bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEDD4L Inhibits the Proliferation and Migration of Keloid Fibroblasts by Regulating YY1 Ubiquitination‐Mediated Glycolytic Metabolic Reprogramming
Authors: Jin Jun , Wang Kai , Lu Chenxi , Yao Chenghao , Xie Feng 
Published: November 2024

ABSTRACTKeloid scarring is a complex fibroproliferative disorder characterised by excessive fibroblast proliferation. Inhibition of cellular glycolysis effectively suppresses the proliferation of keloid fibroblasts (KFs). Neural precursor cell‐expressed developmentally downregulated gene 4‐like (NEDD4L), a ubiquitin ligase, regulates cell proliferation in different diseases. This study investigated the effects of NEDD4L on glucose metabolism, proliferation and migration in KFs. Primary KFs were isolated from keloid skin tissues obtained from patients with active‐stage keloids. Cell transfection was used to upregulate or downregulate NEDD4L and Yin Yang 1 (YY1) in KFs. Protein expression was assessed by immunohistochemistry and western blotting. The viability, proliferative capacity and migration ability of KFs were evaluated using the MTT method and the EdU and wound healing assays, respectively. The regulatory effect of NEDD4L on YY1 ubiquitination was examined by coimmunoprecipitation. The interaction between YY1 and hexokinase 2 (HK2) was confirmed by a dual‐luciferase reporter assay. NEDD4L was downregulated, whereas YY1 and HK2 were highly expressed in keloid tissues compared with normal skin. Overexpression of NEDD4L inhibited the proliferation and migration of KFs. NEDD4L promoted YY1 degradation in KFs by inducing its ubiquitination. Upregulation of YY1 induced glucose consumption and lactate production in KFs via the transcriptional regulation of HK2. Increased expression of YY1 reversed the reduced viability, proliferation, and migration of KFs overexpressing NEDD4L. YY1 also reversed the NEDD4L‐induced inhibition of glucose consumption and lactate production in KFs. Additionally, an in vivo study confirmed the inhibitory roles of NEDD4L overexpression and YY1 knockdown in keloid formation. NEDD4L suppressed the viability, proliferation and migration of KFs by regulating YY1 ubiquitination‐mediated glycolysis through HK2. These findings suggest a novel regulatory axis, NEDD4L/YY1/HK2, that mediates glucose metabolism in keloid formation.
A Two‐Scale Model of Fretting Fatigue Crack Initiation Life Based on Long Short‐Term Memory Networks Improved by Genetic Algorithm
Authors: Xu Yazhou , Wu Yue , Yuan Fang , Feng Yangmin , Hao Bin 
Published: November 2024

ABSTRACTFretting fatigue is a common engineering failure phenomenon, often resulting in a shorter lifespan compared to plain fatigue. To consider the interaction between different scales, this study proposes a fully coupled two‐scale model based on continuum damage mechanics (CDM) and the crystal plastic finite element method (CPFEM) for the fretting fatigue crack initiation. Furthermore, the life data series are generated by employing feature engineering and long short‐term memory (LSTM) networks optimized with a genetic algorithm, ensuring the minimization of redundancy. Additionally, the genetic algorithm, enhanced by the Markov chain Monte Carlo method, was used to optimize the hyperparameters of the LSTM network. Simulation results indicate that the two‐scale model offers improved accuracy in predicting crack initiation life and provides physical information of crack initiation from different scales simultaneously.
Decline in Coupling Between Vegetation Photosynthesis and Greening in Northern Ecosystems During the Photosynthesis‐Up Period
Authors: Liu Duqi , Xu Zhen 
Published: November 2024

