Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression profiling of apoptosis‐related genes in enterocytes isolated from patients with ulcerative colitis

Apoptosis regulation has been implicated as a main cause of epithelial dysfunction in patients with ulcerative colitis. Apoptosis can be divided into distinct pathways, which depend on the expression of a large number of apoptosis‐related genes. The aim was to elucidate which pathways are dominant in normal and inflamed colonic epithelial cells. An apoptosis‐specific gene array expression profiling system of 96 genes was used to determine the expression profile of apoptosis‐related genes. Epithelial cells isolated from three patients with active ulcerative colitis were pooled and compared to pooled epithelial cells isolated from three control subjects. Genes found to be three‐fold or more overexpressed in ulcerative colitis were subsequently analysed by PCR in a larger population (10 patients with ulcerative colitis, 8 control subjects). Selected genes found not to be regulated were additionally tested by PCR in the same population. Six genes were found to be highly expressed in epithelial cells from both controls and ulcerative colitis patients. These included Bcl‐2 antagonist/killer, B lymphoid tyrosine kinase, caspase 14, Harakiri, tumour necrosis factor (TNF) receptor 2, and TNF receptor‐associated factor 1 (TRAF1). Three genes were found to be upregulated in ulcerative colitis (p<0.01): caspase 1 and 5, and inhibitor of apoptosis protein 2 (c‐IAP2). Both receptor‐ and mitochondrion‐dependent apoptosis pathways are well expressed in enterocytes. Mainly activation‐dependent and cytoprotective genes were upregulated in ulcerative colitis.
Impact of Environmental, Social, and Governance Information on Economic Performance: Evidence of a Corporate ‘Sustainability Advantage’ from Europe

Both UN Agenda 2030 and the Directive n. 2014/95/EU have recently promoted a marked improvement in sustainability disclosure, especially for larger companies or groups. Starting from this premise, we carried out an original study on the financial materiality of the E-S-G (environmental, social and governance) information of primary companies listed on major European indices in Belgium, France, Germany, Italy and Spain (BEL, CAC, DAX, FTSE-MIB, IBEX). Within the Stakeholder Theory and the Corporate Social Responsibility (CSR)–Corporate Social Perfomance (CSP) framework, our empirical analysis examined the impact of non-financial results (assessed through sustainability indicators) on economic (financial and market) performance in the timespan 2014–2017. We propose a different approach from previous studies, based on a PLS (Partial least squares)/SEM (Structural equation modeling) methodology together with the unprecedented consideration of “ESG” measures (Environmental, Social and Governance), either absolute (scores) or relative (extra-performance over industry sector). We find that, despite the absolute level of the individual ESG scores not being impactful, the “distance” from the industry average–normal figures (excess or abnormal ESG performance) is positively relevant, collaterally revisiting the notion of competitive advantage in sustainability terms. Corporate size is shown to be a significant background factor (as slack resources proxy). Social, environmental and governance responsibility (to all stakeholders) appear to be important as a competitive factor of the modern firm.
Loss of expression of antigen‐presenting molecules in human pancreatic cancer and pancreatic cancer cell lines

Tumours evade immune recognition and destruction through loss or down‐regulation of expression of antigen processing and antigen‐presenting molecules such as the human leucocyte antigen (HLA class I) and transporter for antigen presentation (TAP). This study examined the expression of HLA class I, class II and TAP in human pancreatic carcinoma tissue and 19 immortalized pancreatic cancer lines using a panel of antibodies directed against allele‐specific as well as monomorphic determinants of these molecules. In tissue samples, reduction or loss of HLA class I and TAP was observed in 76% of cases, loss or down‐regulation of TAP expression in 53%. In pancreatic cell lines down‐regulation or loss of class I and TAP expression was also observed frequently. However, reductions in class I and TAP expression were reversible upon exposure to interferon‐γin vitro, suggesting a regulatory rather than structural defect in these genes. De novo class II expression was observed in 26% of tumours and 42% of cell lines and may reflect the differentiation status of the cells. The high rate of class I and TAP loss has implications for immunotherapy strategies for pancreatic cancer, as such changes could facilitate a selective growth advantage for malignant cells. However, the reinduction of expression of these molecules with cytokines such as interferon‐γ may ultimately allow their cytotoxic T cell‐mediated destruction.
Pilot Investigation of the Association Between Serum Stress Neuropeptide Levels and Lymphocyte Expression of Fas and Fas Ligand in Critical Illness

