bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between NAFLD and retinol-binding protein 4 - an updated systematic review and meta-analysis
Authors: Hu Rui , Yang Xiaoyue , He Xiaoyu , Song Guangyao 
Published: January 2023

AbstractPurposeRetinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD.MethodsA meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases.ResultsIn this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11–0.46, I2: 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10–0.47, I2: 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression.ConclusionThe findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed.
Ups and downs of addiction harm reduction in Iran: key insights and implications for harm reduction policy and policing
Authors: Shafiee S. Ali , Vedadhir AbouAli , Razaghi Emran 
Published: January 2023

AbstractDrug use is a critical behavioral disorder or a delinquency behavior (in the judiciary system's words) that comes with a burden at multiple levels: individual, community, public, and global. These social structures apply different interventions to reduce this burden in their field. Given the society as a whole, these structures must be harmonious and synergistic to optimize these endeavors in terms of cost–benefit. In practice, however, reducing the burden of addiction is followed by conflicting approaches by different organizations, in terms such as “eradicating drugs,” “eliminating drug users,” “obliterating addiction,” and ultimately, drug use harm reduction. In the harm reduction philosophy, drug use is recognized as an inescapable fact in human societies, and tries to control its personal and public consequences in different dimensions (health, economic, and social). Therefore, this approach includes broad measures such as: changing the pattern of consumption (from high-risk substances to less dangerous substances) through modification of the laws and law enforcement measures, distributing disposable syringes to prevent HIV transmission, providing basic life needs such as shelter for street-based drug users to reduce the social consequences like homelessness, prescribing substitute agonists to reduce the committing crime to obtain the needed drugs, and even the drug court program, which prevents the exacerbation of complications in a person with a chronic and relapsing disorder, due to the imposition of inappropriate sentences (like incarceration in unacceptable conditions). It is contrary to the approaches that aim to reduce the drug supply rate and drug use incidence and prevalence to zero. As a result of the conflict of interests, goals discrepancies, and differences in organizational culture, these approaches may contrast with each other. We see this in the harm reduction between the health system and law enforcement. Different factors affect the harmony or conflict between these two structures. This article addresses the impact of ideology, social conditions, and bureaucratic administration on the relationship between the health system and the police in drug use harm reduction in Iran.
Myeloid CCN3 protects against aortic valve calcification
Authors: Tu Peinan , Xu Qian , Zhou Xianming , Villa-Roel Nicolas , Kumar Sandeep , Dong Nianguo , Jo Hanjoong , Ou Caiwen , Lin Zhiyong 
Published: January 2023

Abstract
Background
Cellular communication network factor 3 (CCN3) has been implicated in the regulation of osteoblast differentiation. However, it is not known if CCN3 can regulate valvular calcification. While macrophages have been shown to regulate valvular calcification, the molecular and cellular mechanisms of this process remain poorly understood. In the present study, we investigated the role of macrophage-derived CCN3 in the progression of calcific aortic valve disease.

Methods
Myeloid-specific knockout of CCN3 (Mye-CCN3-KO) and control mice were subjected to a single tail intravenous injection of AAV encoding mutant mPCSK9 (rAAV8/D377Y-mPCSK9) to induce hyperlipidemia. AAV-injected mice were then fed a high fat diet for 40 weeks. At the conclusion of high fat diet feeding, tissues were harvested and subjected to histologic and pathologic analyses. In vitro, bone marrow-derived macrophages (BMDM) were obtained from Mye-CCN3-KO and control mice and the expression of bone morphogenic protein signaling related gene were verified via quantitative real-time PCR and Western blotting. The BMDM conditioned medium was cocultured with human valvular intersititial cells which was artificially induced calcification to test the effect of the conditioned medium via Western blotting and Alizarin red staining.

