Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism

Introduction: Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group). Result: Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including Akkermansia (p < 0.01), Eubacterium (p < 0.01) and Ruminococcus (p < 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine (p < 0.01), phenylalanine (p < 0.05), and arbutin (p < 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., Eubacterium and Ruminococcus) (p < 0.05). Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., Eubacterium) enriched in the BER group were negatively associated with the above-mentioned clinical indices (p < 0.05). Conclusion: Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.
Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression

Cholesterol is an essential lipid primarily synthesized in the liver through the mevalonate pathway. Besides being a precursor of steroid hormones, bile acid, and vitamin D, it is an essential structural component of cell membranes, is enriched in membrane lipid rafts, and plays a key role in intracellular signal transduction. The lipid homeostasis is finely regulated end appears to be impaired in several types of tumors, including breast cancer. In this review, we will analyse the multifaceted roles of cholesterol and its derivatives in breast cancer progression. As an example of the bivalent role of cholesterol in the cell membrane of cancer cells, on the one hand, it reduces membrane fluidity, which has been associated with a more aggressive tumor phenotype in terms of cell motility and migration, leading to metastasis formation. On the other hand, it makes the membrane less permeable to small water-soluble molecules that would otherwise freely cross, resulting in a loss of chemotherapeutics permeability. Regarding cholesterol derivatives, a lower vitamin D is associated with an increased risk of breast cancer, while steroid hormones, coupled with the overexpression of their receptors, play a crucial role in breast cancer progression. Despite the role of cholesterol and derivatives molecules in breast cancer development is still controversial, the use of cholesterol targeting drugs like statins and zoledronic acid appears as a challenging promising tool for breast cancer treatment.
Experienced drivers are quicker to achieve situation awareness than inexperienced drivers in situations of transfer of control within a Level 3 autonomous environment

Previous researchers examining transfers of control from semi-autonomous to manual driving have found that younger drivers engaged in a secondary task while in automated mode need at least 8 seconds to achieve the same level of situation awareness as drivers always in control of their vehicle (Samuel et al., 2016). It is likely that middle-age drivers, with their increased driving experience would require less time. To test this hypothesis, middle-age drivers participated in a driving simulator experiment where they were asked to either drive manually (control) or with a simulated autonomous system (experimental conditions). While in automated mode, drivers either received an alert 4s, 6s, 8s, or 12s prior to the presence of a latent hazard. The proportion of latent hazards anticipated was examined. The results were consistent with the hypothesis that middle-age drivers were better at anticipating hazards overall and were faster to achieve appropriate situation awareness associated with manual driving than younger drivers.
Acupuncture to Improve Patient Discomfort During Upper Gastrointestinal Endoscopy: Systematic Review and Meta-Analysis

Background and Aims Severe discomfort during an upper gastrointestinal endoscopy (UGE) is often a stressful experience for patients undergoing the procedure. An increasing number of studies have shown that acupuncture may reduce discomfort during UGE. A systematic review in 2004 investigated the effect of acupuncture for gastrointestinal endoscopy, but these data have not been recently reviewed. Therefore, this study was conducted to evaluate the current evidence and provide up-to-date knowledge for clinical decision-making. Methods Nine databases were searched from inception to June 2021. Eligible randomized controlled trials (RCTs) were included. The outcome data were synthesized where necessary, and risks of bias of included studies were assessed using RevMan V.5. 3. Results Twenty-three eligible RCTs with 3,349 patients were identified. It was found that acupuncture plus topical pharyngeal anesthesia with lidocaine hydrochloride (TPALH) resulted in greater improvements regarding visual analog scale (VAS) scores and the incidence of nausea and vomiting (INV) when compared with TPALH alone. These results were consistent among studies of manual acupuncture, electroacupuncture, auricular-plaster, superficial needle (SFN) and acupressure. In the meta-analysis, SFN plus TPALH showed significant improvement of VAS scores compared to sham SFN plus TPALH (MD −1.11, 95% CI −1.52 to −0.70, P < 0.00001). Most of included studies did not report any side effects in their findings, and were of medium-to-high risk of bias. Conclusion Acupuncture, as adjunctive therapy to TPA, may result in less patient discomfort than TPA alone. Findings from this review should be interpreted with caution due to the high heterogeneity identified. There is low-quality evidence supporting the use of acupuncture over sham. More rigorously designed RCTs are needed to inform clinical decision-making. Systematic Review Registration PROSPERO [CRD42014008966].
Ready for Vaccination? COVID-19 Vaccination Willingness of Older People in Austria

