Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of Sex on Urinary Organic Acids: A Cross-Sectional Study in Children

The characterization of urinary metabolome, which provides a fingerprint for each individual, is an important step to reach personalized medicine. It is influenced by exogenous and endogenous factors; among them, we investigated sex influences on 72 organic acids measured through GC-MS analysis in the urine of 291 children (152 males; 139 females) aging 1–36 months and stratified in four groups of age. Among the 72 urinary metabolites, in all age groups, 4-hydroxy-butirate and homogentisate are found only in males, whereas 3-hydroxy-dodecanoate, methylcitrate, and phenylacetate are found only in females. Sex differences are still present after age stratification being more numerous during the first 6 months of life. The most relevant sex differences involve the mitochondria homeostasis. In females, citrate cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate, glutamate, and butanoate metabolism had the highest impact. In males, urinary organic acids were involved in phenylalanine metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, butanoate metabolism, and glyoxylate and dicarboxylate metabolism. In addition, age specifically affected metabolic pathways, the phenylalanine metabolism pathway being affected by age only in males. Relevantly, the age-influenced ranking of metabolic pathways varied in the two sexes. In conclusion, sex deeply influences both quantitatively and qualitatively urinary organic acids levels, the effect of sex being age dependent. Importantly, the sex effects depend on the single organic acid; thus, in some cases the urinary organic acid reference values should be stratified according the sex and age.
The landscape of chimeric RNAs in non-diseased tissues and cells

Abstract Chimeric RNAs and their encoded proteins have been traditionally viewed as unique features of neoplasia, and have been used as biomarkers and therapeutic targets for multiple cancers. Recent studies have demonstrated that chimeric RNAs also exist in non-cancerous cells and tissues, although large-scale, genome-wide studies of chimeric RNAs in non-diseased tissues have been scarce. Here, we explored the landscape of chimeric RNAs in 9495 non-diseased human tissue samples of 53 different tissues from the GTEx project. Further, we established means for classifying chimeric RNAs, and observed enrichment for particular classifications as more stringent filters are applied. We experimentally validated a subset of chimeric RNAs from each classification and demonstrated functional relevance of two chimeric RNAs in non-cancerous cells. Importantly, our list of chimeric RNAs in non-diseased tissues overlaps with some entries in several cancer fusion databases, raising concerns for some annotations. The data from this study provides a large repository of chimeric RNAs present in non-diseased tissues, which can be used as a control dataset to facilitate the identification of true cancer-specific chimeras.
Nasal High Flow Use in COPD Patients with Hypercapnic Respiratory Failure: Treatment Algorithm & Review of the Literature

Abstract Nasal high flow (NHF) therapy has recently gained attention as a new respiratory support system and is increasingly being utilized in every day clinical practice. Recent studies suggest that it may also be effective in patients with hypercapnia and suggest NHF as a possible alternative for patients who cannot tolerate standard noninvasive ventilation. The present review discusses the mechanisms of action that make NHF potentially suitable for chronic obstructive pulmonary disease (COPD) patients and evaluates the current evidence of NHF use for treatment of stable hypercapnic COPD patients as well as acute hypercapnic exacerbation of COPD. An algorithm is also proposed for the clinical application of NHF in patients with acute hypercapnic exacerbation of COPD, based on current literature.
A system of radiological criteria for grading and prognosticating temporal lobe contusions

