Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of amino acid deficiency on precaecal amino acid digestibility in broiler chickens.

In this study, we determined whether deficient dietary amino acid (AA) concentrations influence the precaecal (pc) AA digestibility when determined using the regression approach. We mixed two basal diets. Basal diet 1 was deficient in essential AAs, whereas adequate AA concentrations were ensured in basal diet 2 by adding free AAs. Rapeseed cake and full-fat soya beans as test ingredients were included in the basal diets at levels of 100 and 200, and 150 and 300 g/kg, respectively, at the expense of maize starch. Each diet was tested with six replicates of 10 broiler chickens each. The feed intake of the chickens that were fed diets based on basal diet 2 was similar, whereas the feed intake of the chickens that were fed diets based on basal diet 1 differed considerably. The numerical differences in pc AA digestibility determined with basal diet 1 or 2 ranged from 2.6 percentage points to 20.8 percentage points in rapeseed cake and from 0.5 percentage points to 15.2 percentage points in soya beans. Across all measured AAs, the average differences were 10.1 percentage points and 5.4 percentage points in rapeseed cake and soya beans, respectively. The differences in the estimated pc AA digestibility between the basal diets were probably caused by different basal endogenous AA losses in the digesta between treatments as a consequence of different feed intake. Adequate AA concentrations and test ingredient levels that are specifically adjusted to avoid a negative effect on feed intake are recommended for future studies.
Effects of Feedback on Chest Compression Quality: A Randomized Simulation Study

CC performance significantly improved with verbal or visual feedback compared with instructor-led feedback in a randomized, simulation-based pediatric resuscitation training. OBJECTIVES: Our aim for this study was to test whether visual and verbal feedback compared with instructor-led feedback improve the quality of pediatric cardiopulmonary resuscitation (CPR). METHODS: There were 653 third-year medical students randomly assigned to practice pediatric CPR on 1 of 2 manikins (infant and adolescent; n = 344 and n = 309, respectively). They were further randomly assigned to 1 of 3 feedback groups: The instructor feedback (IF) group (n = 225) received traditional, instructor-led feedback without any additional feedback device. The device feedback (DF) group (n = 223) received real-time visual feedback from a feedback device. The instructor and device feedback (IDF) group (n = 205) received verbal feedback from an instructor who continuously reviewed the trainees’ performance using the feedback device. After the training, participants’ CPR performance was assessed on the same manikin while no feedback was being provided. RESULTS: For the primary outcome of total compression score, participants in the DF and IDF groups performed similarly, with both groups showing scores significantly (P < .001) better than those of the IF group. The same findings held for correct hand position and the proportion of complete release. For compression rate, the DF group was at the higher end of the guideline for 100 to 120 chest compressions per minute compared with the IF and IDF groups (both P < .001). No effect of feedback on compression depth was found. CONCLUSIONS: Chest compression performance significantly improved with both visual and verbal feedback compared with instructor-led feedback. Feedback devices should be implemented during pediatric resuscitation training to improve resuscitation performance.
Green Waste-Derived Substances Immobilized on SBA-15 Silica: Surface Properties, Adsorbing and Photosensitizing Activities towards Organic and Inorganic Substrates

Urban wastes are a potential source of environment contamination, especially when they are not properly disposed. Nowadays, researchers are finding innovative solutions for recycling and reusing wastes in order to favour a sustainable development from the viewpoint of circular economy. In this context, the lignin-like fraction of biomass derived from Green Compost is a cost-effective source of soluble Bio-Based Substances (BBS-GC), namely complex macromolecules/supramolecular aggregates characterized by adsorbing and photosensitizing properties. In this work BBS-GC were immobilized on a silica support (SBA-15) and the chemico-physical properties of the resulting hybrid material (BBS-SBA) were analysed by zeta-potential measurements, nitrogen adsorption at 77K and micro-calorimetric techniques. Successively, the BBS-SBA photosensitizing and adsorption abilities were tested. Adsorption in the dark of Rhodamine B and Orange II on BBS-SBA and their degradation upon irradiation under simulated solar light were shown, together with the formation of hydroxyl radicals detected by Electron Paramagnetic Resonance spectroscopy. Furthermore, the adsorption of six inorganic ions (Al, Ni, Mn, As, Hg, Cr) on BBS-SBA was studied in pure water at two different pH values and in a landfill leachate, showing the good potential of this kind of materials in the removal of wastewater contaminants.
Noncoding RNAs in alcoholic liver disease

