bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methotrexate Polyglutamates Exposure – Response Modeling in a Large Cohort of Rheumatoid Arthritis Patients Starting Methotrexate
Authors: Hebing Renske C. F. , Bartelink Imke H. , Gosselt Helen R. , Heil Sandra G. , de Rotte Mauritis C. F. J. , de Jong Pascal H. P. , Nurmohamed Mike T. , de Jonge Robert , Mathôt Ron A. A. 
Published: June 2023

Methotrexate polyglutamates (MTX‐PG) concentrations in red blood cells (RBCs) have been suggested as a biomarker of response in patients with rheumatoid arthritis (RA) receiving low‐dose MTX therapy. We investigated the association and interpatient variability between RBC‐MTX‐PG3‐5‐exposure and response in patients with RA starting MTX. Data of three prospective cohorts were available. The relationship between exposure and Disease Activity Score in 28 joints (DAS28) was analyzed using a population pharmacokinetic‐pharmacodynamic model. Relevant covariates were tested using full covariate modeling and backward elimination. From 395 patients, 3,401 MTX‐PG concentrations and 1,337 DAS28 measurements were available between 0 and 300 days after MTX treatment onset. The developed model adequately described the time course of MTX‐PG3‐5 and DAS28. The median MTX‐PG3‐5 level at month 1 was 30.9 nmol/L (interquartile range (IQR): 23.6–43.7; n = 41) and at month 3: 69.3 nmol/L (IQR: 17.9–41.2; n = 351). Clearance of MTX‐PG3‐5 from RBCs was 28% lower (95% confidence interval (CI): 23.6–32.8%) in a woman and 10% lower (95% CI: 7.7–12.4%) in a 65‐year‐old compared with a 35‐year‐old patient. MTX‐PG3‐5 concentrations associated with DAS28: half‐maximal effective concentration (EC50) was 9.14 nmol/L (95% CI: 4.2 nmol/L‐14.1 nmol/L). EF at 80% (EC80) above 47 nmol/L was regarded as the optimal response. Independent of the MTX‐PG 3–5 – response association, co‐administration of disease‐modifying antirheumatic drugs and corticosteroids improved response (additive effect on maximum effect (Emax)), whereas smoking, high body mass index and low albumin decreased Emax. In patients with RA starting MTX, RBC‐MTX‐PG3‐5 was associated with clinical response. A dose increase is suggested when MTX‐PG3‐5 at month 1 is below 9.15 nmol/L, continued with the same dose when the concentration is above 47 nmol/L, and consider other treatment options above 78 nmol/L from 3 months onwards.
Directing the Selectivity of Oxygen Reduction to Water by Confining a Cu Catalyst in a Metal Organic Framework
Authors: Hoefnagel Marlene E. , Rademaker Dana , Hetterscheid Dennis G. H. 
Published: June 2023

AbstractElectrocatalysis is to play a key role in the transition towards a sustainable chemical and energy industry and active, stable and selective redox catalysts are much needed. Porous structures such as metal organic frameworks (MOFs) are interesting materials as these may influence selectivity of chemical reactions through confinement effects. In this work, the oxygen reduction catalyst Cu‐tmpa was incorporated into the NU1000 MOF. Confinement of the catalyst within NU1000 steers the selectivity of the oxygen reduction reaction (ORR) towards water rather than peroxide. This is attributed to retention of the obligatory H2O2 intermediate in close proximity to the catalytic center. Moreover, the resulting NU1000|Cu‐tmpa MOF shows an excellent activity and stability in prolonged electrochemical studies, illustrating the potential of this approach.
Linear Scaling Relationships for Furan Hydrodeoxygenation over Transition Metal and Bimetallic Surfaces
Authors: Kanchan Dipika Rajendra , Banerjee Arghya 
Published: June 2023

