Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-inflammatory and Pro-apoptotic Effects of 18beta-Glycyrrhetinic Acid In Vitro and In Vivo Models of Rheumatoid Arthritis

18β-Glycyrrhetinic acid (18β-GA), an active component from Glycyrrhiza glabra L. root (licorice), has been demonstrated to be able to protect against inflammatory response and reduce methotrexate (MTX)-derived toxicity. This study was therefore designed to test the therapeutic possibility of 18β-GA on rheumatoid arthritis (RA) and to explore the underlying mechanism. LPS or TNF-α-induced inflammatory cell models and collagen-induced arthritis (CIA) animal models were applied in this study. Real-time quantitative PCR (RT-qPCR) was used to measure the mRNA levels of various cytokines and FOXO family members. The protein levels of molecules in the MAPK/NF-κB signaling pathway were analyzed using western blot. The cell proliferation assay and colony-forming assay were used to test the influence of 18β-GA on cell viability. The cell apoptosis assay and cell cycle assay were performed to detect the effect of 18β-GA on cell proliferative capacity by using flow cytometry. Hematoxylin and eosin (H&E) staining was performed to evaluate pathological changes after drug administration. The enzyme-linked immunosorbent assay (ELISA) was carried out for the detection of cytokines in serum. In vitro, we found that 18β-GA decreased the mRNA levels of IL-1β, IL-6, and COX-2 by inhibiting the MAPK/NF-κB signaling pathway in MH7A and RAW264.7 cell lines. Moreover, 18β-GA was able to suppress cell viability, trigger cell apoptosis, and G1 phase cell cycle arrest in our in vitro studies. 18β-GA dramatically enhanced the mRNA level of FOXO3 in both TNF-α- and LPS-induced inflammation models in vitro. Interestingly, after analyzing GEO datasets, we found that the FOXO3 gene was significantly decreased in the RA synovial tissue as compared to healthy donors in multiple microarray studies. In vivo, 18β-GA exhibited a promising therapeutic effect in a collagen-induced arthritis mouse model by alleviating joint pathological changes and declining serum levels of TNF-α, IL-1β, and IL-6. Finally, we observed that 18β-GA administration could mitigate liver damage caused by collagen or MTX. Collectively, the current study demonstrates for the first time that 18β-GA can inhibit inflammation and proliferation of synovial cells, and the underlying mechanism may be associated with its inhibition of MAPK/NF-κB signaling and promotion of FOXO3 signaling. Therefore, 18β-GA is expected to be a new drug candidate for RA therapy.
Neuropsychobiological Fingerprints of Chronic Fatigue in Sarcoidosis

Background Chronic fatigue is a prominent symptom in many sarcoidosis patients, affecting quality of life and interfering with treatment. This study investigated neuropsychobiological mechanisms and markers of chronic fatigue in sarcoidosis. Methods Thirty patients with a histological diagnosis of sarcoidosis were included. The Multidimensional Fatigue Inventory was used to define patients with and without chronic fatigue. All patients were then characterised using several depression, quality of life questionnaires, and executive functioning. Cognitive functioning and underlying neural correlates were assessed using an n-back task measuring working memory and (sustained) attention during functional magnetic resonance imaging. Sarcoidosis disease activity was determined using lung function, laboratory parameters, and exercise capacity. Results Nineteen patients had chronic fatigue and 11 did not; both groups had similar demographic and disease activity characteristics. Chronic fatigue patients showed more symptoms of depression and anxiety, and lower quality of life. During the n-back task, chronic fatigue was associated with a smaller increase in brain activation with increasing task difficulty versus the group without fatigue, especially in the angular gyrus. Conclusion Inadequate adjustment of brain activation with increasing demands appears to be a potential neurobiological marker of chronic fatigue in sarcoidosis patients. The angular gyrus, which plays an important role in the working memory system, was the major area in which fatigue patients showed smaller increase of brain activation compared to those without fatigue. These findings might be relevant for a deeper understanding of chronic fatigue mechanisms in sarcoidosis and future clinical treatment of this disabling syndrome. Trial Registration ClinicalTrials.gov, Trial registration number: NCT04178239 Date of registration: November 26, 2019, retrospectively registered URL: https://clinicaltrials.gov/ct2/show/NCT04178239.
Borderline Personality Disorder in a “Life History Theory” Perspective: Evidence for a Fast “Pace-of-Life-Syndrome”

