bluuebunny/crossref_metadata_2025_split huggingface dataset:
FXR-mediated inhibition of autophagy contributes to FA-induced TG accumulation and accordingly reduces FA-induced lipotoxicity
Authors: Wu Kun , Zhao Tao , Hogstrand Christer , Xu Yi-Chuang , Ling Shi-Cheng , Chen Guang-Hui , Luo Zhi 
Published: March 2020

Abstract
Background
Excessive dietary fat intake induces lipid deposition and contributes to the progress of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are still unclear.

Methods
Yellow catfish were given two experimental diets with dietary lipid levels of 11.3 and 15.4%, respectively, for 56 days, and the contents of triglyceride (TG), nonesterified free fatty acids (NEFA) and bile acid (BA), RNA-seq, enzymatic activities and mRNA expression were deteremined in the liver tissues. Hepatocytes from yellow catfish liver tissues were isolated and cultured. Fatty acids (FA) (palmitic acid: OA, oleic acid =1:1), pathway inhibitors (MA, autophagy inhibitor; guggulsterone, FXR inhibitor) and agonist (rapamyicn, autophagy agonist; GW4064, FXR agonist) were used to incubate the cells. TG and NEFA contents, ultrastructural observation, autophagic vesicles and intracellular LD,apoptosis,western blot and Co-IP, and Immunofluorescence analysis, enzymatic activities and Q-PCR were decided.

Results
Using RNA sequencing, we found that high fat diets induced changes in expression of many genes associated with the pathways of lipid metabolism and autophagy. The mRNA profiles of the differentially expressed genes (DEG) indicated that high dietary fat-induced lipid deposition was predominantly influenced by the inhibition of autophagy. Using primary hepatocytes, we found that fatty acids (FA) suppressed autophagy, which in turn reduced cellular free FA level by decreasing triglyceride (TG) breakdown. Moreover, our study indicated that farnesoid X receptor (FXR)-cyclic AMP-responsive element-binding protein (CREB) axis was the pivotal physiological switch regulating FA-induced changes of autophagy and lipid metabolism, which represented cellular defenses against FA-induced lipotoxicity.

Conclusion
This discovery may provide new targets for treating pathological changes involved in the dysfunction of autophagy and metabolism, including NAFLD.

Graphical abstract
Advanced oxidation protein products induce microglia-mediated neuroinflammation via MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury
Authors: Liu Zhongyuan , Yao Xinqiang , Jiang Wangsheng , Li Wei , Zhu Siyuan , Liao Congrui , Zou Lin , Ding Ruoting , Chen Jianting 
Published: March 2020

Abstract
Background
Inflammatory response mediated by oxidative stress is considered as an important pathogenesis of spinal cord injury (SCI). Advanced oxidation protein products (AOPPs) are novel markers of oxidative stress and their role in inflammatory response after SCI remained unclear. This study aimed to investigate the role of AOPPs in SCI pathogenesis and explore the possible underlying mechanisms.

Methods
A C5 hemi-contusion injury was induced in Sprague-Dawley rats to confirm the involvement of AOPPs after SCI. For in vivo study, apocynin, the NADPH oxidase inhibitor was used to study the neuroprotective effects after SCI. For in vitro study, the BV2 microglia cell lines were pretreated with or without the inhibitor or transfected with or without small interference RNA (siRNA) and then stimulated with AOPPs. A combination of molecular and histological methods was used to clarify the mechanism and explore the signaling pathway both in vivo and in vitro. One-way analysis of variance (ANOVA) was conducted with Bonferroni post hoc tests to examine the differences between groups.

Results
The levels of AOPPs in plasma and cerebrospinal fluid as well as the contents in the spinal cord showed significant increase after SCI. Meanwhile, apocynin ameliorated tissue damage in the spinal cord after SCI, improving the functional recovery. Immunofluorescence staining and western blot analysis showed activation of microglia after SCI, which was in turn inhibited by apocynin. Pretreated BV2 cells with AOPPs triggered excessive generation of reactive oxygen species (ROS) by activating NADPH oxidase. Increased ROS induced p38 MAPK and JNK phosphorylation, subsequently triggering nuclear translocation of NF-κB p65 to express pro-inflammatory cytokines. Also, treatment of BV2 cells with AOPPs induced NLRP3 inflammasome activation and cleavage of Gasdermin-d (GSDMD), causing pyroptosis. This was confirmed by cleavage of caspase-1, production of downstream mature interleukin (IL)-1β and IL-18 as well as rupture of rapid cell membrane.