AbstractBrønsted‐Evans‐Polanyi (BEP) and transition‐state‐scaling (TSS) relationships have become valuable tools for the rational design of catalysts for complex reactions like hydrodeoxygenation (HDO) of bio‐oil (containing heterocyclic and homocyclic molecules). In this work, BEP and TSS relationships are developed for all the elementary steps of furan activation (C and O hydrogenation and CHx−OHy scission, for both ring and open‐ring intermediates) to oxygenates, ring‐saturated compounds and deoxygenated products on the most stable facets of Ni, Co, Rh, Ru, Pt, Pd, Fe and Ir surfaces using Density Functional Theory (DFT) calculations. Furan ring opening barriers were found to be facile and strongly dependent on carbon and oxygen binding strength on the investigated surfaces. Our calculations suggest linear chain oxygenates form on Ir, Pt, Pd and Rh surfaces due to their low hydrogenation and high CHx−OHy scission barriers, while deoxygenated linear products are favoured on Fe and Ni surfaces due to their low CHx−OHy scission and moderate hydrogenation barriers. Bimetallic alloy catalysts were also screened for their potential HDO activity and PtFe catalysts were found to significantly lower the ring opening and deoxygenation barriers relative to the corresponding pure metals. The developed BEPs for monometallic surfaces can be extended to estimate the barriers on bimetallic surfaces for ring opening and ring hydrogenation reactions but fails to predict the barriers for open‐ring activation reactions due to the change in transition state binding sites on the bimetallic surface. The obtained BEP and TSS relationships can be used to develop microkinetic models for facilitating accelerated catalyst discovery for HDO.
Interplay Between Particle Size and Hierarchy of Zeolite ZSM‐5 During the CO2‐to‐aromatics Process
Authors: Liu Kun , Ramirez Adrian , Zhang Xin , Çağlayan Mustafa , Gong Xuan , Gascon Jorge , Chowdhury Abhishek Dutta 
Published: June 2023

AbstractThe CO2‐to‐aromatics process is a chemical reaction that converts carbon dioxide (CO2) into valuable petrochemical, i. e., aromatics (especially, benzene, toluene, and xylene) over the metal/zeolite bifunctional catalytic systems. These aromatics are used in producing plastics, fibers, and other industrial products, which are currently exclusively sourced from fossil‐derived feedstocks. The significance of this process lies in its potential to mitigate climate change by reducing greenhouse gas emissions and simultaneously producing valuable chemicals. Consequently, these CO2‐derived aromatics can reduce the reliance on fossil fuels as a source of feedstocks, which can help to promote a more sustainable and circular economy. Owing to the existence of a wider straight channel favoring the aromatization process, zeolite ZSM‐5 is extensively used to yield aromatics during CO2 hydrogenation over bifunctional (metal/zeolite) catalytic systems. To provide a better understanding of this unique property of zeolite ZSM‐5, this work investigates the impact of particle size and hierarchy of the zeolite and how these govern the reaction performance and the overall selectivity. As a result, an improved understanding of the zeolite‐catalyzed hydrocarbon conversion process has been obtained.
Sustained increase in physical fitness independently predicts improvements in cardiometabolic risk profile in type 2 diabetes
Authors: Balducci Stefano , Haxhi Jonida , Vitale Martina , Mattia Lorenza , Sacchetti Massimo , Orlando Giorgio , Cardelli Patrizia , Iacobini Carla , Bollanti Lucilla , Conti Francesco , Zanuso Silvano , Nicolucci Antonio , Pugliese Giuseppe ,   for the Italian Diabetes and Exercise Study 2 (IDES_2) Investigators
Published: June 2023

AbstractAimsTo investigate the relationship between changes in physical fitness and cardiovascular risk factors and scores in patients with type 2 diabetes receiving either a behavioural counselling intervention to increase moderate‐to‐vigorous‐intensity physical activity (MVPA) and decrease sedentary‐time (SED‐time) or standard care.Materials and MethodsThis is a pre‐specified ancillary analysis of the Italian Diabetes and Exercise Study_2, a 3‐year randomized clinical trial in which 300 physically inactive and sedentary patients were randomized 1:1 to receive either a one‐month theoretical and practical counselling each year or standard care. Mean changes from baseline throughout the 3‐year period in MVPA, SED‐time, cardiorespiratory fitness (VO2max), muscle strength, flexibility, cardiovascular risk factors and scores were calculated for study completers (n = 267) and considered irrespective of study arm.ResultsHaemoglobin (Hb) A1c and coronary heart disease (CHD) risk scores decreased with quartiles of VO2max and lower body muscle strength changes. Multivariable linear regression analysis showed that increases in VO2max independently predicted decreases in HbA1c, blood glucose, diastolic blood pressure (BP), CHD and total stroke 10‐year risk and increases in HDL cholesterol, whereas increases in lower body muscle strength independently predicted decreases in body mass index (BMI), waist circumference, triglycerides, systolic BP, CHD and fatal stroke 10‐year risk. These associations remained after including changes in BMI, waist circumference, fat mass and fat‐free mass, or MVPA and SED‐time as covariates.ConclusionsImprovement in physical fitness predicts favourable changes in cardiometabolic risk profile, independent of changes not only in (central) adiposity or body composition but also in MVPA and SED‐time.Trial RegistrationClinicalTrials.gov; NCT01600937; URL https://clinicaltrials.gov/ct2/show/NCT01600937.
Addressing Uncertainties in Potential Human Dietary Exposure to Mercury in the Watershed of the South River, Virginia, USA
Authors: McCue Dana , Mancini Ceil , Liberati Michael R. , Stahl Ralph G. 
Published: June 2023