“Borderline Personality Disorder” (BPD) is associated with heightened risk for cardiovascular disease and other stress-associated somatic consequences, which is poorly understood in terms of causal mechanisms, such as childhood trauma. Here, we tested the hypothesis suggesting that BPD reflects a fast “Pace-of-Life-Syndrome” (PoLS). Ninety-five women (44 diagnosed with BPD) were recruited to examine psychological correlates of PoLS, including life history features, personality dimensions, aggressiveness, chronic stress, borderline symptom severity, childhood trauma, and allostatic load (AL). In line with expectations, BPD patients had significantly higher scores suggestive of a fast PoLS than controls, they were more aggressive, more burdened with chronic stress and were exposed to more severe childhood adversity. Childhood trauma predicted PoLS, which in turn predicted AL. The present study thus provides direct evidence of psychological and somatic traits associated with the fast end of the PoLS spectrum in females with BPD. Findings are discussed with regard to clinical implications.
Human Texture Vision as Multi-Order Spectral Analysis

Texture information plays a critical role in the rapid perception of scenes, objects, and materials. Here, we propose a novel model in which visual texture perception is essentially determined by the 1st-order (2D-luminance) and 2nd-order (4D-energy) spectra. This model is an extension of the dimensionality of the Filter-Rectify-Filter (FRF) model, and it also corresponds to the frequency representation of the Portilla-Simoncelli (PS) statistics. We show that preserving two spectra and randomizing phases of a natural texture image result in a perceptually similar texture, strongly supporting the model. Based on only two single spectral spaces, this model provides a simpler framework to describe and predict texture representations in the primate visual system. The idea of multi-order spectral analysis is consistent with the hierarchical processing principle of the visual cortex, which is approximated by a multi-layer convolutional network.
Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren’s Syndrome

Primary Sjögren’s syndrome is an autoimmune disease that is predominantly seen in women. The disease is characterized by exocrine gland dysfunction in combination with serious systemic manifestations. At present, the causes of pSS are poorly understood. Pulmonary and renal inflammation are observed in pSS mice, reminiscent of a subset of pSS patients. A growing body of evidence indicates that inflammation mediated by Damage-Associated Molecular Patterns (DAMPs) contributes to autoimmunity, although this is not well-studied in pSS. Degraded extracellular matrix (ECM) constituents can serve as DAMPs by binding pattern-recognition receptors and activating Myd88-dependent signaling cascades, thereby exacerbating and perpetuating inflammatory cascades. The ECM components biglycan (Bgn) and decorin (Dcn) mediate sterile inflammation and both are implicated in autoimmunity. The objective of this study was to determine whether these ECM components and anti-ECM antibodies are altered in a pSS mouse model, and whether this is dependent on Myd88 activation in immune cells. Circulating levels of Bgn and Dcn were similar among pSS mice and controls and tissue expression studies revealed pSS mice had robust expression of both Bgn and Dcn in the salivary tissue, saliva, lung and kidney. Sera from pSS mice displayed increased levels of autoantibodies directed against ECM components when compared to healthy controls. Further studies using sera derived from conditional knockout pSS mice demonstrated that generation of these autoantibodies relies, at least in part, on Myd88 expression in the hematopoietic compartment. Thus, this study demonstrates that ECM degradation may represent a novel source of chronic B cell activation in the context of pSS.
Acupuncture as an Add-On Treatment for Functional Dyspepsia: A Systematic Review and Meta-Analysis

