Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of Flavonoid Extraction from Red and Brown Rice Bran and Evaluation of the Antioxidant Properties

Recently, the quality-by-design concept has been widely implemented in the optimization of pharmaceutical processes to improve batch-to-batch consistency. As flavonoid compounds in pigmented rice bran may provide natural antioxidants, extraction of flavonoid components from red and brown rice bran was optimized using central composite design (CCD) and response surface methodology (RSM). Among the solvents tested, ethanol was most efficient for extracting flavonoids from rice bran. The examined parameters were temperature, solvent percentage, extraction time, and solvent-to-solid ratio. The highest total flavonoid content (TFC) in red rice bran was predicted as 958.14 mg quercetin equivalents (QE)/100 g dry matter (DM) at 58.5 °C, 71.5% (v/v), 36.2 min, and 7.94 mL/g, respectively, whereas the highest TFC in brown rice bran was predicted as 782.52 mg QE/100 g DM at 56.7 °C, 74.4% (v/v), 36.9 min, and 7.18 mL/g, respectively. Verification experiment results under these optimized conditions showed that the TFC values for red and brown rice bran were 962.38 and 788.21 mg QE/100 g DM, respectively. No significant differences were observed between the predicted and experimental TFC values, indicating that the developed models are accurate. Analysis of the extracts showed that apigenin and p-coumaric acid are abundant in red and brown rice bran. Further, red rice bran with its higher flavonoid content exhibited higher nitric oxide and 2,2-diphenyl-1-picrylhydrazyl scavenging activities (EC50 values of 41.3 and 33.6 μg/mL, respectively) than brown rice bran. In this study, an extraction process for flavonoid compounds from red and brown rice bran was successfully optimized. The accuracy of the developed models indicated that the approach is applicable to larger-scale extraction processes.
Incidence of type 1 and type 2 diabetes, between 2012-2016, among children and adolescents in Qatar

Introduction: Diagnoses of type 1 DM (T1DM) and type 2 diabetes mellitus (T2DM) in youths present a substantial clinical and public health burden. The aim of this study was to determine the incidence and trend of T1DM and T2DM, among children aged 0–14 years, in Qatar. Methods:This prospective cohort study was performed to ascertain all new cases of T1DM and T2DM 2 in Qatar as per the registry of the National Paediatric Diabetes Centre (the only tertiary care center treating children with DM in Qatar. Age-standardized and age-specific annual incidence rates for age groups 0.5-14 years were calculated.Results: A total of 440 youths with T1DM (0.5 to 14 years of age) and 45 with T2DM (5 to 14 years of age) were identified in Qatar. The inclusive unadjusted estimated incidence rates of T1DM in this population over the period between 2012-2016 was 28.39/100,000 with a 95% CI of 31.82-40.03. This was significantly higher compared to the unadjusted estimated incidence registered between 2006-2011 (23.15/100,000). No case of T2DM were registered before 2008. In the following years the incidence of T2DM increased from 1.82 per 100,000 in 2012 to 2.7 per 100,000 in 2016, with an incidence of T2DM equal to 2.9/100,000 per year. Conclusions:A relatively higher incidence of T1DM compared to incidence reported worldwide have been documented in Qatar. The incidence rate increased in the period 2012-2016 compared to 2006-2011. Further studies are required to determine the causes of these increases. (www.actabiomedica.it)
Detection of HBV Genotype C in Hepatocellular Carcinoma Patients from North East India: a Brief Report

Background and Objectives Newer genotypes of HBV have been reported from India. This study was aimed to determine the circulating genotypes of HBV in hepatocellular carcinoma patients from three different geographical locations of India. Methods 141 HBV related HCC cases were included from three different hospitals across the country. Genotyping of HBV was performed by PCR using type specific primers specially designed in 70 cases. Samples of interest were confirmed by direct sequencing of the precore/core region of HBV genome. Results Genotypes could be detected in 40 (57.14%) out of the 70 HBV DNA positive HCC cases by type specific primers. HBV genotype D was documented in 20 (50%), genotype A in 10 (25.0%) and genotype C in 10 (25.0%) of these HCC cases. Genotype C of HBV was detected only in the samples from North East India. No significant difference was observed for the biochemical profile. Conclusion Although Genotype D is the major HBV genotype in India followed by A, detection of HBV genotypes C in HCC patients indicates a changing epidemiology of the virus in India that may require region based management of the virus.
Admixture of hybrid swarms of native and introduced lizards in cities is determined by the cityscape structure and invasion history