Abstract
Much has been published about the harmful effects to humans when they are exposed to mercury (Hg) in environmental media including their diet. Numerous health advisories around the world, including for the South River, Virginia, USA, warn against consumption of Hg-contaminated fish species. Fewer studies have focused on other dietary sources of Hg and how to advise humans potentially exposed by this route. In undertaking a human health risk assessment for the former DuPont facility in Waynesboro, Virginia, USA, and the nearby South River and surrounding watershed, the available published information on Hg exposure through dietary consumption of nonfish items proved unsuitable for extrapolation purposes. In response, an evaluation of potential Hg exposure to residents who might consume livestock, poultry, and wildlife raised or collected in the South River watershed was conducted to inform the risk-assessment process. The newly collected data on Hg in these dietary items filled an important data gap, suggesting that there was little concern about limiting dietary consumption for most items. These results were communicated to the public through print and electronic platforms, in the form of “fact sheets.” We describe the studies and actions taken to better explain the potential for human exposures to Hg in nonfish dietary items from a portion of the watershed of the South River. Environ Toxicol Chem 2023;42:2237–2252. © 2023 SETAC
Cryptic Species in Ecotoxicology
Authors: Jourdan Jonas , Bundschuh Mirco , Copilaș-Ciocianu Denis , Fišer Cene , Grabowski Michał , Hupało Kamil , Jemec Kokalj Anita , Kabus Jana , Römbke Jörg , Soose Laura J. , Oehlmann Jörg 
Published: June 2023

Abstract
The advent of genetic methods has led to the discovery of an increasing number of species that previously could not be distinguished from each other on the basis of morphological characteristics. Even though there has been an exponential growth of publications on cryptic species, such species are rarely considered in ecotoxicology. Thus, the particular question of ecological differentiation and the sensitivity of closely related cryptic species is rarely addressed. Tackling this question, however, is of key importance for evolutionary ecology, conservation biology, and, in particular, regulatory ecotoxicology. At the same time, the use of species with (known or unknown) cryptic diversity might be a reason for the lack of reproducibility of ecotoxicological experiments and implies a false extrapolation of the findings. Our critical review includes a database and literature search through which we investigated how many of the species most frequently used in ecotoxicological assessments show evidence of cryptic diversity. We found a high proportion of reports indicating overlooked species diversity, especially in invertebrates. In terrestrial and aquatic realms, at least 67% and 54% of commonly used species, respectively, were identified as cryptic species complexes. The issue is less prominent in vertebrates, in which we found evidence for cryptic species complexes in 27% of aquatic and 6.7% of terrestrial vertebrates. We further exemplified why different evolutionary histories may significantly determine cryptic species' ecology and sensitivity to pollutants. This in turn may have a major impact on the results of ecotoxicological tests and, consequently, the outcome of environmental risk assessments. Finally, we provide a brief guideline on how to deal practically with cryptic diversity in ecotoxicological studies in general and its implementation in risk assessment procedures in particular. Environ Toxicol Chem 2023;42:1889–1914. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Experimental testing on timber connections considering the influence of gap size and intumescent sealants
Authors: du Plessis Marika , Sulon Darren , Streicher Dirk , Walls Richard 
Published: June 2023

