Miracle-dz/UniFAR-FTUs huggingface dataset:
Abscisic Acid: A Conserved Hormone in Plants and Humans and a Promising Aid to Combat Prediabetes and the Metabolic Syndrome

Abscisic acid (ABA) is a hormone with a very long evolutionary history, dating back to the earliest living organisms, of which modern (ABA-producing) cyanobacteria are likely the descendants, well before separation of the plant and animal kingdoms, with a conserved role as a signal regulating cell responses to environmental challenges. In mammals, nanomolar ABA controls the metabolic response to glucose availability by stimulating glucose uptake in skeletal muscle and adipose tissue with an insulin-independent mechanism and increasing energy expenditure in the brown and white adipose tissues. Activation by ABA of AMP-dependent kinase (AMPK), in contrast to the insulin-induced activation of AMPK-inhibiting Akt, is responsible for stimulation of GLUT4-mediated muscle glucose uptake, and for the browning effect on white adipocytes. Intake of micrograms per Kg body weight of ABA improves glucose tolerance in both normal and in borderline subjects and chronic intake of such a dose of ABA improves blood glucose, lipids and morphometric parameters (waist circumference and body mass index) in borderline subjects for prediabetes and the metabolic syndrome. This review summarizes the most recent results obtained in vivo with microgram amounts of ABA, the role of the receptor LANCL2 in the hormone’s action and the significance of the endowment by mammals of two different hormones controlling the metabolic response to glucose availability. Finally, open issues in need of further investigation and perspectives for the clinical use of nutraceutical ABA are discussed.
ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.
Intestinal parasitic infections in children under five in the Central Hospital of Nampula, Northern Mozambique.

INTRODUCTION Intestinal parasites are known to cause infection in humans worldwide, with higher prevalence in low- and middle- incoming countries. Children are greatly affected leading to malnutrition and subsequently to physical and cognitive development impairment. Despite the scale and importance of this issue, there are few studies conducted in Mozambique concerning parasitic intestinal infections in hospitalized children. To our knowledge this is the first published report with data on this subject from Northern Mozambique. METHODOLOGY A cross-sectional study was conducted in 2012 and 2013 in 831 children, attending the Central Hospital of Nampula in Northern Mozambique. One single stool sample was obtained from each child. Socio-demographic and clinical data were also obtained. Parasitological analysis of feces was performed through direct examination and Ritchie concentration technique and Giardia duodenalis antigen detection by rapid immunochromatographic test. Modified Ziehl-Neelsen staining was used for coccidia detection. RESULTS The global prevalence of pathogenic intestinal parasites was 31.6%. G. duodenalis (23.9%) was by far the most prevalent parasite followed by Strongyloides stercoralis (4.1%) and Cryptosporidium sp. (3.4%). Intestinal parasites were more frequent in older children (p = 0.005; aOR = 1.025). CONCLUSIONS This work is one of the few published studies reporting intestinal parasites infection in hospitalized children. The percentage of children affected with G. duodenalis is higher than found in other studies in the African region. This highlights the need of particular attention being given to this intestinal protozoan and its resistance to water treatment, as well as to environmental health and personal hygiene.
Programmed intermittent epidural bolus vs. patient‐controlled epidural analgesia for maintenance of labour analgesia: a two‐centre, double‐blind, randomised study †

The programmed intermittent epidural bolus technique has shown superiority to continuous epidural infusion techniques, with or without patient‐controlled epidural analgesia for pain relief, reduced motor block and patient satisfaction. Many institutions still use patient‐controlled epidural analgesia without a background infusion, and a comparative study between programmed intermittent epidural bolus and patient‐controlled epidural analgesia without a background infusion has not yet been performed. We performed a randomised, two‐centre, double‐blind, controlled trial of these two techniques. The primary outcome was the incidence of breakthrough pain requiring a top‐up dose by an anaesthetist. Secondary outcomes included: motor block; pain scores; patient satisfaction; local anaesthetic consumption; and obstetric and neonatal outcomes. We recruited 130 nulliparous women who received initial spinal analgesia, and then epidural analgesia was initiated and maintained with either programmed intermittent epidural bolus or patient‐controlled epidural analgesia using ropivacaine 0.12% with sufentanil 0.75 µg·ml‐1. The programmed intermittent epidural bolus group had a programmed bolus of 10 ml every hour, with on‐demand patient‐controlled epidural analgesia boluses of 5 ml with a 20 min lockout, and the patient‐controlled epidural analgesia group had a 5 ml bolus with a 12 min lockout interval; the potential maximum volume per hour was the same in both groups. The patients in the programmed intermittent epidural bolus group had less frequent breakthrough pain compared with the patient‐controlled epidural analgesia group, 7 (10.9%) vs. 38 (62.3%; p < 0.0001), respectively. There was a significant difference in motor block (modified Bromage score ≤ 4) frequency between groups, programmed intermittent epidural bolus group 1 (1.6%) vs. patient‐controlled epidural analgesia group 8 (13.1%); p = 0.015. The programmed intermittent epidural bolus group had greater local anaesthetic consumption with fewer patient‐controlled epidural analgesia boluses. Patient satisfaction scores and obstetric or neonatal outcomes were not different between groups. In conclusion, we found that a programmed intermittent epidural bolus technique using 10 ml programmed boluses and 5 ml patient‐controlled epidural analgesia boluses was superior to a patient‐controlled epidural analgesia technique using 5 ml boluses and no background infusion.
Vasculometabolic and Inflammatory Effects of Aldosterone in Obesity

