bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early origins of health and disease risk: The case for investigating adverse exposures and biological aging in utero, across childhood, and into adolescence
Authors: Etzel Laura , Garrett‐Petters Patricia , Shalev Idan 
Published: October 2023

AbstractIn this article, we suggest that aging and development are two sides of the same coin, and that developing a comprehensive understanding of health and disease risk requires examining age‐related processes occurring throughout the earliest years of life. Compared to other periods in life, it is during this early period of acute vulnerability, when children's biological and regulatory systems are developing, that biological aging occurs most rapidly. We review theory and empirical research suggesting that processes of development and aging are intricately linked, and that early adversity may program biological parameters for accelerated aging and disease risk early in life, even though clinical signs of age‐related disease onset may not be evident until many years later. Following from this, we make the case for widespread incorporation of biological aging constructs into child development research.
Dollar Liquidity, Financial Vulnerability and Monetary Sovereignty
Authors: Jump Rob Calvert , Michell Jo 
Published: October 2023

ABSTRACTPeriods of dollar‐led global monetary tightening generate negative effects in many lower‐ and middle‐income countries. The tightening cycle which commenced in early 2022 has exacerbated the financial dislocation experienced by countries including Zambia, Sri Lanka and Pakistan. How can policy makers protect their economies from such external shocks and foster a stable developmental environment? Some recent contributions argue that the capacity of countries to insulate domestic policy from global financial conditions depends upon ‘monetary sovereignty’. This contribution argues that this misrepresents the constraints to macroeconomic policy and development strategy. Monetary sovereignty, if narrowly defined, is necessary but not sufficient for domestic policy autonomy. Stronger definitions impose unrealistic requirements on debt denomination and exchange rate regimes. The authors argue that, outside of currency unions, the main policy constraints for developing countries are limited domestic productive capacity and integration into global trade and financial networks rather than monetary arrangements. The discussion is illustrated with an empirical examination of three recent episodes of global illiquidity and/or policy tightening: the 2013 taper tantrum, the March 2020 liquidity shock and the 2022 dollar tightening cycle. The authors find evidence that monetary sovereignty does not insulate a country from episodes of dollar illiquidity. While ‘fundamentals’ such as current account deficits and foreign exchange reserves provide limited power in identifying vulnerability, measures of financial depth and activity do appear related to vulnerability.
Application of CRISPR‐Cas9 technology in diabetes research
Authors: Lotfi Malihe , Butler Alexandra E. , Sukhorukov Vasily N. , Sahebkar Amirhossein 
Published: October 2023

AbstractDiabetes is a chronic disorder with rapidly increasing prevalence that is a major global issue of our current era. There are two major types of diabetes. Polygenic forms of diabetes include type 1 diabetes (T1D) and type 2 diabetes (T2D) and its monogenic forms are maturity‐onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM). There are no permanent therapeutic approaches for diabetes and current therapies rely on regular administration of various drugs or insulin injection. Recently, gene editing strategies have offered new promise for treating genetic disorders. Targeted genome editing is a fast‐growing technology, recruiting programmable nucleases to specifically modify target genomic sequences. These targeted nucleases generate double‐strand breaks at target regions in the genome, which induce cellular repair pathways including non‐homologous end joining (NHEJ) and homology‐directed repair (HDR). Clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) is a novel gene‐editing system, permitting precise genome modification. CRISPR/Cas9 has great potential for various applications in diabetic research such as gene screening, generation of diabetic animal models and treatment. In this article, gene‐editing strategies are summarized with a focus on the CRISPR/Cas9 approach in diabetes research.
Societal health and economic burden of cardiovascular diseases in the population with type 2 diabetes in Qatar. A 10‐year forecasting model
Authors: Abushanab Dina , Al‐Badriyeh Daoud , Marquina Clara , Liew Danny , Al‐Zaidan Manal , Ghaith Al‐Kuwari Mohammed , Abdulmajeed Jazeel , Ademi Zanfina 
Published: October 2023