In spite of findings highlighting higher health risk from infection compared to younger people, a certain percentage of older people in Austria still lack a valid vaccination certificate. The current gaps in vaccination coverage in countries such as Austria are likely to be in large part due to vaccination refusal and pose or will pose problems for the health system and consequently for all of society should the initial findings on Omicron coronavirus infectivity prove true. Surprisingly, only a few studies around the globe explicitly address older people's COVID-19 vaccination willingness. The present work therefore intends to contribute to this field by identifying factors associated with the decision for or against a vaccination among the older population in Austria. Data collected between late 2020 and early 2021 via the cross-national panel study Survey of Health, Aging and Retirement in Europe (SHARE) are used to perform multinomial logistic regression to analyse differences between COVID-19 vaccination supporters, undecided persons and rejectors. The results show that persons exhibiting a low risk assessment toward COVID-19, less health protection behaviors, lower education and belonging to households with financial burdens are significantly more likely to refuse vaccination or be ambivalent. Although multimorbidity reduces risk of vaccination refusal, poor subjective health was significantly related to a higher risk of refusing vaccination. The results point to the importance of addressing the factors related to refusal. Only by understanding these factors will it be possible to increase vaccination rates and thus minimize other restrictive measures.
Pathologic Inflammation in Malnutrition Is Driven by Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, and Translocation of Bacterial Lipopolysaccharide

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate of failure or relapse that plague current approaches. Here we use a mouse model of MAM to investigate the mechanisms that promote inflammation in the malnourished host. We found that mice with MAM exhibited increased systemic inflammation at baseline, increased translocation of bacteria and bacterial LPS, and an exaggerated response to inflammatory stimuli. An exaggerated response to bacterial LPS was associated with increased acute weight loss. Remarkably, intestinal inflammation and barrier dysfunction was found in the cecum and colon. The cecum showed a dysbiotic microbiota with expansion of Gammaproteobacteria and some Firmicutes, and contraction of Bacteroidetes. These changes were paralleled by an increase in fecal LPS bioactivity. The inflammatory phenotype and weight loss was modulated by oral administration of non-absorbable antibiotics that altered the proportion of cecal Gammaproteobacteria. We propose that the heightened inflammation of acute malnutrition is the result of changes in the intestinal microbiota, intestinal barrier dysfunction in the cecum and colon, and increased systemic exposure to LPS.
From Haphazard to a Sustainable Normothermic Regional Perfusion Service: A Blueprint for the Introduction of Novel Perfusion Technologies

Normothermic Regional Perfusion (NRP) has shown encouraging clinical results. However, translation from an experimental to routine procedure poses several challenges. Herein we describe a model that led to the implementation of NRP into standard clinical practice in our centre following an iterative process of refinement incorporating training, staffing and operative techniques. Using this approach we achieved a four-fold increase in trained surgical staff and a 6-fold increase in competent senior organ preservation practitioners in 12 months, covering 93% of the retrieval calls. We now routinely provide NRP throughout the UK and attended 186 NRP retrievals from which 225 kidneys, 26 pancreases and 61 livers have been transplanted, including 5 that were initially declined by all UK transplant centres. The 61 DCD(NRP) liver transplants undertaken exhibited no primary non-function or ischaemic cholangiopathy with up to 8 years of follow-up. This approach also enabled successful implementation of ex situ normothermic liver perfusion which together with NRP contributed 37.5% of liver transplant activity in 2021. Perfusion technologies (in situ and ex situ) are now supported by a team of Advanced Perfusion and Organ Preservation Specialists. The introduction of novel perfusion technologies into routine clinical practice presents significant challenges but can be greatly facilitated by developing a specific role of Advanced Perfusion and Organ Preservation Specialist supported by a robust education, training and recruitment programme. GRAPHICAL ABSTRACT
Influence of Wheelchair Type on Kinematic Parameters in Wheelchair Rugby