Introduction Temporal contusions are common in patients with head injuries and require close monitoring due to the propensity of these patients to deteriorate rapidly and fatally. This study attempts to introduce a radiological grading system for temporal lobe contusions and analyse its prognostic value so as to better identify patients at risk of deterioration. Methods The study was conducted as a cross-sectional observational study from April 2011–March 2017 on 42 patients with temporal lobe contusion. Each patients was graded according to the proposed system from a minimum of four to a maximum of 13 and then further grouped in three grades – grade 1 (score = 4), grade 2 (score 5–7) and grade 3 (score > 7) – and their clinical course was closely observed. Results The minimum and maximum scores observed were four and 11 respectively. The proposed grading system has statistically significant correlation to the Glasgow Coma Scale (p-value < 0.05). All patients in grade 1 (17) could be managed conservatively, while all those in grade 3 (five) needed immediate surgical intervention. Of 20 patients in grade 2, 11 had a score of 5–6 and did not require surgery, whereas nine patients had a score of seven and of these eight required delayed surgical intervention. This correlation was statistically significant (p-value < 0.05) Conclusion The proposed temporal lobe contusion grading system is a good radiological tool to predict the clinical course of patients and thereby identify patients at higher risk of delayed deterioration.
Development of Low-Cost Portable Spectrometers for Detection of Wood Defects

Portable spectroscopic instruments are an interesting alternative for in-field and on-line measurements. However, the practical implementation of visible-near infrared (VIS-NIR) portable sensors in the forest sector is challenging due to operation in harsh environmental conditions and natural variability of wood itself. The objective of this work was to use spectroscopic methods as an alternative to visual grading of wood quality. Three portable spectrometers covering visible and near infrared range were used for the detection of selected naturally occurring wood defects, such as knots, decay, resin pockets and reaction wood. Measurements were performed on wooden discs collected during the harvesting process, without any conditioning or sample preparation. Two prototype instruments were developed by integrating commercially available micro-electro-mechanical systems with for-purpose selected lenses and light source. The prototype modules of spectrometers were driven by an Arduino controller. Data were transferred to the PC by USB serial port. Performance of all tested instruments was confronted by two discriminant methods. The best performing was the microNIR instrument, even though the performance of custom prototypes was also satisfactory. This work was an essential part of practical implementation of VIS-NIR spectroscopy for automatic grading of logs directly in the forest. Prototype low-cost spectrometers described here formed the basis for development of a prototype hyperspectral imaging solution tested during harvesting of trees within the frame of a practical demonstration in mountain forests.
Effects of Decreasing Dietary Crude Protein Level on Growth Performance, Nutrient Digestion, Serum Metabolites, and Nitrogen Utilization in Growing Goat Kids (Capra. hircus)

Simple Summary Reducing the dietary protein content could potentially reduce losses of nitrogen from ruminant farms and mitigate pressure on the protein ingredient supply. However, there is little information in the literature on the effect of low-protein diets in growing Anhui white goat kids. We demonstrated that decreasing the dietary crude protein level in Anhui white goat kids affected growth performance, improved nitrogen utilization, and reduced environmental nitrogen pollution. The key finding of this study was that a diet containing 13.4% crude protein supplied adequate protein to improve nitrogen utilization in white goat kids without any adverse effect on growth performance. Abstract The effects of decreasing dietary crude protein (CP) level on growth performance, nutrient digestion, serum metabolites, and nitrogen utilization in growing goat kids were investigated in the current study. Thirty-six male Anhui white goat kids were randomly assigned to one of three CP content diets: 14.8% (control), 13.4%, and 12.0% of dry matter, respectively. Diets were isoenergetic. The experiment lasted for 14 weeks, with the first two weeks being for adaptation. Results showed that the low-CP diet decreased average daily gain, feed efficiency, digestibility of dry matter, organic matter, crude protein, and fiber. No significant changes were observed in dry-matter intake. With a decrease in dietary CP level, fecal nitrogen excretion (% of nitrogen intake) increased linearly, whereas CP intake, blood urea nitrogen, urinary nitrogen excretion (% of nitrogen intake), and total nitrogen excretion (% of nitrogen intake) decreased. Serum glucose concentration decreased, while concentrations of low-density lipoproteins and non-esterified fatty acids increased with the low-CP diet. In conclusion, decreasing the dietary CP level decreased goats’ nitrogen excretion, but with restrictive effects on growth performance. A diet containing 13.4% CP is optimal for reducing nitrogen excretion without any adverse effect on growth performance of Anhui white goat kids. This concentration is 1.4% points lower than the NRC recommendations and thus is also environmentally beneficial on the input side because it decreases the use of feed (soy) protein.
Bariatric surgery‐induced weight loss in patients with and without type 2 diabetes mellitus

