bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRD4 promotes gouty arthritis through MDM2-mediated PPARγ degradation and pyroptosis
Authors: Xu Xiaoxia , Qiu Hongbin 
Published: May 2024

Abstract
Background
Gouty arthritis (GA) is characterized by monosodium urate (MSU) crystal accumulation that instigates NLRP3-mediated pyroptosis; however, the underlying regulatory mechanisms have yet to be fully elucidated. The present research endeavors to elucidate the regulatory mechanisms underpinning this MSU-induced pyroptotic cascade in GA.

Methods
J774 cells were exposed to lipopolysaccharide and MSU crystals to establish in vitro GA models, whereas C57BL/6 J male mice received MSU crystal injections to mimic in vivo GA conditions. Gene and protein expression levels were evaluated using real-time quantitative PCR, Western blotting, and immunohistochemical assays. Inflammatory markers were quantified via enzyme-linked immunosorbent assays. Pyroptosis was evaluated using immunofluorescence staining for caspase-1 and flow cytometry with caspase-1/propidium iodide staining. The interaction between MDM2 and PPARγ was analyzed through co-immunoprecipitation assays, whereas the interaction between BRD4 and the MDM2 promoter was examined using chromatin immunoprecipitation and dual-luciferase reporter assays. Mouse joint tissues were histopathologically evaluated using hematoxylin and eosin staining.

Results
In GA, PPARγ was downregulated, whereas its overexpression mitigated NLRP3 inflammasome activation and pyroptosis. MDM2, which was upregulated in GA, destabilized PPARγ through the ubiquitin–proteasome degradation pathway, whereas its silencing attenuated NLRP3 activation by elevating PPARγ levels. Concurrently, BRD4 was elevated in GA and exacerbated NLRP3 activation and pyroptosis by transcriptionally upregulating MDM2, thereby promoting PPARγ degradation. In vivo experiments showed that BRD4 silencing ameliorated GA through this MDM2–PPARγ–pyroptosis axis.

Conclusion
BRD4 promotes inflammation and pyroptosis in GA through MDM2-mediated PPARγ degradation, underscoring the therapeutic potential of targeting this pathway in GA management.
Metabolic equivalents intensity thresholds for physical activity classification in older adults
Authors: Leal-Martín Javier , Muñoz-Muñoz Miguel , Sierra-Ramón Miguel , Cerezo-Arroyo Mónica , Gómez-Redondo Paola , Alegre Luis M. , Ara Ignacio , García-García Francisco José , Mañas Asier 
Published: May 2024

Abstract
Background
Although the metabolic equivalents (METs) system is a common procedure to quantify the intensity of physical activity in older adults, it remains unclear whether the conventional METs intensity thresholds (CTs) used for this purpose are appropriate in this population. Therefore, this study aimed (i) to derive overall and fitness-specific METs intensity thresholds in older adults ≥ 60 years old (OATs) expressed both in standard METs (VO2/3.5 mL O2·kg−1·min−1) and older adults METs60+ (VO2/2.7 mL O2·kg−1·min−1), and (ii) to compare them with the CTs.

Methods
A total of 93 subjects were assessed for cardiorespiratory fitness. Graded exercise test protocols using indirect calorimetry were performed to calculate individual VO2max and categorize subjects as "very poor/fair" or "good/superior" fitness. Overall and fitness-specific OATs expressed in standard METs (OATsstandard) and METs60+ (OATs60+) were derived based on the %VO2max and the ventilatory thresholds (VTs) physical intensity categories.

