bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empowerment interventions designed for persons living with chronic disease - a systematic review and meta-analysis of the components and efficacy of format on patient-reported outcomes
Authors: Stepanian Natalie , Larsen Marie Hamilton , Mendelsohn Joshua B. , Mariussen Kari L. , Heggdal Kristin 
Published: August 2023

Abstract
Background
Empowerment approaches are essential for building the capacity of individuals with chronic disease to be in control of their health. Reviews of empowerment interventions have been focused on specific chronic diseases, thereby limiting the scope of findings. This study had three aims: 1) to describe the characteristics of empowerment interventions covering a broad range of chronic diseases, 2) to clarify consistency with the World Health Organization`s (WHO) definition of empowerment as a process composed of four fundamental components and 3) to summarize outcome measures and estimate the effects in group and individual intervention formats.

Methods
Systematic literature review and meta-analysis. CINAHL, Medline, Embase, PsycINFO, Web of Science, COCHRANE and Central Register of Controlled Trials were searched using Chronic Disease, NCD, Empowerment, as MeSH terms. Eligible randomized and quasi randomized controlled trials were included. Review Manager 5.4 was used to conduct the meta-analysis. Risk of bias was assessed with the Cochrane risk-of-bias tool (ROB 2).

Results
Thirty-nine articles representing 8,011 participants were included in the review. A majority (82%) of studies reported robust evidence for changes on study-defined outcome measures in favor of interventions. Intervention content was assessed against WHO’s four fundamental components of empowerment, showing that all studies incorporated one component, but none targeted all components. Components reflecting knowledge acquisition, patient engagement with their health care providers and facilitating environment were scarcely reported. Meta-analyses found evidence for positive effects of group-format interventions measuring empowerment, HbA1c, and self-efficacy. Effects on empowerment were also found in some individual-format interventions. High levels of heterogeneity and variability among the conceptual frameworks were identified.

Conclusion
Empowerment interventions in group-format were most efficient, however, considerable conceptual inconsistencies were identified. Future studies should consolidate conceptual understandings by using WHO’s empowerment framework to ensure that fundamental components of empowerment are explicitly included in intervention design. Furthermore, there is a need to clarify the role of empowerment through pathways that include patient activation, self- management, and clinical outcomes. This systematic review will inform the clinicians and researchers who aim to develop novel empowerment interventions to assist patients in the process of gaining control of their health.

Trial registration
PROSPERO: International Prospective register of systematic reviews ID=CRD42020178286.
Metabolic characteristics and pathogenesis of precocious puberty in girls: the role of perfluorinated compounds
Authors: Wu Jinxia , Chen Jing , Huang Rong , Zhu Hongwei , Che Lin , Lin Yanyan , Chang Yajie , Shen Guiping , Feng Jianghua 
Published: August 2023

Abstract
Background
Precocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP.

Methods
Nuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP.

Results
The disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT.

Conclusions
The elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.
Lipid profiles in patients with juvenile idiopathic arthritis: a systematic literature review and meta-analysis
Authors: Zhao Wen-Jia , Deng Jiang-Hong , Li Cai-Feng 
Published: August 2023

Abstract
Objective
The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA).

Methods
The literature and relevant reviews were searched for published clinical studies on the relationship between JIA and blood lipid levels. The Newcastle–Ottawa scale (NOS) was applied to evaluate the risk and methodological value of the included case‒control and cohort studies. Standardized mean differences (SMDs) and 95% confidence intervals were derived for all variables with adequate unprocessed data. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.

Results
In total, 16 studies were incorporated through screening. The analysis findings revealed that the levels of very low-density lipoprotein cholesterol [SMD=-0.411, 95% CI (-0.774~-0.048), P = 0.026], high-density lipoprotein cholesterol [SMD=-0.528, 95% CI (-0.976~-0.079), P = 0.021], and apolipoprotein A1 [SMD=-1.050, 95% CI (-1.452~-0.647), P = 0.000] in JIA patients were statistically lower than those observed in healthy controls. The level of low-density lipoprotein cholesterol [SMD = 0.202, 95% CI (0.003 ~ 0.400), P = 0.046] was significantly higher in JIA patients than in healthy controls. In JIA patients, body mass index [SMD=-0.189, 95% CI (-0.690 ~ 0.311), P = 0.459], high-density lipoprotein [SMD =-1.235, 95% CI (-2.845 ~ 0.374), P = 0.133), low-density lipoprotein [SMD = 0.616, 95% CI (-0.813 ~ 2.046), P = 0.398), triglycerides (SMD = 0.278, 95% CI (-0.182 ~ 0.738), P = 0.236], total cholesterol [SMD=-0.073, 95% CI (-0.438 ~ 0.293), P = 0.696] and apolipoprotein B levels [SMD = 0.226, 95% CI (-0.133 ~ 0.585), P = 0.217] were not significantly different from those in healthy controls.