Results
Echocardiography revealed that both male and female Mye-CCN3-KO mice displayed compromised aortic valvular function accompanied by exacerbated valve thickness and cardiac dysfunction. Histologically, Alizarin-Red staining revealed a marked increase in aortic valve calcification in Mye-CCN3-KO mice when compared to the controls. In vitro, CCN3 deficiency augmented BMP2 production and secretion from bone marrow-derived macrophages. In addition, human valvular interstitial cells cultured with conditioned media from CCN3-deficient BMDMs resulted in exaggerated pro-calcifying gene expression and the consequent calcification.

Conclusion
Our data uncovered a novel role of myeloid CCN3 in the regulation of aortic valve calcification. Modulation of BMP2 production and secretion in macrophages might serve as a key mechanism for macrophage-derived CCN3’s anti-calcification function in the development of CAVD.
The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer
Authors: Wang Jieyu , Zhong Fangfang , Li Jun , Yue Huiran , Li Wenzhi , Lu Xin 
Published: January 2023

Abstract
Background
The overall survival rate of patients with advanced ovarian cancer (OC) has remained static for several decades. Advanced ovarian cancer is known for its poor prognosis due to extensive metastasis. Epigenetic alterations contribute to tumour progression and therefore are of interest for potential therapeutic strategies.

Methods
Following our previous study, we identified that CHD4, a chromatin remodelling factor, plays a strong role in ovarian cancer cell metastasis. We investigated the clinical significance of CHD4 through TCGA and GEO database analyses and explored the effect of CHD4 expression modulation and romidepsin treatment on the biological behaviour of ovarian cancer through CCK-8 and transwell assays. Bioluminescence imaging of tumours in xenografted mice was applied to determine the therapeutic effect of romidepsin. GSEA and western blotting were used to screen the regulatory mechanism of CHD4.

Results
In ovarian cancer patient specimens, high CHD4 expression was associated with a poor prognosis. Loss of function of CHD4 in ovarian cancer cells induced suppression of migration and invasion. Mechanistically, CHD4 knockdown suppressed the expression of EZH2 and the nuclear accumulation of β-catenin. CHD4 also suppressed the metastasis of ovarian cancer cells and prevented disease progression in a mouse model. To inhibit the functions of CHD4 that are mediated by histone deacetylase, we evaluated the effect of the HDAC1/2 selective inhibitor romidepsin. Our findings indicated that treatment with romidepsin suppressed the progression of metastases in vitro and in vivo.

Conclusions
Collectively, our results uncovered an oncogenic function of CHD4 in ovarian cancer and provide a rationale for clinical trials of romidepsin in ovarian cancer patients.
Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging
Authors: Wan Wei , Zhang Lieliang , Lin Yue , Rao Xiuqing , Wang Xifeng , Hua Fuzhou , Ying Jun 
Published: January 2023

AbstractMOTS-c is a peptide encoded by the short open reading frame of the mitochondrial 12S rRNA gene. It is significantly expressed in response to stress or exercise and translocated to the nucleus, where it regulates the expression of stress adaptation-related genes with antioxidant response elements (ARE). MOTS-c mainly acts through the Folate-AICAR-AMPK pathway, thereby influencing energy metabolism, insulin resistance, inflammatory response, exercise, aging and aging-related pathologies. Because of the potential role of MOTS-c in maintaining energy and stress homeostasis to promote healthy aging, especially in view of the increasing aging of the global population, it is highly pertinent to summarize the relevant studies. This review summarizes the retrograde signaling of MOTS-c toward the nucleus, the regulation of energy metabolism, stress homeostasis, and aging-related pathological processes, as well as the underlying molecular mechanisms.
An iceberg I can’t handle: a qualitative inquiry on perceptions towards paediatric rheumatology among healthcare workers in Kenya
Authors: Migowa Angela , Bernatsky Sasha , Ngugi Anthony , Foster Helen E. , Muriuki Peter , Lusambili Adelaide , Luchters Stanley 
Published: January 2023

Abstract
Background
Delay in diagnosis and access to specialist care is a major problem for many children and young people with rheumatic disease in sub-Saharan Africa. Most children with symptoms of rheumatic disease present to non-specialists for care. There is an urgent need to understand and scale-up paediatric rheumatology knowledge and skills amongst non-specialist healthcare workers to promote early diagnosis, prompt referral, and management.

