Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of Long Non-Coding RNAs in Biological Characteristics and Aerobic Glycolysis of Glioma

Glioma is the most common and aggressive tumor of the central nervous system. The uncontrolled proliferation, cellular heterogeneity, and diffusive capacity of glioma cells contribute to a very poor prognosis of patients with high grade glioma. Compared to normal cells, cancer cells exhibit a higher rate of glucose uptake, which is accompanied with the metabolic switch from oxidative phosphorylation to aerobic glycolysis. The metabolic reprogramming of cancer cell supports excessive cell proliferation, which are frequently mediated by the activation of oncogenes or the perturbations of tumor suppressor genes. Recently, a growing body of evidence has started to reveal that long noncoding RNAs (lncRNAs) are implicated in a wide spectrum of biological processes in glioma, including malignant phenotypes and aerobic glycolysis. However, the mechanisms of diverse lncRNAs in the initiation and progression of gliomas remain to be fully unveiled. In this review, we summarized the diverse roles of lncRNAs in shaping the biological features and aerobic glycolysis of glioma. The thorough understanding of lncRNAs in glioma biology provides opportunities for developing diagnostic biomarkers and novel therapeutic strategies targeting gliomas.
Adipose-Derived Stem/Stromal Cells in Kidney Transplantation: Status Quo and Future Perspectives

Kidney transplantation (KT) is the gold standard treatment of end-stage renal disease. Despite progressive advances in organ preservation, surgical technique, intensive care, and immunosuppression, long-term allograft survival has not significantly improved. Among the many peri-operative complications that can jeopardize transplant outcomes, ischemia–reperfusion injury (IRI) deserves special consideration as it is associated with delayed graft function, acute rejection, and premature transplant loss. Over the years, several strategies have been proposed to mitigate the impact of IRI and favor tolerance, with rather disappointing results. There is mounting evidence that adipose stem/stromal cells (ASCs) possess specific characteristics that could help prevent, reduce, or reverse IRI. Immunomodulating and tolerogenic properties have also been suggested, thus leading to the development of ASC-based prophylactic and therapeutic strategies in pre-clinical and clinical models of renal IRI and allograft rejection. ASCs are copious, easy to harvest, and readily expandable in culture. Furthermore, ASCs can secrete extracellular vesicles (EV) which may act as powerful mediators of tissue repair and tolerance. In the present review, we discuss the current knowledge on the mechanisms of action and therapeutic opportunities offered by ASCs and ASC-derived EVs in the KT setting. Most relevant pre-clinical and clinical studies as well as actual limitations and future perspective are highlighted.
Continuous Sugarcane Planting Negatively Impacts Soil Microbial Community Structure, Soil Fertility, and Sugarcane Agronomic Parameters

Continuous planting has a negative impact on sugarcane plant growth and reduces global sugarcane crop production, including in China. The response of soil bacteria, fungal, and arbuscular mycorrhizae (AM) fungal communities to continuous sugarcane cultivation has not been thoroughly documented. Using MiSeq sequencing technology, we analyzed soil samples from sugarcane fields with 1, 10, and 30 years of continuous cropping to see how monoculture time affected sugarcane yield, its rhizosphere soil characteristics and microbiota. The results showed that continuous sugarcane planting reduced sugarcane quality and yield. Continuous sugarcane planting for 30 years resulted in soil acidification, as well as C/N, alkali hydrolyzable nitrogen, organic matter, and total sulfur content significantly lower than in newly planted fields. Continuous sugarcane planting affected soil bacterial, fungal, and AM fungal communities, according to PCoA and ANOSIM analysis. Redundancy analysis (RDA) results showed that bacterial, fungal, and AM fungal community composition were strongly associated with soil properties and attributes, e.g., soil AN, OM, and TS were critical environmental factors in transforming the bacterial community. The LEfSe analysis revealed bacterial families (e.g., Gaiellaceae, Pseudomonadaceae, Micromonosporaceae, Nitrosomonadaceae, and Methyloligellaceae) were more prevalent in the newly planted field than in continuously cultivated fields (10 and 30 years), whereas Sphingomonadaceae, Coleofasciculaceae, and Oxyphotobacteria were depleted. Concerning fungal families, the newly planted field was more dominated than the continuously planted field (30 years) with Mrakiaceae and Ceratocystidaceae, whereas Piskurozymaceae, Trimorphomycetaceae, Lachnocladiaceae, and Stigmatodisc were significantly enriched in the continuously planted fields (10 and 30 years). Regarding AMF families, Diversisporaceae was considerably depleted in continuously planted fields (10 and 30 years) compared to the newly planted field. These changes in microbial composition may ultimately lead to a decrease in sugarcane yield and quality in the monoculture system, which provides a theoretical basis for the obstruction mechanism of the continuous sugarcane planting system. However, continuous planting obstacles remain uncertain and further need to be coupled with root exudates, soil metabolomics, proteomics, nematodes, and other exploratory methods.
Comparison and Performance Validation of Calculated and Established Anaerobic Lactate Thresholds in Running

