Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of dexmedetomidine on liver transplantation: a meta-analysis

Background: Dexmedetomidine (DEX), an adjuvant anesthetic, may improve the clinical outcomes of liver transplantation (LT). Methods: We summarized the relevant clinical trials of DEX in patients undergoing LT. As of 30 January 2023, we searched The Cochrane Library, MEDLINE, EMBASE, Clinical Trial.gov and the WHO ICTRP. The main outcomes were postoperative liver and renal function. The random effect model or fixed effect model was used to summarize the outcomes across centers based on the differences in heterogeneity. Results: The meta-analysis included nine studies in total. Compared with the control group, the DEX group had a reduced warm ischemia time (MD-4.39; 95% CI-6.74−2.05), improved postoperative liver (peak aspartate transferase: MD-75.77, 95% CI-112.81−38.73; peak alanine transferase: MD-133.51, 95% CI-235.57−31.45) and renal function (peak creatinine: MD-8.35, 95% CI-14.89−1.80), and a reduced risk of moderate-to-extreme liver ischemia-reperfusion injury (OR 0.28, 95% CI 0.14-0.60). Finally, the hospital stay of these patients was decreased (MD-2.28, 95% CI-4.00−0.56). Subgroup analysis of prospective studies showed that DEX may have better efficacy in living donors and adult recipients. Conclusion: DEX can improve short-term clinical outcomes and shorten the hospital stay of patients. However, the long-term efficacy of DEX and its interfering factors deserves further study. Systematic Review: identifier CRD42022351664. Graphical Abstract
Molecular differences in brain regional vulnerability to aging between males and females

Background Aging-related cognitive decline is associated with brain structural changes and synaptic loss. However, the molecular mechanisms of cognitive decline during normal aging remain elusive. Results Using the GTEx transcriptomic data from 13 brain regions, we identified aging-associated molecular alterations and cell-type compositions in males and females. We further constructed gene co-expression networks and identified aging-associated modules and key regulators shared by both sexes or specific to males or females. A few brain regions such as the hippocampus and the hypothalamus show specific vulnerability in males, while the cerebellar hemisphere and the anterior cingulate cortex regions manifest greater vulnerability in females than in males. Immune response genes are positively correlated with age, whereas those involved in neurogenesis are negatively correlated with age. Aging-associated genes identified in the hippocampus and the frontal cortex are significantly enriched for gene signatures implicated in Alzheimer’s disease (AD) pathogenesis. In the hippocampus, a male-specific co-expression module is driven by key synaptic signaling regulators including VSNL1, INA, CHN1 and KCNH1; while in the cortex, a female-specific module is associated with neuron projection morphogenesis, which is driven by key regulators including SRPK2, REPS2 and FXYD1. In the cerebellar hemisphere, a myelination-associated module shared by males and females is driven by key regulators such as MOG, ENPP2, MYRF, ANLN, MAG and PLP1, which have been implicated in the development of AD and other neurodegenerative diseases. Conclusions This integrative network biology study systematically identifies molecular signatures and networks underlying brain regional vulnerability to aging in males and females. The findings pave the way for understanding the molecular mechanisms of gender differences in developing neurodegenerative diseases such as AD.
High immunogenicity of virus-like particles (VLPs) decorated with Aeromonas salmonicida VapA antigen in rainbow trout

The Gram-negative bacterium A. salmonicida is the causal agent of furunculosis and used to be one of the most loss-causing bacterial infections in the salmonid aquaculture industry with a mortality rate of about 90% until the 1990s, when an inactivated vaccine with mineral oil as adjuvant was successfully implemented to control the disease. However, the use of this vaccine is associated with inflammatory side effects in the peritoneal cavity as well as autoimmune reactions in Atlantic salmon, and incomplete protection has been reported in rainbow trout. We here aimed at developing and testing a recombinant alternative vaccine based on virus-like particles (VLPs) decorated with VapA, the key structural surface protein in the outer A-layer of A. salmonicida. The VLP carrier was based on either the capsid protein of a fish nodavirus, namely red grouper nervous necrotic virus (RGNNV) or the capsid protein of Acinetobacter phage AP205. The VapA and capsid proteins were expressed individually in E. coli and VapA was fused to auto-assembled VLPs using the SpyTag/SpyCatcher technology. Rainbow trout were vaccinated/immunized with the VapA-VLP vaccines by intraperitoneal injection and were challenged with A. salmonicida 7 weeks later. The VLP vaccines provided protection comparable to that of a bacterin-based vaccine and antibody response analysis demonstrated that vaccinated fish mounted a strong VapA-specific antibody response. To our knowledge, this is the first demonstration of the potential use of antigen-decorated VLPs for vaccination against a bacterial disease in salmonids.
Utility of MF-non coding region for measles molecular surveillance during post-elimination phase, Spain, 2017–2020