ABSTRACTThe maximum seasonal vegetation photosynthesis (Phomax) is crucial to regulating the global carbon dynamics. Of particular importance are the seasonal increments in vegetation photosynthesis (ΔPho), which provide key insights into understanding Phomax. However, the interannual variability of ΔPho within the photosynthesis‐up period (PUP) and its influencing factors remain unclear. To address this gap, we identified PUP and quantified the multi‐year characteristics of ΔPho using satellite‐derived solar‐induced chlorophyll fluorescence. We further investigated the response of ΔPho in northern ecosystems to climate change and vegetation greening by integrating climate data and the normalized difference vegetation index. In the northern ecosystems, longer PUP often spatially correlated with a higher ΔPho. An increasing trend was evident regarding the multi‐year variations in ΔPho, suggesting enhanced vegetation photosynthesis within the PUP. This phenomenon is primarily driven by increased solar radiation and intensified vegetation greening. Additionally, based on the results derived from satellite data, we found three pieces of evidence for the decoupling trend between vegetation photosynthesis and greening under the influence of climate change: first, the inconsistent trends between ΔPho and greening; second, the declining moving trend in the correlation coefficient between ΔPho and greening, approximately 9.17 × 10−4; and third, the weakened dominant role of greening on ΔPho. These findings were further supported by results from ecosystem model simulations. In summary, this study provides insights into the interannual variability of ΔPho and its influencing factors and indicates that vegetation dynamics and terrestrial carbon cycle are likely to become more complex under future climate change scenarios.
Outcome Domains of Professional Doctorates in Nursing: An International Three‐Phase Exploratory Study
Authors: McBride‐Henry Karen , Butcher Dan , Jukema Jan S. , Händler‐Schuster Daniela 
Published: November 2024

ABSTRACTAimProfessional Doctorate Programmes (PDP) in nursing continue to develop across many countries. However, there is a lack of evidence demonstrating the impact on nurses who graduate from these programmes and the outcomes they deliver. This exploratory study aims to identify graduate outcome domains that can be applied internationally to evaluate professional doctorate programmes in nursing.Design and MethodsUnderpinned by Kim's theory of knowledge development in nursing, this innovative exploratory study was carried out in three phases: (1) a scoping review of literature published between 1 January 2000 and 1 July 2023, guided by the methodology developed by Arksey and O'Malley; (2) a document analysis of the graduate outcomes of three different universities' Professional Doctorate Programmes in Nursing and (3) a thematic analysis and coalescence of the findings from the initial two study phases.ResultsA scoping review revealed three patterns in the literature related to graduate outcomes: personal transformation, critical self‐awareness and bridging the theory–practice divide. An analysis of three universities' Professional Doctorate Programmes revealed insights into documented graduate outcomes. The third and final research phase identified five graduate outcome domains: Personal achievement, critical self‐awareness and professional identity, professional citizenship, discipline, research and information literacy and community‐based academic practice.ConclusionsThe impact of Professional Doctorate Programmes in nursing has traditionally lacked consensus and clarity. However, this research has led to the identification of graduate outcome domains that offer valuable insights for establishing new professional doctoral programmes and conducting meaningful evaluations of the outcomes of existing PDP and their graduates globally.ImpactThis exploratory study establishes five graduate outcome domains for evaluating the effectiveness of PDP in nursing internationally. These domains offer valuable benchmarks for the development and assessment of such nursing programmes globally.Patient or Public ContributionNot applicable.
Adolescent Chlamydia Screening in Pediatric Primary Care: A Quality Improvement Project
Authors: Foppert Leigh , Bowles Wendy , Belardo Haley , Zeno Rosie , Hosley Stephanie , Wood Sarah 
Published: November 2024

ABSTRACTAimTo increase Chlamydia trachomatis screening in adolescents 15–19 years of age from 7.8% to 15% following a 6‐week implementation of universal chlamydia screening at three paediatric primary care (PPC) sites.MethodsPre‐implementation (1 January 2022–19 October 2022) and post‐implementation (20 October 2022–1 June 2023) screening rates were tracked through run charts and compared via Chi‐square testing. Universal opt‐out chlamydia screening with universal urine collection for 15‐ to 19‐year‐old was implemented at well visits, along with patient and staff education, and sexually transmitted infection treatment protocols.ResultsChlamydia trachomatis screening increased from 7.8% to 34.1% with implementation of universal opt‐out chlamydia screening. Proportions of patients screened increased significantly among White individuals, males and privately insured individuals.ConclusionsA universal C. trachomatis screening project can be feasibly implemented in pediatric primary care and successfully increase adolescent chlamydia screening rates.Implications for the ProfessionImplementing a universal opt‐out C. trachomatis screening project is feasible in PPC and can help achieve the public health goal of chlamydia identification and treatment.ImpactThese findings will be impactful for both paediatric primary care and adolescent patients. The universal, opt‐out C. trachomatis screening approach facilitated screening increases, improved equity in screening and led to increased case detection and treatment which has vast significance for those patients.Reporting MethodThis manuscript is submitted using the SQUIRE 2.0 guidelines for quality improvement reporting.Patient ContributionPatient contribution included de‐identified data collection of chlamydia screening rates of eligible adolescents 15–19 years old who attended routine well visits at the three PPC locations. The data were reviewed on a dashboard, then stratified by race, ethnicity, payor and sex assigned at birth.
Etiology and Medication of Hospitalized Children With Hypertension: A Retrospective Study
Authors: Jia Chenhong , Ding Weijing , Ding Xiangyu 
Published: November 2024