Surgical treatment of obesity leads to weight loss and metabolic improvement, but it is unclear if the response differs between patients with and without type 2 diabetes. Retrospective cohort study comparing weight loss and metabolic outcomes between patients with and without type 2 diabetes, matched for body mass index (BMI), gender and age, 12 months after Roux‐en‐Y gastric bypass. Forty‐eight patients with type 2 diabetes (D) and 48 without type 2 diabetes (ND) were evaluated, 87.5% female, mean age 42.2 ± 0.9 years. The mean baseline weight and BMI of the D and ND groups were, respectively, 120.3 ± 21.6 vs 123.7 ± 20.8 kg (P = .45) and 47.2 ± 7.5 vs 47.2 ± 6.9 kg/m2 (P = .70). After 12 months, there was no significant difference in weight (40.4 ± 16.9 vs 44.1 ± 12.2 kg, P = .28) and BMI (15.8 ± 6.5 vs 16.9 ± 4.5 kg/m2, P = .26) variation between groups. The parameters that presented significant variation were (D vs ND): fasting blood glucose (41.6 ± 43.0 vs 12.7 ± 17.2 mg/dL, P < .01), HbA1c (1.8 ± 1.6 vs 0.6 ± 0.7%; P < .01), triglycerides (91.1 ± 100.4 vs 54.2 ± 43.8 mg/dL; P = .04), low‐density lipoprotein (27.2 ± 41.5 vs 37.5 ± 24.2 mg/dL; P < .01) and gamma glutamyl transferase (46.5 ± 55.3 vs 17.7 ± 11.9 UI/L; P = .04). Weight loss 12 months after a gastric bypass was similar in patients with and without type 2 diabetes, the greater metabolic benefits appearing in patients with type 2 diabetes as they had more pronounced changes at baseline.
Poly(ADP-ribosyl)ation mediates early phase histone eviction at DNA lesions

Abstract Nucleosomal histones are barriers to the DNA repair process particularly at DNA double-strand breaks (DSBs). However, the molecular mechanism by which these histone barriers are removed from the sites of DNA damage remains elusive. Here, we have generated a single specific inducible DSB in the cells and systematically examined the histone removal process at the DNA lesion. We found that histone removal occurred immediately following DNA damage and could extend up to a range of few kilobases from the lesion. To examine the molecular mechanism underlying DNA damage-induced histone removal, we screened histone modifications and found that histone ADP-ribosylation was associated with histone removal at DNA lesions. PARP inhibitor treatment suppressed the immediate histone eviction at DNA lesions. Moreover, we examined histone chaperones and found that the FACT complex recognized ADP-ribosylated histones and mediated the removal of histones in response to DNA damage. Taken together, our results reveal a pathway that regulates early histone barrier removal at DNA lesions. It may also explain the mechanism by which PARP inhibitor regulates early DNA damage repair.
Detection of DDT and carbaryl pesticides in honey by means of immunosensors based on High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCM).

BACKGROUND In the last years, there is a concern about the presence of pesticides in honey since residues of DDT and carbaryl were found in honey samples. The traditional techniques, such as chromatography, reach the required limits of detection (LOD) but are not suitable for in-situ implementation in honey packaging industry due to their high cost and the need of highly qualified staff for routine operation. Biosensors offer simplicity, low cost and easy handling for analytical purposes in food applications. RESULTS Piezoelectric immunosensors based on High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCM) have been developed for detection of carbaryl and DDT in honey. The biorecognition was based on competitive immunoassays in the conjugate-coated format, using monoclonal antibodies as specific immunoreagents. The assay LODs attained by the HFF-QCM immunosensors were 0.05 μg L-1 for carbaryl and 0.24 μg L-1 for DDT, thus reaching a similar detectability to that of the usual reference techniques. The practical LODs in honey samples were 8 μg kg-1 for carbaryl and 24 μg kg-1 for DDT. The immunosensors analytical performance allow the detection of these pesticides in honey at EU regulatory levels with good accuracy (recovery percentages ranging from 94 to 130% within the working range of each pesticide standard curve) and precision (coefficients of variation in the 9-36% range). CONCLUSION The proposed immunosensor is a promising analytical tool that could be implemented for quality control in the honey packaging industry, in order to ease and to cheapen the routine pesticide analysis in this appreciated natural food. This article is protected by copyright. All rights reserved.
Implementation of a Bowel Protocol to Improve Enteral Nutrition and Reduce Clostridium difficile Testing.