Introductions of non-native lineages increase opportunities for hybridization. Non-native lineages of the common wall lizard, Podarcis muralis, are frequently introduced in cities where they hybridize with native populations. We aimed at unravelling the invasion history and admixture of native and non-native wall lizards in four German cities using citywide, comprehensive sampling. We barcoded and genotyped 826 lizards and tested if gene flow in populations composed of admixed native and introduced lineages is facilitated by similar environmental factors to those in native populations by comparing fine-scale landscape genetic patterns. In cities with non-native lineages, lizards commonly occurred in numerous clusters of hybrid swarms, which showed variable lineage composition, consisting of up to four distinct evolutionary lineages. Hybrid swarms held vast genetic diversity and showed recent admixture with other hybrid swarms. Landscape genetic analyses showed differential effects of cityscape structures across cities, but identified water bodies as strong barriers to gene flow in both native and admixed populations. By contrast, railway tracks facilitated gene flow of admixed populations only. Our study shows that cities represent unique settings for hybridization, caused by multiple introductions of non-native taxa. Cityscape structure and invasion histories of cities will determine future evolutionary pathways at these novel hybrid zones.
Nogo‐A inhibits vascular regeneration in ischemic retinopathy

Nogo‐A is a potent glial‐derived inhibitor of axon growth in the injured CNS and acts as a negative regulator of developmental angiogenesis by inhibiting vascular endothelial cell migration. However, its function in pathological angiogenesis has never been studied after ischemic injury in the CNS. Using the mouse model of oxygen‐induced retinopathy (OIR) which yields defined zones of retinal ischemia, our goal was to investigate the role of Nogo‐A in vascular regeneration. We demonstrate a marked upregulation of the Nogo‐A receptor sphingosine 1‐phosphate receptor 2 in blood vessels following OIR, while Nogo‐A is abundantly expressed in surrounding glial cells. Acute inhibition of Nogo‐A with function‐blocking antibody 11C7 significantly improved vascular regeneration and consequently prevented pathological pre‐retinal angiogenesis. Ultimately, inhibition of Nogo‐A led to restoration of retinal function as determined by electrophysiological response of retinal cells to light stimulation. Our data suggest that anti‐Nogo‐A antibody may protect neuronal cells from ischemic damage by accelerating blood vessel repair in the CNS. Targeting Nogo‐A by immunotherapy may improve CNS perfusion after vascular injuries.
Forms and Functions of Aggression in Early Childhood

Evidence supports the distinctions between forms (relational vs. physical) and functions (proactive vs. reactive) of aggression; however, little research has investigated these two subtype frameworks simultaneously or by teacher-report in early childhood. We examined the factor structures, interrelations, and longitudinal associations of teacher-reported forms and functions of aggression in young children. Preschool and kindergarten students (N = 133; ages 3–6 years; 58.6% male) were rated by their teachers during the spring semester and on two subsequent occasions over the following school year (a three-wave cross-sequential design). Bayesian confirmatory factor analyses and path models were estimated, controlling for covariates and cross-classification of students within classrooms. Correlated two-factor models showed acceptable measurement characteristics for both aggression frameworks. Within and between frameworks, aggression subtypes were highly correlated with one another. Physical aggression showed greater stability than, and was a precursor to, relational aggression, whereas both proactive and reactive aggression were stable and bidirectional. All subtypes—especially reactive and physical aggression—were robustly associated with peer rejection but not with academic performance or depressive symptoms. Results suggest that brief, teacher-reported rating scales can be used to measure forms and functions of aggression during early childhood. However, examination of one framework should elicit questions regarding the other (e.g., to what extent are measures of proactive and reactive aggression capturing physical aggression? ), and research following a form-by-function approach may be particularly useful. Given their stability and outcomes, physical, reactive, and proactive aggression may be important targets for screening and intervention in early childhood settings.
Pattern of patients’ attendance to the dental clinic of federal college of dental technology and therapy, Enugu, Nigeria