ABSTRACTWith the increasing incidence of hypertension in children, the lack of high‐quality research data on antihypertensive drugs in pediatric patients restricts treatment options for clinicians and can lead to suboptimal outcomes. We conducted a retrospective analysis of clinical data from hospitalized pediatric patients diagnosed with hypertension and treated with antihypertensive drugs in the past 3 years. The study included 203 pediatric patients (119 males and 84 females), with an average age of 8.9 ± 4.7 years (range: 0.1–17 years). Clinical symptoms of hypertension were observed in 132 participants (65.0%), and the conditions in all cases were classified as primary or secondary hypertension. Renal causes (71 patients, 35.0%) and drug‐induced factors (39 patients, 19.2%) were the main causes of secondary hypertension. Nifedipine (137 patients, 67.5%) was the most commonly prescribed medication, followed by captopril (84 patients, 41.4%). Multiple antihypertensive medications were prescribed to 99 participants (48.8%), and blood pressure returned to normal in 111 patients (54.7%). Hypertension‐related organ damage was observed in 47 patients (23.2%). Timely diagnosis and treatment of hypertension are critical to prevent organ damage in pediatric patients. Although nifedipine was widely used in this pediatric cohort, the appropriateness of this treatment remains unclear. Emphasis should be placed on monitoring target organs affected by pediatric hypertension, and post‐discharge antihypertensive treatment should include thorough follow‐ups and documentation.
Hypertension Induced by Hypoxia‐Inducible Factor Prolyl Hydroxylase Inhibitors in Treating Anemia in Patients With Chronic Kidney Disease: A Mini‐Review
Authors: Zhang Wei , Li Yan , Wang Ji‐Guang 
Published: November 2024

ABSTRACTHypoxia‐inducible factor prolyl hydroxylase (HIF‐PH) inhibitors are a new class of agents for the treatment of anemia in chronic kidney disease (CKD). Unlike traditional treatments such as erythropoiesis‐stimulating agents (ESAs), HIF‐PH inhibitors are orally administered drugs and may increase endogenous erythropoietin and improve iron homeostasis. However, a significant concern is their possible side effect on blood pressure. The current mini‐review summarizes the data of 26 randomized controlled (placebo or ESAs) trials on six different HIF‐PH inhibitors with regard to their potential influence on blood pressure and hypertension in the management of anemia in CKD. Overall, the use of HIF‐PH inhibitors was associated with a higher risk of hypertension than placebo (pooled risk ratio 1.36, 95% confidence interval [CI] 1.16–1.59), but a lower risk of hypertension than ESA treatment (pooled risk ratio 0.92, 95% CI 0.86–0.98), especially in CKD patients not undergoing dialysis (pooled risk ratio 0.85, 95% CI 0.73–0.98). This review highlights the importance of blood pressure monitoring during the treatment of HIF‐PH inhibitors, especially out‐of‐office blood pressure measurement.
The combination of FLCWK with 5‐FU inhibits colon cancer and multidrug resistance by activating PXR to suppress the IL‐6/STAT3 pathway
Authors: Zhong Lifan , Wang Qianru , Kou Zhixiong , Gan Lianfang , Yang Zhaoxin , Pan Junhua , Huang Ling , Chen Yunqiang 
Published: November 2024