Alcoholic liver disease (ALD) is a complex process with high morbitity and can cause liver dysfunction, which contains a wide spectrum of hepatic lesions, including steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. To date, the molecular mechanisms for ALD have not been fully explored and an effective therapy is still missing. Overwhelming evidence shows dysregulation of noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), is correlated with etiopathogenesis and progress of ALD including hepatocyte damage, disrupted lipid metabolism, aggressive inflammatory responses, oxidative stress, programmed cell death, fibrosis, and epigenetic changes induced by alcohol. For example, circulating miRNA‐122 is a marker of hepatocyte damage, and miRNA‐155 is a potential marker of inflammation, indicating their diagnosis therapeutic potential in ALD. In addition, roles for long noncoding RNAs (lncRNAs) and circular RNAs in ALD are being uncovered. Further, circulating ncRNAs and exosome‐derived ncRNAs have attracted more attention lately, suggesting a role in the prevention and treatment of ALD. This review covers the roles of ncRNAs in ALD, and the potential uses as markers for diagnosis and therapeutic options.
Association between genetic polymorphism of heme oxygenase 1 promoter and neonatal hyperbilirubinemia: a meta-analysis

Abstract Objective: The association between a (GT)n dinucleotide length polymorphism in the promoter region of heme oxygenase 1 (HMOX1) and the risk of neonatal hyperbilirubinemia remains controversial. This meta-analysis was, therefore, performed with aims to examine the correlation between the HMOX1 (GT)n repeat length polymorphism and neonatal hyperbilirubinemia susceptibility. Materials and methods: We searched the databases including PubMed, Embase, Cochrane Library, China national knowledge infrastructure (CNKI), and Wanfang Data, with all reviewed studies published before 28 June 2018. After the evaluation of quality, we used RevMan to perform the meta-analyses. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the effect of HMOX1 gene promoter polymorphisms on the risk of neonatal hyperbilirubinemia. Results: Seven studies, involving 584 patients with neonatal hyperbilirubinemia and 1655 controls, were included. A statistically significant association was found between the HMOX1 (GT)n repeat length polymorphism and risk of neonatal hyperbilirubinemia under the allele (allele S vs. allele L: OR = 1.81, 95% CI = 1.22–2.67, p = .003), recessive (genotype SS vs. genotypes LS + LL: OR = 1.38, 95% CI = 1.02–1.86, p = .04), dominant (genotypes SS + LS vs. LL: OR = 1.37, 95% CI = 1.01–1.76, p = .01), and homozygous genetic models (genotype SS vs. genotype LL: OR = 1.47, 95% CI = 1.02–2.11, p = .003), but not under the heterozygous genetic model. Interestingly, subgroup analysis revealed that the cutoffs of the S allele < 25 showed significant associations in any of the five genetic models (allele S vs. allele L: OR = 2.26, 95% CI = 1.68–3.05, p < .00001; genotype SS vs. genotypes LS + LL: OR = 2.56, 95% CI = 1.41–4.65, p = .002; genotypes SS + LS vs. genotype LL: OR = 1.82, 95% CI = 1.28–2.59, p = .0009; genotype SS vs. genotype LL: OR = 3.09, 95% CI = 1.50–6.36, p = .002; genotype LS vs. genotype LL: OR = 1.64, 95% CI = 1.11–2.42, p = .01); however, this association was not observed in the cutoffs of the S allele ≥25. Conclusion: The results of this study indicate that there is a significant association between the HMOX1 (GT)n repeat length polymorphism and susceptibility to neonatal hyperbilirubinemia. Newborns carrying shorter (GT)n repeats in the HMOX1 gene promoter may have a higher risk of neonatal hyperbilirubinemia.
Deleting Full Length Titin Versus the Titin M-Band Region Leads to Differential Mechanosignaling and Cardiac Phenotypes