Introduction In wheelchair rugby, players use either an offensive or defensive wheelchair depending on their field position and level of impairment. Performance of wheelchair rugby players is related to several parameters, however it is currently unclear if differences in performance are related to wheelchair type or no: the effect of wheelchair type on performance variables has not been evaluated. The aim of this study was to compare offensive and defensive wheelchairs on performance variables during a straight-line sprint. Methods Thirteen able-bodied people performed two 20 m sprint trials: one with an offensive and one with a defensive wheelchair. Data were collected using inertial measurement units fixed on the wheelchair. Peak wheelchair velocities and left-right asymmetries in peak wheel velocities were measured during the acceleration and constant peak velocity phases. Sprint time, cycle frequency, and mean and maximum velocity were calculated over the entire sprint. Results The peak velocities of the first 2 pushes (acceleration phase) were significantly higher with the defensive than the offensive wheelchair (p < 0.04 and p < 0.02). Mean and maximum sprint velocity were significantly higher (p < 0.03 and p < 0.04, respectively) with the defensive wheelchair. Cycle frequency and asymmetry did not differ between wheelchairs. Conclusion Performance was higher with the defensive than the offensive wheelchair, suggesting that the frequent finding that the higher performance of offensive as compared to defensive players is not related to the use of an offensive wheelchair.
Prognostic Significance and Immunological Role of FBXO5 in Human Cancers: A Systematic Pan-Cancer Analysis

F-box protein 5 (FBXO5), an essential subunit of the ubiquitin protein ligase complex, is increasingly recognized to exhibit important biological effects in regulating tumor occurrence and progression. The present research was intended to systematically investigate the latent roles of FBXO5 in prognosis and immunological function across cancers. Pan-cancer analyses of FBXO5 were performed based upon publicly available online databases, mainly including the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UCSC Xena, cBioPortal, and ImmuCellAI, revealing the possible relationships between FBXO5 and prognosis, DNA methylation, tumor microenvironment (TME), infiltration of immune cells, immune-related genes, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI). The results suggested that FBXO5 was expressed at a high level in numerous tumor cell lines with significant upregulation in most cancers as opposed to normal tissues. Of note, elevated expression of FBXO5 was significantly related to an unfavorable prognosis in many cancer types. Furthermore, DNA methylation and TME were confirmed to display evident correlation with the expression of FBXO5 in several malignancies. Moreover, FBXO5 expression was remarkably positively correlated with the levels of infiltrating Treg cells and Tcm cells in most tumors, but negatively correlated with tumor-infiltrating CD8+ T cells, NK/NKT cells, and Th2 cells. Meanwhile, FBXO5 was demonstrated to be co-expressed with the genes encoding immune activating and suppressive factors, chemokines, chemokine receptors, and major histocompatibility complex (MHC). Immune checkpoints, TMB, and MSI were also overtly associated with FBXO5 dysregulation among diverse kinds of cancers. Additionally, the enrichment analyses showed close relationships between FBXO5 expression and the processes related to cell cycle and immune inflammatory response. These findings provided a detailed comprehension of the oncogenic function of FBXO5. Because of its crucial roles in cancer immunity and tumorigenesis, FBXO5 may serve as a novel prognostic indicator and immunotherapeutic target for various malignancies.
Mechanisms and Drug Therapies of Bioprosthetic Heart Valve Calcification

Valve replacement is the main therapy for valvular heart disease, in which a diseased valve is replaced by mechanical heart valve (MHV) or bioprosthetic heart valve (BHV). Since the 2000s, BHV surpassed MHV as the leading option of prosthetic valve substitute because of its excellent hemocompatible and hemodynamic properties. However, BHV is apt to structural valve degeneration (SVD), resulting in limited durability. Calcification is the most frequent presentation and the core pathophysiological process of SVD. Understanding the basic mechanisms of BHV calcification is an essential prerequisite to address the limited-durability issues. In this narrative review, we provide a comprehensive summary about the mechanisms of BHV calcification on 1) composition and site of calcifications; 2) material-associated mechanisms; 3) host-associated mechanisms, including immune response and foreign body reaction, oxidative stress, metabolic disorder, and thrombosis. Strategies that target these mechanisms may be explored for novel drug therapy to prevent or delay BHV calcification.
The Association Between FT3 With the Outcome and Inflammation/Coagulopathy/Fibrinolysis of COVID-19

