bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reprogramming mitochondrial metabolism of macrophages by miRNA-released microporous coatings to prevent peri-implantitis
Authors: Zhang Hongming , Yuan Yun , Xue Hanxiao , Yu Runping , Jin Xiayue , Wu Xiaolin , Huang Hui 
Published: December 2023

AbstractAlthough various new biomaterials have enriched the methods for peri-implant inflammation treatment, their efficacy is still debated, and secondary operations on the implant area have also caused pain for patients. Recently, strategies that regulate macrophage polarization to prevent or even treat peri-implantitis have attracted increasing attention. Here, we prepared a laser-drilled and covered with metal organic framework-miR-27a agomir nanomembrane (L-MOF-agomir) implant, which could load and sustain the release of miR-27a agomir. In vitro, the L-MOF-agomir titanium plate promoted the repolarization of LPS-stimulated macrophages from M1 to M2, and the macrophage culture supernatant promoted BMSCs osteogenesis. In a ligation-induced rat peri-implantitis model, the L-MOF-agomir implants featured strong immunomodulatory activity of macrophage polarization and alleviated ligation-induced bone resorption. The mechanism of repolarization function may be that the L-MOF-agomir implants promote the macrophage mitochondrial function and metabolism reprogramming from glycolysis to oxidative phosphorylation. Our study demonstrates the feasibility of targeting cell metabolism to regulate macrophage immunity for peri-implantitis inhibition and provides a new perspective for the development of novel multifunctional implants.
Graphical Abstract
How the COVID-19 pandemic and related school closures reduce physical activity among children and adolescents in the WHO European Region: a systematic review and meta-analysis
Authors: Ludwig-Walz Helena , Siemens Waldemar , Heinisch Sarah , Dannheim Indra , Loss Julika , Bujard Martin 
Published: December 2023

Abstract
Background
Emerging research suggests that physical activity among children and adolescents decreased during the COVID-19 pandemic. However, a differentiated overview of European youth is lacking. In particular, no systematic analysis has been conducted to date on the impact of heterogeneous pandemic restrictions and school closures within European countries, and with regard to potentially vulnerable groups.

Methods
We searched seven databases and included studies for children and adolescents (≤ 19 years) of the WHO European Region that compared physical activity during the COVID-19 pandemic with a pre-pandemic baseline using validated measurement instruments. We used the Oxford Stringency Index and School Closure Index as indicators of restriction stringency. Screening for eligibility, data extraction, assessment of the study risk of bias (using the ‘Risk of Bias in Non-randomized Studies - of Exposure’ [ROBINS-E]) and certainty grading of evidence (using the GRADE approach), were all done in duplicate. Unpublished data was requested from study authors. Data were pooled in random effects models. An a priori protocol was published, reporting is carried out in accordance with the ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ (PRISMA) statement.

Results
Of 14,897 non-duplicate records, 26 publications (n = 15,038 pre-pandemic, n = 13,041 during pandemic) met full inclusion criteria. Comparison before and during the COVID-19 pandemic revealed a significant reduction in total physical activity (standardized mean difference [SMD], -0.57 [95%CI, -0.95; -0.20]) and moderate-to-vigorous physical activity (SMD, -0.43 [95% CI, -0.75; -0.10]), corresponding to a decrease of 12 min per day (a 20% reduction of the WHO recommendation). A decrease in sporting activity was also recorded. Subgroup analyses suggested that middle childhood (aged 8–12) and adolescents were particularly affected by the decline. School closures were associated with a reduction in physical activity. The certainty of evidence for all outcomes was low.

Conclusions
A sharp decline in all forms of physical activity was recorded among European children and adolescents during the COVID-19 pandemic. This decline was higher during periods of school closure and mainly affected younger schoolchildren and adolescents. Immediate action by policy-makers and practitioners, as well as evidence-based public health strategies, are imperative in reversing this trend.

Trial registration
PROSPERO: CRD42023395871
Phenylpropanoid-enriched broccoli seedling extract can reduce inflammatory markers and pain behavior
Authors: Gurgul Aleksandra A. , Najjar Yahya , Chee Ana , An Howard , Che Chun-Tao , Park Thomas J. , Warpeha Katherine M. 
Published: December 2023

Abstract
Background
Pain is a worldwide problem requiring an effective, affordable, non-addictive therapy. Using the edible plant broccoli, a growth protocol was developed to induce a concentrated combinatorial of potential anti-inflammatories in seedlings.

