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• Discusses ethical issues in research social networks in business and management contexts. • Considers ethical challenges at each stage of the research process. • Discusses ethics in commissioning, research design, data collection, analysis and reporting. • Provides big and small data examples from the author's own experience. • Proposes mitigating remedies for the ethical problems identified. Reflecting on the compilation and analysis of a range of network datasets drawn from our own work and some prominent examples, we consider the ethical challenges in dealing with network data in business and management settings. We argue that the managerial processes that characterize such settings introduce particular ethical sensitivities in the stages of commissioning and research design, and when collecting, analyzing and reporting network data. These sensitivities arise from the imperatives of business, motivations for commissioning network analyses and the legal authority that managers have over employees. We argue that ethical considerations are much more pervasive in business and management network research than in many other fields. In this contribution, we present a range of ethical challenges in network research in business and management settings that arise at several stages of the research process. For each issue identified, we describe the ethical problem and propose mitigation remedies. From this reflection, we suggest guidelines for other researchers to consider when designing research projects in this application area. [ABSTRACT FROM AUTHOR]

In critically ill patients with liver disease, vitamin D deficiency is associated with higher disease severity, increased frequency of infections, and worse outcomes. This study sought to describe the trend of vitamin D in orthotopic liver transplantation (OLT) recipients and its association with outcomes. Prospective observational study of 67 consecutive OLT recipients enrolled between September, 2016 and August, 2017 at IRCCS-ISMETT, Palermo (Italy). Trend of vitamin D levels and potential factors influencing it levels were evaluated through a generalized linear mixed regression model. Sixty-four (95.5%) recipients were vitamin D deficient (<20 ng/ml), with a median value of 8.8 ng/ml [6.2–12.9], and forty-seven of these (70.1%) showed severe deficiency (<12 ng/ml) at baseline, 7.9 ng/ml [5.4–8.9]. The baseline vitamin D showed an inverse correlation with liver disease severity: Child-Pugh, MELD score, bilirubin, INR, and organ failure (p < 0.01) at baseline. Vitamin D increased on postoperative day (POD) 28 compared with POD1: +4.5 ng/ml, C.I. 95% 3.6–5.3 ng/ml, p < 0.01. Lower baseline vitamin D, donor age, transfusion of fresh frozen plasma (negative impact, all p < 0.05), and intra-operative bypass (positive impact at POD 28, p < 0.01) were associated with variation of vitamin D levels after transplantation. Incomplete graft recovery was associated with lower vitamin D on POD28: 8.2 ± 4.4 versus 13.8 ± 9.4 ng/ml, p < 0.01; the odds ratio (OR) was 0.84; CI 95% 0.73–0.97, p = 0.014. The OR for infections within POD 28 was inversely associated with baseline vitamin D: 0.87; CI 95% 0.79–0.98, p = 0.02, and with vitamin D level at baseline <12 ng/ml: OR 6.44; CI 95% 1.66–24.94; p < 0.01. Preoperative Vitamin D is correlated with disease severity, and was highly associated with invasive infection in the first 28 PODs. After OLT, the value on POD 28 had a strong association with graft function. • Vitamin D has pleiotropic biological effects relevant for critically ill patients. • The majority of liver transplantation recipients have vitamin D deficiency. • Vitamin D level is inversely associated with disease severity in liver disease. • During tansplantation recipients be supplemented with vitamin D routie day 28. • Liver transplantation recipients should be supplemented with vitamin D routinely. [ABSTRACT FROM AUTHOR]

This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve. A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal component analysis followed by logistic regression allowed the development of a predictive model of aortic surgery by combining biomechanical descriptors and biomarkers. The protein activity of MMP-1, TIMP-1, and MMP-2 was positively correlated to the systolic WSS and TAWSS observed in the proximal ascending aorta (eg, R = 0.52, P <.001, for MMP-1 with TAWSS) where local maxima of WSS were found. For bicuspid patients, aortic wall strain was associated with miR-26a (R = 0.55, P =.041) and miR-320a (R = 0.69, P <.001), which shows a significant difference between bicuspid and tricuspid patients. Receiver-operating characteristics curves revealed that the combination of WSS, MMP-1, TIMP-1, and MMP-12 is predictive of aortic surgery (area under the curve 0.898). Increased flow-based and structural descriptors of ascending aortic aneurysms are associated with high levels of circulating biomarkers, implicating adverse vascular remodeling in the dilated aorta by mechanotransduction. A combination of shear stress and circulating biomarkers has the potential to improve the decision-making process for ascending aortic aneurysms to a highly individualized level. [ABSTRACT FROM AUTHOR]