Conclusions
Collectively, these data indicated AOPPs as biomarkers of oxidative stress, modulating inflammatory response in SCI by multiple signaling pathways, which also included the induction of NADPH oxidase dependent ROS, and NLRP3-mediated pyroptosis, and activation of MAPKs and NF-κB.
Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure
Authors: Abbink Maralinde R. , Kotah Janssen M. , Hoeijmakers Lianne , Mak Aline , Yvon-Durocher Genevieve , van der Gaag Bram , Lucassen Paul J. , Korosi Aniko 
Published: March 2020

AbstractBackgroundEarly-life stress (ES) is an emerging risk factor for later life development of Alzheimer’s disease (AD). We have previously shown that ES modulates amyloid-beta pathology and the microglial response to it in the APPswe/PS1dE9 mouse model. Because astrocytes are key players in the pathogenesis of AD, we studied here if and how ES affects astrocytes in wildtype (WT) and APP/PS1 mice and how these relate to the previously reported amyloid pathology and microglial profile.MethodsWe induced ES by limiting nesting and bedding material from postnatal days (P) 2–9. We studied in WT mice (at P9, P30, and 6 months) and in APP/PS1 mice (at 4 and 10 months) (i) GFAP coverage, cell density, and complexity in hippocampus (HPC) and entorhinal cortex (EC); (ii) hippocampal gene expression of astrocyte markers; and (iii) the relationship between astrocyte, microglia, and amyloid markers.ResultsIn WT mice, ES increased GFAP coverage in HPC subregions at P9 and decreased it at 10 months. APP/PS1 mice at 10 months exhibited both individual cell as well as clustered GFAP signals. APP/PS1 mice when compared to WT exhibited reduced total GFAP coverage in HPC, which is increased in the EC, while coverage of the clustered GFAP signal in the HPC was increased and accompanied by increased expression of several astrocytic genes. While measured astrocytic parameters in APP/PS1 mice appear not be further modulated by ES, analyzing these in the context of ES-induced alterations to amyloid pathology and microglial shows alterations at both 4 and 10 months of age.ConclusionsOur data suggest that ES leads to alterations to the astrocytic response to amyloid-β pathology.
Treating AO/OTA 44B lateral malleolar fracture in patients over 50 years of age: periarticular locking plate versus non-locking plate
Authors: Shih Chien-An , Jou I-Ming , Lee Pei-Yuan , Lu Chin-Li , Su Wei-Ren , Yeh Ming-Long , Wu Po-Ting 
Published: March 2020

Abstract
Background
The role of locking plate in lateral malleolar fracture fixation for the elderly remains unclear. The aim of our study is to compare radiological and functional outcomes in older patients (> 50 years) with AO/OTA 44B lateral malleolar fractures after locking plate (PLP) or one-third non-locking tubular plate (TP) lateral fixation.

Methods
We retrospectively reviewed the medical records of 72 patients (PLP group, 34 patients; TP group, 38 patients; mean age, 61.9 ± 7.6 years; range, 51–80 years; follow-up, 1 year). Patients with open fractures, syndesmosis injuries, and a previous ankle trauma or surgery were excluded. Demographic data, union rate, complications, radiographic outcomes, visual analog scale (VAS) scores, and foot and ankle outcome scores (FAOSs) between the groups were recorded and compared. We also investigated the association of clinical features with pain and function. Statistically, the Fisher’s exact test was used for categorical variables and the Mann-Whitney U test for the continuous variables. The final model for the multiple regression analysis was used to predict factors related to functional outcomes.

Results
There were no significant between-group differences in demographic data, complication rates, immediately postoperative distal fibula lengths, ankle osteoarthritis (OA) grades, talar tilt angles (TTAs) ≥ 2°, or reduction accuracy. All fractures achieved union. The PLP group had significantly lower rates of distal screw loosening, fibula shortening > 2 mm, OA grade progression, and TTAs ≥ 2°, and better FAOSs and VAS scores than was the case for the TP group after 1 year of follow-up (all p < 0.05). The severity of OA, TTA ≥ 2°, and distal screw loosening were positively associated with VAS scores, and negatively associated with FAOSs.

Conclusions
When treating AO/OTA 44B fractures in patients over 50 years of age, PLPs provided better VAS scores, FAOSs, and radiological outcomes, including less fibula shortening > 2 mm, less osteoarthritic (OA) ankle progression, less implant removal rate, and fewer TTAs ≥ 2° than was the case for TPs after a 1-year follow-up.