Background In countries entering the post-elimination phase for measles, the study of variants by sequencing of 450 nucleotides of the N gene (N450) does not always allow the tracing of chains of transmission. Indeed, between 2017 and 2020, most measles virus sequences belonged to either the MVs/Dublin.IRL/8.16 (B3-Dublin) or the MVs/Gir Somnath.IND/42.16 (D8-Gir Somnath) variants. We evaluated the additional use of a non-coding region (MF-NCR) as a tool to enhance resolution and infer case origin, chains of transmission and characterize outbreaks. Methods We obtained 115 high-quality MF-NCR sequences from strains collected from Spanish patients infected with either B3-Dublin or D8-Gir Somnath variants between 2017 and 2020, performed epidemiological, phylogenetic and phylodynamic analyses and applied a mathematical model to determine relatedness among identified clades. Results Applying this model allowed us to identify phylogenetic clades potentially derived from concomitant importations of the virus rather than single chain of transmission, inferred based on only N450 and epidemiology data. In a third outbreak, we found two related clades that corresponded to two chains of transmission. Discussion Our results show the ability of the proposed method to improve identification of simultaneous importations in the same region which could trigger enhanced contact tracing. Moreover, the identification of further transmission chains indicates that the size of import-related outbreaks was smaller than previously found, supporting the interpretation that endemic measles transmission was absent in Spain between 2017 and 2020. We suggest considering the use of the MF-NCR region in conjunction with the study of N450 variants in future WHO recommendations for measles surveillance.
Continuous low-dose cyclophosphamide plus prednisone in the treatment of relapsed and refractory multiple myeloma with severe complications

Background/objective We retrospectively analyzed the effective and safety of continuous low-dose cyclophosphamide combined with prednisone (CP) in relapsed and refractory multiple myeloma (RRMM) patients with severe complications. Methods A total of 130 RRMM patients with severe complications were enrolled in this study, among which 41 patients were further given bortezomib, lenalidomide, thalidomide or ixazomib on the basis of CP regimen (CP+X group). The response to therapy, adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were recorded. Results Among the 130 patients, 128 patients received therapeutic response assessment, with a complete remission rate (CRR) and objective response rate (ORR) of 4.7% and 58.6%, respectively. The median OS and PFS time were (38.0 ± 3.6) and (22.9±5.2) months, respectively. The most common AEs were hyperglycemia (7.7%), pneumonia (6.2%) and Cushing’s syndrome (5.4%). In addition, we found the pro-BNP/BNP level was obviously decreased while the LVEF (left ventricular ejection fraction) was increased in RRMM patients following CP treatment as compared with those before treatment. Furthermore, CP+X regimen further improved the CRR compared with that before receiving the CP+X regimen (24.4% vs. 2.4%, P=0.007). Also, both the OS and PFS rates were significantly elevated in patients received CP+X regimen following CP regimen as compared with the patients received CP regimen only. Conclusion This study demonstrates the metronomic chemotherapy regimen of CP is effective to RRMM patients with severe complications.
A novel T-cell exhaustion-related feature can accurately predict the prognosis of OC patients