Abstract Context Not all obese individuals develop cardiovascular disease (CVD). Hyperaldosteronism is suggested to cause inflammation and metabolic dysregulation, and might contribute to CVD development in obese individuals. Objective We aimed to investigate the association of aldosterone concentrations with inflammation, metabolic disturbances, and atherosclerosis in overweight and obese individuals. Additionally, we measured renin concentrations to investigate whether the observed effects reflected general activation of the renin-angiotensin-aldosterone system (RAAS). Design A cross-sectional cohort study (300-OB study) was conducted. Various inflammatory parameters, traits of the metabolic syndrome, lipidome and metabolome parameters, fat distribution, and carotid atherosclerosis were associated with plasma aldosterone and renin levels. Setting The setting of this study was the Radboudumc (i.o. Radboudumc), the Netherlands. Patients A total of 302 individuals with a body mass index greater than or equal to 27 kg/m2 participated. Main Outcome Measures and Results Aldosterone was associated with various markers of inflammation and metabolic dysregulation, which partly differed from the associations observed for renin. Although both were associated with inflammatory cell numbers, only renin was associated with classical markers of systemic inflammation. Both were associated with the metabolic syndrome and hepatic steatosis. Of the traits that constitute metabolic syndrome, aldosterone, but not renin, was associated with triglyceride concentrations. Accordingly, aldosterone was associated with large very low-density lipoprotein particles; metabolomics studies further associated aldosterone with urate concentrations and derivatives of the linoleic acid metabolism pathway. Neither aldosterone nor renin was associated with atherosclerotic plaque thickness. Conclusions Aldosterone is not an important driver of systemic inflammation in the obese, whereas aldosterone concentrations and metabolic dysregulation are strongly intertwined in these individuals. Although prospective studies are necessary to validate these results, the independent effects of aldosterone on carotid atherosclerosis appear modest.
Direct Supplementation of Yeast with Lipids as a Means to Reduce Sulfur Dioxide Formation

In traditional brewing practice, yeast is cropped and repitched in subsequent fermentations. However, at the end of fermentation, yeast are lipid-depleted and require lipid levels to be restored in order to initiate cellular growth. Adverse effects on biochemical fermentative processes are experienced if lipid levels are not restored to functioning levels. In such a situation, high levels of sulfur dioxide are produced, which may create issues for the brewery, necessitating a warning on the label if the level is not kept below 10 mg/L. This study investigates the supplementation of cropped brewer's yeast with a mixture of lipids, its effects on certain fermentation parameters, and its ability to reduce sulfur dioxide produced during fermentation of a synthetic media. Successful results were observed using this method, because a 64.3% reduction in total sulfur dioxide was obtained using the supplemented yeast. Cellular growth, under anaerobic conditions, was also improved with growth rates nearly four times that of the control. Although comparable final concentrations of ethanol were achieved in both fermentations, the supplemented fermentation produced ethanol at a faster rate, reducing overall fermentation time. In addition, production of higher alcohols was increased along with utilization of tested amino acids. Ethyl acetate and isoamyl acetate were tested to determine the impact of lipid supplementation on ester synthesis, because past studies have reported decreases in both. Only ethyl acetate was reduced by 7.5%, with no change in isoamyl acetate. The results indicate that direct yeast supplementation with lipids can be used as an effective means to reduce the amount of sulfur dioxide produced during fermentation while stimulating overall yeast growth.
Harmless Effects of Sterilizing 222‐nm far‐UV Radiation on Mouse Skin and Eye Tissues

In this issue, Yamano et al. provide further evidence that germicidal 222‐nm far UV light has no immediate and delayed harmful effects on the skin and ocular tissue of rats. The safety of 222‐nm krypton–chlorine excimer lamps, highlighted in the commentary article, has already received relevant applications in the treatment of surgical site infections and in the control of airborne and foodborne pathogens.
Complementary Use of Carbohydrate Antigens Lewis a, Lewis b, and Sialyl-Lewis a (CA19.9 Epitope) in Gastrointestinal Cancers: Biological Rationale towards a Personalized Clinical Application