Background: We aimed to critically evaluate the effectiveness and safety of acupuncture as an add-on therapy to conventional Western medication (WM) and assess the quality of evidence (QoE) of these findings. Methods: A total of 12 English, Korean, and Chinese databases were searched on December 18, 2020. Randomized controlled trials (RCTs) assessing the effectiveness of acupuncture as an add-on therapy to conventional WM for functional dyspepsia (FD) were included. The primary outcome was the symptom score of FD. The risk of bias of the included studies and QoE were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation method, respectively. Results: A total of 22 RCTs were included. The total and individual FD symptom scores were significantly improved in the acupuncture combined with WM groups compared with the WM alone groups, except for in one study. The Nepean dyspepsia index score and total effective rate mostly improved significantly in the acupuncture group, regardless of the WM used and acupuncture type. FD-related biomarkers, such as ghrelin and gastrin levels, showed mixed results. The acupuncture group showed a significantly lower recurrence rate after 3–6 months of follow-up than the WM alone group. There were no differences in the incidence of adverse events between the two groups. The included studies generally had low methodological quality. The QoE for the main findings was generally very low to moderate. Conclusion: Limited evidence suggests that acupuncture has the potential to improve FD treatment in combination with conventional WM. Furthermore, the methodological quality of the included studies and QoE of the main findings were generally low. Therefore, RCTs with a rigorous methodology, including sham acupuncture and multiethnic subjects, should be performed. Systematic Review Registration: OSF registries [https://osf.io/mxren], PROSPERO [CRD42021226608].
A Scarless Healing Tale: Comparing Homeostasis and Wound Healing of Oral Mucosa With Skin and Oesophagus

Epithelial tissues are the most rapidly dividing tissues in the body, holding a natural ability for renewal and regeneration. This ability is crucial for survival as epithelia are essential to provide the ultimate barrier against the external environment, protecting the underlying tissues. Tissue stem and progenitor cells are responsible for self-renewal and repair during homeostasis and following injury. Upon wounding, epithelial tissues undergo different phases of haemostasis, inflammation, proliferation and remodelling, often resulting in fibrosis and scarring. In this review, we explore the phenotypic differences between the skin, the oesophagus and the oral mucosa. We discuss the plasticity of these epithelial stem cells and contribution of different fibroblast subpopulations for tissue regeneration and wound healing. While these epithelial tissues share global mechanisms of stem cell behaviour for tissue renewal and regeneration, the oral mucosa is known for its outstanding healing potential with minimal scarring. We aim to provide an updated review of recent studies that combined cell therapy with bioengineering exporting the unique scarless properties of the oral mucosa to improve skin and oesophageal wound healing and to reduce fibrotic tissue formation. These advances open new avenues toward the ultimate goal of achieving scarless wound healing.
Flood Inundation Mapping with Limited Observations Based on Physics-Aware Topography Constraint

Spatial classification with limited observations is important in geographical applications where only a subset of sensors are deployed at certain spots or partial responses are collected in field surveys. For example, in observation-based flood inundation mapping, there is a need to map the full flood extent on geographic terrains based on earth imagery that partially covers a region. Existing research mostly focuses on addressing incomplete or missing data through data cleaning and imputation or modeling missing values as hidden variables in the EM algorithm. These methods, however, assume that missing feature observations are rare and thus are ineffective in problems whereby the vast majority of feature observations are missing. To address this issue, we recently proposed a new approach that incorporates physics-aware structural constraint into the model representation. We design efficient learning and inference algorithms. This paper extends our recent approach by allowing feature values of samples in each class to follow a multi-modal distribution. Evaluations on real-world flood mapping applications show that our approach significantly outperforms baseline methods in classification accuracy, and the multi-modal extension is more robust than our early single-modal version. Computational experiments show that the proposed solution is computationally efficient on large datasets.
Effect of frozen storage temperature on quality-related changes in fish muscle Changes in physical, chemical and biochemical quality indicators during short- and long-term storage