Abstract5‐fluorouracil (5‐FU) is a preferred chemotherapeutic agent for the treatment of colon cancer. Nonetheless, its clinical effectiveness is frequently hampered by suboptimal therapeutic outcomes and the emergence of drug resistance. Therefore, there exists a pressing demand for novel therapeutic agents to circumvent chemoresistance. The pregnane X receptor (PXR) exerts a pivotal regulatory influence on the proliferation, invasion, and chemoresistance mechanisms in colon cancer. Activation of PXR drives up the transcription of the multidrug resistance gene (MDR1), thus prompting the expression of P‐glycoprotein (P‐gp) responsible for conferring tumour resistance. This study scrutinized the potential of Fengliao Changweikang (FLCWK) in augmenting the efficacy of 5‐FU in the management of colon cancer. To this end, we engineered colon cancer cells with varied levels of PXR expression via lentiviral transfection, subsequently validating the findings in nude mice. By means of MTT assays, flow cytometry apoptosis analysis, Western blotting and immunofluorescence, we probed into the prospective impacts of FLCWK and 5‐FU on cellular viability and resistance. Our results revealed that while upregulation of PXR amplified the therapeutic benefits in colon cancer treatment, it concurrently heightened resistance levels. FLCWK demonstrated a capacity to reduce P‐gp expression, with the combined administration of FLCWK and 5‐FU effectively reversing resistance mechanisms. Furthermore, activation of PXR was found to impede the IL‐6/STAT3 signalling pathway. In an effort to mimic the development of colon cancer, we established an azomethane oxide (AOM)/ dextran sodium sulfate (DSS) mouse model, showing that FLCWK bolstered the inhibitory effects of 5‐FU, impeding the progression of colon cancer. In summation, our findings point towards the potential of FLCWK in the treatment of colon cancer, particularly in strengthening the therapeutic efficacy of 5‐FU in the prevention and control of the disease.
CARD9 protein SUMOylation regulates HOXB5 nuclear translocation and Parkin‐mediated mitophagy in myocardial I/R injury
Authors: Li Yuanbin , Tang Yuting , Yan Xu , Lin Hui , Jiang Wanjin , Zhang Luwei , Zhao Hu , Chen Zhuang 
Published: November 2024

AbstractMyocardial injury induced by ischemia–reperfusion (I/R) remains a difficult clinical problem. However, the exact mechanisms underlying I/R‐induced have yet to be clarified. CARD9 is an important cytoplasmic‐binding protein. In this study, an immunocoprecipitation assay showed that SUMOylation of the CARD9 protein promoted the binding of CARD9 to HOXB5, but hindered the O‐GlcNAc glycosylation of HOXB5, a predicted transcription factor of Parkin and a key factor in mitophagy. O‐GlcNAc glycosylation is an important signal for translocation of proteins from the cytoplasm to the nucleus. CARD9 protein SUMOylation is regulated by PIAS3, which is related to I/R‐induced myocardial injury. Therefore, we propose that knockdown of PIAS3 inhibits SUMOylation of the CARD9 protein, facilitates the dissociation of CARD9 and HOXB5, which increases the O‐GlcNAc‐mediated glycosylation of HOXB5, while the resulting HOXB5 nuclear translocation promotes Parkin‐induced mitophagy and alleviates myocardial I/R injury.
Reconstruction and Prediction of Invasive Cydia pomonella Population Dynamics: A Laboratory Study
Authors: Wang Yan , Wei Zi‐Han , Gao Ping , Li Yu‐Ting , Lv Yun‐Tong , Yang Xue‐Qing 
Published: November 2024

ABSTRACTInvasive species pose a significant threat to global biodiversity and ecological services. The specific threshold of the initial population size necessary for the successful establishment of an invasive species remains uncertain. This research delves into the effects of different initial population sizes on the colonisation and population dynamics of the globally recognised invasive pest, Cydia pomonella, within a controlled laboratory setting. The results revealed that even a single pair of C. pomonella displayed notable eggs laid (fecundity) and hatched (fertility) by producing offspring upon mating. Larger initial population size exhibited increased mating rates, leading to enhanced fecundity and subsequently more offspring, indicating that the development of C. pomonella population is directly impacted by the mating rate of the initial individuals. Projections based on F1 data indicate that the C. pomonella population size could persistently increase over a span of 150 days, with varying growth rates influenced by the initial population size. These findings indicate the importance of heightened monitoring and management in non‐invaded regions to avert early colonisation of C. pomonella, thus mitigating the threat of invasion and subsequent population expansion.
The Impact of Drying Techniques on Stabilizing Microencapsulated Astaxanthin From Shrimp Shells: A Comparative Study of Spray Drying Versus Freeze Drying
Authors: Sharayei Parvin , Rohani Abbas , Sabeghi Yeganeh , Gandomzadeh Danial 
Published: November 2024