Carbohydrate antigen 19.9 (CA19.9) is used as a tumor marker for clinical and research purposes assuming that it is abundantly produced by gastrointestinal cancer cells due to a cancer-associated aberrant glycosylation favoring its synthesis. Recent data has instead suggested a different picture, where immunodetection on tissue sections matches biochemical and molecular data. In addition to CA19.9, structurally related carbohydrate antigens Lewis a and Lewis b are, in fact, undetectable in colon cancer, due to the down-regulation of a galactosyltransferase necessary for their synthesis. In the pancreas, no differential expression of CA19.9 or cognate glycosyltransferases occurs in cancer. Ductal cells only express such Lewis antigens in a pattern affected by the relative levels of each glycosyltransferase, which are genetically and epigenetically determined. The elevation of circulating antigens seems to depend on the obstruction of neoplastic ducts and loss of polarity occurring in malignant ductal cells. Circulating Lewis a and Lewis b are indeed promising candidates for monitoring pancreatic cancer patients that are negative for CA19.9, but not for improving the low diagnostic performance of such an antigen. Insufficient biological data are available for gastric and bile duct cancer. Studying each patient in a personalized manner determining all Lewis antigens in the surgical specimens and in the blood, together with the status of the tissue-specific glycosylation machinery, promises fruitful advances in translational research and clinical practice.
Chemical variability in propolis from Santiago del Estero, Argentina, related to the arboreal environment as the sources of resins

BACKGROUND: Propolis composition is extremely variable and depends on the plant resin sources that grow around the apiary. Polyphenols have been reported to be responsible of its pharmacological and biological properties. The contents of polyphenols and flavonoid aglycones were studied in propolis from different provenances to correlate these contents with the nature of the flora surrounding the hive. RESULTS: Nineteen of these bioactive substances were identified in 30 samples classified into three arboreal categories according to their main species. A noticeable variability was observed in the concentration of each component depending on the plant origin of the samples. Higher amounts were found for pinocembrin (0.2–102.3 g kg−1), quercetin (0.08–86.6 g kg−1) and chrysin (0.8–18.8 g kg−1). Salicylic, 4-hydroxybenzoic, benzoic, ferulic and gallic acids were other remarkable constituents. CONCLUSION: Statistical significant differences in polyphenol and flavonoid contents were observed among arboreal groups, while very strong linear correlations were found between polyphenol and flavonoid contents for all the samples as well as for all the groups (R2% > 87). Copyright © 2009 Society of Chemical Industry
Maternal education and offspring birth weight for gestational age: the mediating effect of smoking during pregnancy.

BACKGROUND Small for gestational age (SGA) birth weight, a risk factor for infant mortality and delayed child development, is associated with maternal educational attainment. Maternal tobacco smoking during pregnancy could contribute to this association. We aimed to quantify the contribution of maternal smoking during pregnancy to social inequalities in child birth weight for gestational age (GA). METHODS Data come from the French nation-wide ELFE cohort study, which included 17 155 singletons. Birth weights for GA were calculated using z-scores. Associations between maternal educational attainment, tobacco smoking during pregnancy and child birth weight for GA were ascertained using mediation analysis. Mediation analyses were also stratified by maternal pre-pregnancy body mass index. RESULTS Low maternal educational attainment was associated with an increased odd of tobacco smoking during pregnancy [adjusted OR (ORa) = 2.58 (95% CI 2.34-2.84)] as well as a decrease in child birth weight for GA [RRa = 0.94 (95% CI 0.91-0.98)]. Tobacco smoking during pregnancy was associated with a decrease in offspring birth weight for GA [RRa = 0.73 (95% CI 0.70-0.76)]. Mediation analysis suggests that 39% of the effect of low maternal educational attainment on offspring birth weight for GA was mediated by smoking during pregnancy. A more important direct effect of maternal educational attainment on child birth weight for GA was observed among underweight women [RRa = 0.82 (95% CI 0.72-0.93)]. CONCLUSIONS The relationship between maternal educational attainment and child birth weight for GA is strongly mediated by smoking during pregnancy. Reducing maternal smoking could lessen the occurrence of infant SGA and decrease socioeconomic inequalities in birth weight for GA.
The Fourth International Workshop on Clinical Transplant Tolerance

The International Workshop on Clinical Transplant Tolerance is a biennial meeting that aims to provide an update on the progress of studies of immunosuppression minimization or withdrawal in solid organ transplantation. The Fourth International Workshop on Clinical Tolerance was held in Pittsburgh, Pennsylvania, September 5‐6, 2019. This report is a summary of presentations on the status of clinical trials designed to minimize or withdraw immunosuppressive drugs in kidney, liver, and lung transplantation without subsequent evidence of rejection. All protocols had in common the use of donor or recipient cell therapy combined with organ transplantation. The workshop also included presentations of mechanistic studies designed to improve understanding of the cellular and molecular basis of tolerance and to identify potential predictors/biomarkers of tolerance. Strategies to enhance the safety of hematopoietic cell transplantation and to improve patient selection/risk stratification for clinical trials were also discussed.
Impact of thrombus surface on first pass reperfusion in contact aspiration and stent retriever thrombectomy

