command, offering a rare glimpse into elite perceptions. We find little evidence that technical differences between weapons yield systematically different assessments. Bureaucrats perceive that conventional and cyber weapons have statistically indistinguishable coercive utility and battlefield effects. Replicating the study on a public sample, we find that bureaucrats are more optimistic about coercion across all domains and their optimism stems from organizational culture, rather than parochial interests or technical expertise. The findings show how who is responsible for assessing a technology's coercive value can shape estimates even more than which technology is being assessed. Unique perspectives clustered within influential bureaucracies may shape state assessments and policies in ways that diverge from the expectations of analyses that emphasize technical characteristics of military capabilities.
Using Eye-Tracking to Demonstrate Children’s Attention to Detail When Evaluating Low-Fidelity Prototypes
Authors: Sim Gavin , Read Janet C 
Published: January 2024

Abstract
This study used eye-tracking glasses to better understand how children explore low-fidelity prototypes in the context of user experience studies and to explore the potential of eye tracking in this context. The main research question that was being explored was whether the aesthetic refinement, either wireframe or high-resolution images, would affect children’s self-report and if so, or if not, what could be learned from knowing where children looked when exploring the prototypes. The results showed that the aesthetic refinement had little influence over the children’s overall ratings of the game. The eye-tracking data demonstrated that there were no differences in the time spent viewing the prototypes and most of the children focused on both the visuals and text on all the pages. However, there were a higher number of fixations recorded in the wireframe prototype compared to the photo-realistic version. This paper contributes to the design of prototypes through an understanding of how children interact with prototypes, demonstrating the importance of the text along with the visuals when evaluating game concepts with children. Further research is required to understand the differences and whether similar results are replicated with different games.
To kill a microRNA: emerging concepts in target-directed microRNA degradation
Authors: Buhagiar Amber F , Kleaveland Benjamin 
Published: January 2024

Abstract
MicroRNAs (miRNAs) guide Argonaute (AGO) proteins to bind mRNA targets. Although most targets are destabilized by miRNA–AGO binding, some targets induce degradation of the miRNA instead. These special targets are also referred to as trigger RNAs. All triggers identified thus far have binding sites with greater complementarity to the miRNA than typical target sites. Target-directed miRNA degradation (TDMD) occurs when trigger RNAs bind the miRNA–AGO complex and recruit the ZSWIM8 E3 ubiquitin ligase, leading to AGO ubiquitination and proteolysis and subsequent miRNA destruction. More than 100 different miRNAs are regulated by ZSWIM8 in bilaterian animals, and hundreds of trigger RNAs have been predicted computationally. Disruption of individual trigger RNAs or ZSWIM8 has uncovered important developmental and physiologic roles for TDMD across a variety of model organisms and cell types. In this review, we highlight recent progress in understanding the mechanistic basis and functions of TDMD, describe common features of trigger RNAs, outline best practices for validating trigger RNAs, and discuss outstanding questions in the field.
A tentative anatomy of Christian responses to anthropogenic climate change
Authors: Siddall Mark 
Published: January 2024

Abstract
This pilot study addresses the differences in responses to anthropogenic climate change expressed in published normative statements for a cross section of Christian denominations and groupings from the UK and USA as well as international groupings. Grid-group cultural theory is tentatively employed to better understand these differences. Because the cosmologies identified by grid-group theory have as their basis the metaphor of the body, this is in effect a tentative anatomy of Christian responses to anthropogenic climate change. As a test case, this paper explores whether or not it is fruitful to attempt to challenge a given cosmological outlook to better communicate climate change and how this might be achieved or whether to speak to that cosmological perspective and how this might be achieved. In addition, this paper explores how each distinctive cosmology might contribute helpfully in responding to anthropogenic climate change. Finally, avenues of further work to expand this approach are explored.
Outcomes of Follow-up Imaging After Pediatric Spinal Trauma Confirmed With Magnetic Resonance Imaging
Authors: Sirén Aapo , Syvänen Johanna , Nyman Mikko , Mattila Kimmo , Hirvonen Jussi 
Published: January 2024

Background:
Imaging plays a crucial role in the diagnostic workup of pediatric spinal trauma. Computed tomography and conventional radiographs are widely used as the primary imaging methods. Magnetic resonance imaging (MRI) is a radiation-free alternative with high sensitivity for bony and soft tissue injuries. There is no consensus on the optimal use of follow-up imaging in pediatric spinal trauma without immediate surgical treatment, especially if the injury is primarily confirmed with MRI. This study aimed to assess the diagnostic value of follow-up imaging after MRI-confirmed spinal trauma in children.

