Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Eucalyptus, Chestnut and Heather Honeys from Portugal Using Multi-Parameter Analysis and Chemo-Calculus

The present study was conducted to evaluate the quality and bio-functional properties of Portuguese honeys of different botanical and geographical origins. Quality parameter analyses included the determination of palynological (predominant, secondary, minor and isolated pollen percentage), physicochemical (°Brix, moisture content, pH, electrical conductivity, free acidity, total dissolved solids, salinity, vitamin C content and specific weight) including colour-metrics (CIELAB, Pfund and colour intensity determinations), along with volatile compounds identification using solid phase micro-extraction coupled to gas chromatography mass spectrometry. Bio-activity parameter analysis included the determination of in vitro antioxidant activity and total phenolic content using the 2,2-diphenyl-1-picryl-hydrazyl and Folin-Ciocalteu assays, respectively. Melissopalynological analysis showed that Portuguese honeys were classified as eucalyptus, chestnut and heather, recording significant variations (p < 0.05) among physicochemical, volatile and bio-activity parameter analyses according to both: botanical and geographical origin. Based on the multi-parameter analysis data Portuguese honeys could be characterized by a distinctive colour, a characteristic aroma, whereas conform to the European legislation relating to honey identity and quality. Specific attention should be given in the case of heather honey which showed the highest in vitro antioxidant activity and total phenolic content. Parameters that were also highly correlated using bivariate statistics.
The brain basis of emotion: A meta-analytic review

Abstract Researchers have wondered how the brain creates emotions since the early days of psychological science. With a surge of studies in affective neuroscience in recent decades, scientists are poised to answer this question. In this target article, we present a meta-analytic summary of the neuroimaging literature on human emotion. We compare the locationist approach (i.e., the hypothesis that discrete emotion categories consistently and specifically correspond to distinct brain regions) with the psychological constructionist approach (i.e., the hypothesis that discrete emotion categories are constructed of more general brain networks not specific to those categories) to better understand the brain basis of emotion. We review both locationist and psychological constructionist hypotheses of brain–emotion correspondence and report meta-analytic findings bearing on these hypotheses. Overall, we found little evidence that discrete emotion categories can be consistently and specifically localized to distinct brain regions. Instead, we found evidence that is consistent with a psychological constructionist approach to the mind: A set of interacting brain regions commonly involved in basic psychological operations of both an emotional and non-emotional nature are active during emotion experience and perception across a range of discrete emotion categories.
Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation

We have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-Apc Min/+ X C57BL/6J-Lep ob/+ mice. Obesity was induced by the obese (ob) mutation in the lep gene coding for the hormone leptin, or by a 45% fat diet. The effects of obesity were examined on spontaneous intestinal tumors caused by the multiple intestinal neoplasia (Min) mutation in the adenomatous polyposis coli (Apc) gene and on tumors induced by the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). F1 ob/ob (homozygous mutated) mice had increased body weight (bw) and number of spontaneous and PhIP-induced small intestinal tumors (in Apc Min/+ mice), versus ob/wt (heterozygous mutated) and wt/wt mice (homozygous wild-type). A 45% fat diet exacerbated bw and spontaneous tumor numbers versus 10% fat, but not PhIP-induced tumors. Except for bw, ob/wt and wt/wt were not significantly different. The obesity caused hyperglucosemia and insulinemia in ob/ob mice. A 45% fat diet further increased glucose, but not insulin. Inflammation was seen as increased TNFα levels in ob/ob mice. Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis. Ob/ob mice had shorter lifespan than ob/wt and wt/wt mice.
Thioredoxin plays a key role in retinal neuropathy prior to endothelial damage in diabetic mice

Diabetes is a chronic metabolic syndrome that results in changes in carbohydrate, lipid and protein metabolism. With diabetes for a long time, it increases the risk of diabetic retinopathy (DR) and long-term morbidity and mortality. Moreover, emerging evidence suggests that neuron damage occurs earlier than microvascular complications in DR patients, but the underlying mechanism is unclear. We investigated diabetes-induced retinal neuropathy and elucidated key molecular events to identify new therapeutic targets for the clinical treatment and prevention of DR. For in vivo studies, a high-fat diet and streptozotocin (STZ) injection were used to generate the diabetes model. Hematoxylin-eosin staining was used for morphological observations and measurements of the outer nuclear layer thickness. Electroretinography (ERG) was used to assess retinal function. For in vitro studies, Neuro2a cells were incubated in normal (5.5 mM) and high-glucose (30 mM) conditions. Flow cytometry assays were performed to analyze apoptosis. Additionally, real-time PCR and Western blotting analyses were carried out to determine gene and protein expression in vitro and in vivo. Taken together, the results indicated that retinal neuropathy occurred prior to endothelial damage induced by diabetes, and thioredoxin (Trx) plays a key role in this process. This underlying mechanism may be related to activation of the Trx/ASK1/p-p38/Trx-interacting protein pathway.
Efficiency evaluation of electricity distribution utilities in India: A two-stage DEA with bootstrap estimation