Results
Significantly higher VO2max, VO2 at VT1 and VO2 at VT2 (p < 0.001) were obtained in the "good/superior" subgroup compared to the "very poor/fair" fitness subgroup. Accordingly, OATs were approximately 69% higher in individuals with a "good/superior" fitness compared to those with a "very poor/fair" fitness. Furthermore, this study showed that OATsstandard were approximately 21–24% lower than OATs60+, and 10–22% higher OATs were observed when following the VTs intensity categories (heavy-intensity physical activity [HPA] and severe-intensity physical activity [SPA]) compared to the %VO2max categories (moderate-intensity physical activity [MPA] and vigorous-intensity physical activity [VPA]). When compared with the CTs, similar or higher OATsstandard and OATs60+ for MPA, and HPA were obtained compared to the conventional MPA threshold (3.0 METs). Conversely, for VPA and SPA, lower, similar, or higher OATs were obtained depending on the METs derivation approach (OATsstandard or OATs60+) or the intensity categories (VO2max or VTs), compared to the conventional VPA threshold (6.0 METs).

Conclusions
None of the derived OATs were concurrently similar to the CTs, suggesting that fitness-specific METs intensity thresholds adapted to the METs derivation approach should be used in older adults.

Trial registration
FenotipAGING (Non-health-care intervention study), PRO-Training (NCT05619250).
Multiscale modelling of transport in polymer-based reverse-osmosis/nanofiltration membranes: present and future
Authors: Zhu Haochen , Szymczyk Anthony , Ghoufi Aziz 
Published: May 2024

AbstractNanofiltration (NF) and reverse osmosis (RO) processes are physical separation technologies used to remove contaminants from liquid streams by employing dense polymer-based membranes with nanometric voids that confine fluids at the nanoscale. At this level, physical properties such as solvent and solute permeabilities are intricately linked to molecular interactions. Initially, numerous studies focused on developing macroscopic transport models to gain insights into separation properties at the nanometer scale. However, continuum-based models have limitations in nanoconfined situations that can be overcome by force field molecular simulations. Continuum-based models heavily rely on bulk properties, often neglecting critical factors like liquid structuring, pore geometry, and molecular/chemical specifics. Molecular/mesoscale simulations, while encompassing these details, often face limitations in time and spatial scales. Therefore, achieving a comprehensive understanding of transport requires a synergistic integration of both approaches through a multiscale approach that effectively combines and merges both scales. This review aims to provide a comprehensive overview of the state-of-the-art in multiscale modeling of transport through NF/RO membranes, spanning from the nanoscale to continuum media.
Factors and clinical prediction score for complication development after cellulitis diagnosis in adult patients
Authors: Tienpratarn Welawat , Yuksen Chaiyaporn , Pauly Joseph Daniel , Vu Diana , Benbourenane Anisa Noiwong , Sangskul Nuttamon 
Published: May 2024

Abstract
Background
Cellulitis is defined as a bacterial infection of the skin and subcutaneous tissue that can cause multiple complications, such as sepsis and necrotizing fasciitis. In extreme cases, it may lead to multiorgan failure and death. We sought to analyze the clinical factors that contribute to the development of complicated disease, including demographics, clinical presentation, initial vital signs, and laboratory studies.

Methods
Our study is a retrospective cohort study carried out in a university-based tertiary care hospital in Bangkok, Thailand. Adult patients who presented with cellulitis from January 1, 2018, to December 31, 2022, were evaluated for eligibility and inclusion in this study. All related variables for both outcomes, bacteremia and necrotizing fasciitis, were gathered from electronic medical records and analyzed using multivariable logistic regression analysis.

Results
Of the 1,560 visits to this hospital, 47 cases reported at least one complication, with bacteremia noted in 27 visits (1.73%) and necrotizing fasciitis in 20 visits (1.27%). From the multivariable logistic regression analysis, six variables emerge as predictors of cellulitis complications. These are: Age ≥ 65 years, Body Mass Index ≥ 30 kg/m2, diabetes mellitus, body temperature ≥ 38 °C, systolic blood pressure ≤ 100 mmHg, and involvement of lower extremities. The predictive score was developed from these factors and was named the Ramathibodi Necrotizing Fasciitis/Bacteremia (RAMA-NFB) Prediction Score. Our predictive score has an accuracy of 82.93% (95% CI, 0.77–0.89). Patients in the high-risk group (RAMA NFB score > 6) have a likelihood ratio of 8.75 (95% CI, 4.41–18.12; p < 0.001) times to develop complications of cellulitis.