Methods:
The medical records and the imaging data of children and adolescents with emergency spinal MRI and follow-up imaging over 8 years were retrospectively reviewed. The primary study outcome was the outcome of follow-up imaging and its effect on management.

Results:
The study population consisted of 127 patients. The follow-up imaging did not alter the management in any patient with presumably stable injury in emergency MRI. Short-term follow-up imaging showed no clinically significant progression in thoracolumbar compression fractures. Flexion-extension radiographs had no additional value in cases with stable cervical spinal injury on emergency MRI.

Conclusions:
The clinical utility of short-term follow-up imaging is low in children with stable spinal injury on emergency MRI.

Level of evidence:
Level III—retrospective observational study.
Outcomes of the Nuss procedure in children with pectus excavatum: 14 years of experience
Authors: Chu Chih-Chun , Chang Jei-Wen , Yang Hui-Hsin , Kuo Fang-Cheng , Tsai Hsin-Lin 
Published: January 2024

Background:
We aimed to assess the effectiveness of the Nuss procedure for pectus excavatum (PE) and explore the impacts of sex and age on outcomes.

Methods:
We retrospectively reviewed 594 consecutive children ≤18 years of age who underwent the thoracoscopy-assisted Nuss technique between January 2006 and July 2019. The severity of pectus deformity was calculated according to the Haller index (HI). The classification of PE and clinical data including complications was analyzed.

Results:
Of the 594 patients, 456 (76.8%) were boys and 138 (23.2%) were girls. The mean age at surgery was 10.0 ± 5.0 years. The most common types of PE were 1A and 2A2 according to Park classification. Intraoperative and postoperative complication rates were 2/594 (0.3%) and 74/594 (12.5%), respectively. The most common complication was bar displacement. The bar was removed in 414 patients 3.5 ± 0.8 years later. The mean preoperative HI, postoperative HI with bar, and HI after bar removal were 4.2 ± 1.7, 2.4 ± 0.3, and 2.7 ± 0.5, respectively. Compared to the preoperative HI, both the postoperative HI with bar and HI after bar removal were significantly lower (p < 0.001). For preschool-age children, the preoperative HI was significantly higher (p = 0.027) and the change in HI significantly improved compared to school-age children (p = 0.004). Boys and adolescents needed significantly more bars and stabilizers.

Conclusion:
Surgical correction of PE using the Nuss procedure is a safe procedure and improves the HI in children of different ages, even in those younger than 6 years of age.
Bidirectional Associations Between Pain and Perceived Stress Among Veterans: Depressive Disorder as a Predisposing Factor
Authors: Saba Shaddy K. , Davis Jordan P. , Prindle John J. , Howe Esther , Tran Denise D. , Bunyi John , Hummer Justin F. , Castro Carl Andrew , Pedersen Eric R. 
Published: January 2024

ABSTRACT

Objective
Military veterans who were injured in combat very often report pain along with co-occurring perceived stress and preexisting depressive disorder. The systems model of pain is a theoretical model suggesting that pain and perceived stress are bidirectionally associated at the within-person level, and associations are heightened among those with depressive disorder. However, the systems model of pain has not been adequately tested. Testing the systems model of pain could illuminate salient treatment targets for combat-injured veterans with pain and co-occurring psychological problems.