Abstract The efficiency of the energy sector in India, the world’s third-largest energy consumer, is becoming an important issue amid growing concerns about global warming. This paper examines the efficiency of electricity distribution utilities in India using panel data from 2005 to 2012. We perform a two-stage data envelopment analysis with a bootstrap estimation, in which bias-corrected efficiency estimates are calculated in the first stage and then regressed on external environmental variables in the second stage. First, we find positive effects of customer structure and population density on the efficiency of utilities. Second, we find efficiency advantages of public utilities in the Indian power distribution sector. However, the interaction between ownership and population density is negative, implying that public utilities are less efficient than private enterprises in high population density areas. Finally, we find that government subsidies are negatively related to the efficiency of utilities.
Tenascin-C and fibronectin in normal esophageal mucosa, Barrett’s esophagus, dysplasia and adenocarcinoma

Background Tenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages. Results Stromal tenascin-C and fibronectin expression were found in all evaluated lesion types. Expression of both molecules increased from gastric metaplasia towards adenocarcinoma (p<0.05). In carcinomas, tenascin-C expression in the bulk was associated with T-stage (p=0.006), presence of lymph node (p=0.004) and distant organ metastases (p=0.007). Abundant tenascin-C expression associated with poor survival (p=0.034) in univariate analysis. Fibronectin expression associated to T-stage (p=0.030). Expression of tenascin-C or fibronectin in the tumor invasive front was not associated to clinicopathological variables or survival. No significant correlation with tumor/stroma percentage, cancer-associated fibroblasts or mean vascular density was observed with either tenascin-C or fibronectin. Methods Tenascin-C and fibronectin were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal adenocarcinoma (n=90) or dysplasia (n=30). Structures and lesion were evaluated including normal esophagus (n=77), gastric (n=61) or intestinal (n=51) metaplasia without dysplasia, and low-grade (n=42) or high-grade (n=34) dysplasia, and esophageal adenocarcinoma (n=90). In carcinomas, both bulk and invasive front were separately evaluated. In addition, tumor/stroma percentage, cancer-associated fibroblasts and mean vascular density were evaluated. Conclusions Tenascin-C and fibronectin are upregulated in esophageal adenocarcinoma when compared to Barrett’s esophagus and dysplasia. Increased tenascin-C expression is associated with metastasis and poor prognosis in esophageal adenocarcinoma.
How pupil responses track value-based decision-making during and after reinforcement learning

Cognition can reveal itself in the pupil, as latent cognitive processes map onto specific pupil responses. For instance, the pupil dilates when we make decisions and these pupil size fluctuations reflect decision-making computations during and after a choice. Surprisingly little is known, however, about how pupil responses relate to decisions driven by the learned value of stimuli. This understanding is important, as most real-life decisions are guided by the outcomes of earlier choices. The goal of this study was to investigate which cognitive processes the pupil reflects during value-based decision-making. We used a reinforcement learning task to study pupil responses during value-based decisions and subsequent decision evaluations, employing computational modeling to quantitatively describe the underlying cognitive processes. We found that the pupil closely tracks reinforcement learning processes independently across participants and across trials. Prior to choice, the pupil dilated as a function of trial-by-trial fluctuations in value beliefs about the to-be chosen option and predicted an individual’s tendency to exploit high value options. After feedback a biphasic pupil response was observed, the amplitude of which correlated with participants’ learning rates. Furthermore, across trials, early feedback-related dilation scaled with value uncertainty, whereas later constriction scaled with signed reward prediction errors. These findings show that pupil size fluctuations can provide detailed information about the computations underlying value-based decisions and the subsequent updating of value beliefs. As these processes are affected in a host of psychiatric disorders, our results indicate that pupillometry can be used as an accessible tool to non-invasively study the processes underlying ongoing reinforcement learning in the clinic.
Undesirable financial effects of head and neck cancer radiotherapy during the initial treatment period.

