bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroplastic ascorbate modifies plant metabolism and may act as a metabolite signal regardless of oxidative stress
Authors: Tóth Dávid , Tengölics Roland , Aarabi Fayezeh , Karlsson Anna , Vidal-Meireles André , Kovács László , Kuntam Soujanya , Körmöczi Tímea , Fernie Alisdair R , Hudson Elton P , Papp Balázs , Tóth Szilvia Z 
Published: August 2024

Abstract
Ascorbate (Asc) is a major plant metabolite that plays crucial roles in various processes, from reactive oxygen scavenging to epigenetic regulation. However, to what extent and how Asc modulates metabolism is largely unknown. We investigated the consequences of chloroplastic and total cellular Asc deficiencies by studying chloroplastic Asc transporter mutant lines lacking PHOSPHATE TRANSPORTER 4; 4 and the Asc-deficient vtc2-4 mutant of Arabidopsis (Arabidopsis thaliana). Under regular growth conditions, both Asc deficiencies caused minor alterations in photosynthesis, with no apparent signs of oxidative damage. In contrast, metabolomics analysis revealed global and largely overlapping alterations in the metabolome profiles of both Asc-deficient mutants, suggesting that chloroplastic Asc modulates plant metabolism. We observed significant alterations in amino acid metabolism, particularly in arginine metabolism, activation of nucleotide salvage pathways, and changes in secondary metabolism. In addition, proteome-wide analysis of thermostability revealed that Asc may interact with enzymes involved in arginine metabolism, the Calvin–Benson cycle, and several photosynthetic electron transport components. Overall, our results suggest that, independent of oxidative stress, chloroplastic Asc modulates the activity of diverse metabolic pathways in vascular plants and may act as an internal metabolite signal.
Predictors of persistent opioid use in Australian primary care: a retrospective cohort study, 2018–2022
Authors: Jung Monica , Xia Ting , Ilomäki Jenni , Pearce Christopher , Aitken Angela , Nielsen Suzanne 
Published: August 2024

Abstract

Objective
To examine the predictors of persistent opioid use (“persistence”) in people initiating opioids for non-cancer pain in Australian primary care.

Design
A retrospective cohort study.

Setting
Australian primary care.

Subjects
People prescribed opioid analgesics between 2018 and 2022, identified through the Population Level Analysis and Reporting (POLAR) database.

Methods
Persistence was defined as receiving opioid prescriptions for at least 90 days with a gap of less than 60 days between subsequent prescriptions. Multivariable logistic regression was used to examine the predictors of persistent opioid use.

Results
The sample consisted of 343 023 people initiating opioids for non-cancer pain; of these, 16 527 (4.8%) developed persistent opioid use. Predictors of persistence included older age (≥75 vs 15–44 years: adjusted odds ratio: 1.67, 95% CI: 1.58–1.78); concessional beneficiary status (1.78, 1.71–1.86); diagnosis of substance use disorder (1.44, 1.22–1.71) or chronic pain (2.05, 1.85–2.27); initiation of opioid therapy with buprenorphine (1.95, 1.73–2.20) or long-acting opioids (2.07, 1.90–2.25); provision of higher quantity of opioids prescribed at initiation (total oral morphine equivalents of ≥750 mg vs &lt;100 mg: 7.75, 6.89–8.72); provision of repeat/refill opioid prescriptions at initiation (2.94, 2.77–3.12); and prescription of gabapentinoids (1.59, 1.50–1.68), benzodiazepines (1.43, 1.38–1.50), and z-drugs (eg, zopiclone, zolpidem; 1.61, 1.46–1.78).

Conclusions
These findings add to the limited evidence of individual-level factors associated with persistent opioid use. Further research is needed to understand the clinical outcomes of persistent opioid use in people with these risk factors to support the safe and effective prescribing of opioids.
Immunoprofiles of COVID-19 uniquely differentiated from other viruses: A machine learning investigation of multiplex immunoassay data
Authors: Kaur Ashneet , Krishnan Viswanathan V 
Published: August 2024