Background and Objectives: This study aimed to compare the calculated running velocity at the anaerobic lactate threshold (cLTAn), determined by a mathematical model for metabolic simulation, with two established threshold concepts (onset of blood lactate accumulation (OBLA; 4 mmol∙L−1) and modified maximal deviation method (mDmax)). Additionally, all threshold concepts were correlated with performance in different endurance running events. Materials and Methods: Ten sub-elite runners performed a 30 s sprint test on a cycle ergometer adjusted to an isokinetic mode set to a cadence of 120 rpm to determine maximal lactate production rate (VLamax), and a graded exercise test on a treadmill to determine maximal oxygen uptake (VO2max). Running velocities at OBLA, mDmax, and cLTAn were then compared with each other, and further correlated with running performance over various distances (3000 m, 5000 m, and 10,000 m). Results: The mean difference in cLTAn was −0.13 ± 0.43 m∙s−1 and −0.32 ± 0.39 m∙s−1 compared to mDmax (p = 0.49) and OBLA (p < 0.01), respectively. cLTAn indicated moderate to good concordance with the established threshold concepts (mDmax: ICC = 0.87, OBLA: ICC = 0.74). In comparison with other threshold concepts, cLTAn exhibited comparable correlations with the assessed running performances (cLTAn: r = 0.61–0.76, mDmax: r = 0.69–0.79, OBLA: r = 0.56–0.69). Conclusion: Our data show that cLTAn can be applied for determining endurance performance during running. Due to the consideration of individual physiological profiles, cLTAn offers a physiologically justified approach to assess an athlete’s endurance performance.
Precision Neurosurgery: A Path Forward

Since the inception of their profession, neurosurgeons have defined themselves as physicians with a surgical practice. Throughout time, neurosurgery has always taken advantage of technological advances to provide better and safer care for patients. In the ongoing precision medicine surge that drives patient-centric healthcare, neurosurgery strives to effectively embrace the era of data-driven medicine. Neuro-oncology best illustrates this convergence between surgery and precision medicine with the advent of molecular profiling, imaging and data analytics. This convenient convergence paves the way for new preventive, diagnostic, prognostic and targeted therapeutic perspectives. The prominent advances in healthcare and big data forcefully challenge the medical community to deeply rethink current and future medical practice. This work provides a historical perspective on neurosurgery. It also discusses the impact of the conceptual shift of precision medicine on neurosurgery through the lens of neuro-oncology.
Chronic Kidney Disease on Health-Related Quality of Life in Patients with Diabetes Mellitus: A National Representative Study

Importance: With an increasing prevalence of diabetes mellitus (DM) and comorbid chronic kidney disease (CKD), health-related quality of life (HRQoL) in patients with DM and CKD needs to be better understood. Objective: To investigate the association between the severity of CKD on HRQoL in DM patients. Design: A cross-sectional study of a nationally representative population-based survey, the Korea National Health and Nutrition Examination Survey (KNHANES). Setting: Data collected between 2007 and 2018 from the KNHANES. Participants: Adult participants with DM who completed the self-administered European Quality of Life Questionnaire Five Dimension (EQ-5D) questionnaire (n = 7243). Exposures: CKD stages defined by the Kidney Disease Improving Global System (KDIGO) staging system. Main Outcomes and Measures: We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of the presence of having problems in the 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of EQ-5D by CKD stage after adjusting for socio-demographic parameters and comorbid conditions. In addition, the EQ-5D index, reflecting the overall health status, was compared across CKD stages. Results: Among 7243 participants (mean (standard error) age 58.2 (0.2) 56.9% male), 24.0% (n = 1768) had CKD and 8.6% (n = 775) had stage 3–5 CKD. Pain/discomfort was the most common problem (30.5%) among patients with DM. Participants with more advanced CKD were more likely to experience problems in all dimensions of EQ-5D except the anxiety/depression dimension. In particular, compared to those without CKD, the adjusted ORs (95% CI) for any problem in the usual activities dimension was 1.65 (1.30, 2.10) in CKD stage 3 and 4.23 (2.07, 8.67) in CKD stage 4–5. Moreover, participants with stage 3 (−0.016 (−0.029, −0.003)) and stage 4–5 CKD (−0.088 (−0.129, −0.048)) had significantly lower EQ-5D index than those without CKD. However, compared with no CKD, CKD stage 1–2 was not significantly associated with having any problem in any dimensions. Conclusions and Relevance: In this nationally representative study, patients with DM had a high prevalence of self-reported poor HRQoL and the prevalence increased with more advanced stages of CKD. Therefore, assessment of HRQoL and interventions are necessary at early stages of CKD in DM patients.
MiRNA: Involvement of the MAPK Pathway in Ischemic Stroke. A Promising Therapeutic Target