Background: Titin is a giant elastic protein that spans the half-sarcomere from Z-disk to M-band. It acts as a molecular spring and mechanosensor and has been linked to striated muscle disease. The pathways that govern titin-dependent cardiac growth and contribute to disease are diverse and difficult to dissect. Methods: To study titin deficiency versus dysfunction, the authors generated and compared striated muscle specific knockouts (KOs) with progressive postnatal loss of the complete titin protein by removing exon 2 (E2-KO) or an M-band truncation that eliminates proper sarcomeric integration, but retains all other functional domains (M-band exon 1/2 [M1/2]-KO). The authors evaluated cardiac function, cardiomyocyte mechanics, and the molecular basis of the phenotype. Results: Skeletal muscle atrophy with reduced strength, severe sarcomere disassembly, and lethality from 2 weeks of age were shared between the models. Cardiac phenotypes differed considerably: loss of titin leads to dilated cardiomyopathy with combined systolic and diastolic dysfunction—the absence of M-band titin to cardiac atrophy and preserved function. The elastic properties of M1/2-KO cardiomyocytes are maintained, while passive stiffness is reduced in the E2-KO. In both KOs, we find an increased stress response and increased expression of proteins linked to titin-based mechanotransduction (CryAB, ANKRD1, muscle LIM protein, FHLs, p42, Camk2d, p62, and Nbr1). Among them, FHL2 and the M-band signaling proteins p62 and Nbr1 are exclusively upregulated in the E2-KO, suggesting a role in the differential pathology of titin truncation versus deficiency of the full-length protein. The differential stress response is consistent with truncated titin contributing to the mechanical properties in M1/2-KOs, while low titin levels in E2-KOs lead to reduced titin-based stiffness and increased strain on the remaining titin molecules. Conclusions: Progressive depletion of titin leads to sarcomere disassembly and atrophy in striated muscle. In the complete knockout, remaining titin molecules experience increased strain, resulting in mechanically induced trophic signaling and eventually dilated cardiomyopathy. The truncated titin in M1/2-KO helps maintain the passive properties and thus reduces mechanically induced signaling. Together, these findings contribute to the molecular understanding of why titin mutations differentially affect cardiac growth and have implications for genotype-phenotype relations that support a personalized medicine approach to the diverse titinopathies.
Current pharmacotherapy options for conduct disorders in adolescents and children

ABSTRACT Introduction: Conduct disorder (CD) is a common mental health disorder of childhood and adolescence. CD’s complexity, with its heterogenous clinical manifestations and overlapping comorbidities makes the application of evidence-based management approaches challenging. This article aims to combine a systematic review of the available literature, with a consensus opinion from both child and adolescent psychiatrists and developmental pediatricians on the clinical and pharmacological management of children and adolescents with conduct disorder (CD). Areas covered: The authors review the CD population and provide a systematic review and meta-analysis of the effectiveness and safety of pharmacotherapies using preferred reporting items for systematic review and meta-analysis (PRISMA) and strength of evidence recommendation taxonomy (SORT) guidelines. The authors then provide an expert clinical opinion for the use of different pharmacotherapies to address aggressive and disruptive behavior in children. Expert opinion: Atypical antipsychotics (e.g. risperidone) demonstrate evidence for efficacy in CD. Other pharmacotherapies (e.g. mood stabilizers, anticonvulsants, psychostimulants and selective norepinephrine reuptake inhibitors) have a low level of evidence for CD alone, however, can sometimes be effective in managing the symptoms of CD when other psychiatric disorders are also present.
Prognostic role of disease extent and lymphocyte-monocyte ratio in advanced melanoma.