Abstract
Cytokines and chemokines are vital in maintaining a healthy state by efficiently controlling invading microbes. In addition, the dysregulation of these immune mediators can contribute to viral infection pathology. We comprehensively analyzed the profiles of host immunomodulators in response to infections with members of several virus families, particularly if the SARS-CoV-2 infection produces a unique immune profile compared with other viral infections. Multiplex microbead immunoassay results from 219 datasets with a range of viruses were curated systematically. The curated immunoassay data, obtained using Luminex technology, include 35 different viruses in 18 different viral families; this analysis also incorporated data from studies performed in 7 different cell model systems with 28 different sample types. A multivariate statistical analysis was performed with a specific focus involving many investigations (&gt;10), which include the viral families of Coronaviridae, Orthomyxoviridae, Retroviridae, Flaviviridae, and Hantaviridae. A random forest-based classification of the profiles indicates that IL1-RA, C-X-C motif chemokine ligand 9, C-C motif chemokine ligand 4, interferon (IFN)-λ1, IFN-γ-inducing protein 10, and interleukin (IL)-27 are the top immunomodulators among human samples. Similar approaches only between Coronaviridae (COVID-19) and Orthomyxoviridae (influenza A/B) indicated that transforming growth factor-β, IFN-λ1, IL-9, and eotaxin-1 are important features. In particular, the IFN-λ1 protein was implicated as one of the significant immunomodulators differentiating viral family infection. It is evident that Coronaviridae infection, including SARS-CoV-2, induces a unique cytokine–chemokine profile and can lead to specific immunoassays for diagnosing and prognosis of viral diseases based on host immune responses. Alternatively, we can use diagnosing and prognosing. It is also essential to note that meta-analysis-based predictions must be appropriately validated before clinical implementation.
Unveiling the environmental significance of acetylperoxyl radical: Reactivity quantification and kinetic modeling
Authors: Wang Junyue , Schaefer Thomas , Lisouskaya Aliaksandra , Firak Daniele S , Xin Xiaoyue , Meng Lingjun , Herrmann Hartmut , Sharma Virender K , Huang Ching-Hua 
Published: August 2024

Abstract
Acetylperoxyl radical (CH3C(O)OO•) is among highly reactive organic radicals which are known to play crucial roles in atmospheric chemistry, aqueous chemistry and, most recently, peracetic acid (PAA)-based advanced oxidation processes. However, fundamental knowledge for its reactivity is scarce and severely hampers the understanding of relevant environmental processes. Herein, three independent experimental approaches were exploited for revelation and quantification of the reaction rates of acetylperoxyl radical. First, we developed and verified laser flash photolysis of biacetyl, ultraviolet (UV) photolysis of biacetyl, and pulse radiolysis of acetaldehyde, each as a clean source of CH3C(O)OO•. Then, using competition kinetics and selection of suitable probe and competitor compounds, the rate constants between CH3C(O)OO• and compounds of diverse structures were determined. The three experimental approaches complemented in reaction time scale and ease of operation, and provided cross-validation of the rate constants. Moreover, the formation of CH3C(O)OO• was verified by spin-trapped electron paramagnetic resonance, and potential influence of other reactive species in the systems was assessed. Overall, CH3C(O)OO• displays distinctively high reactivity and selectivity, reacting especially favorably with naphthyl and diene compounds (k ∼ 107–108 M−1 s−1) but sluggishly with N- and S-containing groups. Significantly, we demonstrated that incorporating acetylperoxyl radical-oxidation reactions significantly improved the accuracy in modeling the degradation of environmental micropollutants by UV/PAA treatment. This study is among the most comprehensive investigation for peroxyl radical reactivity to date, and establishes a robust methodology for investigating organic radical chemistry. The determined rate constants strengthen kinetic databases and improve modeling accuracy for natural and engineered systems.
Therapeutic Biomaterials with Liver X Receptor Agonists Based on the Horizon of Material Biology to Regulate Atherosclerotic Plaque Regression in Situ for Devices Surface Engineering
Authors: Liu Sainan , Huang Jinquan , Luo Jiayan , Bian Qihao , Weng Yajun , Li Li , Chen Junying 
Published: August 2024

Abstract
Percutaneous coronary interventional is the main treatment for coronary atherosclerosis. At present, most studies focus on blood components and smooth muscle cells to achieve anti-coagulation or anti-proliferation effects, while the mediated effects of materials on macrophages are also the focus of attention. Macrophage foam cells loaded elevated cholesterol is a prominent feature of atherosclerotic plaque. Activation Liver X receptor (LXR) to regulate cholesterol efflux and efferocytosis and reduce the number of macrophage foam cells in plaque are feasible for the regression of atherosclerosis. However, cholesterol efflux promotion remains confined to targeted therapies. Herein, LXR agonists (GW3965) were introduced on the surface of the material and delivered in situ to atherogenic macrophages to improve drug utilization for anti-atherogenic therapy and plaque regression. LXR agonists act as plaque inhibition mediated by multichannel regulation macrophages, including lipid metabolism (ABCA1, ABCG1 and LDLR), macrophage migration (CCR7) and efferocytosis (MerTK). Material loaded with LXR agonists significantly reduced plaque burden in atherosclerotic model rats, most importantly, it did not cause hepatotoxicity and adverse reactions such as restenosis and thrombosis after material implantation. Both in vivo and in vitro evaluations confirmed its anti-atherosclerotic capability and safety. Overall, multi-functional LXR agonist-loaded materials with pathological microenvironment regulation effect are expected to be a promising candidate for anti-atherosclerosis and have potential applications in cardiovascular devices surface engineering.
The Lifetime Costs of Bad Health
Authors: De Nardi Mariacristina , Pashchenko Svetlana , Porapakkarm Ponpoje 
Published: August 2024