Introduction Oral health is part of general health and should not be considered in isolation, as it contributes to the individual's health related quality of life. The study aimed at assessing the pattern of attendance to the dental clinic using dental records of patients. Methods This was a retrospective study of 6008 retrieved case notes from the dental clinic of Federal College of Dental Technology and Therapy, Enugu, from June, 2016 to May, 2017. Data on age, sex and occupation were retrieved from the dental records of the institution. Association between age, sex, occupation and patient flow to dental clinic was determined. Results More females (55.7%) than males (44.3%) attended the dental clinic within the study period. Also, those aged 16 to 30 years (39.5%) and school pupils/students (40.8%) attended dental clinic the most when compared to other attendees. Patient flow was greatest in the first quarter of the year (27.1%), followed by the third quarter (26.1%). However, patient flow was least in the last quarter (20.9%). There was significant association between age (P < 0.001), occupation (P = 0.03) and patient flow to dental clinic in yearly quarters. Conclusion Being an adolescent or young adult and being a student were significantly associated with patient flow to the dental clinic in yearly quarters in the study area. Patient flow was greatest in the first quarter and least in the last quarter of the year. There is need to increase dental awareness, especially for preventive visit among older age group and non-students in the populace.
Genome-wide copy number analyses of samples from LACE-Bio project identify novel prognostic and predictive markers in early stage non-small cell lung cancer.

Background Adjuvant chemotherapy (ACT) provides modest benefit in resected non-small cell lung cancer (NSCLC) patients. Genome-wide studies have identified gene copy number aberrations (CNA), but their prognostic implication is unknown. Methods DNA from 1,013 FFPE tumor samples from three pivotal multicenter randomized trials (ACT vs. control) in the LACE-Bio consortium (median follow-up: 5.2 years) was successfully extracted, profiled using a molecular inversion probe SNP assay, normalized relative to a pool of normal tissues and segmented. Minimally recurrent regions were identified. P values were adjusted to control the false discovery rate (Q values). Results A total of 976 samples successfully profiled, 414 (42%) adenocarcinoma (ADC), 430 (44%) squamous cell carcinoma (SCC) and 132 (14%) other NSCLC; 710 (73%) males. We identified 431 recurrent regions, with on average 51 gains and 43 losses; 253 regions (59%) were ≤3 Mb. Most frequent gains (up to 48%) were on chr1, 3q, 5p, 6p, 8q, 22q; most frequent losses (up to 40%) on chr3p, 8p, 9p. CNA frequency of 195 regions was significantly different (Q≤0.05) between ADC and SCC. Fourteen regions (7p11-12, 9p21, 18q12, and 19p11-13) were associated with disease-free survival (DFS) (univariate P≤0.005, Q<0.142), with poorer DFS for losses of regions including CDKN2A/B [hazard ratio (HR) for 2-fold lower CN: 1.5 (95% CI: 1.2-1.9), P<0.001, Q=0.020] and STK11 [HR =2.4 (1.3-4.3), P=0.005, Q=0.15]. Chromosomal instability was associated with poorer DFS (HR =1.5, P=0.015), OS (HR =1.2, P=0.189) and lung-cancer specific survival (HR =1.7, P=0.003). Conclusions These large-scale genome-wide analyses of gene CNA provide new candidate prognostic markers for stage I-III NSCLC.
Target enrichment sequencing of 307 germplasm accessions identified ancestry of ancient and modern hybrids and signatures of adaptation and selection in sugarcane (Saccharum spp.), a ‘sweet’ crop with ‘bitter’ genomes

Summary Sugarcane (Saccharum spp.) is a highly energy‐efficient crop primarily for sugar and bio‐ethanol production. Sugarcane genetics and cultivar improvement have been extremely challenging largely due to its complex genomes with high polyploidy levels. In this study, we deeply sequenced the coding regions of 307 sugarcane germplasm accessions. Nearly five million sequence variations were catalogued. The average of 98× sequence depth enabled different allele dosages of sequence variation to be differentiated in this polyploid collection. With selected high‐quality genome‐wide SNPs, we performed population genomic studies and environmental association analysis. Results illustrated that the ancient sugarcane hybrids, S. barberi and S. sinense, and modern sugarcane hybrids are significantly different in terms of genomic compositions, hybridization processes and their potential ancestry contributors. Linkage disequilibrium (LD) analysis showed a large extent of LD in sugarcane, with 962.4 Kbp, 2739.2 Kbp and 3573.6 Kbp for S. spontaneum, S. officinarum and modern S. hybrids respectively. Candidate selective sweep regions and genes were identified during domestication and historical selection processes of sugarcane in addition to genes associated with environmental variables at the original locations of the collection. This research provided an extensive amount of genomic resources for sugarcane community and the in‐depth population genomic analyses shed light on the breeding and evolution history of sugarcane, a highly polyploid species.
Exercise cardiorespiratory and thermoregulatory responses in normoxic, hypoxic and hot environment following 10-day continuous hypoxic exposure.