Introduction: In critical illness, apoptotic loss of immunocytes is associated with immunosuppression. Aim: To explore expression of Fas/Fas ligand (FasL) on B and T cells from critically ill patients without sepsis compared to matched controls and associations with disease severity and neuropeptide Y (NPY), cortisol, adrenocorticotropic hormone (ACTH), and prolactin (PRL) levels. Methods: Repeated-measures correlational design with 36 critically ill patients (14-day follow-up) and 36 controls. Disease severity was assessed using the Multiple Organ Dysfunction Score (MODS) and Multi Organ Failure scale. Fas/FasL values were standardized for viable cell counts. An enzyme-linked immunosorbent assay (NPY) and electrochemiluminescence immunoassay (cortisol, ACTH, and PRL) were employed. Results: Fas and FasL expression on T-helper (p < .0001–.03) and T-cytotoxic cells (p < .0001–.002) and Fas expression on B cells (p < .0001–.03) were higher in patients. MODS severity was associated with FasL expression on cytotoxic T cells (r = .752–.902, p = .023–.037). There was an inverse association between Day 1 NPY levels and Fas expression on T-helper cells (r = −.447, p = .019). On the day of maximum severity, we report for the first time an inverse association between NPY levels and FasL expression on helper (r = −.733, p = .016) and cytotoxic (r = −.862, p = .003) T cells. Cortisol levels were positively associated with counts of FasL-positive helper (r = .828) and cytotoxic (r = .544, p < .05) T cells. Conclusion: Results suggest a potential role for stress neuropeptides in lymphocyte survival and activation in critical illness.
High‐throughput screening techniques for rapid PEG‐based precipitation of IgG4 mAb from clarified cell culture supernatant

Locating optimal protein precipitation conditions for complex biological feed materials is problematic. This article describes the application of a series of high‐throughput platforms for the rapid identification and selection of conditions for the precipitation of an IgG4 monoclonal antibody (mAb) from a complex feedstock using only microliter quantities of material. The approach uses 96‐microwell filter plates combined with high‐throughput analytical methods and a method for well volume determination for product quantification. The low material, time and resource requirements facilitated the use of a full factorial Design of Experiments (DoE) for the rapid investigation into how critical parameters impact the IgG4 precipitation. To aid the DoE, a set of preliminary range‐finding studies were conducted first. Data collected through this approach describing Polyethylene Glycol (PEG) precipitation of the IgG4 as a function of mAb concentration, precipitant concentration, and pH are presented. Response surface diagrams were used to explore interactions between parameters and to inform selection of the most favorable conditions for maximum yield and purification. PEG concentrations required for maximum yield and purity were dependant on the IgG4 concentration; however, concentrations of 14 to 20% w/v, pH 6.5, gave optimal levels of yield and purity. Application of the high‐throughput approach enabled 1,155 conditions to be examined with less than 1 g of material. The level of insights gained over such a short time frame is indicative of the power of microwell experimentation in allowing the rapid identification of appropriate processing conditions for key bioprocess operations. © 2009 American Institute of Chemical Engineers Biotechnol. Prog. , 2010
Inflammatory markers in patients with coronary artery disease with and without inflammatory rheumatic disease.