Methods
A growth method was utilized to produce a phenylpropanoid-rich broccoli sprout extract, referred to as Original Extract (OE). OE was concentrated and then resuspended for study of the effects on inflammation events. A rabbit disc model of inflammation and degeneration, and, a mouse model of pain behavior were used for in vivo and in vitro tests. To address aspects of mammalian metabolic processing, the OE was treated with the S9 liver microsome fraction derived from mouse, for use in a mouse in vivo study. Analytical chemistry was performed to identify major chemical species. Continuous variables were analyzed with a number of methods including ANOVA, and two-tailed t tests, as appropriate.

Results
In a rabbit spine (disc) injury model, inflammatory markers were reduced, and levels of regenerative markers were increased as a result of OE treatment, both in vivo and in vitro. In a mouse pain behavioral model, after treatment with S9 liver microsome fraction, the resultant extract significantly reduced early and late pain behavior in response to a pain stimulus. The OE itself reduced pain behavior in the mouse pain model, but did not achieve the level of significance observed for S9-treated extract. Analytical chemistry undertaken on the extract constituents revealed identities of the chemical species in OE, and how S9 liver microsome fraction treatment altered species identities and proportions.

Conclusions
In vitro and in vivo results indicate that the OE, and S9-treated OE broccoli extracts are worthwhile materials to develop a non-opiate inflammation and pain-reducing treatment.
Central activation of the fatty acid sensor GPR120 suppresses microglia reactivity and alleviates sickness- and anxiety-like behaviors
Authors: Nakajima Shingo , Demers Geneviève , Machuca-Parra Arturo Israel , Pour Zahra Dashtehei , Bairamian Diane , Bouyakdan Khalil , Fisette Alexandre , Kabahizi Anita , Robb Josephine , Rodaros Demetra , Laurent Cyril , Ferreira Guillaume , Arbour Nathalie , Alquier Thierry , Fulton Stephanie 
Published: December 2023

AbstractG protein-coupled receptor 120 (GPR120, Ffar4) is a sensor for long-chain fatty acids including omega-3 polyunsaturated fatty acids (n-3 PUFAs) known for beneficial effects on inflammation, metabolism, and mood. GPR120 mediates the anti-inflammatory and insulin-sensitizing effects of n-3 PUFAs in peripheral tissues. The aim of this study was to determine the impact of GPR120 stimulation on microglial reactivity, neuroinflammation and sickness- and anxiety-like behaviors by acute proinflammatory insults. We found GPR120 mRNA to be enriched in both murine and human microglia, and in situ hybridization revealed GPR120 expression in microglia of the nucleus accumbens (NAc) in mice. In a manner similar to or exceeding n-3 PUFAs, GPR120 agonism (Compound A, CpdA) strongly attenuated lipopolysaccharide (LPS)-induced proinflammatory marker expression in primary mouse microglia, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and inhibited nuclear factor-ĸB translocation to the nucleus. Central administration of CpdA to adult mice blunted LPS-induced hypolocomotion and anxiety-like behavior and reduced TNF-α, IL-1β and IBA-1 (microglia marker) mRNA in the NAc, a brain region modulating anxiety and motivation and implicated in neuroinflammation-induced mood deficits. GPR120 agonist pre-treatment attenuated NAc microglia reactivity and alleviated sickness-like behaviors elicited by central injection TNF-α and IL-1β. These findings suggest that microglial GPR120 contributes to neuroimmune regulation and behavioral changes in response to acute infection and elevated brain cytokines. GPR120 may participate in the protective action of n-3 PUFAs at the neural and behavioral level and offers potential as treatment target for neuroinflammatory conditions.
TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria
Authors: Dvorak Nolan M. , Domingo Nadia D. , Tapia Cynthia M. , Wadsworth Paul A. , Marosi Mate , Avchalumov Yosef , Fongsaran Chanida , Koff Leandra , Di Re Jessica , Sampson Catherine M. , Baumgartner Timothy J. , Wang Pingyuan , Villarreal Paula P. , Solomon Olivia D. , Stutz Sonja J. , Aditi  , Porter Jacob , Gbedande Komi , Prideaux Brendan , Green Thomas A. , Seeley Erin H. , Samir Parimal , Dineley Kelley T. , Vargas Gracie , Zhou Jia , Cisneros Irma , Stephens Robin , Laezza Fernanda 
Published: December 2023

Abstract
Background
Excess tumor necrosis factor (TNF) is implicated in the pathogenesis of hyperinflammatory experimental cerebral malaria (eCM), including gliosis, increased levels of fibrin(ogen) in the brain, behavioral changes, and mortality. However, the role of TNF in eCM within the brain parenchyma, particularly directly on neurons, remains underdefined. Here, we investigate electrophysiological consequences of eCM on neuronal excitability and cell signaling mechanisms that contribute to observed phenotypes.