AbstractThis paper investigates the influence of gap size (openings/spaces between two structural members) and the presence of intumescent sealants on the development of temperature when timber connections are exposed to fire conditions. The experimental results of 21 samples representing a concealed steel‐to‐timber connection configuration that was exposed with a 0, 3, 6, and 10 mm gap to the ISO834 standard fire for 120 min are presented. Half of the samples in each sample group were protected with an intumescent fire protection sealant. The temperatures in the timber were measured at various locations around the gap and directly next to the steel component. The experimental results show that the presence of a gap increases the temperature of the timber more than predicted by the thermal penetration models available, with current code guidelines (e.g., Eurocode 5) possibly being non‐conservative. The use of an intumescent fire protection sealant in the gap is shown to be an effective protection method, but that the application configuration is important to ensure effective protection, especially as the gap becomes smaller. The results also show that the use of an intumescent fire protection sealant in a gap increases the predictability of the temperatures in the timber in longer duration fires. Unprotected samples and 0 mm gap samples exhibited large variability in the thermal development outcomes over time.
In their own words: An exploration of primary children's participation in a dementia education program
Authors: Pawlicka Nataszia , Eady Michelle J. , Green Corinne A. , Harris Penny , Traynor Victoria , Barkley Carinya , Primmer Jennine , Baker Jess R , Burns Pippa 
Published: June 2023

AbstractIssue AddressedAs the population ages the prevalence of dementia increases and children are increasingly experiencing family members and older friends living with dementia. Unfortunately, stigma about living with dementia is common. Increasing understanding about dementia among children has the potential to reduce this stigma. This paper reports on the qualitative findings of Project DARE (dementia knowledge, art, research and education), a school‐based, multi‐modal, arts program designed to increase understanding about dementia among children aged 8–10 years.MethodsA constructivist grounded theory approach was used to understand students' experience of the intervention. Thematic analysis was used to identify key themes emerging from interviews with randomly selected students (n = 40) who had taken part in the program.ResultsThe data analysis generated three themes related to students' awareness of dementia and experiences of the program: (1) nurturing empathy, (2) memory loss is complex, (3) learning about dementia through the arts to promote resilience. These themes show that the intervention increased students' awareness of dementia, and empathy towards people who are both directly and indirectly affected by dementia.ConclusionsAlthough dementia education can be viewed as too sensitive for primary aged students, the current study demonstrates that such initiatives are feasible and can be effectively implemented with this age group.So What?Changing student's beliefs about dementia can positively impact their relationships with people living with dementia.
Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
Authors: Xiong Xin , Yu Mengjia , Wang Dinghang , Wang Yange , Cheng Longxian 
Published: June 2023

AbstractObjectiveAutoimmune myocarditis is caused by both innate and adaptive immune responses. Many studies have found that myeloid‐derived suppressor cells (MDSCs) suppress T‐cell responses and reduce immune tolerance, while MDSCs may serve as a key player in inflammatory responses and pathogenesis in variety of autoimmune diseases. However, research into the role of MDSCs in experimental autoimmune myocarditis (EAM) remains lacking.Methods and ResultsWe discovered that the expansion of MDSCs in EAM was closely related to the severity of myocardial inflammation. At an early stage of EAM, both adoptive transfer (AT) and selective depletion of MDSCs could inhibit the expression of IL‐17 in CD4+ cells and downregulate the Th17/Treg ratio, alleviating excessive inflammation of EAM myocarditis. In another experiment, in addition, MDSCs transferred after selective depletion could increase IL‐17 and Foxp3 expressions in CD4+ cells, as well as the Th17/Treg ratio, contributing to the aggravation of myocardial inflammation. MDSCs promoted the Th17 cell induction under Th17‐polarizing conditions in vitro but suppressed Treg expansion.ConclusionThese findings suggest that MDSCs play a plastic role in sustaining mild inflammation in EAM by shifting Th17/Treg balance.
Clinical features and prognostic factors of anti‐melanoma differentiation‐associated gene 5 antibody‐positive dermatomyositis with rapidly progressive interstitial lung disease in Chinese patients
Authors: Lian Li , Tong Jing‐jing , Xu Sheng‐qian 
Published: June 2023