AbstractAimsTo predict the future health and economic burden of cardiovascular disease (CVD) in type 2 diabetes (T2D) in Qatar.Materials and MethodsA dynamic multistate model was designed to simulate the progression of fatal and non‐fatal CVD events among people with T2D in Qatar aged 40‐79 years. First CVD events [i.e. myocardial infarction (MI) and stroke] were calculated via the 2013 Pooled Cohort Equation, while recurrent CVD events were sourced from the REACH registry. Key model outcomes were fatal and non‐fatal MI and stroke, years of life lived, quality‐adjusted life years, total direct medical costs and total productivity loss costs. Utility and cost model inputs were drawn from published sources. The model adopted a Qatari societal perspective. Sensitivity analyses were performed to test the robustness of estimates.ResultsOver 10 years among people with T2D, model estimates 108 195 [95% uncertainty interval (UI) 104 249‐112 172] non‐fatal MIs, 62 366 (95% UI 60 283‐65 520) non‐fatal strokes and 14 612 (95% UI 14 472‐14 744) CVD deaths. The T2D population accrued 4 786 605 (95% UI 4 743 454, 4 858 705) total years of life lived and 3 781 833 (95% UI 3 724 718‐3 830 669) total quality‐adjusted life years. Direct costs accounted for 57.85% of the total costs, with a projection of QAR41.60 billion (US$11.40 billion) [95% UI 7.53‐147.40 billion (US$2.06‐40.38 billion)], while the total indirect costs were expected to exceed QAR30.31 billion (US$8.30 billion) [95% UI 1.07‐162.60 billion (US$292.05 million‐44.55 billion)].ConclusionsThe findings suggest a significant economic and health burden of CVD among people with T2D in Qatar and highlight the need for more enhanced preventive strategies targeting this population group.
Wicked Insights into Design Learning
Authors: Wells‐Papanek Doris 
Published: October 2023

It started with a group of about 50 highly motivated K‐12 teachers, college educators, practitioners, administrators, business leaders, and forward‐thinking college students. They called themselves the Design Learning Network, and their aim was to figure out what students need to know in order to survive and thrive in the twenty‐first century.What will our students need to know in order to prepare for careers that may not even exist yet? The Design Learning Network is looking for suggestions.
Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin‐1
Authors: Del Buono Marco Giuseppe , Bonaventura Aldo , Vecchié Alessandra , Moroni Francesco , Golino Michele , Bressi Edoardo , De Ponti Roberto , Dentali Francesco , Montone Rocco Antonio , Kron Jordana , Lazzerini Pietro Enea , Crea Filippo , Abbate Antonio 
Published: October 2023

AbstractBackgroundAn exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs).MethodsThis narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: “acute pericarditis,” “recurrent pericarditis,” “myocarditis,” “cardiac sarcoidosis,” “atherosclerosis,” “acute myocardial infarction,” “inflammation,” “NLRP3 inflammasome,” “Interleukin‐1” and “treatment.”ResultsRecent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine‐rich repeat and pyrin‐domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL‐1β, the prototypical pro‐inflammatory cytokine involved in CVDs. Other pro‐inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL‐1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome.ConclusionTailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies.
Effects of jaw clenching and mental stress on persistent inward currents estimated by two different methods
Authors: Mesquita Ricardo N. O. , Taylor Janet L. , Trajano Gabriel S. , Holobar Aleš , Gonçalves Basílio A. M. , Blazevich Anthony J. 
Published: October 2023

AbstractSpinal motoneuron firing depends greatly on persistent inward currents (PICs), which in turn are facilitated by the neuromodulators serotonin and noradrenaline. The aim of this study was to determine whether jaw clenching (JC) and mental stress (MS), which may increase neuromodulator release, facilitate PICs in human motoneurons. The paired motor unit (MU) technique was used to estimate PIC contribution to motoneuron firing. Surface electromyograms were collected using a 32‐channel matrix on gastrocnemius medialis (GM) during voluntary, ramp, plantar flexor contractions. MU discharges were identified, and delta frequency (ΔF), a measure of recruitment–derecruitment hysteresis, was calculated. Additionally, another technique was used (VibStim) that evokes involuntary contractions that persist after cessation of combined Achilles tendon vibration and triceps surae neuromuscular electrical stimulation. VibStim measures of plantar flexor torque and soleus activity may reflect PIC activation. ΔF was not significantly altered by JC (p = .679, n = 18, 9 females) or MS (p = .147, n = 14, 5 females). However, all VibStim variables quantifying involuntary torque and muscle activity during and after vibration cessation were significantly increased in JC (p < .011, n = 20, 10 females) and some, but not all, increased in MS (p = .017–.05, n = 19, 10 females). JC and MS significantly increased the magnitude of involuntary contractions (VibStim) but had no effect on GM ΔF during voluntary contractions. Effects of increased neuromodulator release on PIC contribution to motoneuron firing might differ between synergists or be context dependent. Based on these data, the background level of voluntary contraction and, hence, both neuromodulation and ionotropic inputs could influence neuromodulatory PIC enhancement.
Eco‐evolution from deep time to contemporary dynamics: The role of timescales and rate modulators
Authors: Fronhofer Emanuel A. , Corenblit Dov , Deshpande Jhelam N. , Govaert Lynn , Huneman Philippe , Viard Frédérique , Jarne Philippe , Puijalon Sara 
Published: October 2023