BACKGROUND Underfeeding is common among adult patients receiving enteral nutrition. Constipation and diarrhea have been associated with low enteral nutrition volume in critically ill patients. In patients with diarrhea, Clostridium difficile is often suspected and tested for, although medications, illness, or enteral formulas are usually the cause. The use of bowel protocols to proactively address constipation, diarrhea, and inappropriate testing for hospital-onset C difficile infection, thereby improving enteral nutrition, remains unclear. OBJECTIVE To evaluate the efficacy of implementing protocols to decrease constipation, diarrhea, and inappropriate testing for hospital-onset C difficile infection, and to deliver larger enteral nutrition volumes in a critical care unit. METHODS A prospective convenience sample was used. The primary outcome was the proportion of patients receiving greater than or equal to 80% of their prescribed caloric volume 1 week (minimum 4 days) after initiating enteral nutrition. Rates of testing for hospital-onset C difficile infection were analyzed before and after the protocol was implemented. RESULTS After the protocol was implemented, patients experienced significant increases in delivery of enteral nutrition volume-up to 78% of the goal volume (P = .048). The standardized infection ratio of hospital-onset C difficile infection decreased 43% (P = .04). CONCLUSIONS The implementation of bowel protocols improved delivery of total enteral volumes and reduced inappropriate testing for hospital-onset infections with C difficile, and they may improve patient safety and facilitate positive patient outcomes.
Prevention of DNA Replication Stress by CHK1 Leads to Chemoresistance Despite a DNA Repair Defect in Homologous Recombination in Breast Cancer

Chromosomal instability not only has a negative effect on survival in triple-negative breast cancer, but also on the well treatable subgroup of luminal A tumors. This suggests a general mechanism independent of subtypes. Increased chromosomal instability (CIN) in triple-negative breast cancer (TNBC) is attributed to a defect in the DNA repair pathway homologous recombination. Homologous recombination (HR) prevents genomic instability by repair and protection of replication. It is unclear whether genetic alterations actually lead to a repair defect or whether superior signaling pathways are of greater importance. Previous studies focused exclusively on the repair function of HR. Here, we show that the regulation of HR by the intra-S-phase damage response at the replication is of overriding importance. A damage response activated by Ataxia telangiectasia and Rad3 related-checkpoint kinase 1 (ATR-CHK1) can prevent replication stress and leads to resistance formation. CHK1 thus has a preferred role over HR in preventing replication stress in TNBC. The signaling cascade ATR-CHK1 can compensate for a double-strand break repair error and lead to resistance of HR-deficient tumors. Established methods for the identification of HR-deficient tumors for Poly(ADP-Ribose)-Polymerase 1 (PARP1) inhibitor therapies should be extended to include analysis of candidates for intra-S phase damage response.
Whole grain consumption and human health: an umbrella review of observational studies