Methods
The split-luciferase complementation assay (LCA) was used to investigate cell signaling mechanisms downstream of tumor necrosis factor receptor 1 (TNFR1) that could contribute to changes in neuronal excitability in eCM. Whole-cell patch-clamp electrophysiology was performed in brain slices from eCM mice to elucidate consequences of infection on CA1 pyramidal neuron excitability and cell signaling mechanisms that contribute to observed phenotypes. Involvement of identified signaling molecules in mediating behavioral changes and sickness behavior observed in eCM were investigated in vivo using genetic silencing.

Results
Exploring signaling mechanisms that underlie TNF-induced effects on neuronal excitability, we found that the complex assembly of fibroblast growth factor 14 (FGF14) and the voltage-gated Na+ (Nav) channel 1.6 (Nav1.6) is increased upon tumor necrosis factor receptor 1 (TNFR1) stimulation via Janus Kinase 2 (JAK2). On account of the dependency of hyperinflammatory experimental cerebral malaria (eCM) on TNF, we performed patch-clamp studies in slices from eCM mice and showed that Plasmodium chabaudi infection augments Nav1.6 channel conductance of CA1 pyramidal neurons through the TNFR1–JAK2–FGF14–Nav1.6 signaling network, which leads to hyperexcitability. Hyperexcitability of CA1 pyramidal neurons caused by infection was mitigated via an anti-TNF antibody and genetic silencing of FGF14 in CA1. Furthermore, knockdown of FGF14 in CA1 reduced sickness behavior caused by infection.

Conclusions
FGF14 may represent a therapeutic target for mitigating consequences of TNF-mediated neuroinflammation.
Effects of hormonal contraceptives on lipid profile among women attending family planning unit in Goba Town Public Health Facilities, Bale, Southeast Ethiopia: a comparative cross-sectional study
Authors: Turki Awel , Ayalew Almaz , Mossie Andualem , Mitiku Shimelis 
Published: December 2023

Abstract
Background
Hormonal contraceptives are a widely used contraceptive method for the prevention of pregnancy in women. It is associated with change in lipid profile which results in congestive heart failure, coronary heart disease, angina, deep vein thrombosis and stroke which are the major cause of premature death. We aim to investigate the effects of hormonal contraceptive use on lipid profile among women attending family planning unit in Goba Town Public Health Facilities.

Methods
A comparative cross-sectional study design was conducted on 93 hormonal contraceptive users and 93 non-users’ women in Goba Town Public Health Facilities from September to November, 2022. Blood samples for the estimation of TC, TG, HDL-c and LDL-c levels were collected. Student's independent t-test was used to compare the results of lipid profiles. One-way ANOVA was used to identify the variation of lipid profile between progestin only pills, DMPA and implant users. Simple linear regression was used to determine the change in lipid profiles in relation to the duration of hormonal contraceptive use. P-value less than 0.05 was considered as statistically significant.

Result
The mean serum level of TC, TG and LDL-c was significantly increases in hormonal contraceptive users in comparison with non-users. The mean serum level TC, TG, LDL-c and HDL-c was significantly different between DMPA, implanon and POP users. The mean serum level of TC, TG and LDL-c in implanon users was lower than DMPA and POP users. As the duration of DMPA and POP use increases, the serum level of TC, TG and LDL-c were significantly increased. But, the serum level of HDL-c was significantly decreased. LDL-c was significantly increased with the duration of implanon use.