Conclusions
The outcomes of this meta-analysis suggest that dyslipidemia is common in JIA patients compared to healthy controls. Patients with JIA have a significantly increased risk of atherosclerosis and cardiovascular disease later in life.
RNF173 suppresses RAF/MEK/ERK signaling to regulate invasion and metastasis via GRB2 ubiquitination in Hepatocellular Carcinoma
Authors: Zhou Jie , Tu Daoyuan , Peng Rui , Tang Yuhong , Deng Qiangwei , Su Bingbing , Wang Shunyi , Tang Hao , Jin Shengjie , Jiang Guoqing , Wang Qian , Jin Xin , Zhang Chi , Cao Jun , Bai Dousheng 
Published: August 2023

Abstract
Background
The role of the membrane-associated RING-CH (MARCH) family in carcinogenesis has been widely studied, but the member of this family, RNF173, has not yet been thoroughly explored in the context of hepatocellular carcinoma (HCC).

Methods
With the use of an HCC tissue microarray and IHC staining, we aim to determine the differential expression of RNF173 in HCC patients and its clinical significance. The biological role of RNF173 is investigated through in vitro and in vivo experiments. RNA sequencing, mass spectrometry, and immunoprecipitation are performed to uncover the underlying mechanism of RNF173's impact on the development of HCC.

Results
The mRNA and protein levels of RNF173 were significantly lower in HCC tissues than in normal tissues. HCC patients with low RNF173 expression had shorter overall survival and recurrence-free survival, and RNF173 was significantly correlated with tumor number, tumor capsule, tumor differentiation, and BCLC stage. In addition, in vitro and in vivo experiments showed that RNF173 downregulation exacerbated tumor progression, including migration, invasion, and proliferation. GRB2 is a key molecule in the RAF/MEK/ERK pathway. RNF173 inhibits the RAF/MEK/ERK signaling by ubiquitinating and degrading GRB2, thereby suppressing HCC cell proliferation, invasion and migration. Combining clinical samples, we found that HCC patients with high RNF173 and low GRB2 expression had the best prognosis.

Conclusion
RNF173 inhibits the invasion and metastasis of HCC by ubiquitinating and degrading GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. RNF173 is an independent risk factor for the survival and recurrence of HCC patients. RNF173 may serve as a novel prognostic molecule and potential therapeutic target for HCC.

Graphical Abstract
Graphical abstract Model of RNF173 on RAF/MEK/ERK signaling. RNF173 knockdown resulted in impaired ubiquitination and degradation of GRB2, leading to the activation of the RAF/MEK/ERK signaling pathway and promotion of invasion and metastasis in HCC cells.
Estimation of transpulmonary driving pressure during synchronized mechanical ventilation using a single lower assist maneuver (LAM) in rabbits: a comparison to measurements made with an esophageal balloon
Authors: Liu Ling , Li Hong-Liang , Lu Cong , Patel Purab , Wang Danqiong , Beck Jennifer , Sinderby Christer 
Published: August 2023

Abstract
Background
Mechanical ventilation is applied to unload the respiratory muscles, but knowledge about transpulmonary driving pressure (ΔPL) is important to minimize lung injury. We propose a method to estimate ΔPL during neurally synchronized assisted ventilation, with a simple intervention of lowering the assist for one breath (“lower assist maneuver”, LAM).

Methods
In 24 rabbits breathing spontaneously with imposed loads, titrations of increasing assist were performed, with two neurally synchronized modes: neurally adjusted ventilatory assist (NAVA) and neurally triggered pressure support (NPS). Two single LAM breaths (not sequentially, but independently) were performed at each level of assist by acutely setting the assist to zero cm H2O (NPS) or NAVA level 0 cm H2O/uV (NAVA) for one breath. NPS and NAVA titrations were followed by titrations in controlled-modes (volume control, VC and pressure control, PC), under neuro-muscular blockade. Breaths from the NAVA/NPS titrations were matched (for flow and volume) to VC or PC. Throughout all runs, we measured diaphragm electrical activity (Edi) and esophageal pressure (PES). We measured ΔPL during the spontaneous modes (PL_PES) and controlled mechanical ventilation (CMV) modes (PL_CMV) with the esophageal balloon. From the LAMs, we derived an estimation of ΔPL (“PL_LAM”) using a correction factor (ratio of volume during the LAM and volume during assist) and compared it to measured ΔPL during passive (VC or PC) and spontaneous breathing (NAVA or NPS). A requirement for the LAM was similar Edi to the assisted breath.