AbstractEco‐evolutionary dynamics, or eco‐evolution for short, are often thought to involve rapid demography (ecology) and equally rapid heritable phenotypic changes (evolution) leading to novel, emergent system behaviours. We argue that this focus on contemporary dynamics is too narrow: Eco‐evolution should be extended, first, beyond pure demography to include all environmental dimensions and, second, to include slow eco‐evolution which unfolds over thousands or millions of years. This extension allows us to conceptualise biological systems as occupying a two‐dimensional time space along axes that capture the speed of ecology and evolution. Using Hutchinson's analogy: Time is the ‘theatre’ in which ecology and evolution are two interacting ‘players’. Eco‐evolutionary systems are therefore dynamic: We identify modulators of ecological and evolutionary rates, like temperature or sensitivity to mutation, which can change the speed of ecology and evolution, and hence impact eco‐evolution. Environmental change may synchronise the speed of ecology and evolution via these rate modulators, increasing the occurrence of eco‐evolution and emergent system behaviours. This represents substantial challenges for prediction, especially in the context of global change. Our perspective attempts to integrate ecology and evolution across disciplines, from gene‐regulatory networks to geomorphology and across timescales, from today to deep time.
SEED: A framework for integrating ecological stoichiometry and eco‐evolutionary dynamics
Authors: El‐Sabaawi Rana W. , Lemmen Kimberley D. , Jeyasingh Punidan D. , Declerck Steven A. J. 
Published: October 2023

AbstractCharacterising the extent and sources of intraspecific variation and their ecological consequences is a central challenge in the study of eco‐evolutionary dynamics. Ecological stoichiometry, which uses elemental variation of organisms and their environment to understand ecosystem patterns and processes, can be a powerful framework for characterising eco‐evolutionary dynamics. However, the current emphasis on the relative content of elements in the body (i.e. organismal stoichiometry) has constrained its application. Intraspecific variation in the rates at which elements are acquired, assimilated, allocated or lost is often greater than the variation in organismal stoichiometry. There is much to gain from studying these traits together as components of an ‘elemental phenotype’. Furthermore, each of these traits can have distinct ecological effects that are underappreciated in the current literature. We propose a conceptual framework that explores how microevolutionary change in the elemental phenotype occurs, how its components interact with each other and with other traits, and how its changes can affect a wide range of ecological processes. We demonstrate how the framework can be used to generate novel hypotheses and outline pathways for future research that enhance our ability to explain, analyse and predict eco‐evolutionary dynamics.
Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study
Authors: Bril Vera , Howard James F. , Karam Chafic , De Bleecker Jan L. , Murai Hiroyuki , Utsugisawa Kimiaki , Ulrichts Peter , Brauer Edward , Zhao Sihui , Mantegazza Renato , Vu Tuan ,   the ADAPT Study Group
Published: October 2023

AbstractBackground and purposeGeneralized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration.MethodsThe safety and efficacy of efgartigimod were evaluated in the ADAPT study. Key efficacy outcome measures included Myasthenia Gravis Activities of Daily Living (MG‐ADL) and Quantitative Myasthenia Gravis (QMG) scores. Efgartigimod demonstrated significant improvement in both the MG‐ADL and QMG scores. This post hoc analysis aimed to determine whether all subdomains of MG‐ADL and QMG improved with efgartigimod treatment. Individual items of MG‐ADL and QMG were grouped into four subdomains: bulbar, ocular, limb/gross motor and respiratory. Change from baseline over 10 weeks in each subdomain was calculated for each group.ResultsGreater improvements from baseline were seen across MG‐ADL subdomains in participants treated with efgartigimod compared with placebo. These improvements were typically observed 1 to 2 weeks after the first infusion and correlated with reductions in IgG. Similar results were observed across most QMG subdomains.ConclusionsThese post hoc analyses of MG‐ADL and QMG subdomain data from ADAPT suggest that efgartigimod is beneficial in improving muscle function and strength across all muscle groups, leading to the observed efficacy in participants with gMG.
Precision‐milled simulated curved root canals in bovine dentine for the assessment of chemo‐mechanical root canal preparation
Authors: Hofpeter Kevin , Zehnder Matthias , Hülsmann Michael , Al‐Jadaa Anas , Deari Shengjile 
Published: October 2023