Conclusion
The mean serum level of TC, TG and LDL-c were significantly increased among hormonal contraceptive users. The mean serum level of lipid profile was significantly different between DMPA, implanon and POP users. The serum level of TC, TG, LDL-c were directly proportional to the duration of DMPA and POP use. Routine evaluation of lipid profiles is advisable before and after initiation of hormonal contraceptives.
Biomechanical comparison of different fixation methods in tibiotalocalcaneal arthrodesis: a cadaver study
Authors: Trost Matthias , Yarkin Suzan , Knieps Matthias , Frey Sönke , Neiss Wolfram Friedrich , Eysel Peer , Gick Sascha , Dargel Jens 
Published: December 2023

Abstract
Background
Various fixation methods are available for tibiotalocalcaneal arthrodesis: nail, plate, or screws. An intramedullary bone stabilization system within a balloon catheter has not previously been used in tibiotalocalcaneal arthrodesis. The aim of this study was to compare the stability of these techniques.

Methods
Twenty-four lower legs from fresh-frozen human cadavers were used. Tibiotalocalcaneal arthrodesis was performed with a retrograde nail, a lateral locking plate, three cancellous screws, or an intramedullary bone stabilization system. The ankles were loaded cyclically in plantarflexion and dorsiflexion.

Results
For cyclic loading at 125 N, the mean range of motion was 1.7 mm for nail, 2.2 mm for plate, 6.0 mm for screws, and 9.0 mm for the bone stabilization system (P < .01). For cyclic loading at 250 N, the mean range of motion was 4.4 mm for nail, 7.5 mm for plate, 12.1 mm for screws, and 14.6 mm for the bone stabilization system (P < .01). The mean cycle of failure was 4191 for nail, 3553 for plate, 3725 for screws, and 2132 for the bone stabilization system (P = .10).

Conclusions
The stability of the tibiotalocalcaneal arthrodesis differs depending on the fixation method, with nail or plate showing the greatest stability and the bone stabilization system the least. When three screws are used for tibiotalocalcaneal arthrodesis, the stability is intermediate. As the biomechanical stability of the bone stabilization system is low, it cannot be recommended for tibiotalocalcaneal arthrodesis.
Efficacy and safety of voriconazole in the treatment of invasive pulmonary aspergillosis in patients with liver failure: study protocol for a randomized controlled clinical trial
Authors: Yu Xue , Xu Lejia , Zheng Jiaxing , Lei Ziying , Pang Yihua , Li Xiaojie , Zhu Jianyun , Liu Jing 
Published: December 2023

Abstract
Background
Acute-on-chronic liver failure (ACLF) is a common clinical type of liver failure, and patients with acute-on-chronic liver failure are prone to fungal infections, especially the increasing incidence of invasive pulmonary aspergillosis (IPA). Voriconazole is recommended as the first-line antifungal agent in the treatment of invasive aspergillosis; however, no recommendation has been given for patients with severe liver cirrhosis (Child–Pugh C) and liver failure. This trial aims to examine the therapeutic effects and safety of voriconazole in the treatment of IPA in patients with liver failure.

Methods
This study is a non-double-blind randomized controlled trial. The 96 eligible acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis will be randomly assigned to receive either the optimized voriconazole regimen or the recommended voriconazole regimen for patients with mild to moderate liver cirrhosis (Child–Pugh A and B), at a 1:1 ratio, with an 8-week follow-up period. The antifungal efficacy of voriconazole will be the primary outcome measure. Plasma voriconazole trough concentration, the laboratory examination (CRP, PCT, ESR, etc.), chest CT, adverse events, and mortality at week 4 and 8 will be the secondary outcome measures.

Discussion
This trial aims to demonstrate the efficacy and safety of voriconazole in the treatment of IPA in patients with liver failure, which is expected to provide a reference for scientific optimization of voriconazole regimens and a realistic basis for the standardized treatment of acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis.

Trial registration
The trial was registered with the Chinese Clinical Trial Registry, ChiCTR2100048259. Registered on 5 July 2021.
Association between non-high-density lipoprotein to high-density lipoprotein ratio and reversion to normoglycemia in people with impaired fasting glucose: a 5-year retrospective cohort study
Authors: Mo Zihe , Han Yong , Cao Changchun , Huang Qingli , Hu Yanhua , Yu Zhiqun , Hu Haofei 
Published: December 2023

Abstract
Objective
The relationship between the non-high-density lipoprotein to high-density lipoprotein ratio (non-HDL-c/HDL-c ratio) and changes in glycemic status as well as the development of type 2 diabetes mellitus (T2DM) has been well established. However, there is a lack of evidence concerning the association between the non-HDL-c/HDL-c ratio and the reversal of normoglycemia in individuals with impaired fasting glucose (IFG). Therefore, this study aimed to examine the connection between the non-HDL-c/HDL-c ratio and the likelihood of reverting to normoglycemia among people with IFG.