Conclusion
In our study, the RAMA-NFB Prediction Score predicts complications of necrotizing fasciitis and bacteremia in adult patients who present with cellulitis. External validation of this predictive score is still needed for further practical application.
Emergency medicine residents and performance under pressure: learning from elite athletes’ experience
Authors: Trepanier Gabrielle , Falardeau Viviane , Sohi Gurpreet , Richard Veronique 
Published: May 2024

Abstract
Objective
The skills of coping with stress and pressure within emergency medicine are conveyed informally and inconsistently throughout residency training. This study aims to identify key psychological competencies used by elite athletes in high-pressure situations, which can be integrated into a formal curriculum to support emergency medicine residents’ performance in high acuity settings.

Design
We conducted a scoping review spanning 20 years to identify the relevant psychological competencies used by elite athletes (Olympic or World level) to perform under pressure. We used controlled vocabulary to search within Medline, PsycInfo and SportDiscuss databases. A standardized charting method was used by the team of four authors to extract relevant data.

Results
The scoping review identified 18 relevant articles, including 707 athletes from 49 different sports and 11 countries, 64 data items were extracted, and 6 main themes were identified. The main psychological competencies included the ability to sustain a high degree of motivation and confidence, to successfully regulate thoughts, emotions and arousal levels, and to maintain resilience in the face of adversity.

Conclusion
We used the main psychological competencies identified from our scoping review to develop a hypothesis generated framework to guide the integration of performance psychology principles into future emergency medicine residency programs.
Grouping strategies for assessing and managing persistent and mobile substances
Authors: Chirsir Parviel , Palm Emma H. , Baskaran Sivani , Schymanski Emma L. , Wang Zhanyun , Wolf Raoul , Hale Sarah E. , Arp Hans Peter H. 
Published: May 2024

Abstract
Background
Persistent, mobile and toxic (PMT), or very persistent and very mobile (vPvM) substances are a wide class of chemicals that are recalcitrant to degradation, easily transported, and potentially harmful to humans and the environment. Due to their persistence and mobility, these substances are often widespread in the environment once emitted, particularly in water resources, causing increased challenges during water treatment processes. Some PMT/vPvM substances such as GenX and perfluorobutane sulfonic acid have been identified as substances of very high concern (SVHCs) under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. With hundreds to thousands of potential PMT/vPvM substances yet to be assessed and managed, effective and efficient approaches that avoid a case-by-case assessment and prevent regrettable substitution are necessary to achieve the European Union's zero-pollution goal for a non-toxic environment by 2050.

Main
Substance grouping has helped global regulation of some highly hazardous chemicals, e.g., through the Montreal Protocol and the Stockholm Convention. This article explores the potential of grouping strategies for identifying, assessing and managing PMT/vPvM substances. The aim is to facilitate early identification of lesser-known or new substances that potentially meet PMT/vPvM criteria, prompt additional testing, avoid regrettable use or substitution, and integrate into existing risk management strategies. Thus, this article provides an overview of PMT/vPvM substances and reviews the definition of PMT/vPvM criteria and various lists of PMT/vPvM substances available. It covers the current definition of groups, compares the use of substance grouping for hazard assessment and regulation, and discusses the advantages and disadvantages of grouping substances for regulation. The article then explores strategies for grouping PMT/vPvM substances, including read-across, structural similarity and commonly retained moieties, as well as the potential application of these strategies using cheminformatics to predict P, M and T properties for selected examples.

Conclusions
Effective substance grouping can accelerate the assessment and management of PMT/vPvM substances, especially for substances that lack information. Advances to read-across methods and cheminformatics tools are needed to support efficient and effective chemical management, preventing broad entry of hazardous chemicals into the global market and favouring safer and more sustainable alternatives.
MicroRNA Nano-Shuttles: Engineering Extracellular Vesicles as a Cutting-Edge Biotechnology Platform for Clinical Use in Therapeutics
Authors: Menjivar Nico G. , Oropallo Jaiden , Gebremedhn Samuel , Souza Luca A. , Gad Ahmed , Puttlitz Christian M. , Tesfaye Dawit 
Published: May 2024