Abstract
What generates the observed differences in economic outcomes by health? How costly it is to be unhealthy? We show that health dynamics are largely driven by ex-ante fixed heterogeneity, or health types, even when controlling for one’s past health history. In fact, health types are the key driver of long spells of bad health. We incorporate these rich health dynamics in an estimated structural model and show that health types and their correlation with other fixed characteristics are important to account for the observed gap in economic outcomes by health. Monetary and welfare losses due to bad health over the life-cycle are large, concentrated, and to a large extent due to factors pre-determined earlier in life. A large portion of the related monetary costs is due to income losses, especially for people of working age, while a substantial portion of the welfare losses arises because health affects life expectancy.
Economic Integration and the Transmission of Democracy
Authors: Tabellini Marco , Magistretti Giacomo 
Published: August 2024

Abstract
In this paper, we study the effects of economic integration with democratic partners on democracy. We assemble a large country-level panel dataset from 1960 to 2015, and exploit improvements in air, relative to sea, transportation to derive a time-varying instrument for economic integration. We find that economic integration with democracies increases countries’ democracy scores, whereas the impact of economic integration with non-democracies is muted. Results are stronger when democratic partners have a longer history of democracy, grow faster, spend more on public goods, are culturally closer, and export higher quality goods. The effects we document are driven by imports, rather than exports, and by integration with democratic partners that account for a larger share of a country’s trade in institutionally intensive, cultural, and consumer goods, as well as in goods that involve more face-to-face interactions and entail higher levels of bilateral trust. These patterns are consistent with economic integration favouring the transmission of democracy by signalling the (actual or perceived) desirability of democratic institutions. Alternative mechanisms—including human capital accumulation and economic growth—cannot, alone, explain our findings.
Tendon involvement and its association with pain and hand function in patients with osteoarthritis of the hand
Authors: Gessl Irina , Vinatzer Anna , Supp Gabriela , Zauner Michael , Durechova Martina , Lechner Lisa , Ritschl Valentin , Smolen Josef , Stamm Tanja , Aletaha Daniel , Mandl Peter 
Published: August 2024

Abstract

Objective
To characterize the frequency and influence of tenosynovitis and tendon damage on pain and hand function using clinical examination and US in hand OA.

Methods
We included 86 patients with hand OA and 23 age- and sex-matched control subjects. Extensor and flexor tendons of both hands were assessed by clinical examination and US for tenosynovitis and tendon damage. Conventional radiographs were acquired. Hand function was evaluated by the function subtest of the M-SACRAH (modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands) questionnaire and the Moberg pick-up test. K-means cluster analyses was calculated to assess clusters based on radiographic features and sonographic tendon scores.

Results
US identified the involvement of one or more tendon in 60/86 (69.8%) hand OA patients compared with 2/23 (8.7%) subjects (P &lt; 0.01) in the control group. In the hand OA group, US detected tendon damage more often in flexor tendons compared with extensor tendons (2.1% vs 0.9%, P = 0.03), while tenosynovitis was observed more often in extensor tendons compared with flexor tendons (8% vs 0.6%, P &lt; 0001). The sensitivity and specificity of clinical examination to detect tendon involvement was 81.4% and 34.6%, respectively, on the patient level and 14.5% and 83.8% on the tendon level. The cluster analyses revealed one cluster with more radiographic features of hand OA and more tendon damage while more tenosynovitis was found in cluster 2. M-SACRAH function did not correlate with tendon involvement on US.

Conclusion
This study revealed a high frequency of tendon involvement in hand OA. Tendon involvement on US did not impact hand function or self-reported pain.
Epidemiology of ANCA vasculitis in northern Spain
Authors: Benavides-Villanueva Fabricio , Herrero-Morant Alba , Prieto-Peña Diana , Al Fazazi Salma , Calvo-Río Vanesa , Renuncio-García Mónica , Martín-Gutierrez Adrián , Sánchez-Lopez María del Amparo , Poo-Fernandez Claudia , Escagedo-Cagigas Clara , Rodríguez-Vidriales María , Blanco Ricardo 
Published: August 2024

Abstract

Objectives
The incidence of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) shows disparate results due to variable classification criteria and heterogeneous population series. We aimed to estimate the incidence of AAV in a well-defined population with standardized classification criteria.

Methods
This was a population-based study of AAV patients diagnosed from January 2000 to December 2023 in Cantabria, northern Spain. Patients were classified according to ACR/EULAR 2022 into granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or unclassified vasculitis if the criteria were not met. Eosinophilic granulomatosis with polyangiitis patients were not included. The annual incidence rates were estimated by cases over 1 000 000 (106) (95% CI) including overall AVV, type of AAV, sex and year of diagnosis. A literature review was also performed.

