Uncovering excellence in academic rankings: a closer look at the Shanghai ranking

In this paper, we examine whether the quality of academic research can be accurately captured by a single aggregated measure such as a ranking. With Shanghai University’s Academic Ranking of World Universities as the basis for our study, we use robust principal component analysis to uncover the underlying factors measured by this ranking. Based on a sample containing the top 150 ranked universities, we find evidence that, for the majority of these institutions, the Shanghai rankings reflect not one but in fact two different and uncorrelated aspects of academic research: overall research output and top-notch researchers. Consequently, the relative weight placed upon these two factors determines to a large extent the final ranking.     

DBPs formation and toxicity monitoring in different origin water treated by ozone and alum/PAC coagulation

In this study, aluminium sulphate (alum) and polyaluminum chloride (PAC) coagulation were used for coagulation of different origin water (Buyukcekmece, BC and Omerli, OM in Istanbul, Turkey and Carmine, CR in Salerno, Italy) treatment. The effect of pre-ozonation alone and combined with coagulation on NOM removal which was characterized by TOC, UV254 was investigated. DBPs formation and acute toxicity on Daphnia magna of chlorinated raw and treated samples were defined in parallel. Moreover, bromide spiking was evaluated for DBPs speciation. Optimum alum dose for TOC removal was found to be 40 mg/L for OM while 80 mg/L of alum exhibited the lowest total trihalomethane formation potential (TTHMFP). Pre-ozonation enhanced the removal of TOC and reduction of TTHMFP when it was used in combination with both coagulants. In contrast, total haloacetic acid formation potential (THAAFP) increased after each coagulation, ozonation and their combination. 300 µg/L bromide spiking (around the same level with BC) in raw sample collected from CR increased the formation of brominated disinfection byproducts. Raw and treated samples displayed acute toxicity on Daphnia magna in different pattern and practically “no dose-response behavior” was observed.     

A second-generation voltage conveyor (VCII)–based simulated grounded inductor

In this paper, an implementation of a simulated grounded inductor (SGI) based on a recently developed active building block called second-generation voltage conveyor (VCII) is proposed. The proposed SGI employs two VCIIs, two resistors, and one grounded capacitor, which is preferred when integration is involved. More importantly, unlike most of the other previously reported SGIs, this one is free from any restrictive matching conditions. A complete analysis of nonidealities along with sensitivity treatment by considering parasitic impedances and nonideal gains of the VCII are performed. A simple VCII circuit is designed to be used in the implementation of the proposed SGI. To support the presented theory, Pspice simulation results using 0.18-μm CMOS technology parameters and supply voltage of ±0.9 V are provided. On the basis of the achieved results, the proposed SGI operates in a good agreement with an ideal inductor. The power consumption is only 0.65 mW, and the parasitic series impedance is approximately 191.9 Ω. The applicability of the proposed SGI is tested by using it in a standard second-order high-pass RLC filter.     

A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 10⁶ or 2 × 10⁶ hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 μL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.     

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are malignancies of the hematopoietic stem cell (HSC) arising as a consequence of clonal proliferation driven by somatically acquired driver mutations in discrete genes (JAK2, CALR, MPL). In recent years, along with the advances in molecular characterization, the role of immune dysregulation has been achieving increasing relevance in the pathogenesis and evolution of MPNs. In particular, a growing number of studies have shown that MPNs are often associated with detrimental cytokine milieu, expansion of the monocyte/macrophage compartment and myeloid-derived suppressor cells, as well as altered functions of T cells, dendritic cells and NK cells. Moreover, akin to solid tumors and other hematological malignancies, MPNs are able to evade T cell immune surveillance by engaging the PD-1/PD-L1 axis, whose pharmacological blockade with checkpoint inhibitors can successfully restore effective antitumor responses. A further interesting cue is provided by the recent discovery of the high immunogenic potential of JAK2V617F and CALR exon 9 mutations, that could be harnessed as intriguing targets for innovative adoptive immunotherapies. This review focuses on the recent insights in the immunological dysfunctions contributing to the pathogenesis of MPNs and outlines the potential impact of related immunotherapeutic approaches.     

Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration

Transient receptor potential channels-vanilloid receptor 1 (TRPV1) regulates thermotaxis in sperm-oriented motility. We investigated the role of membrane cholesterol (Chol) on TRPV1-mediated human sperm migration. Semen samples were obtained from five normozoospemic healthy volunteers. Sperm membrane Chol content, quantified by liquid chromatography-mass spectrometry, was modified by incubating cells with 2-hydroxypropyl-ß-cyclodextrin (CD) or the complex between CD and Chol (CD:Chol). The effect on sperm migration on a 10 μM capsaicin gradient (CPS), a TRPV1 agonist, was then investigated. Motility parameters were evaluated by Sperm Class Analyser. Intracellular calcium concentration and acrosome reaction were measured by staining with calcium orange and FITC-conjugated anti-CD46 antibody, respectively. TRPV1-Chol interaction was modelled by computational molecular-modelling (MM). CD and CD:Chol, respectively, reduced and increased membrane Chol content in a dose-dependent manner, resulting in a dose-dependent increase and reduction of sperm migration in a CPS gradient. MM confirmed a specific interaction of Chol with a TRPV1 domain that appeared precluded to the Chol epimer epicholesterol (Epi-Chol). Accordingly, CD:Epi-Chol was significantly less efficient than CD:Chol, in reducing sperm migration under CPS gradient. Chol inhibits TRPV1-mediated sperm function by directly interacting with a consensus sequence of the receptor.     