Background Healthcare cost and reforms are at the forefront of international debates. One of the current discussion themes in oncology is whether and how patients' life changes due to costs of cancer care. In Norway, the main part of the treatment costs is supported by general taxpayer revenues. Objectives The objective of this study was to clarify whether head and neck cancer patients (n=67) in northern Norway experienced financial health-related quality of life (HRQOL) deterioration due to costs associated with treatment. Design HRQOL was examined by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 in the beginning and in the end of radiation treatment in patients treated at the University Hospital in Northern Norway. Changes in financial HRQOL were calculated and compared by paired sample T-tests. Multiple regression analyses were used to examine correlations among gender, marital status, age and treatment with or without additional chemotherapy and changes in the HRQOL domain of financial difficulties. Results The majority of score results at both time points were in the lower range (mean 15-25), indicating limited financial difficulties. We observed no statistically significant differences by gender, marital status and age. Increasing financial difficulties during treatment were reported by male patients and those younger than 65, that is, patients who were younger than retirement age. The largest effect was seen in singles. However, differences were not statistically significant. Conclusions During the initial phase of the disease trajectory, no significant increase in financial difficulties was found. This is in line with the aims of the Norwegian public healthcare model. However, long-term longitudinal studies should be performed, especially with regard to the trends we observed in single, male and younger patients.
Predictive Value of Endocan Based on TIMI Risk Score on Major Adverse Cardiovascular Events After Acute Coronary Syndrome

We assessed the prognostic value of serum levels of endocan in patients with the acute coronary syndrome (ACS) through its correlation with the Thrombolysis in Myocardial Infarction (TIMI) risk score and compared the possible association with clinical outcomes. In this prospective cross-sectional study, we enrolled 320 patients with documented ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina (UA) who underwent diagnostic coronary angiography. Endocan was measured soon after admission in the emergency department. In-hospital death, heart failure, and recurrent infarction were considered major adverse cardiac events (MACEs). There was a significant positive correlation between endocan level and TIMI risk score and MACE. The optimal cutoff values of endocan to predict clinical end points were 3.45 ng/mL in patients with STEMI and 2.85 ng/mL in patients with UA/NSTEMI. Multivariate logistic regression analysis indicated that endocan independently correlated with MACE. Moreover, cardiac troponin I, creatine kinase-MB, and circulating endocan were found to be independently associated with MACE in patients with ACS. In conclusion, a high endocan level on hospital admission is an independent predictor of worse cardiovascular outcomes and higher TIMI risk score in patients with ACS.
Incidence of cardiovascular diseases and type-2-diabetes mellitus in patients with psychiatric disorders

Abstract Objective: To assess the incidence of cardiovascular diseases (CVD) and type-2-diabetes in patients with psychiatric disorders. Methods: A population-based study was conducted using the Swedish national health registries. Patients were identified from the Electronic Medical Records (EMR) in 20 primary care centers and were categorized in four diagnosis cohorts according to their first psychiatric diagnosis: bipolar disorder, schizophrenia, major depressive disorder, or other mood disorder. A control cohort of patients with no psychiatric disorders followed in the same primary care centers was also identified. Incident CVD and type-2-diabetes were defined as the presence of a diagnosis of CVD or diabetes during the follow-up period in patients without prior event. Results: The age and sex standardized incidence rate of CVD was 13.5 per 1000 patient-year in the patients with any psychiatric disorder versus 6.3 per 1000 patient-year in the controls. A similar trend was observed for incident diabetes (5.7 versus 3.4 per 1000 patient-year, respectively). The bipolar disorder and the schizophrenia cohorts showed the highest standardized incidence rates. Conclusion: Incidence of CVD and to a lesser extent type-2-diabetes was particularly high in patients with psychiatric disorders. This carries strong clinical implications for the prevention of CVD and type-2-diabetes in these patients.
Better visual outcome at 1 year with antivascular endothelial growth factor treatment according to treat‐and‐extend compared with pro re nata in eyes with neovascular age‐related macular degeneration

To evaluate treatment outcome at 12 months in eyes with neovascular age‐related macular degeneration (nAMD) treated with antivascular endothelial growth factor (anti‐VEGF) injections according to either pro re nata (PRN)‐ or treat‐and‐extend (TE)‐regimen in one clinical setting in Sweden.
KF-LAX: Kronecker-factored curvature estimation for control variate optimization in reinforcement learning

A key challenge for gradient based optimization methods in model-free reinforcement learning is to develop an approach that is sample efficient and has low variance. In this work, we apply Kronecker-factored curvature estimation technique (KFAC) to a recently proposed gradient estimator for control variate optimization, RELAX, to increase the sample efficiency of using this gradient estimation method in reinforcement learning. The performance of the proposed method is demonstrated on a synthetic problem and a set of three discrete control task Atari games.
Amplification of endothelium‐dependent vasodilatation in contracting human skeletal muscle: role of KIR channels