The phenomenon of T Cell exhaustion (TEX) entails a progressive deterioration in the functionality of T cells within the immune system during prolonged conflicts with chronic infections or tumors. In the context of ovarian cancer immunotherapy, the development, and outcome of treatment are closely linked to T-cell exhaustion. Hence, gaining an in-depth understanding of the features of TEX within the immune microenvironment of ovarian cancer is of paramount importance for the management of OC patients. To this end, we leveraged single-cell RNA data from OC to perform clustering and identify T-cell marker genes utilizing the Unified Modal Approximation and Projection (UMAP) approach. Through GSVA and WGCNA in bulk RNA-seq data, we identified 185 TEX-related genes (TEXRGs). Subsequently, we transformed ten machine learning algorithms into 80 combinations and selected the most optimal one to construct TEX-related prognostic features (TEXRPS) based on the mean C-index of the three OC cohorts. In addition, we explored the disparities in clinicopathological features, mutational status, immune cell infiltration, and immunotherapy efficacy between the high-risk (HR) and low-risk (LR) groups. Upon the integration of clinicopathological features, TEXRPS displayed robust predictive power. Notably, patients in the LR group exhibited a superior prognosis, higher tumor mutational load (TMB), greater immune cell infiltration abundance, and enhanced sensitivity to immunotherapy. Lastly, we verified the differential expression of the model gene CD44 using qRT-PCR. In conclusion, our study offers a valuable tool to guide clinical management and targeted therapy of OC.
Pipeline for precise insoluble matrisome coverage in tissue extracellular matrices

The extracellular matrix (ECM) is assembled by hundreds of proteins orchestrating tissue patterning and surrounding cell fates via the mechanical–biochemical feedback loop. Aberrant ECM protein production or assembly usually creates pathological niches eliciting lesions that mainly involve fibrogenesis and carcinogenesis. Yet, our current knowledge about the pathophysiological ECM compositions and alterations in healthy or diseased tissues is limited since the methodology for precise insoluble matrisome coverage in the ECM is a “bottleneck. ” Our current study proposes an enhanced sodium dodecyl sulfonate (E-SDS) workflow for thorough tissue decellularization and an intact pipeline for the accurate identification and quantification of highly insoluble ECM matrisome proteins. We tested this pipeline in nine mouse organs and highlighted the full landscape of insoluble matrisome proteins in the decellularized ECM (dECM) scaffolds. Typical experimental validations and mass spectrometry (MS) analysis confirmed very little contamination of cellular debris remaining in the dECM scaffolds. Our current study will provide a low-cost, simple, reliable, and effective pipeline for tissue insoluble matrisome analysis in the quest to comprehend ECM discovery proteomic studies.
Exploring the relationship between abnormally high expression of NUP205 and the clinicopathological characteristics, immune microenvironment, and prognostic value of lower-grade glioma

Nuclear pore complex (NPC) is a major transport pivot for nucleocytoplasmic molecule exchange. Nucleoporin 205 (NUP205)—a main component of NPC—plays a key regulatory role in tumor cell proliferation; however, few reports document its effect on the pathological progression of lower-grade glioma (LGG). Therefore, we conducted an integrated analysis using 906 samples from multiple public databases to explore the effects of NUP205 on the prognosis, clinicopathological characteristics, regulatory mechanism, and tumor immune microenvironment (TIME) formation in LGG. First, multiple methods consistently showed that the mRNA and protein expression levels of NUP205 were higher in LGG tumor tissue than in normal brain tissue. This increased expression was mainly noted in the higher WHO Grade, IDH-wild type, and 1p19q non-codeleted type. Second, various survival analysis methods showed that the highly expressed NUP205 was an independent risk indicator that led to reduced survival time of patients with LGG. Third, GSEA analysis showed that NUP205 regulated the pathological progress of LGG via the cell cycle, notch signaling pathway, and aminoacyl-tRNA biosynthesis. Ultimately, immune correlation analysis suggested that high NUP205 expression was positively correlated with the infiltration of multiple immune cells, particularly M2 macrophages, and was positively correlated with eight immune checkpoints, particularly PD-L1. Collectively, this study documented the pathogenicity of NUP205 in LGG for the first time, expanding our understanding of its molecular function. Furthermore, this study highlighted the potential value of NUP205 as a target of anti-LGG immunotherapy.
COVID-19 government measures and their impact on mental health: a cross-sectional study of older primary care patients in Germany