Purpose
We evaluated the knowledge, attitudes and practices towards diagnosis and care of paediatric rheumatology patients among health care workers in Kenya.

Methods
We conducted 12 focus group discussions with clinical officers (third-tier community health workers) nurses, general practitioners and paediatricians across 6 regions in Kenya. Interviews were conducted on zoom, audio-recorded, transcribed, and analysed using NVIVO software.

Results
A total of 68 individuals participated; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and 7 others. Most (n = 53) were female, and the median age was 36 years (range 31–40 years). Fifty per cent of the participants (34 of 68) worked in public health facilities. Our study revealed gaps in knowledge of paediatric rheumatology amongst healthcare workers which contributes to delayed diagnosis and poor management. Healthcare workers reported both positive and negative attitudes towards diagnosis and care of paediatric rheumatology patients. Perceived complexity and lack of knowledge in diagnosis, management and lack of health system clinical pathways made all cadres of healthcare workers feel helpless, frustrated, inadequate and incompetent to manage paediatric rheumatology patients. Positive attitudes arose from a perceived feeling that paediatric rheumatology patients pose unique challenges and learning opportunities.

Conclusion
There is an urgent need to educate healthcare workers and improve health systems to optimize clinical care for paediatric rheumatology patients.
Abcc8 (sulfonylurea receptor-1) knockout mice exhibit reduced axonal injury, cytotoxic edema and cognitive dysfunction vs. wild-type in a cecal ligation and puncture model of sepsis
Authors: Cummings Jessica , Wu Yijen L. , Dixon C. Edward , Henchir Jeremy , Simard J. Marc , Panigrahy Ashok , Kochanek Patrick M. , Jha Ruchira M. , Aneja Rajesh K. 
Published: January 2023

AbstractSepsis-associated brain injury (SABI) is characterized by an acute deterioration of mental status resulting in cognitive impairment and acquisition of new and persistent functional limitations in sepsis survivors. Previously, we reported that septic mice had evidence of axonal injury, robust microglial activation, and cytotoxic edema in the cerebral cortex, thalamus, and hippocampus in the absence of blood–brain barrier disruption. A key conceptual advance in the field was identification of sulfonylurea receptor 1 (SUR1), a member of the adenosine triphosphate (ATP)-binding cassette protein superfamily, that associates with the transient receptor potential melastatin 4 (TRPM4) cation channel to play a crucial role in cerebral edema development. Therefore, we hypothesized that knockout (KO) ofAbcc8(Sur1 gene) is associated with a decrease in microglial activation, cerebral edema, and improved neurobehavioral outcomes in a murine cecal ligation and puncture (CLP) model of sepsis. Sepsis was induced in 4–6-week-oldAbcc8KO and wild-type (WT) littermate control male mice by CLP. We used immunohistochemistry to define neuropathology and microglial activation along with parallel studies using magnetic resonance imaging, focusing on cerebral edema on days 1 and 4 after CLP.Abcc8KO mice exhibited a decrease in axonal injury and cytotoxic edema vs. WT on day 1.Abcc8KO mice also had decreased microglial activation in the cerebral cortex vs. WT. These findings were associated with improved spatial memory on days 7–8 after CLP. Our study challenges a key concept in sepsis and suggests that brain injury may not occur merely as an extension of systemic inflammation. We advance the field further and demonstrate that deletion of the SUR1 gene ameliorates CNS pathobiology in sepsis including edema, axonal injury, neuroinflammation, and behavioral deficits. Benefits conferred byAbcc8KO in the murine CLP model warrant studies of pharmacologicalAbcc8inhibition as a new potential therapeutic strategy for SABI.
Cost-effectiveness analysis of overground robotic training versus conventional locomotor training in people with spinal cord injury
Authors: Pinto Daniel , Heinemann Allen W. , Chang Shuo-Hsiu , Charlifue Susan , Field-Fote Edelle C. , Furbish Catherine L. , Jayaraman Arun , Tefertiller Candace , Taylor Heather B. , French Dustin D. 
Published: January 2023