Ischemic stroke (IS) is a cerebrovascular disease with a high rate of disability and mortality. It is classified as the second leading cause of death that arises from the sudden occlusion of small vessels in the brain with consequent lack of oxygen and nutrients in the brain tissue. Following an acute ischemic event, the cascade of events promotes the activation of multiple signaling pathways responsible for irreversible neuronal damage. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to different stimuli, regulating proliferation, differentiation, inflammation, and apoptosis. Several lines of evidence showed that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease; indeed, it can impair blood–brain barrier (BBB) integrity and exacerbate neuroinflammation through the release of pro-inflammatory mediators implementing neurovascular damage after ischemic stroke. This review aims to illustrate the miRNAs involved in the regulation of MAPK in IS, in order to highlight possible targets for potential neuroprotective treatments. We also discuss some miRNAs (miR), including miR-145, miR-137, miR-493, and miR-126, that are important as they modulate processes such as apoptosis, neuroinflammation, neurogenesis, and angiogenesis through the regulation of the MAPK pathway in cerebral IS. To date, limited drug therapies are available for the treatment of IS; therefore, it is necessary to implement preclinical and clinical studies aimed at discovering novel therapeutic approaches to minimize post-stroke neurological damage.
Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals

Drug-induced liver injury, including cholestasis, is an important clinical issue and economic burden for pharmaceutical industry and healthcare systems. However, human-relevant in vitro information on the ability of other types of chemicals to induce cholestatic hepatotoxicity is lacking. This work aimed at investigating the cholestatic potential of non-pharmaceutical chemicals using primary human hepatocytes cultured in 3D spheroids. Spheroid cultures were repeatedly (co-) exposed to drugs (cyclosporine-A, bosentan, macitentan) or non-pharmaceutical chemicals (paraquat, tartrazine, triclosan) and a concentrated mixture of bile acids for 4 weeks. Cell viability (adenosine triphosphate content) was checked every week and used to calculate the cholestatic index, an indicator of cholestatic liability. Microarray analysis was performed at specific time-points to verify the deregulation of genes related to cholestasis, steatosis and fibrosis. Despite the evident inter-donor variability, shorter exposures to cyclosporine-A consistently produced cholestatic index values below 0.80 with transcriptomic data partially supporting its cholestatic burden. Bosentan confirmed to be hepatotoxic, while macitentan was not toxic in the tested concentrations. Prolonged exposure to paraquat suggested fibrotic potential, while triclosan markedly deregulated genes involved in different types of hepatotoxicity. These results support the applicability of primary human hepatocyte spheroids to study hepatotoxicity of non-pharmaceutical chemicals in vitro.
A Six-Day, Lifestyle-Based Immersion Program Mitigates Cardiovascular Risk Factors and Induces Shifts in Gut Microbiota, Specifically Lachnospiraceae, Ruminococcaceae, Faecalibacterium prausnitzii: A Pilot Study

Cardiovascular disease (CVD) prevalence remains elevated globally. We have previously shown that a one-week lifestyle “immersion program” leads to clinical improvements and sustained improvements in quality of life in moderate to high atherosclerotic CVD (ASCVD) risk individuals. In a subsequent year of this similarly modeled immersion program, we again collected markers of cardiovascular health and, additionally, evaluated intestinal microbiome composition. ASCVD risk volunteers (n = 73) completed the one-week “immersion program” involving nutrition (100% plant-based foods), stress management education, and exercise. Anthropometric measurements and CVD risk factors were compared at baseline and post intervention. A subgroup (n = 22) provided stool, which we analyzed with 16S rRNA sequencing. We assessed abundance changes within-person, correlated the abundance shifts with clinical changes, and inferred functional pathways using PICRUSt. Reductions in blood pressure, total cholesterol, and triglycerides, were observed without reduction in weight. Significant increases in butyrate producers were detected, including Lachnospiraceae and Oscillospirales. Within-person, significant shifts in relative abundance (RA) occurred, e.g., increased Lachnospiraceae (+58.8% RA, p = 0.0002), Ruminococcaceae (+82.1%, p = 0.0003), Faecalibacterium prausnitzii (+54.5%, p = 0.002), and diversification and richness. Microbiota changes significantly correlated with body mass index (BMI), blood pressure (BP), cholesterol, high-sensitivity C-reactive protein (hsCRP), glucose, and trimethylamine N-oxide (TMAO) changes. Pairwise decreases were inferred in microbial genes corresponding to cancer, metabolic disease, and amino acid metabolism. This brief lifestyle-based intervention improved lipids and BP and enhanced known butyrate producers, without significant weight loss. These results demonstrate a promising non-pharmacological preventative strategy for improving cardiovascular health.
Independence of a Marine Unicellular Diazotroph to the Presence of NO3−