Abstract: We reconstruct the dual network structure generated by the association between 72 contributors and 737 software bugs engaged during a full development cycle of the free/open source software project Epiphany. Estimates of structural parameters of Exponential Random Graph Models for two-mode networks reveal the structural logics shaping activities of collaborative problem solving. After controlling for contributor-specific and software bug-specific characteristics, we find that contributors (“problem solvers”) tend to distribute their activity over multiple software bugs. At the same time, however, we find that software bugs (“problems”) tend not to share multiple contributors. This dual tendency toward de-specialization and exclusivity is sustained by specific local network dependencies revealed by our analysis which also suggests possible organizational mechanisms that may be underlying the puzzling macro-structural regularities frequently observed, but rarely explained, in the production of open source software. By combining these mechanisms with the influence of contributors characterized by different levels of involvement in the project, we provide micro-level evidence of structural interdependence between “core” and “peripheral” members identified exclusively on the basis of their individual level of contribution to the project. [Copyright &y& Elsevier]

B Background: b Our study focuses on a cytofluorimetric examination of a monocentric series of consecutive liver perfusates (LPs) after whole graft washout in consecutive series of adult deceased brain donors (DBDs). B Conclusion: b Based on our experience a novel potential role of T and NK cells could be determined in IRI in humans, and this might be of high relevance for liver graft procurement management. [Extracted from the article]

B Background: b Hepatocellular carcinoma (HCC) recurrence (HR) after liver transplantation (LT) remains a challenging issue, because HCC size and number tell only a partial tale of the characteristics that predict post-transplant outcomes. FAI index has correctly classified on average 74% of patients, predicted HR within 2 years of LT for 69% of patients, and confirmed the high predictive role of allelic imbalance in D9S251. [Extracted from the article]

The global prevalence of end-stage liver disease (ESLD) has reached very high levels, and, to date, the best treatment option is orthotopic liver transplantation (1). However, due to the complexity of this procedure and the limited numbers of healthy organ donors, new therapeutic options are being sought. Liver progenitor and multipotent stem cells offer potential cell sources that could be used clinically (2). Different studies have reported therapeutic effects of transplanted mesenchymal stem cells (MSCs) on ESLD (3). Indeed, an improvement of liver function has been achieved in patients with liver cirrhosis after autologous MSCs injection (4). Based on our recent work where we showed that a three-dimensional (3D) culture method is effective to improve MSCs paracrine activity (5), in this work, we used a human liver organoid system to study if the paracrine signal secreted by human amnion-derived MSCs (hAMSCs) affect liver stem/progenitor cells to differentiate (Fig. 1). Epithelial organoids recapitulate multiple aspects of real organs, making them promising models of organ function to model and treat human disease (6). Our data show that the expanded human liver organoids had distinct traits in the ALB production, Krt19 and HNF1β expression when compared to the reference cell line HepG2 cells. On liver organoids, we tested conventional differentiation medium (DM) conditioned by both 2D (2D CM) and 3D (3D CM) hAMSCs cultures observing that ALB, NTCP (markers of mature hepatocytes), and LGR5 (stem cell marker) expression were significantly upregulated by 3D CM compared with both 2D CM and conventional DM. Furthermore, CYP3A4 expression (marker of mature hepatocytes) was upregulated in both 2D and 3D CM. These data were also confirmed by the over-production/activity of both ALB and CYP3A4 observed in organoids grown with 3D CM. Liver epithelial dysfunctional repair play a role in the development of liver disease, and, effective repair likely requires the normal functioning of liver stem/progenitor cells. Herein, we showed that hAMSCs, principally grown in 3D cultures, has the potential to increase hepatic stem/progenitor cell differentiation, demonstrating that soluble factors secreted by hAMSCs are likely responsible for the response. This work revealing a potential approach to improve cell transplantation with the ultimate goal being efficient liver regeneration. [ABSTRACT FROM AUTHOR]