Results
We included 152 patients [80M/72F; mean age 70.6 (13.18) years]. They were classified as MPA (67; 44%), GPA (64; 42.2%), and unclassified vasculitis (21; 13.8%). Annual incidence was 13.4 (95% CI: 10, 16.8)/106 [male 14.5 (95% CI: 10.5, 18.5); female 12.1 (95% CI: 8.7, 15.6)]. The Annual incidence of MPA was 5.9 (95% CI: 4, 7.8)/106 and GPA 5.6 (95% CI: 3.9, 7.3)/106. The mean annual incidence increased from 6.1 (95% CI: 4.5, 7.7)/106 to 16.5 (595% CI: .6, 27.4)/106 in the last 3 years, particularly in GPA from 2.3 (95% CI: 0.3, 4.9)/106 to 8.2 (95% CI: 2, 14.5)/106. The prevalence of AAV was 184.7 (95% CI: 181, 188)/106.

Conclusion
During a 20-year period we found that the incidence of AAV (GPA and MPA) in northern Spain was higher than in southern Spain, but lower than northern European countries. An increase in the incidence was observed in the last years.
Heart Preparation for Short-Term Missions
Authors: Meilner Shauna L. 
Published: August 2024

ABSTRACT:
Involvement in short-term missions experiences can be most beneficial when intentional personal and group preparation takes place. Learning about the people and history of the destination, identifying one's purpose in making the trip, asking God for direction and affirmation, meditation on Scripture, and prayer for oneself and for those who will be on the receiving end of care or ministry are wise. Willingness to take a servant's mindset and to give time and goods from a biblical perspective shows respect for those to be served.
Promotion in Nursing Higher Education
Authors: Richards Brandie , Taylor Elizabeth Johnston 
Published: August 2024

ABSTRACT:
Nurses in education, especially at smaller universities, may not be socialized or mentored in ways that would support seeking promotion in academia. Barriers and questions about the promotion process and recommendations about frequently asked questions are given in this article, along with biblical encouragement. Seeking promotion to a higher academic rank can bring enhanced credibility with which to serve God and can be an opportunity to improve one's character and ability to glorify God.
The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design
Authors: Collin Lindsay J. , Waller Lance A. , Cronin-Fenton Deirdre P. , Ahern Thomas P. , Goodman Michael , McCullough Lauren E. , Kjærsgaard Anders , Woolpert Kirsten M. , Silliman Rebecca A. , Christiansen Peer M. , Ejlertsen Bent , Toft Sørensen Henrik , Lash Timothy L. 
Published: August 2024

Purpose:
Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies—tamoxifen and trastuzumab—on recurrence using the trend-in-trend pharmacoepidemiologic study design.

Methods:
We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007.

Results:
For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4).

Conclusions:
We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.
Accuracy and Completeness of Large Language Models About Antibody–Drug Conjugates and Associated Ocular Adverse Effects
Authors: Marshall Rayna , Xu Hannah , Dalvin Lauren A. , Mishra Kapil , Edalat Camellia , Kirupaharan Nila , Francis Jasmine H. , Berkenstock Meghan 
Published: August 2024

Purpose:The purpose of this study was to assess the accuracy and completeness of 3 large language models (LLMs) to generate information about antibody–drug conjugate (ADC)-associated ocular toxicities.Methods:There were 22 questions about ADCs, tisotumab vedotin, and mirvetuximab soravtansine that were developed and input into ChatGPT 4.0, Bard, and LLaMa. Answers were rated by 4 ocular toxicity experts using standardized 6-point Likert scales on accuracy and completeness. ANOVA tests were conducted for comparison between the 3 subgroups, followed by pairwiset-tests. Interrater variability was assessed with Fleiss kappa tests.Results:The mean accuracy score was 4.62 (SD 0.89) for ChatGPT, 4.77 (SD 0.90) for Bard, and 4.41 (SD 1.09) for LLaMA. Both ChatGPT (P= 0.03) and Bard (P= 0.003) scored significantly better for accuracy when compared with LLaMA. The mean completeness score was 4.43 (SD 0.91) for ChatGPT, 4.57 (SD 0.93) for Bard, and 4.42 (SD 0.99) for LLaMA. There were no significant differences in completeness scores between groups. Fleiss kappa assessment for interrater variability was good (0.74) for accuracy and fair (0.31) for completeness.Conclusions:All 3 LLMs had relatively high accuracy and completeness ratings, showing LLMs are able to provide sufficient answers for niche topics of ophthalmology. Our results indicate that ChatGPT and Bard may be slightly better at providing more accurate answers than LLaMA. As further research and treatment plans are developed for ADC-associated ocular toxicities, these LLMs should be reassessed to see if they provide complete and accurate answers that remain in line with current medical knowledge.