AbstractExtracellular vesicles (EVs) are nano-sized, membranous transporters of various active biomolecules with inflicting phenotypic capabilities, that are naturally secreted by almost all cells with a promising vantage point as a potential leading drug delivery platform. The intrinsic characteristics of their low toxicity, superior structural stability, and cargo loading capacity continue to fuel a multitude of research avenues dedicated to loading EVs with therapeutic and diagnostic cargos (pharmaceutical compounds, nucleic acids, proteins, and nanomaterials) in attempts to generate superior natural nanoscale delivery systems for clinical application in therapeutics. In addition to their well-known role in intercellular communication, EVs harbor microRNAs (miRNAs), which can alter the translational potential of receiving cells and thus act as important mediators in numerous biological and pathological processes. To leverage this potential, EVs can be structurally engineered to shuttle therapeutic miRNAs to diseased recipient cells as a potential targeted ‘treatment’ or ‘therapy’. Herein, this review focuses on the therapeutic potential of EV-coupled miRNAs; summarizing the biogenesis, contents, and function of EVs, as well as providing both a comprehensive discussion of current EV loading techniques and an update on miRNA-engineered EVs as a next-generation platform piloting benchtop studies to propel potential clinical translation on the forefront of nanomedicine.
Protein expression patterns and metal metabolites in a protogynous hermaphrodite fish, the ricefield eel (Monopterus albus)
Authors: He Zhi , Xiao Feng , Yang Deying , Deng Faqiang , Ding Wenxiang , He Zhide , Wang Siqi , Chen Qiqi , Wang Haochen , Chen Mingqiang , Gao Kuo , Xiong Jinxing , Tang Ziting , Zhang Mingwang , Yan Taiming 
Published: May 2024

Abstract
Background
The ricefield eel Monopterus albus undergoes a natural sex change from female to male during its life cycle, and previous studies have shown the potential mechanisms of this transition at the transcriptional and protein levels. However, the changes in protein levels have not been fully explored, especially in the intersexual stage.

Results
In the present study, the protein expression patterns in the gonadal tissues from five different periods, the ovary (OV), early intersexual stage gonad (IE), middle intersexual stage gonad (IM), late intersexual stage gonad (IL), and testis (TE), were determined by untargeted proteomics sequencing. A total of 5125 proteins and 394 differentially expressed proteins (DEPs) were detected in the gonadal tissues. Of the 394 DEPs, there were 136 between the OV and IE groups, 20 between the IM and IE groups, 179 between the IL and IM groups, and 59 between the TE and IL groups. Three candidate proteins, insulin-like growth factor 2 mRNA-binding protein 3 isoform X1 (Igf2bp3), triosephosphate isomerase (Tpi), and Cu-Zn superoxide dismutase isoform X1 [(Cu-Zn) Sod1], were validated by western blotting to verify the reliability of the data. Furthermore, metal metabolite-related proteins were enriched in the IL vs. IM groups and TE vs. IL groups, which had close relationships with sex change, including Cu2+-, Ca2+-, Zn2+- and Fe2+/Fe3+-related proteins. Analysis of the combined transcriptome data revealed consistent protein/mRNA expression trends for two metal metabolite-related proteins/genes [LOC109953912 and calcium Binding Protein 39 Like (cab39l)]. Notably, we detected significantly higher levels of Cu2+ during the sex change process, suggesting that Cu2+ is a male-related metal metabolite that may have an important function in male reproductive development.