Advanced melanoma (AM) represents the leading cause of death from skin cancer. To date, the crucial role of the immune system in AM pathogenesis and progression is well known, but the prognostic value of clinicopathological characteristics remains unclear. Lactate dehydrogenase (LDH) is an ascertained prognostic indicator and previous data showed that AM patients treated with BRAF and MEK inhibitors with normal LDH values and fewer than three metastatic sites achieved a better outcome. Moreover, the neutrophil-to-lymphocytes ratio and the lymphocyte-to-monocyte ratio (LMR) have been suggested as other potential prognostic factors. The aim of this study was to evaluate the prognostic value of LMR together with other clinical biomarkers in patients with AM. We retrospectively analyzed 162 consecutive patients with AM treated between January 2010 and March 2016. Outcome was measured in terms of overall survival (OS). In our cohort, the BRAF mutation was present in 74 (46%) patients. Overall, 42 and 26% of the patients received targeted therapy and immunotherapy, respectively. After 48 months of follow-up, 129 (78%) patients died; the median OS was 12.8 months. High LMR was associated with the following clinicopathological characteristics: absence of central nervous system localization (P=0.011), fewer than three metastatic sites (P=0.014), and normal LDH (P=0.006). In multivariate analysis, Eastern Cooperative Oncology Group Performance Status>1 [hazard ratio (HR) 7.87, P=0.001], high LDH (HR 2.76, P=0.006), and high LMR (HR 0.76, P=0.033) were associated significantly with OS. In conclusion, LMR seems to be associated with OS. Further prospective investigations are needed to confirm these data and introduce peripheral blood cell count in daily clinical use.
Implementing Anaerobic Speed Reserve Testing in the Field: Validation of vVO2max Prediction from 1500m Race Performance in Elite Middle-Distance Runners.

PURPOSE: The anaerobic speed reserve (ASR) defined as the speed range from vVO2max to maximal sprint speed (MSS) has recently been shown to be an important tool for middle-distance coaches to meet event surge demands and inform on the complexity of athlete profiles. To enable field application of ASR, the relationship between gun-to tape 1500 m average speed (1500v) and the velocity associated with maximal oxygen uptake (vVO2max) for the determination of lower landmark of the ASR was assessed in elite middle-distance runners. METHODS: Eight national and four international middle-distance runners completed a laboratory-measured vVO2max assessment within six weeks of a non-championship 1500m gun-to-tape race. ASR was calculated using both laboratory-derived vVO2max (ASR-LAB) and 1500v (ASR-1500v), with MSS measured via radar technology. RESULTS: 1500v was on average +2.06 ± 1.03 km/hr faster than vVO2max (moderate effect, very likely). ASR-LAB and ASR-1500v mean differences were -2.1 ± 1.5 km/hr (large effect, very likely). 1500v showed an extremely large relationship with vVO2max; r=0.90 ± 0.12 (most likely). Using this relationship, a linear regression vVO2max estimation equation was derived as: vVO2max (km/hr) = (1500v (km/hr) -14.921)/0.4266. CONCLUSIONS: A moderate difference was evident between 1500v and vVO2max in elite middle-distance runners. The present regression equation should be applied for an accurate field prediction of vVO2max from gun-to-tape 1500 m races. These findings have strong practical implications for coaches lacking access to a sports physiology laboratory that seek to monitor and profile middle-distance runners.
Predictions of genotoxic potential, mode of action, molecular targets, and potency via a tiered multiflow® assay data analysis strategy