OBJECTIVES Patients with inflammatory rheumatic diseases (IRDs) have a higher morbidity and mortality from accelerated atherosclerosis than the general population. We hypothesized that patients with the combination of IRD and coronary artery disease (CAD) would have a certain inflammatory phenotype compared with CAD patients without this comorbidity. METHODS Four groups of patients were included: patients with IRD, referred to coronary artery bypass grafting (CABG) (CAD-IRD, n = 67), patients without IRD, referred to CABG (CAD, n = 52), patients with IRD without CAD (IRD, n = 32) and healthy controls (n = 30). Plasma levels of several inflammatory markers were analysed by enzyme immunoassays. RESULTS (i) Plasma levels of markers of endothelial cell activation [i.e. vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor] and osteoprotegerin (OPG) were significantly increased and plasma levels of CCL21 significantly decreased in CAD-IRD patients as compared with CAD patients without IRD. (ii) Within the CAD-IRD group, acute coronary syndrome was a significant predictor of OPG, suggesting an enhanced inflammatory response during plaque destabilization in CAD-IRD patients. (iii) Plasma levels of VCAM-1, OPG and CCL21, but not lipid parameters, IRD characteristics and several other inflammatory markers (e.g. CRP), were significant predictors of CAD-IRD as opposed to CAD in two logistic regression models. CONCLUSION Our findings further support a role for inflammation in the accelerated form of atherosclerosis in IRD patients, and suggest that certain inflammatory pathways, such as the enhanced endothelial cell activation and the RANK ligand/RANK/OPG system, may be of particular importance.
Regional context and realization of fertility intentions: the role of the urban context

ABSTRACT Despite regional variation in fertility, rural–urban differences in the realization of fertility intentions have not been addressed in previous research. This paper analyzes the realization with data from 11 European countries, employing binomial and multinomial logistic regression models, decomposition analyses, and examining the role of contextual factors. The results demonstrate that realization is lower in urban than in rural regions. In cities, postponement of childbearing is much more common. This can be partly explained by differences in characteristics (e.g., age, partnership status) of inhabitants who intend to have a(nother) child. Furthermore, contextual factors such as educational and economic opportunities play a role.
SWITCHING TO GOOD POLICY? THE CASE OF CENTRAL AND EASTERN EUROPEAN INFLATION TARGETERS

The paper analyzes how actual monetary policy changed following the official adoption of inflation targeting in the Czech Republic, Hungary, and Poland and how it affected the volatilities of important macroeconomic variables in the years thereafter. To disentangle the effects of the policy shift from exogenous changes in the volatilities of these variables, a Markov-switching dynamic stochastic general equilibrium model is estimated that allows for regime switches in the policy parameters and the volatilities of shocks hitting the economies. Whereas estimation results reveal periods of high and low volatility for all three economies, the presence of different policy regimes is supported by the underlying data for the Czech Republic and Poland, only. In both economies, monetary policy switched from weak and unsystematic to strong and systematic responses to inflation dynamics. Simulation results suggest that the policy shifts of both central banks successfully reduced inflation volatility in the following years. The observed reduction in output volatility, on the other hand, is attributed more to a reduction in the size of external shocks.
In Vitro and In Silico Antidiabetic and Antimicrobial Evaluation of Constituents from Kickxia ramosissima (Nanorrhinum ramosissimum)

Background and Aims: Kickxia ramosissima (Wall.) Janch (or Nanorrhinum ramosissimum (Wall.) Betsche is a well-known medicinal plant in Pakistan that is traditionally used in diabetic and inflammatory conditions. Because little information is available on its phytochemical composition, a range of constituents were isolated and evaluated in vitro in assays related to the traditional use. Methods: Dried whole plant material was extracted and chromatographically fractionated. Isolated constituents were evaluated in silico and in vitro in assays related to the traditional use against diabetes (inhibition of α-glucosidase activity; inhibition of advanced glycation endproducts) and in inflammatory conditions (inhibition of AAPH induced linoleic acid peroxidation, inhibition of 15-LOX, antimicrobial activity). Results: Phytochemical analysis of the extracts and fractions led to isolation of 7 compounds, including the iridoids kickxiasine (being a new compound), mussaenosidic acid, mussaenoside and linarioside; the flavonoids pectolinarigenin and pectolinarin; and 4-hydroxy-benzoic acid methyl ester. The iridoids showed weak antiglycation activity. The flavonoids, however, showed interesting results as pectolinarigenin was highly active compared to pectolinarin. In the α-glucosidase inhibition assay, only weak activity was observed for the iridoids. However, the flavonoid pectolinarigenin showed good activity, followed by pectolinarin. In the 15-LOX experiment, moderate inhibition was recorded for most compounds, the iridoids mussaenosidic acid and mussaenoside being the most active. In the AAPH assay, weak or no inhibition was recorded for all compounds. The in silico assays for the α-glucosidase and 15-LOX assays confirmed the results of respective in vitro assays. Pectolinarigenin showed moderate antimicrobial activity against Staphylococcus aureus, Plasmodium falciparum K1, and Trypanosoma cruzi, but it was not cytotoxic on a human MRC-5 cell line. Conclusion: Our findings may in part contribute to explain the traditional use of K. ramosissima.
Linking transformational leadership to nurses' extra-role performance: the mediating role of self-efficacy and work engagement.