AbstractBackgroundFew, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort.MethodsA probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight support, overground training, and stationary robotic systems. The outcome measures included the calculation of quality adjusted life years (QALYs) using the EQ-5D and therapy costs. We estimate cost-effectiveness using the incremental cost utility ratio and present results on the cost-effectiveness plane and on cost-effectiveness acceptability curves.ResultsParticipants in the prospective, practice-based cohort with complete EQ-5D data (n = 99) qualified for the analysis. Both conventional training and overground robotic training experienced an improvement in QALYs. Only people with incomplete SCI improved with conventional locomotor training, 0.045 (SD 0.28), and only people with complete SCI improved with overground robotic training, 0.097 (SD 0.20). Costs were lower for conventional training, $1758 (SD $1697) versus overground robotic training $3952 (SD $3989), and lower for those with incomplete versus complete injury. Conventional overground training was more effective and cost less than robotic therapy for people with incomplete SCI. Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost utility ratio for overground robotic training for people with complete spinal cord injury was $12,353/QALY.ConclusionsThe most cost-effective locomotor training strategy for people with SCI differed based on injury completeness. Conventional training was more cost-effective than overground robotic training for people with incomplete SCI. Overground robotic training was more cost-effective than conventional training for people with complete SCI. The effect estimates may be subject to limitations associated with small sample sizes and practice-based evidence methodology. These estimates provide a baseline for future research.
Differential proteomic profile of lumbar and ventricular cerebrospinal fluid
Authors: Rostgaard Nina , Olsen Markus Harboe , Ottenheijm Maud , Drici Lylia , Simonsen Anja Hviid , Plomgaard Peter , Gredal Hanne , Poulsen Helle Harding , Zetterberg Henrik , Blennow Kaj , Hasselbalch Steen Gregers , MacAulay Nanna , Juhler Marianne 
Published: January 2023

AbstractBackgroundPathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue.MethodsCSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-β (Aβ40, Aβ42), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullary cistern closely related to the ventricles.ResultsIn total 1231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer’s disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, Aβ40, Aβ42) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF.ConclusionsThe overall proteomic profile differs between the ventricular and the lumbar CSF compartments, and so does the distribution of clinically employed biomarkers. However, for a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF if or a lumbar/cranial index for the particular molecule has been established. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.
Qualitative description of outreach and engagement in perinatal substance treatment in Finland
Authors: Sorsa Minna , Hohenthal Maria , Pikulinsky Miia , Sellergren Hanna , Puura Kaija 
Published: January 2023

Abstract
Background
Women with perinatal substance problems experience a multitude of barriers to care. They have specific early intervention needs, they endure societal stigma, and both substances and mental health issues influence the way they navigate within support and treatment systems. Early interventions for women with perinatal substance problems are underresearched contexts. The aim of the study is to describe building relationships and engagement within an outreach and low threshold service encounter tailored for pregnant women with SUD (substance use disorder).

Methods
The data consist of online written narratives from 11 workers involved in the program and feedback from 504 families in the recovery process comprising 228 open-ended answers. The data were analyzed with a thematic analysis.

Results
The programs are characterized by flexibility and the implementation of inclusive ways to approach families. The themes for enhancing relationships and engagement within outreach and low threshold programs are Acceptance and attitude: a sensitive approach of approval; flexibility within strictness to allow for diversity and individuality; availability and space to ensure a trustful atmosphere; negotiating via doing to build connections; and everyday life changes: imagining recovery. The themes represent the need of being available, focusing on the worker’s attitudes and building connections by doing together, and visioning recovery together.

Conclusions
The study results can add to the understanding of SUD outreach and low threshold work during pregnancy. The elements described in this study need further theoretical development, research and critical assessment. Building relationships during pregnancy were characterized by connecting within everyday life situations and supporting the development of an attachment relationship between the baby and the parents. To promote recovery, a comprehensive approach in which substance-related issues and mental health conditions are interconnected can be favored. Engaging early on during pregnancy might enhance success during future rehabilitation.