ABSTRACTThe research aimed to study how different drying methods (spray and freeze drying) affect the release kinetics of microencapsulated astaxanthin in various environmental conditions. Shrimp shell extract containing astaxanthin was encapsulated using different wall components (maltodextrin with different dextrose equivalents and modified starch) via a simplex lattice mixture design. The encapsulated extract was then subjected to storage at different temperatures (25°C ± 2°C and 2°C ± 4°C) and humidity conditions (52% ± 2% and 75% ± 2%), as well as exposure to UV light (four 15 W lamps, 254 nm, for 10 h). The release kinetics of astaxanthin were analyzed using various models (page, Newton Korsmeyer–Peppas model, Modified Henderson and Pabis, Diffusion approach, and Two‐term exponential). The evaluation results of correlation coefficient (R2), root mean square deviation (RMSE), and mean absolute percentage error (MAPE) values of different models showed that the astaxanthin degradation followed a two‐term exponential kinetics in both types of microcapsules. Astaxanthin degradation increased with higher temperatures, humidity, and UV light exposure. However, microcapsules with equal wall compound ratios exhibited better preservation of astaxanthin. The study also emphasized the significance of optimizing storage conditions and wall materials for microencapsulated astaxanthin, as well as the utility of the two‐term exponential model in enhancing stability and shelf life.
Evaluating the effects of 5‐aminosalicylic acid on tofacitinib treatment in ulcerative colitis
Authors: Nishida Yu , Hosomi Shuhei , Fujimoto Koji , Kobayashi Yumie , Nakata Rieko , Maruyama Hirotsugu , Ominami Masaki , Nadatani Yuji , Fukunaga Shusei , Otani Koji , Tanaka Fumio , Fujiwara Yasuhiro 
Published: November 2024

AbstractBackground and AimTofacitinib and aminosalicylic acid (5‐ASA) are commonly used to treat ulcerative colitis (UC). However, evidence on the effect of concomitant 5‐ASA use in patients receiving tofacitinib is limited. This study investigated the effects of 5‐ASA combined with tofacitinib in UC patients.MethodsThis retrospective cohort study used data from the Medical Data Vision database, including patients with UC treated with tofacitinib from May 2018 to April 2022. Patients were grouped according to tofacitinib dosage and assessed for the efficacy of concomitant 5‐ASA use. The primary endpoint was clinical relapse.ResultsA total of 1213 patients with UC were included in the analysis, with 416 in the 5 mg BID group and 797 in the 10 mg BID group. In the 5 mg BID group, the cumulative relapse‐free rate was significantly higher in patients receiving concomitant 5‐ASA (P < 0.0001). Multivariate Cox regression analysis confirmed that concomitant 5‐ASA use significantly reduced the risk of clinical relapse (adjusted hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.31–0.70). In the 10 mg BID group, no significant difference was noted in the cumulative relapse‐free rate between patients treated with and without 5‐ASA (P = 0.445). Similarly, multivariate Cox regression analysis indicated that concomitant 5‐ASA use did not significantly affect relapse risk (adjusted HR, 0.97; 95% CI, 0.71–1.32).ConclusionsConcomitant 5‐ASA use reduced the risk of relapse in patients on 5 mg tofacitinib BID, suggesting benefits at lower doses. However, no significant benefit was observed with 5‐ASA use in those 10 mg tofacitinib BID.
Long‐term outcomes and quality of life in congenital diaphragmatic hernia survivors treated with extracorporeal life support: A cross‐sectional survey
Authors: Mattke Adrian C , Alphonso Nelson , Ren Chanelle , Jardine Luke , Johnson Kerry E , Venugopal Prem , McBride Craig A 
Published: November 2024

AimFew reports have shown Quality‐of‐Life long‐term outcomes in children with congenital diaphragmatic hernia (CDH) who received extracorporeal membrane oxygenation (ECMO) support. We reviewed the short‐ and long‐term outcomes in CDH patients that were supported with ECMO during their neonatal treatment.MethodsTelephone interviews of parents of CDH children were performed. The Functional Status Scale (FSS) and the Paediatric Quality of Life Inventory (PedQL, Version 4.0) were completed with the parents. All children with a CDH and supported with ECMO from 2010 to 2023 were included in the study.ResultsTwenty children were identified, with two having two ECMO runs. Birth weight was 3.2 kg (median). ECMO support lasted for (median) 13.6 days (range 3.8 to 39). Twelve patients were alive at the time of the survey. The age (median) at time of the interview was 6.3 years (range 1 to 12). The FSS score showed no impairment (FSS score 6) in any domain in eight patients. Two patients had a score of 7, and two patients had a score of 8 and 9, respectively. The PedQL showed a median score 84.5, with a physical health summary score of 92.5 and a psychosocial health summary score of 78.7. The cardiac specific PedQL inventory score was 77.ConclusionsECMO support for CDH patients is associated with functional and Quality of Life outcomes that are similar to that in other PICU discharge populations. Denying ECMO support to CDH patients on the basis of predicted poor long‐term outcomes does not appear to be justified.