The Nucleolar Protein Nucleophosmin Is Physiologically Secreted by Endothelial Cells in Response to Stress Exerting Proangiogenic Activity Both In Vitro and In Vivo

Nucleophosmin (NPM), a nucleolar multifunctional phosphoprotein, acts as a stress sensor in different cell types. NPM can be actively secreted by inflammatory cells, however its biology on endothelium remains unexplored. In this study, we show for the first time that NPM is secreted by human vein endothelial cells (HUVEC) in the early response to serum deprivation and that NPM acts as a pro-inflammatory and angiogenic molecule both in vitro and in vivo. Accordingly, 24 h of serum starvation condition induced NPM relocalization from the nucleus to cytoplasm. Interestingly, NPM was increasingly excreted in HUVEC-derived conditioned media in a time dependent fashion upon stress conditions up to 24 h. The secretion of NPM was unrelated to cell necrosis within 24 h. The treatment with exogenous and recombinant NPM (rNPM) enhanced migration as well as the Intercellular Adhesion Molecule 1 (ICAM-1) but not Vascular cell adhesion protein 1 (VCAM-1) expression and it did not affect cell proliferation. Notably, in vitro tube formation by Matrigel assay was significantly increased in HUVEC treated with rNPM compared to controls. This result was confirmed by the in vivo injection of Matrigel plug assay upon stimulation with rNPM, displaying significant enhanced number of functional capillaries in the plugs. The stimulation with rNPM in HUVEC was also associated to the increased expression of master genes regulating angiogenesis and migration, including Vascular Endothelial Growth Factor-A (VEGF-A), Hepatocyte Growth Factor (HGF), Stromal derived factor-1 (SDF-1), Fibroblast growth factor-2 (FGF-2), Platelet Derived Growth Factor-B (PDGF-B), and Matrix metallopeptidase 9 (MMP9). Our study demonstrates for the first time that NPM is physiologically secreted by somatic cells under stress condition and in the absence of cell necrosis. The analysis of the biological effects induced by NPM mainly related to a pro-angiogenic and inflammatory activity might suggest an important autocrine/paracrine role for NPM in the regulation of both phenomena.     

Repurposing of FDA-Approved Drugs for Treating Iatrogenic Botulism: A Paired 3D-QSAR/Docking Approach†

Botulinum neurotoxin (BoNT) is widely used for the treatment of spasticity, focal dystonia, chronic migraine, facial hemispasm, and facial aesthetic treatments. Generally, treatment with botulinum toxin is a safe procedure when conducted by clinicians with expertise, and local side effects are rare and transient. However, occasionally adverse effects can occur due to the spread of the drug to nontargeted muscles and organs, producing dry mouth, fatigue, and flu-like symptoms, up to signs of systemic botulism, which appears to be more frequent in children treated for spasticity than in adults. In silico 3D-QSAR and molecular docking studies were performed to build a structure-based model on selected potent known botulinum neurotoxin type A inhibitors; this was used to screen the US Food and Drug Administration (FDA) database. Thirty molecules were identified as possible light-chain BoNT/A inhibitors. In this study, we applied a well-established ligand- and structure-based methodology for the identification of hit compounds among a database of FDA-approved drugs. The identification of budesonide, protirelin, and ciclesonide followed by other compounds can be considered a starting point for investigations of selected compounds that could bypass much of the time and costs involved in the drug approval process.     

Comparison of Different Possible Technologies for Epoxidation of Cynara cardunculus Seed Oil

The world production of epoxidized vegetable oil, mainly epoxidized soybean oil, is continuously increasing because this product can have a wide range of applications. Non‐edible vegetable oils, recovered by the plants growing on marginal and polluted lands, represent a possible answer to industry versus food chain debate. Cardoon (Cynara cardunculus L.) seed oil can be considered as an interesting and sustainable alternative to edible soybean oil to make plasticizers. In this work, a comparison between different epoxidation methods of cardoon oil is depicted and argued, focusing on strong points and weaknesses for each of them. It is found that cardoon seed oil can be successfully epoxidized through feasible existing technologies, by peracids and hydrogen peroxide equally. Moreover, it is demonstrated that a “greener” cardoon oil epoxidation process is possible, by using hydrogen peroxide in the presence of commercial γ‐alumina as heterogeneous solid catalyst. Practical Applications: The paper analyzes the advantages and the problems of different epoxidation methods in order to obtain a final product with high quality and answer the environmental, social, and economic sustainability requirements.     

NPM1-Mutated Myeloid Neoplasms with <20% Blasts: A Really Distinct Clinico-Pathologic Entity?

Nucleophosmin (NPM1) gene mutations rarely occur in non-acute myeloid neoplasms (MNs) with <20% blasts. Among nearly 10,000 patients investigated so far, molecular analyses documented NPM1 mutations in around 2% of myelodysplastic syndrome (MDS) cases, mainly belonging to MDS with excess of blasts, and 3% of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) cases, prevalently classified as chronic myelomonocytic leukemia. These uncommon malignancies are associated with an aggressive clinical course, relatively rapid progression to overt acute myeloid leukemia (AML) and poor survival outcomes, raising controversies on their classification as distinct clinico-pathologic entities. Furthermore, fit patients with NPM1-mutated MNs with <20% blasts could benefit most from upfront intensive chemotherapy for AML rather than from moderate intensity MDS-directed therapies, although no firm conclusion can currently be drawn on best therapeutic approaches, due to the limited available data, obtained from small and mainly retrospective series. Caution is also suggested in definitely diagnosing NPM1-mutated MNs with blast count <20%, since NPM1-mutated AML cases frequently present dysplastic features and multilineage bone marrow cells showing abnormal cytoplasmic NPM1 protein delocalization by immunohistochemical staining, therefore belonging to NPM1-mutated clone regardless of blast morphology. Further prospective studies are warranted to definitely assess whether NPM1 mutations may become sufficient to diagnose AML, irrespective of blast percentage.