The in vitro MultiFlow® DNA Damage Assay multiplexes γH2AX, p53, phospho‐histone H3, and polyploidization biomarkers into a single flow cytometric analysis. The current report describes a tiered sequential data analysis strategy based on data generated from exposure of human TK6 cells to a previously described 85 chemical training set and a new pharmaceutical‐centric test set (n = 40). In each case, exposure was continuous over a range of closely spaced concentrations, and cell aliquots were removed for analysis following 4 and 24 hr of treatment. The first data analysis step focused on chemicals' genotoxic potential, and for this purpose, we evaluated the performance of a machine learning (ML) ensemble, a rubric that considered fold increases in biomarkers against global evaluation factors (GEFs), and a hybrid strategy that considered ML and GEFs. This first tier further used ML output and/or GEFs to classify genotoxic activity as clastogenic and/or aneugenic. Test set results demonstrated the generalizability of the first tier, with particularly good performance from the ML ensemble: 35/40 (88%) concordance with a priori genotoxicity expectations and 21/24 (88%) agreement with expected mode of action (MoA). A second tier applied unsupervised hierarchical clustering to the biomarker response data, and these analyses were found to group certain chemicals, especially aneugens, according to their molecular targets. Finally, a third tier utilized benchmark dose analyses and MultiFlow biomarker responses to rank genotoxic potency. The relevance of these rankings is supported by the strong agreement found between benchmark dose values derived from MultiFlow biomarkers compared to those generated from parallel in vitro micronucleus analyses. Collectively, the results suggest that a tiered MultiFlow data analysis pipeline is capable of rapidly and effectively identifying genotoxic hazards while providing additional information that is useful for modern risk assessments—MoA, molecular targets, and potency. Environ. Mol. Mutagen. 60:513–533, 2019. © 2019 Wiley Periodicals, Inc.
A Droplet Digital PCR Assay for Smoking Predicts All-Cause Mortality.

OBJECTIVES -Determine whether an epigenetic assay for smoking predicts all-cause mortality in adults participating in a longitudinal study of Iowa adoptees. BACKGROUND -Improved biomarkers for smoking are needed given its large public health impact and significant limitations of both self-report and current biomarkers, such as cotinine in detecting smoking. In the past 5 years, multiple epigenome-wide association studies of smoking have identified loci suitable for translation as epigenetic biomarkers for smoking, in particular the CpG cg05575921. Digital polymerase chain reaction methods hold promise for the development of this and other epigenetic biomarkers. METHODS -Participants in the Iowa Adoption Studies were interviewed regarding their smoking habits. DNA was prepared from whole blood and bisulfite-converted for methylation analysis and digital droplet polymerase chain reaction assay of methylation at cg05575921 was performed. National Death Index records were requested for 584 study participants, resulting in 24 complete matches, 210 partial matches and 350 non-matching records. Complete matches were coded as deceased while the remainder were coded as alive (ie, censored). In total, methylation data and vital status information were available for a total of N = 193 subjects, including 15 deceased and 178 non-deceased. Cox regression was used to examine the ability of cg05575921 methylation as a continuous value to predict the timing of mortality with and without the inclusion of age, sex, race, BMI, marital status, educational status, socioeconomic status, cardiovascular risk factors, and a history of cancer as covariates. RESULTS -Methylation at cg05575921 predicted the hazard of mortality as the sole predictor and after accounting for major demographic and clinical risk factors. The fitted model showed the hazard ratio increased by 3.5% for every 1% decrease in methylation. CONCLUSIONS -Decreased methylation at cg05575921, an emerging epigenetic biomarker for smoking, was associated with early mortality in a longitudinal study of adults after accounting for the impact of major demographic and clinical risk factors for all-cause mortality. This approach may be useful in clinical research or actuarial assessments.
Patient perceptions of a comprehensive cancer navigation service.

OBJECTIVE Our aim was to determine the extent to which comprehensive navigation augments the provincial health system for meeting the needs of newly-diagnosed cancer patients (clients). We also assessed reactions of attending physicians to comprehensive navigation. METHODS Clients who completed navigation as an employee benefit or through membership in an insurance organization were polled to determine whether they needed help beyond that provided by the provincial health system and the extent to which that help was provided by navigation. Exit interviews were analyzed for perceptions of the clients about reactions by their attending physicians to navigation. RESULTS Of eligible clients, 72% responded. They reported needing help beyond that which the provincial system could provide in 64%-98% of specified areas. Navigation provided help in more than 90% of those cases. Almost all respondents (98%) appreciated having a designated oncology nurse navigator. Family doctors were perceived to be positive or neutral about navigation in 100% of exit interviews. Oncologists were positive or neutral in 92% (p < 0.001 for difference from family doctors). CONCLUSIONS In many areas, cancer patients need additional help beyond that which the provincial health system can provide. Comprehensive cancer navigation provides that help to a considerable extent. Clients perceived the reactions of attending physicians to comprehensive navigation to be generally supportive or neutral.