Background With the outbreak of COVID-19, government measures including social distancing and restrictions of social contacts were imposed to slow the spread of the virus. Since older adults are at increased risk of severe disease, they were particularly affected by these restrictions. These may negatively affect mental health by loneliness and social isolation, which constitute risk factors for depressiveness. We aimed to analyse the impact of perceived restriction due to government measures on depressive symptoms and investigated stress as mediator in an at-risk-population in Germany. Methods Data were collected in April 2020 from the population of the AgeWell.de-study, including individuals with a Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score ≥9, using the depression subscale of the Brief Symptom Inventory (BSI-18) and the Perceived Stress Scale (PSS-4). Feeling restricted due to COVID-19 government measures was surveyed with a standardized questionnaire. Stepwise multivariate regressions using zero-inflated negative binomial models were applied to analyse depressive symptoms, followed by a general structural equation model to assess stress as mediator. Analysis were controlled for sociodemographic factors as well as social support. Results We analysed data from 810 older adults (mean age = 69.9, SD = 5). Feeling restricted due to COVID-19 government measures was linked to increased depressiveness (b = 0.19; p < 0.001). The association was no longer significant when adding stress and covariates (b = 0.04; p = 0.43), while stress was linked to increased depressive symptoms (b = 0.22; p < 0.001). A final model confirms the assumption that the feeling of restriction is mediated by stress (total effect: b = 0.26; p < 0.001). Conclusion We found evidence that feeling restricted due to COVID-19 government measures is associated with higher levels of depressive symptoms in older adults at increased risk for dementia. The association is mediated by perceived stress. Furthermore, social support was significantly associated with less depressive symptoms. Thus, it is of high relevance to consider possible adverse effects of government measures related to COVID-19 on mental health of older people.
Imaging biofilms using fluorescence in situ hybridization: seeing is believing

Biofilms are complex structures with an intricate relationship between the resident microorganisms, the extracellular matrix, and the surrounding environment. Interest in biofilms is growing exponentially given its ubiquity in so diverse fields such as healthcare, environmental and industry. Molecular techniques (e.g., next-generation sequencing, RNA-seq) have been used to study biofilm properties. However, these techniques disrupt the spatial structure of biofilms; therefore, they do not allow to observe the location/position of biofilm components (e.g., cells, genes, metabolites), which is particularly relevant to explore and study the interactions and functions of microorganisms. Fluorescence in situ hybridization (FISH) has been arguably the most widely used method for an in situ analysis of spatial distribution of biofilms. In this review, an overview on different FISH variants already applied on biofilm studies (e.g., CLASI-FISH, BONCAT-FISH, HiPR-FISH, seq-FISH) will be explored. In combination with confocal laser scanning microscopy, these variants emerged as a powerful approach to visualize, quantify and locate microorganisms, genes, and metabolites inside biofilms. Finally, we discuss new possible research directions for the development of robust and accurate FISH-based approaches that will allow to dig deeper into the biofilm structure and function.
INs and OUTs of faces in consciousness: a study of the temporal evolution of consciousness of faces during binocular rivalry

Contents of consciousness change over time. However, the study of dynamics in consciousness has been largely neglected. Aru and Bachmann have recently brought to the attention of scientists dealing with consciousness the relevance of making inquiries about its temporal evolution. Importantly, they also pointed out several experimental questions as guidelines for researchers interested in studying the temporal evolution of consciousness, including the phases of formation and dissolution of content. They also suggested that these two phases could be characterized by asymmetric inertia. The main objective of the present investigation was to approximate the dynamics of these two phases in the context of conscious face perception. To this aim, we tested the time course of content transitions during a binocular rivalry task using face stimuli and asked participants to map their subjective experience of transitions from one content to the other through a joystick. We then computed metrics of joystick velocity linked to content transitions as proxies of the formation and dissolution phases. We found a general phase effect such that the formation phase was slower than the dissolution phase. Furthermore, we observed an effect specific to happy facial expressions, such that their contents were slower to form and dissolve than that of neutral expressions. We further propose to include a third phase of stabilization of conscious content between formation and dissolution.
Technological advances for analyzing the content of organ-on-a-chip by mass spectrometry