Results
All animals successfully underwent titrations and LAMs for NPS/NAVA. One thousand seven-hundred ninety-two (1792) breaths were matched to passive ventilation titrations (matched Vt, r = 0.99). PL_LAM demonstrated strong correlation with PL_CMV (r = 0.83), and PL_PES (r = 0.77). Bland–Altman analysis revealed little difference between the predicted PL_LAM and measured PL_CMV (Bias = 0.49 cm H2O and 1.96SD = 3.09 cm H2O). For PL_PES, the bias was 2.2 cm H2O and 1.96SD was 3.4 cm H2O. Analysis of Edi and PES at peak Edi showed progressively increasing uncoupling with increasing assist.

Conclusion
During synchronized mechanical ventilation, a LAM breath allows for estimations of transpulmonary driving pressure, without measuring PES, and follows a mathematical transfer function to describe respiratory muscle unloading during synchronized assist.
Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease
Authors: Lee Seung Min , Jun Dae Won , Yoon Eileen Laurel , Oh Ju Hee , Roh Yoon Jin , Lee Eun Jeoung , Shin Ji-Hee , Nam Young-Do , Kim Hyun Sung 
Published: August 2023

AbstractThe response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bile acid metabolite profile analyses revealed that the alternative bile acid synthesis pathway (Cyp7b1 and muricholic acid) in the OCA-responder group were upregulated compared with those in the OCA-non-responder group. Intestinal microbiome analysis also revealed that the abundances of Bacteroidaceae, Parabacteroides, and Bacteroides, which were positively correlated with the alternative bile acid synthesis pathway, were higher in the OCA-responder group than in the non-responder group. Pre-study hepatic mRNA levels of Cyp8b1 (classic pathway) were downregulated in the OCA-responder group. The OCA response rate increased up to 80% in cases with a hepatic Cyp7b1/Cyp8b1 ratio ≥ 5.0. Therefore, the OCA therapeutic response can be evaluated based on the Cyp7b1/Cyp8b1 ratio or the alternative/classic bile acid synthesis pathway activity.
Safety and efficacy of camrelizumab combined with radiotherapy as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a prospective single-arm phase II clinical trial protocol
Authors: Chen Maohui , Huang Yizhou , Zhang Shuliang , Zeng Taidui , Huang Guanglei , Chen Chun , Zheng Bin 
Published: August 2023

Abstract
Background
Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 30% of patients still develop distant metastases and have a high incidence of treatment-related adverse events. Immunotherapy, as a new modality for anti-cancer treatment, has shown promising clinical benefits for patients with ESCC. The synergistic effects of immunotherapy and radiotherapy make their combination promising as neoadjuvant treatment for locally advanced ESCC.

Methods
All participants who meet the inclusion criteria will be enrolled after signing the informed consent form. Patients with thoracic segment esophageal cancer with clinical stage T2–3 N0 M0 or T2–3 N + M0 will be included. A total of 25 patients are to be recruited for the study. Twelve patients will be recruited in phase I, with at least two achieving major pathological response (MPR) before entering phase II. They will be treated with radical surgery within 4–8 weeks after the completion of two cycles of neoadjuvant radiotherapy in combination with camrelizumab according to the study schedule. The primary endpoint is the major pathological remission rate of all per-protocol patients. The secondary endpoints are the R0 resection rate, pathological complete remission rate, and adverse events. The interim analysis will be conducted after 12 patients have been enrolled. The trials will be terminated when more than two treatment-related deaths occur or fewer than five patients have major pathological remission.

Discussion
We designed this prospective single-arm phase II clinical study to evaluate the combination of camrelizumab and standard radiotherapy as preoperative neoadjuvant therapy for patients with resectable ESCC as part of the quest for better treatment options for patients with locally advanced ESCC.