Methods
This retrospective cohort study examined data collected from 15,524 non-selective participants with IFG at the Rich Healthcare Group in China between January 2010 and 2016. The Cox proportional-hazards regression model was used to investigate the connection between the baseline non-HDL-c/HDL-c ratio and the probability of reverting to normoglycemia. We were able to discover the non-linear association between the non-HDL-c/HDL-c ratio and reversion to normoglycemia using a Cox proportional hazards regression model with cubical spline smoothing. We also performed several sensitivity and subgroup analyses. A competing risk multivariate Cox regression was utilized as well to examine the development to diabetes as a competing risk for the reversal of normoglycemic events.

Results
In our study, a total of 15,524 individuals participated, with a mean age of 50.9 ± 13.5 years, and 64.7% were male. The average baseline non-HDL-c/HDL-c ratio was 2.9 ± 0.9. Over a median follow-up period of 2.9 years, we observed a reversion rate to normoglycemia of 41.8%. After adjusting for covariates, our findings revealed a negative association between the non-HDL-c/HDL-c ratio and the likelihood of reverting to normoglycemia (HR = 0.71, 95% CI 0.69–0.74). Notably, we identified a non-linear relationship between the non-HDL-c/HDL-c ratio and the probability of transitioning from IFG to normoglycemia. We found an inflection point at a non-HDL-c/HDL-c ratio of 3.1, with HRs of 0.63 (95% CI 0.69, 0.74) on the left side and 0.78 (95% CI 0.74, 0.83) on the right side of the point. Competing risks multivariate Cox's regression, sensitivity analysis, and subgroup analysis consistently supported our robust results.

Conclusion
Our study has revealed a negative and non-linear relationship between the non-HDL-c/HDL-c ratio and reversion to normoglycemia in Chinese people with IFG. Specifically, when the non-HDL-c/HDL-c ratio was below 3.1, a significant and negative association with reversion to normoglycemia was observed. Furthermore, keeping the non-HDL-c/HDL-c ratio below 3.1 significantly elevated the probability of returning to normoglycemia.
Associations between HT, BMI, and allergic rhinitis in perimenopausal women
Authors: Liu Jingyi , Ma Tingting , Wang Xiaoxue , Bai Wenpei , Wang Xueyan 
Published: December 2023

Abstract
Background
Increasing evidence suggests that hormone therapy (HT) and obesity exert an influence on allergic rhinitis (AR). It is important to investigate the association and interactions between HT, BMI, and AR in perimenopausal women.

Methods
From May 2020 to March 2021, a cross-sectional survey was completed by patients who visited the Allergy Department and Gynecology Department of Shijitan Hospital. The patients completed a questionnaire and stratified analyses by BMI in tertiles were performed. Logistic analyses were performed to evaluate the relationships between HT, BMI, and AR.

Results
A total of 950 patients completed the study, among which, 393 patients were receiving HT. HT was found to be associated with increased risks for AR (OR = 1.51 [95% CI: 1.151–1.985]), asthma (OR = 3.61 [95% CI: 2.21–5.89]), and their accompanying symptoms (OR = 3.54 [95% CI: 2.146–5.831]). In lean women, the use of HT was significantly associated with a higher risks for AR (OR = 2.26 [95% CI: 1.31–3.91]), the time course of AR (OR = 2.54 [95% CI: 1.37–4.74]), hay fever (OR = 2.54 [95% CI: 1.37–4.74]), and accompanying symptoms (including canker sores, diarrhea, and stomachache) (OR = 2.26 [95% CI: 1.309–3.907]) when compared to normal or heavier weight women (course of AR: pinteraction = 0.032; hay fever; pinteraction = 0.006; accompanying symptoms: pinteraction = 0.009).

Conclusions
HT can reduce the risk for AR in perimenopausal women. Lean women who used HT were at a higher risk for AR when compared to overweight women who used AR. There exists an interaction between HT and BMI that influences AR. Furthermore, HT and obesity increase the risk for AR by some common pathways, more follow-up work is needed to explore common pathways.