The ice crystallisation point and the fraction of unfrozen water in tuna (Thunnus albacares), cod (Gadus morhua) and herring (Clupea harengus) muscle were determined by differential scanning calorimetry (DSC). The area of the ice melting curve after annealing at a temperature below the ice crystallisation point and subsequent heating was used to calculate the relative amount of unfrozen water in the fish muscle. The ice crystallisation point was defined as the lowest annealing temperature above which no melting peak could be detected. This point was around -15 °C showing a high degree of super-cooling in the species investigated. At temperatures below the ice crystallisation point, no significant difference in fraction of unfrozen water was found which is in opposition to common belief that the fraction of unfrozen water decreases gradually with decreased temperature. Previously frozen and thawed cod contained a significantly (p<0.001) lower fraction of unfrozen water compared to fresh cod. The results indicate that proper frozen storage of fish requires congelation at a temperature lower than -15 °C.
Patient-Specific Virtual Stent-Graft Deployment for Type B Aortic Dissection: A Pilot Study of the Impact of Stent-Graft Length

Thoracic endovascular aortic repair (TEVAR) has been accepted as a standard treatment option for complicated type B aortic dissection. Distal stent-graft-induced new entry (SINE) is recognised as one of the main post-TEVAR complications, which can lead to fatal prognosis. Previous retrospective cohort studies suggested that short stent-graft (SG) length (<165 mm) might correlate with increased risk of distal SINE. However, the influence of SG length on changes in local biomechanical conditions before and after TEVAR is unknown. In this paper, we aim to address this issue using a virtual SG deployment simulation model developed for application in type B aortic dissection. Our model incorporates detailed SG design and hyperelastic behaviour of the aortic wall. By making use of patient-specific geometry reconstructed from pre-TEVAR computed tomography angiography (CTA) scan, our model can predict post-TEVAR SG configuration and wall stress. Virtual SG deployment simulations were performed on a patient who underwent TEVAR with a short SG (158 mm in length), mimicking the actual clinical procedure. Further simulations were carried out on the same patient geometry but with different SG lengths (183 mm and 208 mm) in order to evaluate the effect of SG length on changes in local stress in the treated aorta. Comparisons of simulation results for different SG lengths showed the location of maximum stress varied with the SG length. With the short SG (deployed in the patient), the maximum von Mises stress of 238.9 kPa was found on the intimal flap at the distal landing zone where SINE was identified at 3-month follow-up. Increasing the SG length caused the maximum von Mises stress to move away from the distal landing zone where stress values were reduced by approximately 17% with the medium-length SG and by 60% with the long SG. This pilot study demonstrates the potential of using the virtual SG deployment model as a pre-surgical planning tool to help select the most appropriate SG length for individual patients.
Efficacy of AST-120 for Patients With Chronic Kidney Disease: A Network Meta-Analysis of Randomized Controlled Trials

AST-120, an oral spherical activated carbon, may delay the need for kidney dialysis and improve uremia symptoms because it can adsorb acidic and basic organic compounds, especially small-molecule uremic toxins. However, previous studies produced no conclusive evidence regarding the benefits of AST-120 in delaying the progression of chronic kidney disease (CKD). Therefore, this systematic review and network meta-analysis evaluated the effects of AST-120 in patients with CKD. Related keywords of CKD and AST-120 were used to search four databases to obtain potential evidence on this topic, and two authors individually completed evidence selection, data extraction, and quality assessment. Network meta-analysis was performed for mortality, end-stage renal disease, composite renal outcomes, and laboratory outcomes based on a frequentist approach. In total, 15 randomized controlled trials (n = 3,763) were included in the present synthesis, and the pooled results revealed non-significant differences in mortality among the treatment strategies. Low- and high-dose AST-120 were not superior to no AST-120 treatment regarding renal outcomes. However, the event rates of end-stage renal disease (risk ratio [RR] = 0.78, 95% confidence interval [CI] = 0.62–0.99) and composite renal outcomes (RR = 0.78, 95% CI: 0.63–0.97) were significantly lower in the tailored-dose AST-120 group than in no AST-120 group. The results did not reveal a small-study effect on the outcomes. Tailored dosing of AST-120 appeared to represent an optimal treatment strategy because it resulted in lower rates of composite renal outcomes and end-stage renal disease.
A GSK3-SRF Axis Mediates Angiotensin II Induced Endothelin Transcription in Vascular Endothelial Cells