AIMS This paper is a report of a social cognitive theory-guided study about the link between supervisors' transformational leadership and staff nurses' extra-role performance as mediated by nurse self-efficacy and work engagement. BACKGROUND Past research has acknowledged the positive influence that transformational leaders have on employee (extra-role) performance. However, less is known about the psychological mechanisms that may explain the links between transformational leaders and extra-role performance, which encompasses behaviours that are not considered formal job requirements, but which facilitate the smooth functioning of the organization as a social system. METHODS Seventeen supervisors evaluated nurses' extra-role performance, the data generating a sample consisting of 280 dyads. The nurses worked in different health services in a large Portuguese hospital and the participation rate was 76·9% for nurses and 100% for supervisors. Data were collected during 2009. A theory-driven model of the relationships between transformation leadership, self-efficacy, work engagement and nurses' extra-role performance was tested using Structural Equation Modelling. RESULTS Data analysis revealed a full mediation model in which transformational leadership explained extra-role performance through self-efficacy and work engagement. A direct relationship between transformational leadership and work engagement was also found. CONCLUSION Nurses' supervisors with a transformational leadership style enhance different 'extra-role' performance in nurses and this increases hospital efficacy. They do so by establishing a sense of self-efficacy but also by amplifying their levels of engagement in the workplace.
The environmental impact of solid-state materials working in an active caloric refrigerator compared to a vapor compression cooler

Received: 29 August 2018 Accepted: 11 November 2018 Caloric refrigeration is an emerging class of cooling technologies based on caloric effects detected in ferro-caloric solid-state materials. Depending of the nature of the driving field, it is possible distinguishing four main caloric refrigerations: magnetocaloric, electrocaloric, elastocaloric and barocaloric. Therefore, caloric refrigeration is based on solid-state materials, unlike vapor compression, nowadays still the most diffused cooling technique, whom employs fluids as refrigerants. Solid-state materials do not provide a direct contribution in global warming, since they do not disperse in the atmosphere, but only an indirect impact is registered when they are employed as refrigerants in cooling systems. On the other side, a vapor compression plant is characterized by both direct and indirect contributions to global warming. The main parameter to evaluate global warming impact and carbon-dioxide emissions coming out from a cooler is the Total Environmental Warming Impact (TEWI) index, which accounts both the direct and indirect contributions produced. In this paper a numerical ∆TEWI analysis is presented, comparing the environmental impact of a caloric refrigerator, operating with different caloric materials, with the one of a vapor compression cooler working with HFC134a.
Postoperative High-Sensitivity Troponin and Its Association With 30-Day and 12-Month, All-Cause Mortality in Patients Undergoing On-Pump Cardiac Surgery

