bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK /ERK1/2 pathway and resisted autophagy-related ferroptosis via AMPK/mTOR pathway in hyperplastic prostate
Authors: Li Yan , Zhou Yongying , Liu Daoquan , Wang Zhen , Qiu Jizhang , Zhang Junchao , Chen Ping , Zeng Guang , Guo Yuming , Wang Xinghuan , DiSanto Michael E. , Zhang Xinhua 
Published: August 2023

Abstract
Background
Benign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH.

Methods
Human prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson’s trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments.

Results
Our study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations.

Conclusions
Our novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.
DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma
Authors: Liu Xu-Sheng , Yuan Ling-Ling , Gao Yan , Ming Xing , Zhang Yao-Hua , Zhang Yu , Liu Zi-Yue , Yang Yi , Pei Zhi-Jun 
Published: August 2023

Abstract
Background
This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells.

Methods
This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments.

Results
DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1.

Conclusions
Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.
Significant pain decrease in children with non-systemic Juvenile Idiopathic Arthritis treated to target: results over 24 months of follow up
Authors: Spekking Katinka , Anink Janneke , de Boer Piroska , Bergstra Sytske Anne , van den Berg J. Merlijn , Schonenberg-Meinema Dieneke , van Suijlekom-Smit Lisette W. A. , van Rossum Marion A. J. , Koopman-Keemink Yvonne , Cate Rebecca ten , Allaart Cornelia F. , Brinkman Daniëlle M. C. , Muller Petra C. E. Hissink 
Published: August 2023

Abstract
Background
The aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.

Methods
In the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up.

Results
Pain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [ -0.34 (-0.55; -0.06)], CHQ Physical [ -0.42 (-0.72; -0.11)] and Psychosocial summary Score [ -0.42 (-0.77; -0.06)] were predictive of lower pain.

Conclusions
Treatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain.

Trial registration
Dutch Trial Registry number 1574.
Remibrutinib (LOU064) inhibits neuroinflammation driven by B cells and myeloid cells in preclinical models of multiple sclerosis
Authors: Nuesslein-Hildesheim Barbara , Ferrero Enrico , Schmid Cindy , Huck Catherine , Smith Paul , Tisserand Sarah , Rubert Joelle , Bornancin Frederic , Eichlisberger Denis , Cenni Bruno 
Published: August 2023

Abstract
Background
Bruton’s tyrosine kinase (BTK) is a key signaling node in B cell receptor (BCR) and Fc receptor (FcR) signaling. BTK inhibitors (BTKi) are an emerging oral treatment option for patients suffering from multiple sclerosis (MS). Remibrutinib (LOU064) is a potent, highly selective covalent BTKi with a promising preclinical and clinical profile for MS and other autoimmune or autoallergic indications.

Methods
The efficacy and mechanism of action of remibrutinib was assessed in two different experimental autoimmune encephalomyelitis (EAE) mouse models for MS. The impact of remibrutinib on B cell-driven EAE pathology was determined after immunization with human myelin oligodendrocyte glycoprotein (HuMOG). The efficacy on myeloid cell and microglia driven neuroinflammation was determined in the RatMOG EAE. In addition, we assessed the relationship of efficacy to BTK occupancy in tissue, ex vivo T cell response, as well as single cell RNA-sequencing (scRNA-seq) in brain and spinal cord tissue.

Results
Remibrutinib inhibited B cell-dependent HuMOG EAE in dose-dependent manner and strongly reduced neurological symptoms. At the efficacious oral dose of 30 mg/kg, remibrutinib showed strong BTK occupancy in the peripheral immune organs and in the brain of EAE mice. Ex vivo MOG-specific T cell recall response was reduced, but not polyclonal T cell response, indicating absence of non-specific T cell inhibition. Remibrutinib also inhibited RatMOG EAE, suggesting that myeloid cell and microglia inhibition contribute to its efficacy in EAE. Remibrutinib did not reduce B cells, total Ig levels nor MOG-specific antibody response. In brain and spinal cord tissue a clear anti-inflammatory effect in microglia was detected by scRNA-seq. Finally, remibrutinib showed potent inhibition of in vitro immune complex-driven inflammatory response in human microglia.