Trial registration
This trial protocol has been registered on the NIH Clinical Trials database (www.clinicaltrials.gov/, NCT05176002. Registered on 2022/01/04). The posted information will be updated as needed to reflect protocol amendments and study progress.
A cysteine proteinase inhibitor ALLN alleviates bleomycin-induced skin and lung fibrosis
Authors: Kasamatsu Hiroshi , Chino Takenao , Hasegawa Takumi , Utsunomiya Natsuko , Utsunomiya Akira , Yamada Masami , Oyama Noritaka , Hasegawa Minoru 
Published: August 2023

Abstract
Background
Systemic sclerosis (SSc) is a connective tissue disease that is characterized by fibrosis in the skin and internal organs, such as the lungs. Activated differentiation of progenitor cells, which are mainly resident fibroblasts, into myofibroblasts is considered a key mechanism underlying the overproduction of extracellular matrix and the resultant tissue fibrosis in SSc. Calpains are members of the Ca2+-dependent cysteine protease family, whose enzymatic activities participate in signal transduction and tissue remodeling, potentially contributing to fibrosis in various organs. However, the roles of calpain in the pathogenesis of SSc remain unknown. This study aimed to examine the anti-fibrotic properties of N-acetyl-Leu-Leu-norleucinal (ALLN), one of the cysteine proteinase inhibitors that primarily inhibit calpain, in vitro and in vivo, to optimally translate into the therapeutic utility in human SSc.

Methods
Normal human dermal and lung fibroblasts pretreated with ALLN were stimulated with recombinant transforming growth factor beta 1 (TGF-β1), followed by assessment of TGF-β1/Smad signaling and fibrogenic molecules.

Results
ALLN treatment significantly inhibited TGF-β1-induced phosphorylation and nuclear transport of Smad2/3 in skin and lung fibroblasts. TGF-β1-dependent increases in α-smooth muscle actin (αSMA), collagen type I, fibronectin 1, and some mesenchymal transcription markers were attenuated by ALLN. Moreover, our findings suggest that ALLN inhibits TGF-β1-induced mesenchymal transition in human lung epithelial cells. Consistent with these in vitro findings, administering ALLN (3 mg/kg/day) three times a week intraperitoneally remarkably suppressed the development of skin and lung fibrosis in a SSc mouse model induced by daily subcutaneous bleomycin injection. The number of skin- and lung-infiltrating CD3+ T cells decreased in ALLN-treated mice compared with that in control-treated mice. Phosphorylation of Smad3 and/or an increase in αSMA-positive myofibroblasts was significantly inhibited by ALLN treatment on the skin and lungs. However, no adverse effects were observed.

Conclusions
Our results prove that calpains can be a novel therapeutic target for skin and lung fibrosis in SSc, considering its inhibitor ALLN.
The inactive X chromosome accumulates widespread epigenetic variability with age
Authors: Liu Yunfeng , Sinke Lucy , Jonkman Thomas H. , Slieker Roderick C. ,   BIOS Consortium, van Zwet Erik W. , Daxinger Lucia , Heijmans Bastiaan T. 
Published: August 2023

AbstractBackgroundLoss of epigenetic control is a hallmark of aging. Among the most prominent roles of epigenetic mechanisms is the inactivation of one of two copies of the X chromosome in females through DNA methylation. Hence, age-related disruption of X-chromosome inactivation (XCI) may contribute to the aging process in women.MethodsWe analyzed 9,777 CpGs on the X chromosome in whole blood samples from 2343 females and 1688 males (Illumina 450k methylation array) and replicated findings in duplicate using one whole blood and one purified monocyte data set (in total, 991/924 females/males). We used double generalized linear models to detect age-related differentially methylated CpGs (aDMCs), whose mean methylation level differs with age, and age-related variably methylated CpGs (aVMCs), whose methylation level becomes more variable with age.ResultsIn females, aDMCs were relatively uncommon (n = 33) and preferentially occurred in regions known to escape XCI. In contrast, many CpGs (n = 987) were found to display an increased variance with age (aVMCs). Of note, the replication rate of aVMCs was also high in purified monocytes (94%), indicating an independence of cell composition. aVMCs accumulated in CpG islands and regions subject to XCI suggesting that they stemmed from the inactive X. In males, carrying an active copy of the X chromosome only, aDMCs (n = 316) were primarily driven by cell composition, while aVMCs replicated well (95%) but were infrequent (n = 37).ConclusionsOur results imply that age-related DNA methylation differences at the inactive X chromosome are dominated by the accumulation of variability.