Methods
The present study empirically tests the systems model of pain among a sample of combat-injured veterans (N = 902) surveyed five times during an 18-month period. We used a multigroup, autoregressive latent trajectory with structured residual statistical model to test the within-person associations between pain and perceived stress and determine whether associations differ between veterans with and without a positive screen for depressive disorder.

Results
In line with the systems model of pain, pain and perceived stress were bidirectionally associated only among combat-injured veterans with depressive disorder. Among such veterans, perceived stress was positively associated with subsequent pain (b = 0.12; 95% confidence interval = 0.06–0.17), and pain was positively associated with subsequent perceived stress (b = 0.44; 95% CI = 0.11–0.77).

Conclusions
Our work highlights the interplay between pain and its psychological correlates among a particularly at-risk population. Clinicians addressing pain and perceived stress among combat-injured veterans should be prepared to identify and address depressive disorder.
Validity of Entrustable Professional Activities in a National Sample of General Surgery Residency Programs
Authors: Montgomery Kelsey B , Mellinger John D , Jones Andrew , McLeod M Chandler , Zmijewski Polina , Sarosi George A , Brasel Karen J , Klingensmith Mary E , Minter Rebecca M , Buyske Jo , Lindeman Brenessa 
Published: January 2024

BACKGROUND:
The American Board of Surgery has endorsed competency-based education as vital to the assessment of surgical training. From 2018 to 2020, a national pilot study was conducted at 28 general surgery programs to evaluate feasibility of implementing entrustable professional activities (EPAs) for 5 common general surgical conditions. ACGME core competency Milestones were also rated for each resident by program clinical competency committees. This study aimed to evaluate the validity of general surgery EPAs compared with Milestones.

STUDY DESIGN:
Prospectively collected, de-identified EPA Pilot Study data were analyzed. EPAs studied were EPA-1 (gallbladder), EPA-2 (inguinal hernia), EPA-3 (right lower quadrant pain), EPA-4 (trauma), and EPA-5 (consult). Variables abstracted included levels of EPA entrustment (1 to 5) and corresponding ACGME Milestone subcompetency ratings (1 to 5) for the same study cycle. Spearman’s correlations were used to evaluate the relationship between summative EPA scores and corresponding Milestone ratings.

RESULTS:
A total of 493 unique residents received a summative entrustment decision. EPA summative entrustment scores had moderate-to-strong positive correlation with mapped Milestone subcompetencies, with median rho value of 0.703. Among operation-focused EPAs, median rho values were similar between EPA-1 (0.688) and EPA-2 (0.661), but higher for EPA-3 (0.833). EPA-4 showed a strong positive correlation with diagnosis and communication competencies (0.724), whereas EPA-5, mapped to the most Milestone subcompetencies, had the lowest median rho value (0.455).

CONCLUSIONS:
Moderate-to-strong positive correlation was noted between EPAs and patient care, medical knowledge, and communication Milestones. These findings support the validity of EPAs in general surgery and suggest that EPA assessments can be used to inform Milestone ratings by clinical competency committees.
From conformal infinity to equations of motion: conserved quantities in general relativity
Authors: Penrose Roger 
Published: January 2024

This paper describes conservation laws in general relativity (GR) dating back to the mass-energy conservation of Bondi and Sachs in the early 1960s but using 2-spinor techniques. The notion of conformal infinity is employed, and the highly original ideas of E. T. Newman are discussed in relation to twistor theory. The controversial NP constants are introduced, and their meaning is considered in a new light related to the problem of equations of motion in GR.
This article is part of a discussion meeting issue ‘At the interface of asymptotics, conformal methods and analysis in general relativity’.
At the interface of asymptotics, conformal methods and analysis in general relativity
Authors: Taujanskas G. , Valiente Kroon J. A. 
Published: January 2024