During active surveillance at the Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT, Palermo, Italy) with the CARBA screening medium, five pairs of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae and Escherichia coli strains were isolated in each of five colonized patients. In each patient, lateral gene transfer was demonstrated by comparing K. pneumoniae and E. coli strains, both possessing KPC-3, Tn 4401a and pKpQIL-IT elements. The isolates were found to be multiclonal by multilocus sequence typing (sequence type (ST) 512 related to ST258, and ST307 belonging to a clonal complex different from the habitual sequence clone ST258 isolated in Italy) and pulsed-field gel electrophoresis. The results of our study highlight the easy transfer of KPC among Enterobacteriaceae colonizing the human intestine, and the active and careful surveillance required to identify and prevent the spread of these multidrug-resistant microorganisms. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the primary cancer of the liver and one of the leading causes of cancer-related mortality. One of the risk factor for HCC is HCV infection. HCC patients are treated with surgery to remove the area affected by cancer. However in advanced liver cancer cases, the most adopted clinical practice is transplant. Unfortunately, post-transplant liver cancer has still high incidence and more advanced and efficacious therapies are therefore necessary. Natural Killer (NK) cells of the innate immune system are capable of recognizing and destroying tumoral and infected cells. Their function can be redirected in vitro by means of specific cytokines. Herein we explore how the innate response to liver cancer and infection can be enhanced and describe the molecular mechanisms involved. Healthy donors NK cells were differentiated with specific cytokine mixes into cytotoxic or cytokine-releasing NK cells. Cell-cell killing function was assessed by CRA. The immune response mediated by soluble factors was assessed using transwell co-cultures with uninfected or HCV-infected Huh7.5 cells; infection and tumor growth were traced by quantification of HCV Core Antigen and Alpha-fetoprotein (AFP), respectively. By Mass Spectrometry we studied the protein content of the NK cells conditioned media after activation with different cytokine mixes. Here we described that the NK cell function can be greatly enhanced by using one specific cytokine mix of the 3 tested. Both anti-viral and anti-tumor response are increased, as demonstrated by increase killing by cell-contact but also in the transwell co-culture, with reduction of released viral particles and AFP, respectively. By proteomics we were able to identify a protein belonging to the β-galactoside family that was differentially produced when NK cells were activated with the strongest stimuli. By neutralization assay using a specific blocking antibody, we were able to confirm that this protein is directly involved in the NK-cell mediated response to HCV-infection and HCC. Our study describes a novel molecular pathway involved in the innate response to cancer and infection. By mean of Mass Spectrometry, a sophisticated high-throughput technology, we were able to discover a protein that is directly responsible for the enhanced NK cell function in certain conditions. This discovery can pave the way to new therapeutic applications that could exploit this biomarker for the treatment of liver-related pathologies. [ABSTRACT FROM AUTHOR]

Natural Killer (NK) cells respond to infection and tumor by releasing cytokines or by up-regulating the molecule TRAIL that induces target cells to apoptosis. The aim of the study was to discover if response to infection or tumor cells can be improved by differentiating NK cells in vitro with selected cytokines. Healthy donors NK cells were differentiated with two mixes of cytokines into cytotoxic TRAIL+ or cytokine-releasing IFNγ+TNFα+ cells and phenotype assessed by Flow Cytometry. Cytotoxicity was determined by CRA. NK immune function was studied in transwell co-cultures with tumor target cells +/- Hepatitis C virus (HCV); miRNome signature was investigated by Next Generation Sequencing and cytokine profiling by Multiplex. NK cell differentiation with any of the cytokine cocktails tested induced stable expression of activating receptors NKp30, NKp44 and NKp46. By cell-cell contact, cytotoxic TRAIL+ NK cells killed with the highest efficiency both tumor and infected target cells, while cytokine-releasing IFNγ+TNFα+ NK were less functional. Surprisingly, transwell co-culture assays demonstrated that TRAIL+ NK cells consistently eradicated HCV infection by releasing soluble factors and drastically diminished the levels of the tumor biomarker ∝FetoProtein released by tumor target cells; in parallel we observed that IFNγ+TNFα+ NK were not so efficient. By comparative miRNome analysis we underpinned a number of novel miRNA that will be herein described. Notably, hierarchical clustering showed systematic variations in the miRNA expression among the different groups. Protein analysis produced pattern of soluble factors, including soluble TRAIL protein implicated in the anti-tumor and anti- viral innate response. The pathways identified in activated TRAIL+ NK cells that specifically characterize their enhanced anti-viral and anti-tumor function compared to IFNγ+TNFα+ NK studied might represent a tool to license fully functional NK cells with translational potential for clinical applications. Directed pre-activation of NK cells prior infusion into patients might highly increase NK cells potential and thus contribute to successful immunotherapy. [ABSTRACT FROM AUTHOR]