Endothelin, encoded by ET1, is a vasoactive substance primarily synthesized in vascular endothelial cells (VECs). Elevation of endothelin levels, due to transcriptional hyperactivation, has been observed in a host of cardiovascular diseases. We have previously shown that serum response factor (SRF) is a regulator of ET1 transcription in VECs. Here we report that angiotensin II (Ang II) induced ET1 transcription paralleled activation of glycogen synthase kinase 3 (GSK3) in cultured VECs. GSK3 knockdown or pharmaceutical inhibition attenuated Ang II induced endothelin expression. Of interest, the effect of GSK3 on endothelin transcription relied on the conserved SRF motif within the ET1 promoter. Further analysis revealed that GSK3 interacted with and phosphorylated SRF at serine 224. Phosphorylation of SRF by GSK3 did not influence its recruitment to the ET1 promoter. Instead, GSK3-mediated SRF phosphorylation potentiated its interaction with MRTF-A, a key co-factor for SRF, which helped recruit the chromatin remodeling protein BRG1 to the ET1 promoter resulting in augmented histone H3 acetylation/H3K4 trimethylation. Consistently, over-expression of a constitutively active GSK enhanced Ang II-induced ET1 transcription and knockdown of either MRTF-A or BRG1 abrogated the enhancement of ET1 transcription. In conclusion, our data highlight a previously unrecognized mechanism that contributes to the transcriptional regulation of endothelin. Targeting this GSK3-SRF axis may yield novel approaches in the intervention of cardiovascular diseases.
Autonomic Nervous System Dysfunction in Primary Sjögren’s Syndrome

Primary Sjögren’s syndrome (pSS) is an autoimmune disease which primarily affects the exocrine glands, but can also affect other organs, including the nervous system. Many studies have reported evidence of autonomic nervous system (ANS) dysfunction in pSS which may contribute to a wide range of symptoms and functional burden. Symptoms of ANS dysfunction are common and widespread among patients with pSS and are associated with other features of the disease, particularly fatigue. Accumulating data on the inter-relationship between the ANS and the immune system via the vagus nerve have been reported. Vagus nerve stimulation (VNS) has also been associated with improvement in fatigue in patients with pSS. Taken together, these data suggest that the ANS may be a potential treatment target for pSS, in particularly those with fatigue being a predominant symptom. Future research to dissect the link between the ANS, immune dysregulation and clinical manifestations in pSS and to evaluate the potential of VNS as a therapy for pSS is warranted.
Associations Between Intellectual and Social Activities With Frailty Among Community-Dwelling Older Adults in China: A Prospective Cohort Study

Background: Frailty is one of the most important global health challenges. We aimed to examine the associations between frequency of intellectual and social activities and frailty among community-dwelling older adults in China. Methods: This is a prospective analysis of older adults (aged ≥60 years) who had intellectual and social activity data and were free of frailty from the national representative China Health and Retirement Longitudinal Study (CHARLS). The exposure was frequency of intellectual and social activities. Frailty was measured by the frailty index (FI) and defined as FI ≥ 0.25. Frailty incidents were followed up for 2 years. We estimated the relative risks (RRs) with 95% confidence intervals (CIs) using log-linear binominal regression adjusting for potential confounders. Results: We documented 655 frailty cases over the past 2 years. Participants who had frequent intellectual activities had a lower frailty risk compared with participants who did not have intellectual activity (adjusted RR = 0.65, 95%CI = 0.47–0.90). The adjusted RRs were 0.51 (95%CI = 0.33–0.77) for participants who did not have a slip or a fall accident and 1.06 (95%CI = 0.65–1.75) for participants who had experienced slip and fall accidents (P = 0.01 for interaction). Having frequent social activities was not associated with a significant decrease in frailty risk compared with participants who did not have social activity (adjusted RR = 0.93, 95%CI = 0.78–1.12). Conclusions: This observational study showed that having frequent intellectual activities was associated with a decreased frailty risk. The association was likely to be stronger in participants without a slip or a fall accident. Randomized controlled trials are needed to confirm this observational finding.