BACKGROUND: Troponin T is a predictor of cardiac morbidity and mortality after cardiac surgery with most data examining fourth generational troponin T assays. We hypothesize that postoperative high-sensitivity troponin T (hsTnT) measured in increments of the upper limit of the norm independently predicts 30-day all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery from February 2010 to March 2012 in a prospective cohort that measured hsTnT at 0600 of the first and second postoperative day. Our primary end point was 30-day, all-cause mortality. The secondary end point was 12-month, all-cause mortality in patients surviving the first 30 days. We divided hsTnT into 5 predetermined categorizes based on the upper limit of the norm (ULN). We used Cox regression to examine an association of hsTnT independent of the EuroSCORE II at both 30 days as well as at 12 months in patients surviving the first 30 days. We assessed the area under the receiver operating characteristics curve and the net reassignment improvement for examining the benefit of adding of hsTnT to the EuroSCORE II for prognostication and restratification of 30-day, all-cause mortality. RESULTS: We included 1122 of 1155 eligible patients (75% male; mean age 66 ± 11 years). We observed 58 (5.2%) deaths at 30 days and another 35 (3.4%) deaths at 12 months in patients surviving 30 days. HsTnT categorized by ULN exhibited a graded response for the mortality. Furthermore, hsTnT remained an independent predictor of all-cause mortality at 30 days (adjusted hazard ratio 1.019 [1.014–1.024] per 10-fold increase in ULN) as well as at 12 months (adjusted hazard ratio 1.019 [1.007–1.032]) in patients surviving the first 30 days. The addition of hsTnT to the EuroSCORE II significantly increased the area under the receiver operating characteristics curve (area under curve: 0.816 [95% confidence interval, 0.754–0.878] versus area under curve: 0.870 [95% confidence interval, 0.822–0.917], respectively; P = .012). Finally, adding hsTnT to the EuroSCORE II improved restratification by the net reassignment improvement, primarily by improving rule-out of events. CONCLUSIONS: This analysis suggests that, similar to previous assays, higher postoperative concentrations of hsTnT are independently associated with all-cause mortality in patients undergoing on-pump cardiac surgery.
Sequence diversity in the large subunit of RNA polymerase I contributes to Mefenoxam insensitivity in Phytophthora infestans.

Phenylamide fungicides have been widely used for the control of oomycete-incited plant diseases for over 30 years. Insensitivity to this chemical class of fungicide was recorded early in its usage history, but the precise protein(s) conditioning insensitivity has proven difficult to determine. To determine the genetic basis of insensitivity and to inform strategies for the cloning of the gene(s) responsible, genetic crosses were established between Mefenoxam sensitive and intermediate insensitive isolates of Phytophthora infestans, the potato late blight pathogen. F1 progeny showed the expected semi-dominant phenotypes for Mefenoxam insensitivity and suggested the involvement of multiple loci, complicating the positional cloning of the gene(s) conditioning insensitivity to Mefenoxam. Instead, a candidate gene strategy was used, based on previous observations that the primary effect of phenylamide compounds is to inhibit ribosomal RNA synthesis. The subunits of RNA polymerase I (RNApolI) were sequenced from sensitive and insensitive isolates and F1 progeny. Single nucleotide polymorphisms (SNPs) specific to insensitive field isolates were identified in the gene encoding the large subunit of RNApolI. In a survey of field isolates, SNP T1145A (Y382F) showed an 86% association with Mefenoxam insensitivity. Isolates not showing this association belonged predominantly to one P. infestans genotype. The transfer of the 'insensitive' allele of RPA190 to a sensitive isolate yielded transgenic lines that were insensitive to Mefenoxam. These results demonstrate that sequence variation in RPA190 contributes to insensitivity to Mefenoxam in P. infestans.
Variable expression of CD3‐ζ chain in tumor‐infiltrating lymphocytes (TIL) derived from renal‐cell carcinoma: Relationship with til phenotype and function

It has been reported that in mice and in humans, tumor‐infiltrating lymphocytes (TIL) may exhibit a defect in CD3‐ζ‐chain expression. Therefore, the level of CD3‐ζ was analyzed in TIL derived from patients with renal‐cell carcinoma, and its correlation with TIL phenotype and function was assessed. We identified 4 out of 13 tumor‐infiltrating lymphocytes derived from renal‐cell carcinoma, with a significant decrease in CD3‐ζ‐chain expression as compared with control peripheral‐blood lymphocytes. This defect was never found after culturing TIL with IL2. In one case, the low expression of ζ chain observed in TIL on day 0 was reversed when TIL were cultured with IL2. The ζ‐chain level did not seem to predict the growth of TIL in response to IL2. All the TIL, irrespective of the level of ζ‐chain expression, exhibited lower proliferative response when stimulated with PHA or anti‐CD3 MAb in comparison with normal peripheral‐blood mononuclear cells. Nevertheless, in this limited series of patients, a correlation was observed between the level of ζ‐chain expression and T‐cell infiltration (p = 0.02). After TIL stimulation with PHA or anti‐CD3, in contrast to IL2 or IFNγ production, a trend towards a relationship between TNF α induction and the level of ζ‐chain expression was observed.