Background The coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people’s physical health and lives, claiming the lives of over 5 million people worldwide. It is imperative to identify the disease severity and intervene with effective therapy as early as possible. Previous studies have shown that low free triiodothyronine (FT3) may possess the predictive value on COVID-19 prognosis. Methods In this retrospective cohort study, 15-day clinical and laboratory data of 186 hospitalized patients of COVID-19 after admission were analyzed. Groups were based on the disease severity of COVID-19, survival or non-survival, and presence or absence of euthyroid sick syndrome (ESS). Categorical variables were compared with the chi-square test or Fisher’s exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between FT3 with clinic parameters of multiple time points. Results The non-survival patients had significant lower levels of FT3 (3.24 ± 0.42 vs. 4.19 ± 0.08 pmol/L, p < 0.05) and thyroid-stimulating hormone (TSH) (0.69 ± 0.19 vs. 2.32 ± 0.2 uIU/ml, p < 0.05), and the FT3 of severe patients was significantly lower than that of non-severe patients (3.67 ± 0.14 vs. 4.33 ± 0.09 pmol/L, p < 0.05). Fifty-nine cases of COVID-19 patients were diagnosed with ESS. Compared with non-ESS patients, those with ESS were older and had higher proportions of fever, shortness of breath, hypertension, diabetes, severe disease, and mortality. In addition, the correlation analysis between FT3 and clinical parameters showed that FT3 were positively related to the lymphocyte count and albumin and negatively correlated with C-reactive protein, erythrocyte sedimentation rate, and D-dimer at all time points in the first 15 days after admission. Conclusion Low FT3 had a significant predictive value on the prognosis of COVID-19 patients, and FT3 was significantly related with clinic parameters of inflammation/coagulopathy/fibrinolysis.
Ventral Attention Network Correlates With High Traits of Emotion Dysregulation in Community Women — A Resting-State EEG Study

In recent years, many studies have focused on resting-state brain activity, and especially on functional connectivity (FC), an approach that typically describes the statistical interdependence of activity in distant brain regions through specific networks. Our aim was to study the neurophysiological correlates of emotion dysregulation. Therefore, we expected that both the Default Mode Network (DMN), and the Ventral Attention Network (VAN) would have been involved. Indeed, the latter plays a role in the automatic orienting of attention towards biologically salient stimuli and includes key regions for emotion control and modulation. Starting from a community sample of 422 female students, we selected 25 women with high traits of emotion dysregulation (HD group) and 25 with low traits (LD group). They underwent a 64-channel EEG recording during a five-minute resting state with eyes open. Seed-based FC was computed on the EEG Alpha band (8–13 Hz) as a control band, and on EEG Gamma power (30–50 Hz) as the relevant measure. The power within each network and inter-network connectivity (Inter-NC) was also calculated. Analysis of the EEG Gamma band revealed, in the HD group, higher levels of Inter-NC between the VAN and all other resting-state networks as compared with the LD group, while no differences emerged in the Alpha band. Concerning correlations, Alpha power in the VAN was negatively correlated in the HD group with affective lability (ALS-18 questionnaire), both for total score (ρ = –0.52, pFDR < 0.01) and the Depression/Elation subscale) ρ = −0.45, pFDR < 0.05). Consistent with this, in the Gamma band, a positive correlation was found between VAN spectral power and the Depression/Elation subscale of ALS-18, again in the HD group only (ρ = 0.47, pFDR < 0.05). In conclusion, both resting state FC and network power in the VAN were found to be related to high emotion dysregulation, even in our non-clinical sample with high traits. Emotion dysregulation was characterized, in the EEG gamma band, by a VAN strongly connected to all other networks, a result that points, in women prone to emotion dysregulation, to a strong automatic orienting of attention towards their internal state, bodily sensations, and emotionally intense related thoughts.
Detachment of Hexokinase II From Mitochondria Promotes Collateral Sensitivity in Multidrug Resistant Chronic Myeloid Leukemia Cells

Chronic Myeloid Leukemia is a neoplastic disease characterized by the abnormal expansion of hematopoietic cells with compromised functions. Leukemic cells often display a multidrug resistance phenotype, enabling them to evade a number of structurally unrelated cytotoxic compounds. One of those mechanisms relies on the high expression of efflux transporters, such as the ABC proteins, whose activity depends on the hydrolysis of ATP to reduce intracellular drug accumulation. In the present work, we employed a well-known erythroleukemia cell line, K562, and a multidrug resistant derivative cell, FEPS, to evaluate how hexokinase II, a key regulator for the rate-limiting step glycolysis, contributes to the establishment of the multidrug resistance phenotype. We found that multidrug resistant cells primarily resort to glycolysis to generate ATP. Clotrimazole reduced the expression of mitochondrial hexokinase II, which destabilized bioenergetic parameters such as reactive oxygen species production, ATP, and glutathione levels on multidrug resistant cells. This impaired the activity of ABCC1, leading to increased drug accumulation and cell death. In summary, we propose that decoupling of hexokinase II from the mitochondria emerges as a promising strategy to generate collateral sensitivity and aid in the management of chronic myeloid leukemia in chemotherapy-refractory patients.