Level of evidence
Therapeutic level III
A comparison between arthroscopic and open surgery for treatment outcomes of chronic lateral ankle instability accompanied by osteochondral lesions of the talus
Authors: Xu Can , Li Mingqing , Wang Chenggong , Liu Hua 
Published: March 2020

AbstractBackgroundThis study aimed to examine the efficacy and safety of the arthroscopic treatment of osteochondral lesion of talus (OLT) and lateral ankle instability. It was hypothesized that the outcome of all-arthroscopic surgery was no worse than that of the combined open and arthroscopic surgery for treating chronic lateral ankle instability accompanied by OLT.MethodsThe patients diagnosed of chronic lateral ankle instability accompanied by OLT, who were surgically treated between May 2015 and May2017, were targeted for inclusion. Specifically, patients who received the arthroscopic treatment of OLT and lateral ankle instability were enrolled in the all-arthroscopic group, while patients who received the arthroscopic treatment of OLT and open lateral ankle stabilization were enrolled in the combined open and arthroscopic group. All the patients were followed up in terms of the Karlsson Ankle Functional Score, visual analog scale (VAS) score, Tegner activity score, and American Orthopaedic Foot & Ankle Society (AOFAS) score. Meanwhile, the satisfaction and complication rates were evaluated and compared.ResultsThis retrospective study included a total of 67 patients, including 32 patients in the all-arthroscopic group and 35 patients in the combined group. At a minimum of 24-month follow-up, the functional outcomes were significantly improved in both groups in relation to the preoperative condition. However, the two groups did not differ significantly from each other in terms of the Karlsson score (83.1 ± 8.2 vs 81.7 ± 9.1;P= 0.89), the VAS score (1.8 ± 1.6 vs 2.1 ± 1.7;P= 0.73), the Tegner score (5.5 ± 2.3 vs 5.0 ± 2.1;P= 0.72), and the AOFAS score (87.7 ± 7.6 vs 86.9 ± 7.3;P= 0.77). In addition, the satisfaction and complication rates exhibited no significant differences between the two groups.ConclusionIn comparison with the open lateral ankle stabilization and arthroscopic treatment of OLT, the all-arthroscopic procedure showed no difference in clinical outcomes at a minimum of 24-month follow-up. Despite the benefits of minimally invasive arthroscopic procedure combined with a relatively aggressive postoperative rehabilitation protocol, the clinical outcomes for patients with chronic lateral ankle instability accompanied by OLT did not yield significant improvement.Trial registrationThe present study was carried out with the approval issued by the Institutional Review Board of Xiangya Hospital (no. 202002010).
When assessing generalisability, focusing on differences in population or setting alone is insufficient
Authors: Burchett Helen E. D. , Kneale Dylan , Blanchard Laurence , Thomas James 
Published: March 2020

AbstractGeneralisability is typically only briefly mentioned in discussion sections of evaluation articles, which are unhelpful in judging whether an intervention could be implemented elsewhere, with similar effects. Several tools to assess generalisability exist, but they are difficult to operationalise and are rarely used. We believe a different approach is needed. Instead of focusing on similarities (or more likely, differences) in generic population and setting characteristics, generalisability assessments should focus on understanding an intervention’s mechanism of action - why or how an intervention was effective. We believe changes are needed to four types of research. First, outcome evaluations should draw on programme theory. Second, process evaluations should aim to understand interventions’ mechanism of action, rather than simply ‘what happened’. Third, small scoping studies should be conducted in new settings, to explore how to enact identified mechanisms. Finally, innovative synthesis methods are required, in order to identify mechanisms of action where there is a lack of existing process evaluations.
Family conferences and shared prioritisation to improve patient safety in the frail elderly (COFRAIL): study protocol of a cluster randomised intervention trial in primary care
Authors:   on behalf of the COFRAIL study group, Mortsiefer Achim , Wilm Stefan , Santos Sara , Löscher Susanne , Wollny Anja , Drewelow Eva , Ritzke Manuela , Thürmann Petra , Mann Nina-Kristin , Meyer Gabriele , Abraham Jens , Icks Andrea , Montalbo Joseph , Wiese Birgitt , Altiner Attila 
Published: March 2020

Abstract
Background
Frailty in elderly patients is associated with an increased risk of poor health outcomes, including falls, delirium, malnutrition, hospitalisation, and mortality. Because polypharmacy is recognised as a possible major contributor to the pathogenesis of geriatric frailty, reducing inappropriate medication exposure is supposed to be a promising approach to improve health-related quality of life and prevent adverse outcomes. A major challenge for the process of deprescribing of inappropriate polypharmacy is to improve the communication between general practitioner (GPs), patient and family carer. This study investigates the effects of a complex intervention in frail elderly patients with polypharmacy living at home.

Methods
This is a cluster randomised controlled trial including 136 GPs and 676 patients. Patients with a positive clinical screening for frailty are eligible if they are aged 70 years or older, receiving family or professional nursing care at home, and taking in five or more drugs per day. Exclusion criteria are higher grade of dementia and life expectancy of 6 months or less. The GPs of the intervention group receive an educational training promoting a deprescribing guideline and providing information on how to conduct a family conference focussing on prioritisation of treatment goals concerning drug therapy. During the 1-year intervention, GPs are expected to perform a total of three family conferences, each including a structured medication review with patients and their family carers. GPs of the control group will receive no training and will deliver care as usual. Geriatric assessment of all patients will be performed by study nurses during home visits at baseline and after 6 and 12 months. The primary outcome is the hospitalisation rate during the observation period of 12 months. Secondary outcomes are number and appropriateness of medications, mobility, weakness, cognition, depressive disorder, health-related quality of life, activities of daily living, weight, and costs of health care use.