Conclusion
Remibrutinib inhibited EAE models by a two-pronged mechanism based on inhibition of pathogenic B cell autoreactivity, as well as direct anti-inflammatory effects in microglia. Remibrutinib showed efficacy in both models in absence of direct B cell depletion, broad T cell inhibition or reduction of total Ig levels. These findings support the view that remibrutinib may represent a novel treatment option for patients with MS.
Levels of health literacy among people living with HIV in outpatient care: a cross-sectional study from Denmark
Authors: Rodkjaer Lotte Ørneborg , Storgaard Merete , Sørensen Nanna Toxvig , Schougaard Liv Marit Valen 
Published: August 2023

Abstract
Background
Low health literacy (HL) among people living with HIV (PLWHIV) encounter more disease related complications, more difficulty understanding health-related information and low adherence. Considering that, the HL levels among PLWHIV needs to be further investigated. The objective of this study was to investigate the levels of HL and patient involvement among PLWHIV in an outpatient clinic in Denmark. A second objective was to examine differences in HL levels across socio-demographic characteristics.

Methods
In 2019, a population of 682 PLWHIV from a Danish outpatient hospital clinic were enrolled in cross-sectional study. Patients who had a digital postbox received an electronic questionnaire including following domains; health literacy, patient involvement, and socio-demographic status. Health literacy was measured using the Health Literacy Questionnaire (HLQ) through scores on three subscales: social support for health (HLQ4), engaging with healthcare providers (HLQ6), and understanding health information (HLQ9). An unpaired t-test was used to investigate mean differences in the HLQ scores across socio-demographic variables.

Results
A total of 338 (55%) patients responded to the questionnaire. The included participants demonstrated high levels of HLQ4 (mean = 4.2) and HLQ6 (mean = 4.2), but lower for HLQ9 (mean = 2.9). In total 70–80% reported being involved in decisions about their health. We found a positive association between high level of HL (HLQ9) and living with a partner and higher levels of HL (HLQ4, HLQ6, and HLQ9) and employment.

Conclusion
PLWHIV in a Danish out-patient care population were found to have high levels of HL despite differences in demographic characteristics. Further research is needed to examine the levels of HL among non-responders to develop HL approaches and strategies to meet the needs of individuals with different HL skills.
Comparative effectiveness of hyaluronic acid, platelet-rich plasma, and platelet-rich fibrin in treating temporomandibular disorders: a systematic review and network meta-analysis
Authors: Xu Jingjing , Ren Hui , Zhao Shuwei , Li Qian , Li Ce , Bao Guangjie , Kang Hong 
Published: August 2023

Abstract
Objective
This study aims to compare the efficacy of intra-articular injections of hyaluronic acid (HA), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) for treating temporomandibular disorders (TMDs) and summarize their mechanisms of action.

Methods
Randomized controlled trials (RCTs) published until November 13, 2021, were identified using electronic and manual searches. Each study was evaluated for the risk of bias using the Cochrane risk of bias tool. The studies found via searches were categorized by follow-up time (1, 3, or 6 months). Evidence quality was graded according to the GRADE system.

Results
Twelve RCTs were included that involved 421 patients with TMD. The network meta-analysis showed that all treatment groups improved compared to the placebo groups in terms of pain and maximal mouth opening (MMO). For pain evaluated via the visual analog scale, PRF exhibited better analgesic effects than PRP or HA after 1 and 3 months. PRP appeared to be more effective than PRF was after 6 months but there were no statistically significant differences between the two. For MMO, the effect of PRP was superior to those of PRF and HA after 1 month. However, after 3 and 6 months, PRF provided more encouraging results in improving MMO.