AbstractObjectiveThe objective of this study is to investigate clinical features and prognostic factors of antimelanoma differentiation‐associated gene 5 (anti‐MDA5)‐positive dermatomyositis with rapidly progressive interstitial lung disease (RP‐ILD) in Chinese patients.MethodsClinical features and prognostic factors of patients with newly diagnosed or recurrent dermatomyositis patients were retrospectively analyzed. All patients were divided into the anti‐MDA5‐positive or negative dermatomyositis, and with or without RP‐ILD groups. Clinical features and prognostic factors were statistically compared among different groups.ResultsThe serum ferritin (SF) levels (1500.0 [658.80, 1844.0]) and γ‐glutamyl transpeptidase (γ‐GT) (125.5 [61.0, 232.0] vs. 28 [16.0, 41.0],Z = 5.528;p < .001) were markedly higher, and phosphocreatine myoenzyme (CK) (73.0 [42.0, 201.0] vs. 1333.0 [79.0, 8000.0],Z = −2.739,p = .006), serum albumin level (32.51 ± 5.23 vs. 35.81 ± 5.88,t = −2.542,p = .013), and lymphocyte count (0.80 ± 0.36 vs. 1.45 ± 0.77,t = −4.717,p < .001) were lower than those in anti‐MDA5‐negative counterparts. Among patients with anti‐MDA5 antibody (Ab) with RP‐ILD, the SF level (1531.0 [1163.8, 2016.5] vs. 584.9 [564.8, 1042.5],Z = 2.664,p = .008), γ‐GT (134.0 [81.0, 204.5] vs. 123.0 [76.0, 189.0],Z = 3.136,p = .002) and positive rate of anti‐RO‐52 Ab (90.9% vs. 50.0%,χ2 = 7.222,p = .013) were higher and lymphocyte count (0.79 ± 0.38 vs. 1.32 ± 0.74,t = −3.025,p = .029) was lower than those in their counterparts without RP‐ILD. The SF level of anti‐MDA5 nonsurvivors (1544 [1447.32, 2089.0] vs. 584.9 [515.7, 1500.0],Z = 2.096,p = .030), anti‐RO‐52 Ab‐positive rate ([16/18, 88.9%] vs. [9/16, 56.2%],χ2 = 4.636,p = .031) were higher than those in survivors. Lymphocytopenia was a risk factor for RP‐ILD and death of patients with anti‐MDA5‐positive dermatomyositis. The area under receiver operating characteristic curve was 0.888 (95% confidence interval: 0.756, 1.000;p < .001), the sensitivity was 85.7%, the specificity was 93.8%, and Youden's index was 0.795.ConclusionsAnti‐MDA5‐positive dermatomyositis patients are prone to developing RP‐ILD. Declined lymphocyte count is a critical risk factor for RP‐ILD, probably acting as a simple and effective predictor for Chinese patients with anti‐MDA5‐positive dermatomyositis.
IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
Authors: Wei Yuzhen , Xing Junhui , Su Xin , Li Xiangrao , Yan Xiaofei , Zhao Jiangtao , Tao Hailong 
Published: June 2023

AbstractBackgroundReperfusion therapy is the most effective approach to resolve coronary occlusion, but myocardial injury caused by excessive inflammation during myocardial ischemia–reperfusion will also pose a new threat to health. Our prior study revealed the expression pattern of interleukin‐38 (IL‐38) in the peripheral blood serum of patients with ischemic cardiomyopathy and the role of IL‐38 in acute myocardial infarction in mice. However, its role and potential mechanisms in myocardial ischemia/reperfusion injury (MIRI) remain to be determined.Methods and ResultsThe left anterior descending artery of C57BL/6 mice was transiently ligated to induce the MIRI model. We found that MIRI induced the expression of endogenous IL‐38, which was mainly produced by locally infiltrating macrophages. Overexpression of IL‐38 in C57BL/6 mice attenuated inflammatory injury and decreased myocardial apoptosis after myocardial ischemia–reperfusion. Furthermore, IL‐38 inhibited lipopolysaccharide‐induced macrophage inflammation in vitro. Cardiomyocytes cocultured with the supernatant of IL‐38‐ and troponin I‐treated macrophages showed a lower rate of apoptosis than controls.ConclusionsIL‐38 attenuates MIRI by inhibiting macrophage inflammation. This inhibitory effect may be partially achieved by inhibiting the activation of NOD‐like receptor pyrin domain‐related protein 3 inflammasome, resulting in decreased expression of inflammatory factors and reduced cardiomyocyte apoptosis.