In humans, the vasodilatory response to skeletal muscle contraction is mediated in part by activation of inwardly rectifying potassium (KIR) channels. Evidence from animal models suggest that KIR channels serve as electrical amplifiers of endothelium‐dependent hyperpolarization (EDH). We found that skeletal muscle contraction amplifies vasodilatation to the endothelium‐dependent agonist ACh, whereas there was no change in the vasodilatory response to sodium nitroprusside, an endothelium‐independent nitric oxide donor. Blockade of KIR channels reduced the exercise‐induced amplification of ACh‐mediated vasodilatation. Conversely, pharmacological activation of KIR channels in quiescent muscle via intra‐arterial infusion of KCl independently amplified the vasodilatory response to ACh. This study is the first in humans to demonstrate that specific endothelium‐dependent vasodilatory signalling is amplified in the vasculature of contracting skeletal muscle and that KIR channels may serve as amplifiers of EDH‐like vasodilatory signalling in humans.
Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a “real-world” study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included objective response rate (ORR), disease control rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9–18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6–39.9 months); the observed ORR and DCR were 30.3 and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (< 3 vs. ≥3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR = 0.05 [95% CI, 0.05–0.55], p = 0.01; HR = 0.10 [95% CI, 0.02–0.43], p = 0.002, respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p = 0.2) and with a high tumor burden (number of metastatic sites < 6 vs. ≥6) (p = 0.08). Worst OS was observed in patients aged ≥70 years old (HR = 6.91 [95% CI, 1.49–31.91], p = 0.01). The treatment was well-tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR = 0.22 [95% CI, 0.05–0.8], p = 0.03). Thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR = 0.12 [95% CI, 0.02–0.78], p = 0.02). Our results are consistent with those reported in prospective phase III trials and the published retrospective “real world” experiences. This analysis confirms the safety and efficacy of pazopanib in first-line setting, both in frail patients with multiple co-morbidities and Karnofsky PS < 80% and in younger, healthier patients with a number of metastatic sites < 6.
Blood contamination in salivary diagnostics: current methods and their limitations

Abstract The use of saliva samples in clinical studies has increased. However, the diagnostic value of whole saliva is compromised in the presence of blood contamination, owing to the higher levels of analytes in blood compared with those in saliva. The aim of this study was to review the existing methods and their limitations for measuring the levels of blood contamination in saliva. A literature search was performed using Web of Science, SCOPUS, and PubMed databases and 49 articles dealing with salivary diagnostics and measurements of blood contamination were included. Five methods for measuring the degree of blood components in saliva were discussed, including “visual inspection”, use of “strip for urinalysis”, and detection of plasma proteins such as “hemoglobin”, “albumin”, and “transferrin”. Each method has its limitations, and transferrin has been regarded as the most reliable and valid marker for blood contamination in saliva. However, transferrin in whole saliva may not be solely a product of blood, and its level in whole saliva can be influenced by several factors such as age, gonadal hormones, salivary flow rate, chewing performance, and oral microorganisms. In conclusion, when quantitatively analyzing whole saliva samples, the influence of blood contamination should be considered.
DNA Methylation Diversification at the Integrated Organellar DNA-Like Sequence

Plants have a lot of diversity in epigenetic modifications such as DNA methylation in their natural populations or cultivars. Although many studies observing the epigenetic diversity within and among species have been reported, the mechanisms how these variations are generated are still not clear. In addition to the de novo spontaneous epi-mutation, the intra- and inter-specific crossing can also cause a change of epigenetic modifications in their progenies. Here we report an example of diversification of DNA methylation by crossing and succeeding selfing. We traced the inheritance pattern of epigenetic modification during the crossing experiment between two natural strains Columbia (Col), and Landsberg electa (Ler) in model plant Arabidopsis thaliana to observe the inheritance of DNA methylation in two organellar DNA-like sequence regions in the nuclear genome. Because organellar DNA integration to the nuclear genome is common in flowering plants and these sequences are occasionally methylated, such DNA could be the novel source of plant genome evolution. The amplicon sequencing, using bisulfite-converted DNA and a next-generation auto-sequencer, was able to efficiently track the heredity of DNA methylation in F1 and F2 populations. One region showed hypomethylation in the F1 population and succeeding elevation of DNA methylation with large variance in the F2 population. The methylation level of Col and Ler alleles in F2 heterozygotes showed a significant positive correlation, implying the trans-chromosomal effect on DNA methylation. The results may suggest the possible mechanism causing the natural epigenetic diversity within plant populations.