Three-dimensional (3D) cell cultures, including organ-on-a-chip (OOC) devices, offer the possibility to mimic human physiology conditions better than 2D models. The organ-on-a-chip devices have a wide range of applications, including mechanical studies, functional validation, and toxicology investigations. Despite many advances in this field, the major challenge with the use of organ-on-a-chips relies on the lack of online analysis methods preventing the real-time observation of cultured cells. Mass spectrometry is a promising analytical technique for real-time analysis of cell excretes from organ-on-a-chip models. This is due to its high sensitivity, selectivity, and ability to tentatively identify a large variety of unknown compounds, ranging from metabolites, lipids, and peptides to proteins. However, the hyphenation of organ-on-a-chip with MS is largely hampered by the nature of the media used, and the presence of nonvolatile buffers. This in turn stalls the straightforward and online connection of organ-on-a-chip outlet to MS. To overcome this challenge, multiple advances have been made to pre-treat samples right after organ-on-a-chip and just before MS. In this review, we summarised these technological advances and exhaustively evaluated their benefits and shortcomings for successful hyphenation of organ-on-a-chip with MS.
Evaluation of the representative of using rumen fluid samples from lambs fed pelleted TMR for analysis of prokaryotic communities

The pelleted TMR pulverized the grass during processing, which may result in more solid attached microorganisms in the filtered rumen fluid. The objective of this study was evaluating the necessity of distinguishing physical phases of rumen contents for analysis of prokaryotes communities in rumen of lambs fed pelleted TMR, considering the dissimilarity of diversity and community of bacteria and archaea between fluid and mixed rumen contents. The yield of microbial DNA, bacterial diversity, abundances of fibrolytic bacteria of phylum Fibrobacterota and Spirochaetota, as well as genus Ruminococcus, Lachnospiraceae_NK3A20, Fibrobacter, and F082, and abundance of archaeal Methanimicrococcus in rumen fluid were lower than those in mixed phase of rumen contents (p ≤ 0.05). In conclusion, it is necessary to consider rumen content physical phases when studying the prokaryotic community in rumen of lambs fed pelleted TMR.
Differential effect of lactate on synovial fibroblast and macrophage effector functions

Introduction The synovial membrane is the main site of inflammation in rheumatoid arthritis (RA). Here several subsets of fibroblasts and macrophages, with distinct effector functions, have been recently identified. The RA synovium is hypoxic and acidic, with increased levels of lactate as a result of inflammation. We investigated how lactate regulates fibroblast and macrophage movement, IL-6 secretion and metabolism via specific lactate transporters. Methods Synovial tissues were taken from patients undergoing joint replacement surgery and fulfilling the 2010 ACR/EULAR RA criteria. Patients with no evidence of degenerative or inflammatory disease were used as control. Expression of the lactate transporters SLC16A1 and SLC16A3 on fibroblasts and macrophages was assessed by immunofluorescence staining and confocal microscopy. To test the effect of lactate in vitro we used RA synovial fibroblasts and monocyte-derived macrophages. Migration was assessed via scratch test assays or using trans-well inserts. Metabolic pathways were analysed by Seahorse analyser. IL-6 secretion was determined by ELISA. Bioinformatic analysis was performed on publicly available single cell and bulk RNA sequencing datasets. Results We show that: i) SLC16A1 and SLC16A3 which regulate lactate intake and export respectively, are both expressed in RA synovial tissue and are upregulated upon inflammation. SLC16A3 is more highly expressed by macrophages, while SLC16A1 was expressed by both cell types. ii) This expression is maintained in distinct synovial compartments at mRNA and protein level. iii) Lactate, at the concentration found in RA joints (10 mM), has opposite effects on the effector functions of these two cell types. In fibroblasts, lactate promotes cell migration, IL-6 production and increases glycolysis. In contrast macrophages respond to increases in lactate by reducing glycolysis, migration, and IL-6 secretion. Discussion In this study, we provide the first evidence of distinct functions of fibroblasts and macrophages in presence of high lactate levels, opening new insights in understanding the pathogenesis of RA and offering novel potential therapeutic targets.