Conclusion
PRP and PRF exhibited similar short-term efficacy in treating TMD, while PRF was more advantageous in terms of long-term efficacy. Therefore, PRF was recommended for treating TMD.
Plant disease prescription recommendation based on electronic medical records and sentence embedding retrieval
Authors: Ding Junqi , Qiao Yan , Zhang Lingxian 
Published: August 2023

Abstract
Background
In the era of Agri 4.0 and the popularity of Plantwise systems, the availability of Plant Electronic Medical Records has provided opportunities to extract valuable disease information and treatment knowledge. However, developing an effective prescription recommendation method based on these records presents unique challenges, such as inadequate labeling data, lack of structural and linguistic specifications, incorporation of new prescriptions, and consideration of multiple factors in practical situations.

Results
This study proposes a plant disease prescription recommendation method called PRSER, which is based on sentence embedding retrieval. The semantic matching model is created using a pre-trained language model and a sentence embedding method with contrast learning ideas, and the constructed prescription reference database is retrieved for optimal prescription recommendations. A multi-vegetable disease dataset and a multi-fruit disease dataset are constructed to compare three pre-trained language models, four pooling types, and two loss functions. The PRSER model achieves the best semantic matching performance by combining MacBERT, CoSENT, and CLS pooling, resulting in a Pearson coefficient of 86.34% and a Spearman coefficient of 77.67%. The prescription recommendation capability of the model is also verified. PRSER performs well in closed-set testing with Top-1/Top-3/Top-5 accuracy of 88.20%/96.07%/97.70%; and slightly worse in open-set testing with Top-1/Top-3/Top-5 accuracy of 82.04%/91.50%/94.90%. Finally, a plant disease prescription recommendation system for mobile terminals is constructed and its generalization ability with incomplete inputs is verified. When only symptom information is available without environment and plant information, our model shows slightly lower accuracy with Top-1/Top-3/Top-5 accuracy of 75.24%/88.35%/91.99% in closed-set testing and Top-1/Top-3/Top-5 accuracy of 75.08%/87.54%/89.84% in open-set testing.

Conclusions
The experiments validate the effectiveness and generalization ability of the proposed approach for recommending plant disease prescriptions. This research has significant potential to facilitate the implementation of artificial intelligence in plant disease treatment, addressing the needs of farmers and advancing scientific plant disease management.
Suprapatellar pouch effusion is associated with an increased risk of neglected osteochondral fractures in primary acute traumatic patellar dislocation: a consecutive series of 113 children
Authors: Miao Mingyuan , Cai Haoqi , Wang Zhigang , Hu Liwei , Bian Jingxia , Cai Haiqing 
Published: August 2023

Abstract
Background
The aim of this study was to investigate the risk factors of neglected osteochondral fractures in primary acute traumatic patellar dislocation in the pediatric population.

Methods
A total of 113 patients with primary acute traumatic patellar dislocation for whom coincident osteochondral fractures could not be confirmed by X-ray examination at initial diagnosis between January 2010 and February 2022 were retrospectively analyzed. Medical history, physical examination, and radiographic images were recorded in detail. The greatest dimension of the suprapatellar pouch (SP) effusion on radiograph was measured. Computed tomography and magnetic resonance imaging were used to confirm the presence of neglected osteochondral fractures and measure the fragment size. Potential risk factors were calculated and correlated with reference to the neglected osteochondral fractures and fragment size using multivariate linear regression analysis.

Results
Weight, walking ability, effusion grade, and SP measurement had a significant correlation with neglected osteochondral fractures in primary acute traumatic patellar dislocation (p = 0.046; p < 0.001; p = 0.048; p < 0.001). The cutoff point was 53.5 kg for weight and 18.45 mm for SP measurement. In the neglected fractures group, SP measurement was statistically significant with larger fragment size (beta value = 0.457; p < 0.001), and the cutoff point was 26.2 mm.