Abstract Whole grains have been associated with a number of health benefits. We systematically reviewed existing meta-analyses of observational studies and evaluated the level of evidence for their putative effects based on pre-selected criteria. Of the 23 included studies, we found convincing evidence of an inverse association between whole grain consumption and risk of type-2 diabetes and colorectal cancer; possible evidence of decreased risk of colon cancer and cardiovascular mortality with increased whole grain intake, as well as increased risk of prostate cancer. Limited or insufficient evidence was available for all other outcomes investigated. Overall findings are encouraging for a positive effect of whole grain consumption on certain diseases, especially highly prevalent metabolic diseases, however, uncertainty of some negative associations deserves further attention.
Cardiac Catheterization versus Echocardiography for Monitoring Pulmonary Pressure: A Prospective Study in Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Standard echocardiography is important for pulmonary arterial hypertension (PAH) screening in patients with connective tissue disease (CTD), but PAH diagnosis and monitoring require cardiac catheterization. Herein, using cardiac catheterization as reference, we tested the hypothesis that follow-up echocardiography is adequate for clinical decision-making in these patients. We prospectively studied 69 consecutive patients with CTD-associated PAH. Invasive baseline pulmonary artery systolic pressure (PASP) was 60.19 ± 16.33 mmHg (mean ± SD) and pulmonary vascular resistance (PVR) was 6.44 ± 2.95WU. All patients underwent hemodynamic and echocardiographic follow-up after 9.47 ± 7.29 months; 27 patients had a third follow-up after 17.2 ± 7.4 months from baseline. We examined whether clinically meaningful hemodynamic deterioration of follow-up catheterization-derived PASP (i.e., > 10% increase) could be predicted by simultaneous echocardiography. Echocardiography predicted hemodynamic PASP deterioration with 59% sensitivity, 85% specificity, and 63/83% positive/negative predictive value, respectively. In multivariate analysis, successful echocardiographic prediction correlated only with higher PVR in previous catheterization (p = 0.05, OR = 1.235). Notably, in patients having baseline PVR > 5.45 WU, echocardiography had both sensitivity and positive predictive values of 73%, and both specificity and negative predictive value of 91% for detecting hemodynamic PASP deterioration. In selected patients with CTD-PAH echocardiography can predict PASP deterioration with high specificity and negative predictive value. Additional prospective studies are needed to confirm that better patient selection can increase the ability of standard echocardiography to replace repeat catheterization.
The citrus flavonoid nobiletin confers protection from metabolic dysregulation in high-fat-fed mice independent of AMPK[S]

Obesity, dyslipidemia, and insulin resistance, the increasingly common metabolic syndrome, are risk factors for CVD and type 2 diabetes that warrant novel therapeutic interventions. The flavonoid nobiletin displays potent lipid-lowering and insulin-sensitizing properties in mice with metabolic dysfunction. However, the mechanisms by which nobiletin mediates metabolic protection are not clearly established. The central role of AMP-activated protein kinase (AMPK) as an energy sensor suggests that AMPK is a target of nobiletin. We tested the hypothesis that metabolic protection by nobiletin required phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in mouse hepatocytes, in mice deficient in hepatic AMPK (Ampkβ1−/−), in mice incapable of inhibitory phosphorylation of ACC (AccDKI), and in mice with adipocyte-specific AMPK deficiency (iβ1β2AKO). We fed mice a high-fat/high-cholesterol diet with or without nobiletin. Nobiletin increased phosphorylation of AMPK and ACC in primary mouse hepatocytes, which was associated with increased FA oxidation and attenuated FA synthesis. Despite loss of ACC phosphorylation in Ampkβ1−/− hepatocytes, nobiletin suppressed FA synthesis and enhanced FA oxidation. Acute injection of nobiletin into mice did not increase phosphorylation of either AMPK or ACC in liver. In mice fed a high-fat diet, nobiletin robustly prevented obesity, hepatic steatosis, dyslipidemia, and insulin resistance, and it improved energy expenditure in Ampkβ1−/−, AccDKI, and iβ1β2AKO mice to the same extent as in WT controls. Thus, the beneficial metabolic effects of nobiletin in vivo are conferred independently of hepatic or adipocyte AMPK activation. These studies further underscore the therapeutic potential of nobiletin and begin to clarify possible mechanisms.