Background To assess whether thrombus surface morphology has an impact on first pass reperfusion in contact aspiration (CA) and stent retriever (SR) thrombectomy. Methods From January 2016 to December 2018, consecutive stroke patients with an occlusion of the middle cerebral artery and thrombectomy (CA or SR) were examined in this retrospective study. We assessed patients’ characteristics, procedural data and clinical outcome. Thrombus surface on pretreatment digital subtraction angiography (DSA) was categorized into regular versus irregular phenotype by blinded three-reader-consensus. Primary outcome was successful reperfusion (modified treatment in cerebral ischemia (mTICI) 2b-3) after first pass. Data analysis was stratified according to thrombectomy technique and thrombus phenotype. Results Among 203 patients (76 years (IQR 65.5–81.9), 47.3% male, National Institutes of Health Stroke Scale Score 16 (IQR 12–20)), 155 patients were treated primarily with CA and 48 with SR. 40% (n=62/155) CA and 41.7% (n=20/48) SR-treated patients had a regular thrombus phenotype. In the CA group, successful reperfusion after first pass was more frequently obtained in patients with regular compared with irregular phenotype (69.4% (n=43/62) vs 34.4% (n=32/93); P<0.0001). In contrast, in the SR group, reperfusion after first pass was achieved in 35% (n=7/20; P=0.01) of patients with regular phenotypes. In the CA group, median number of passes (1 (1–2) vs 2 (1–4); P<0.00001) and time from reaching the thrombus to reperfusion (19±27 vs 38±36 min; P=0.0001) were lower among patients with a regular phenotype. Conclusion Direct CA is associated with higher rates of successful first pass reperfusion in patients with a regular thrombus phenotype in pretreatment DSA.
Calanus oil as a natural source for flesh pigmentation in Atlantic salmon (Salmo salar L.)

The present study was to understand how efficiently the astaxanthin in Calanus oil is utilized for flesh colouration in Atlantic salmon (Salmo salar). Postsmolts of the fish (309 g) were held at 7.9 °C and they were fed diets containing 20 or 60 mg astaxanthin per kilogram feed derived from a synthetic source or from Calanus oil for 181 days. Besides growth and feed intake assessments, at day 81 and 181, fish flesh were subjected to colour analysis and astaxanthin determination. Growth and feed performance did not vary between the groups. There were significant differences in the amount of astaxanthin in muscle between almost all groups both at day 81 (P 0.05) at day 181 indicated that comparable amounts were deposited only with the greater level of the natural source. Tristimuli colorimeter a* values support the analytical results at day 181. Although Calanus oil did serve as a natural dietary pigment source for farmed salmon, its inclusion level should provide more than 60 mg astaxanthin per kilogram feed to achieve colouration preferred by the market.
Role of ultraviolet mutational signature versus tumor mutation burden in predicting response to immunotherapy

Hydrophobic neoantigens are more immunogenic because they are better presented by the major histocompatibility complex and better recognized by T cells. Tumor cells can evade the immune response by expressing checkpoints such as programmed death ligand 1. Checkpoint blockade reactivates immune recognition and can be effective in diseases such as melanoma, which harbors a high tumor mutational burden (TMB). Cancers presenting low or intermediate TMB can also respond to checkpoint blockade, albeit less frequently, suggesting the need for biological markers predicting response. We calculated the hydrophobicity of neopeptides produced by probabilistic in silico simulation of the genomic UV exposure mutational signature. We also computed the hydrophobicity of potential neopeptides and extent of UV exposure based on the UV mutational signature enrichment (UVMSE) score in The Cancer Genome Atlas (TCGA; N = 3543 tumors), and in our cohort of 151 immunotherapy‐treated patients. In silico simulation showed that UV exposure significantly increased hydrophobicity of neopeptides, especially over multiple mutagenic cycles. There was also a strong correlation (R 2 = 0.953) between weighted UVMSE and hydrophobicity of neopeptides in TCGA melanoma patients. Importantly, UVMSE was able to predict better response (P = 0.0026), progression‐free survival (P = 0.036), and overall survival (P = 0.052) after immunotherapy in patients with low/intermediate TMB, but not in patients with high TMB. We show that higher UVMSE scores could be a useful predictor of better immunotherapy outcome, especially in patients with low/intermediate TMB, likely due to increased hydrophobicity (and hence immunogenicity) of neopeptides.