AbstractAimThe aim was to develop a standardized curved root canal model in bovine dentine and to assess whether that natural substrate would behave differently from the resin in standard plastic training blocks when prepared chemo‐mechanically. The impact of substrate microhardness on simulated canal transportation was considered.MethodologyHigh‐precision computer numerical control (CNC) milling was used to recreate a simulated root canal from a resin training block (Endo Training Bloc J‐Shape, size 15) in longitudinally sectioned, dis‐ and re‐assembled bovine incisor roots. Optical overlays obtained from 10 resin blocks were used to identify an average canal and program the CNC milling apparatus accordingly. Resin and dentine microhardness were measured. Simulated root canals in resin training blocks and their bovine counterparts were then instrumented at 37°C using Reciproc R25 instruments (VDW) with water or 17% EDTA (n = 10). Open‐access image processing software was used to superimpose and analyse pre‐ and postoperative images obtained with a digital microscope. Centering ratios were averaged to indicate canal transportation. The effects of substrate and irrigant on canal transportation were assessed by two‐way anova.ResultsSuperimposed images showed that resin blocks under investigation varied considerably in terms of simulated canal length and curvature, whilst the milled canals were highly similar. The microhardness of dentine was more than three times higher than that of the resin. Conversely, canal transportation was considerably greater in dentine compared to resin, and in dentine had a tendency to be increased by EDTA. There was a strong effect of substrate on canal transportation (p < .001), no overall effect of irrigant, and a marginally significant interaction between irrigant and substrate (p = .077).ConclusionsCNC milling allows to create standardized simulated curved root canals in bovine dentine. These models may be useful to test and compare materials and concepts of chemo‐mechanical root canal instrumentation. Microhardness is a bulk feature that does not predict the response to chemo‐mechanical instrumentation of a composite material such as dentine.
A retrospective study of pediatric renal trauma: A single‐center experience in Japan
Authors: Kanjanatarayon Sarayut , Ishikawa Mimu , Tomomasa Naoya , Yamamoto Shutaro , Kimura Takahiro , Hasegawa Yuichi 
Published: October 2023

AbstractObjectivesTo report pediatric renal trauma experiences at the National Center for Child Health and Development in Japan according to the Japanese Association for the Surgery of Trauma (JAST) classification 2008.MethodsMedical records were retrospectively reviewed for 45 children younger than 18 years old diagnosed with renal trauma from February 2004 to December 2021, regarding details of external causes, treatments, complications, and injury scales according to the JAST classification 2008. The cases who cannot be classified into the JAST classification 2008 will be categorized into our original type 0.ResultsThere were 24 males and 21 females with a mean age of 8.5 years. Left kidneys were the predominantly affected side. Blunt injury was involved in every case (mainly falls and traffic accidents). Concomitant organ injuries were found in 13 cases. The injury scales were type Ia (13.3%), II (11.1%), IIIa (13.3%), IIIb (24.4%). Type 0 accounted for 37.8%, which were type 0c (congenital anomalies of the kidney and urinary tract without hematoma and/or laceration of kidney parenchyma) at 11.1% and type 0h (only hematuria and normal radiologic finding) at 26.7%. Treatments were blood transfusion, ureteral stenting, nephrostomy, and no nephrectomy. Complications were pseudoaneurysm, hypertension, and infection.ConclusionsNearly 38% of cases cannot be classified into the JAST classification 2008, comprising at least two irrelevant types (type 0c and type 0h). Accordingly, a pediatric renal injury scale should be established to achieve the precise diagnosis and treatments. However, further studies are still needed.
Characterization of high pathogenicity avian influenza H5Nx viruses from a wild harbor seal and red foxes in Denmark, 2021 and 2022
Authors: Liang Yuan , Hjulsager Charlotte K. , Jensen Tim K. , Hammer Anne Sofie V. , Ovesen Maibritt T. , Larsen Lars E. 
Published: October 2023

AbstractIn 2021 and 2022, clade 2.3.4.4b H5Nx high pathogenicity avian influenza viruses were detected in one harbor seal and in one adult and three fox cubs in Denmark. The viruses were closely related to contemporary viruses found in Europe, and some had obtained amino acid substitutions related to mammalian adaptation. Notably, the virus distribution appeared to have been different in the infected fox cubs, as one exclusively tested positive for the presence of HPAIV in the brain and the other two only in the lung. Collectively, these findings stress the need for increased disease surveillance of wild and farmed mammals.
Two‐step reactive flash sintering of high entropy pyrochlore: Densification, grain growth, and microstructural homogeneity
Authors: Xu Chen , He Jinmao , Chen Zixu , Zhao Guoliang , Cai Shikui , Ni Na , Liu Tianwei 
Published: October 2023

AbstractTwo‐step reactive flash sintering (TSRFS) was employed to achieve fast densification of high entropy pyrochlore (La0.2Nd0.2Sm0.2Eu0.2Gd0.2)2Zr2O7 with suppressed grain growth and improved microstructural homogeneity. Theoretical density of ∼98.15% with a grain size of ∼684 nm was achieved by TSRFS, representing only half the grain size compared with conventional one‐step reactive flash sintering (RFS), while the total holding time of TSRFS was only 1.5 times that of RFS. Although longer duration in step 1 benefited faster densification, it was demonstrated that the shorter time in step 1 not only resulted in smaller grain size in TSRFS samples with identical densities but also helps mitigate the grain size heterogeneity between sample cores and surfaces. Therefore, the art of efficiently using TSRFS lies in the reasonable manipulation of the time and power in step 1 and 2, achieving a balance between densification, grain growth, and microstructural homogeneity.