Discussion
This study will provide evidence for a pragmatic co-operative and patient-centred educational intervention using family conferences to improve patient safety in frail elderly patients with polypharmacy.

Trial registration
German Clinical Trials Register, DRKS00015055 (WHO International Clinical Trials Registry Platform [ICTRP]). Registered on 6 February 2019.
Tongmai Yangxin intervening in myocardial remodeling after PCI for coronary heart disease: study protocol for a double-blind, randomized controlled trial
Authors: Wang Yongxia , Wang Xinlu , Wang Jianru , Li Bin , Yu Rui , Hu Yucai , Li Xingyuan , Peng Guangcao , Zhang Mengmeng , Zhu Mingjun 
Published: March 2020

Abstract
Background
Coronary heart disease (CHD) has become a common cardiovascular disease that seriously threatens the health of people. As reperfusion in the early phase and drug therapy, especially percutaneous coronary intervention (PCI), have become widely used in the clinic, the mortality of acute myocardial infarction in the short term has been reduced significantly. In addition, in 40%–56% of patients who experience myocardial infarction, cardiac dysfunction occurs and about 25%–33% develop heart failure.

Methods
This study was designed as a multicenter, double-blind, randomized, placebo-controlled, parallel-group, superiority trial. Participants were randomly assigned in a 1:1 ratio through a centrally controlled, computer-generated, simple randomization schedule. The primary outcome was left ventricular end-diastolic volume index = left ventricular end-diastolic volume/body surface area. The combined secondary outcomes include traditional Chinese medicine syndrome score, echocardiogram results, 6-minute walk test results, Seattle Angina Questionnaire score, cardiac magnetic resonance imaging results, biological indicators, dynamic electrocardiogram results, and experiment event rate. Assessments will be performed at baseline and at 4, 8, and 12 weeks after randomization.

Discussion
This trial will demonstrate that the addition of a Tongmai Yangxin pill (TMYX) to conventional treatment will intervene in the development of cardiac remodeling and cardiac dysfunction.

Trial registration
This study was registered in the Chinese Clinical Trial Registry on 7 May 2019. The registration number is ChiCRT1900023023 (http://www.chictr.org.cn/showproj.aspx?proj=12370).
Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial
Authors: Bawazeer Mohammed , Amer Marwa , Maghrabi Khalid , Alshaikh Kamel , Amin Rashid , Rizwan Muhammad , Shaban Mohammad , De Vol Edward , Hijazi Mohammed 
Published: March 2020

Abstract
Background
A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h.

Methods/design
This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized post-intubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 μg/kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 μg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first.

Discussion
The first patient was enrolled on 1 September 2019. As of 10 October 2019, a total of 16 patients had been enrolled. We expect to complete the recruitment by 31 December 2020. The findings of this pilot trial will likely justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial.

Trial registration
ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.
PCN-222 metal–organic framework: a selective and highly efficient sorbent for the extraction of aspartame from gum, juice, and diet soft drink before its spectrophotometric determination
Authors: Safaei Moghaddam Zahra , Kaykhaii Massoud , Khajeh Mostafa , Oveisi Ali Reza 
Published: March 2020

AbstractIn this paper, we describe synthesis and application of an iron porphyrinc metal–organic framework PCN-222(Fe) for solid phase extraction of aspartame, an artificial non-saccharine sweetener, from gum, juice and diet soft drink samples prior to its determination by spectrophotometry. The mesoporous MOF was synthesized solvo-thermally and characterized by Fourier transform-infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, and Brunauer–Emmett–Teller techniques. To obtain the best extraction efficiency of aspartame, significant affecting parameters such as pH of sample solution, amount of the sorbent, type and volume of eluting solvent, and adsorption and desorption times were investigated and optimized. Under optimum conditions, the calibration graph for aspartame was linear in the range of 0.1 to 100.0 mg.L−1 and relative standard deviation of aspartame was 1.7% (n = 7). Limit of detection of method calculated as 0.019 mg.L−1 and the enrichment factor of 350 folds was obtained. Adsorption capacity of synthesized sorbent was found to be 356 mg.g−1. Hierarchical porosity, the eight terminal–OH groups of the Zr6 node, and hydrogen bonding possibly play vital role for selective adsorption of aspartame. The optimized method was successfully applied to the determination of aspartame in real samples with reasonable recoveries (> 98%).