Marine nitrogen (N2) fixation was historically considered to be absent or reduced in nitrate (NO3−) rich environments. This is commonly attributed to the lower energetic cost of NO3− uptake compared to diazotrophy in oxic environments. This paradigm often contributes to making inferences about diazotroph distribution and activity in the ocean, and is also often used in biogeochemical ocean models. To assess the general validity of this paradigm beyond the traditionally used model organism Trichodesmium spp. , we grew cultures of the unicellular cyanobacterium Crocosphaera watsonii WH8501 long term in medium containing replete concentrations of NO3−. NO3− uptake was measured in comparison to N2 fixation to assess the cultures’ nitrogen source preferences. We further measured culture growth rate, cell stoichiometry, and carbon fixation rate to determine if the presence of NO3− had any effect on cell metabolism. We found that uptake of NO3− by this strain of Crocosphaera was minimal in comparison to other N sources (~2–4% of total uptake). Furthermore, availability of NO3− did not statistically alter N2 fixation rate nor any aspect of cell physiology or metabolism measured (cellular growth rate, cell stoichiometry, cell size, nitrogen fixation rate, nitrogenase activity) in comparison to a NO3− free control culture. These results demonstrate the capability of a marine diazotroph to fix nitrogen and grow independently of NO3−. This lack of sensitivity of diazotrophy to NO3− suggests that assumptions often made about, and model formulations of, N2 fixation should be reconsidered.
Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice

Significance Coronaviruses (CoVs) have the largest genome among RNA viruses and a proofreading exoribonuclease (nsp14) responsible for high-fidelity RNA synthesis. These properties make CoVs very attractive for the establishment of vaccine platforms or viral vectors since they can stably store large amounts of information without genome integration. Using Middle East respiratory syndrome coronavirus (MERS-CoV) as a model, a propagation-deficient RNA replicon was generated by removing the envelope (E) gene (essential for viral morphogenesis and involved in virulence) and accessory genes 3, 4a, 4b, and 5 (responsible for antagonism of the innate immune response): MERS-CoV-Δ[3,4a,4b,5,E]. This replicon is strongly attenuated and elicits sterilizing protection after a single immunization, making it a promising vaccine candidate and an interesting platform for vector-based vaccine development. Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.
From Mum to Bum: An Observational Study Protocol to Follow Digestion of Human Milk Oligosaccharides and Glycoproteins from Mother to Preterm Infant

The nutritional requirements of preterm infants are challenging to meet in neonatal care, yet crucial for their growth, development and health. Aberrant maturation of the gastrointestinal tract and the microbiota could affect the digestion of human milk and its nutritional value considerably. Therefore, the main objective of the proposed research is to investigate how the intestinal microbiota of preterm and full-term infants differ in their ability to extract energy and nutrients from oligosaccharides and glycoproteins in human milk. This pilot study will be an observational, single-center study performed at the Neonatal Intensive Care Unit at Isala Women and Children’s Hospital (Zwolle, The Netherlands). A cohort of thirty mother–infant pairs (preterm ≤30 weeks of gestation, n = 15; full-term 37–42 weeks of gestation, n = 15) will be followed during the first six postnatal weeks with follow-up at three- and six-months postnatal age. We will collect human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants. A combination of 16S rRNA amplicon sequencing, proteomics, peptidomics, carbohydrate analysis and calorimetric measurements will be performed. The role of the microbiota in infant growth and development is often overlooked yet offers opportunities to advance neonatal care. The ‘From Mum to Bum’ study is the first study in which the effect of a preterm gut microbiota composition on its metabolic capacity and subsequent infant growth and development is investigated. By collecting human milk of all mothers, gastric aspirates of preterm infants and fecal samples of all infants at each timepoint, we can follow digestion of human milk from the breast of the mother throughout the gastrointestinal tract of the infant, or ‘From Mum to Bum’.