This is an introductory article for the proceedings associated with the Royal Society Hooke discussion meeting of the same title which took place in London in May 2023. We review the history of Penrose’s conformal compactification, null infinity and a number of related fundamental developments in mathematical general relativity from the last 60 years.This article is part of a discussion meeting issue ‘At the interface of asymptotics, conformal methods and analysis in general relativity’.
Metformin protects the heart against chronic intermittent hypoxia through AMPK-dependent phosphorylation of HIF-1α
Authors: Moulin Sophie , Blachot-Minassian Britanny , Kneppers Anita , Thomas Amandine , Paradis Stéphanie , Bultot Laurent , Arnaud Claire , Pépin Jean-Louis , Bertrand Luc , Mounier Rémi , Belaidi Elise 
Published: January 2024

AbstractChronic intermittent hypoxia (IH), a major feature of obstructive sleep apnea syndrome (OSA), is associated with a more severe myocardial infarction. In this study, we performed RNA sequencing of cardiac samples from mice exposed to IH, which reveals a specific transcriptomic signature of the disease, relative to mitochondrial remodeling and cell death. Corresponding to its activation under chronic IH, we stabilized the Hypoxia Inducible Factor-1α (HIF-1α) in cardiac cellsin vitro,and observed its association with an increased autophagic flux. In accordance, IH induced autophagy and mitophagy that is decreased in HIF-1α+/_mice compared to wild-type animals suggesting that HIF-1 plays a significant role in IH-induced mitochondrial remodeling. Next, we showed that the AMPK metabolic sensor, typically activated by mitochondrial stress, is inhibited after 3 weeks of IH in hearts. Therefore, we assessed the effect of metformin, an anti-diabetic drug and potent activator of AMPK, on myocardial response to ischemia-reperfusion (I/R) injury. Daily administration of metformin significantly decreases infarct size without any systemic beneficial effect on insulin-resistance under IH conditions. The cardioprotective effect of metformin is lost in AMPKα2 knock-out mice demonstrating that AMPKα2 isoform promotes metformin-induced cardioprotection in mice exposed to IH. Mechanistically, we found that metformin inhibits IH-induced mitophagy in myocardium and decreases HIF-1α nuclear expression in mice subjected to IH.In vitrodemonstrated that metformin induces HIF-1α phosphorylation, decreases its nuclear localization and subsequently HIF-1 transcriptional activity. Collectively, these results identify the AMPKα2 metabolic sensor as a novel modulator of HIF-1 activity. Our data suggest that metformin could be considered as a cardioprotective drug in OSA patients independently of their metabolic status.
Constitutive Photomorphogenesis Protein 1 homolog (COP1) sustains nuclear factor-4 alpha function in human hepatocyte models
Authors: Soubeyrand Sébastien , Lau Paulina , McPherson Ruth 
Published: January 2024

AbstractConstitutive Photomorphogenesis Protein 1 homolog (COP1) is a conserved E3 ligase with key roles in several biological systems. Prior work in hepatocyte derived tumors categorized COP1 as an oncogene but its role in untransformed hepatocytes remains largely unexplored. Here we have investigated the role of COP1 in primary human hepatocytes as well as in two transformed hepatocyte models, HepG2 and HuH-7 cells. Contrary to a previous report, COP1 suppression via siRNA had no noticeable impact on HepG2 and HuH-7 proliferation and was associated with contrasting rather than congruent transcriptome changes. Clustering analyses identified patterns indicative of perturbed metabolism in primary hepatocytes and HepG2 cells whereas patterns pointed to cell proliferation impacts in HuH-7 cells. In HepG2 and primary hepatocytes, COP1 suppression reduced the expression important hepatic regulators and markers, which could be restored by the introduction of a siRNA resistant COP1 transgene. COP1 downregulation reduced hepatic nuclear factor-4 alpha (HNF4A) abundance and function, as assessed by lower abundance of key HNF4A targets and reduced APOB secretion. HNF4A restoration partially rescued COP1 silencing in HepG2 cells. This study identifies COP1 as a key regulator of hepatocyte function, in part via HNF4A. COP1 was required to maintain HNF4A abundance and function in primary hepatocytes and in HepG2 cells, but not in HuH-7 cells. Lastly, by demonstrating contrasting roles of COP1 in HuH-7 and HepG2 cells, our findings also challenge previous work linking COP1 to hepatic tumorigenesis.