Conclusions
In summary, we analyzed the protein profiles of ricefield eel gonadal tissues in five sexual stages (OV, IE, IM, IL, and TE) and verified the plausibility of the data. After preforming the functional enrichment of metal metabolite-related DEPs, we detected the contents of the metal metabolites Zn2+, Cu2+, Ca2+, and Fe2+/Fe3+ at these five stages and screened for (Cu-Zn) Sod1 and Mmp-9 as possible key proteins in the sex reversal process.
Integrated analysis of the DNA methylome and RNA transcriptome during the development of skeletal muscle in Duroc pigs
Authors: Li Shi-yin , Wang Yun-zhou , Chen Wei , Ma Li-xia , Zhang Jian-min , Zhang Yu-lun , Zeng Yong-qing 
Published: May 2024

Abstract
Background
Skeletal muscle development plays a crucial role in yield and quality of pork; however, this process is influenced by various factors. In this study, we employed whole-genome bisulfite sequencing (WGBS) and transcriptome sequencing to comprehensively investigate the longissimus dorsi muscle (LDM), aiming to identify key genes that impact the growth and development of Duroc pigs with different average daily gains (ADGs).

Results
Eight pigs were selected and divided into two groups based on ADGs: H (774.89 g) group and L (658.77 g) group. Each pair of the H and L groups were half-siblings. The results of methylation sequencing revealed 2631 differentially methylated genes (DMGs) involved in metabolic processes, signalling, insulin secretion, and other biological activities. Furthermore, a joint analysis was conducted on these DMGs and the differentially expressed genes (DEGs) obtained from transcriptome sequencing of the same individual. This analysis identified 316 differentially methylated and differentially expressed genes (DMEGs), including 18 DMEGs in promoter regions and 294 DMEGs in gene body regions. Finally, LPAR1 and MEF2C were selected as candidate genes associated with muscle development. Bisulfite sequencing PCR (BSP) and quantitative real-time PCR (qRT–PCR) revealed that the promoter region of LPAR1 exhibited significantly lower methylation levels (P < 0.05) and greater expression levels (P < 0.05) in the H group than in the L group. Additionally, hypermethylation was observed in the gene body region of MEF2C, as was a low expression level, in the H group (P < 0.05).

Conclusions
These results suggest that the differences in the ADGs of Duroc pigs fed the same diet may be influenced by the methylation levels and expression levels of genes related to skeletal muscle development.
Apelin-13 modulates the endometrial transcriptome of the domestic pig during implantation
Authors: Dobrzyn Kamil , Kiezun Marta , Kopij Grzegorz , Zarzecka Barbara , Gudelska Marlena , Kisielewska Katarzyna , Zaobidna Ewa , Makowczenko Karol G. , Dall’Aglio Cecilia , Kamiński Tadeusz , Smolińska Nina 
Published: May 2024

Abstract
Background
The peri-implantation period is a critical time during pregnancy that mostly defines the overall litter size. Most authors agree that the highest percentage of embryo mortality occurs during this time. Despite the brevity of the peri-implantation period, it is the most dynamic part of pregnancy in which the sequential and uninterrupted course of several processes is essential to the animal’s reproductive success. Also then, the maternal uterine tissues undergo an intensive remodelling process, and their energy demand dramatically increases. It is believed that apelin, a member of the adipokine family, is involved in the control of female reproductive functions in response to the current metabolic state. The verified herein hypothesis assumed the modulatory effect of apelin on the endometrial tissue transcriptome on days 15 to 16 of gestation (beginning of implantation).

Results
The analysis of data obtained during RNA-seq (Illumina HiSeq2500) of endometrial slices treated and untreated with apelin (n = 4 per group) revealed changes in the expression of 68 genes (39 up-regulated and 29 down-regulated in the presence of apelin), assigned to 240 gene ontology terms. We also revealed changes in the frequency of alternative splicing events (397 cases), as well as single nucleotide variants (1,818 cases) in the presence of the adipokine. The identified genes were associated, among others, with the composition of the extracellular matrix, apoptosis, and angiogenesis.

Conclusions
The obtained results indicate a potential role of apelin in the regulation of uterine tissue remodelling during the peri-implantation period.
Central nervous system anomalies in 41 Chinese children incontinentia pigmenti
Authors: Yin Li , Li Zhengyuan , Zhan Wenjuan , Kang Yuanjie , Tian Qian , Li Dan , Zhang Huifang 
Published: May 2024

Abstract
Introduction
Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase.

Materials and methods
This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi’an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data.

Results
Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration.

Conclusion
Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.