Conclusions
SP effusion is not only associated with an increased risk of neglected osteochondral fractures in primary acute traumatic patellar dislocation but also with larger fragment size. Knee radiograph, medical history, and physical examination can predict the need for further imaging examination and even surgery in primary acute traumatic patellar dislocation.
Prevalence of sleep disturbance among adolescents with substance use: a systematic review and meta-analysis
Authors: Phiri Doreen , Amelia Vivi Leona , Muslih Muhammad , Dlamini Lindelwa Portia , Chung Min-Huey , Chang Pi-Chen 
Published: August 2023

Abstract
Purpose
Sleep disturbance has become a major challenge among adolescents worldwide. Substance use is among the most common factors contributing to sleep disturbance. This systematic review and meta-analysis examined the prevalence and categories of sleep disturbance among adolescents with substance use.

Methods
We comprehensively searched for relevant studies published in the following databases from inception to August 2022: CINHAL (via EBSCOhost), PubMed, Scopus, Ovid Medline, Embase, ProQuest, and Web of Science. Data analysis was performed using Comprehensive Meta-Analysis version 3 software. We used a random-effects model to pool prevalence rates with 95% confidence intervals (CIs). Forest plots and p values for the Cochran Q statistic were used to evaluate heterogeneity among studies. Subgroup and meta-regression analyses were performed to compare the groups and identify the sources of heterogeneity.

Results
We examined 18 studies that reported insomnia, hypersomnolence, sleep-related breathing disorders as sleep disturbances among adolescents with the use of alcohol, smoking, marijuana, and coffee. The total sample was 124,554. The overall prevalence rate of sleep disturbance was 29% (95% CI: 0.201–0.403). Subgroup analysis revealed that the prevalence rates of insomnia and hypersomnolence were higher among alcohol users (31%; 95% CI: 0.100–0.654) and smokers (46%; 95% CI: 0.232–0.700). The study design and method of assessment groups were the significant moderators that showed the source of variation in the included studies.

Conclusion
Sleep disturbance is highly prevalent among adolescents with substance use. Insomnia and hypersomnolence are more prevalent among alcohol users and smokers, respectively. On the basis of our findings, health-care providers can develop effective targeted interventions to reduce substance use, prevent sleep disturbance, and promote healthy sleep habits among adolescents.
Dingkun pill alleviates metabolic abnormalities in polycystic ovary syndrome through brown adipose tissue activation
Authors: Gu Mengqing , Cai Han , Deng Weinan , Tang Yedong , Du Shuailin , Wang Peiran , Deng Wenbo , Wang Haibin , Sun Aijun , Kong Shuangbo 
Published: August 2023

Abstract
Background
Traditional Chinese medicine has been used for a long time to treat a variety of gynecological diseases. Among various traditional Chinese medicine, Dingkun Pill (DK) has been used for the treatment of female gynecological diseases. However, DK therapeutic effect on PCOS and the target tissue for its potential effect need to be explored. This study aims to explore the therapeutic effect of DK for PCOS in mice from three aspects: metabolism, endocrine and fertility, and determine whether the brown adipose tissue is the target organ to alleviate the PCOS phenotype.

Methods
PCOS mouse model was constructed by subcutaneous injection of DHEA. The estrous cycle, ovulation, and pregnancy outcome was examined in mice. The level of hormone including the LH, FSH, estrogen and testosterone in the serum were measured by ELISA. Both the glucose sensitivity and insulin sensitivity were determined in mice with different treatment. The histomorphology and lipid contents in the brown adipose tissue were analyzed. RNA-Seq was conducted for the brown adipose tissue and different expression of critical metabolism marker genes was confirmed by real-time PCR.

Results
The data showed that the fertility in PCOS mice with DK treatment was significantly increased, and the metabolic disorder was partially restored. Both the whiten of brown adipose tissue and reduced UCP1 expression induced by DHEA was rescued by the DK. The RNA-Seq data further demonstrated both the DHEA induced downregulation of lipolysis genes and oxidative phosphorylation genes were at least partially rescued by DK in the brown adipose tissue.

Conclusions
DK has therapeutic effect on PCOS in DHEA treated mice and the brown adipose tissue is at least one critical target organ to alleviate the PCOS. This is achieved by not only regulating the lipid mobilization of brown adipose, but also restoring its thermogenic function.