We examined the effects of acclimatization to normobaric hypoxia on aerobic performance and exercise thermoregulatory responses under normoxic, hypoxic and hot conditions. Twelve males performed tests of maximal oxygen uptake (V̇O2max) in normoxic (NOR), hypoxic (13.5% FiO2; HYP) and hot (35℃, 50% RH; HE) conditions in a randomized manner before and after a 10-day continuous normobaric hypoxic exposure (FiO2 = 13.65(0.35)%, PiO2 = 87(3) mmHg). The acclimatization protocol included daily exercise (60min @ 50% hypoxia-specific peak power output, Wpeak). All maximal tests were preceded by a steady-state exercise (30 min at 40% Wpeak) to assess the sweating response. Hematological data were assessed from venous blood samples obtained before and after acclimatization. V̇O2max increased by 10.7% (P = 0.002) and 7.9% (P = 0.03) from pre- to post-acclimatization in NOR and HE, respectively, whereas no differences were found in HYP (pre: 39.9(3.8) vs post: 39.4(5.1) mL.kg-1.min-1, P = 1.0). However, the increase in V̇O2max did not translate into increased Wpeak in either NOR or HE. Maximal heart rate and ventilation remained unchanged following acclimatization. Νo differences were noted in the sweating gain and thresholds independent of the acclimatization or environmental conditions. Hypoxic acclimatization markedly increased hemoglobin (P < 0.001), hematocrit (P < 0.001) and extracellular HSP72 (P = 0.01). These data suggest that 10 days of normobaric hypoxic acclimatization combined with moderate-intensity exercise training improves V̇O2max in NOR and HE, but does not seem to affect exercise performance or thermoregulatory responses in any of the tested environmental conditions.
The impact of the age of first blood meal and Zika virus infection on Aedes aegypti egg production and longevity

The impact of senescence and pathogen infection on Aedes aegypti life-history traits remains poorly understood. This laboratory study focused on the impact of Zika virus (ZIKV) infection and the age of first blood intake on blood meal and clutch sizes, and more importantly on the egg production ratio per μL of blood. Three groups of ZIKV-infected and uninfected Ae. aegypti females that received their first blood meal at 7 (young feeders), 14 (mature feeders) and 21 days old (old feeders) were monitored daily for survival and received a blood meal free of ZIKV once a week. The number of eggs laid per female were registered 3–4 days after blood feeding. Infection by ZIKV and age of feeding produced a strong negative impact on survival and oviposition success (e.g. likelihood of laying at least one egg per gonotrophic cycle). Interestingly, clutch size presented a dramatic reduction on uninfected mosquitoes, but raised from 36.5 in clutch1 to 55.1 eggs in clutch 3. Blood meal size remained stable in uninfected females, while a slight increase was observed for the infected counterparts. In uninfected Ae. aegypti, egg production was strongly affected by the age of feeding with younger females laying three times more eggs than when older. On the other hand, ZIKV-infected mosquitoes had a constant but low egg production. Overall, mosquito senescence and ZIKV infection had an impact on mosquito egg production by causing a sharp decrease in the number of eggs along the clutches for uninfected mosquitoes and a slight increase for infected mosquitoes. Despite some study limitations, our results contribute to a better understanding of the effects of mosquito aging and pathogen infection on the vectorial capacity of Ae. aegypti.
Myths and Methodologies: Reducing scientific design ambiguity in studies comparing sexes and/or menstrual cycle phases

What is the topic of this review? We review methodological considerations for the inclusion of women in sex and menstrual cycle phase comparison studies. What advances does it highlight? Improving the methodological design for studies exploring sex differences, menstrual cycle phase differences and/or endogenous versus exogenous female sex hormones will help to close the gap in our understanding of the effects of endogenous and exogenous hormones on exercise science and sports medicine outcomes.
Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children

Background Rare genetic conditions are frequent risk factors for, or direct causes of, paediatric intensive care unit (PICU) admission. Such conditions are frequently suspected but unidentified at PICU admission. Compassionate and effective care is greatly assisted by definitive diagnostic information. There is therefore a need to provide a rapid genetic diagnosis to inform clinical management. To date, whole genome sequencing (WGS) approaches have proved successful in diagnosing a proportion of children with rare diseases, but results may take months to report. Our aim was to develop an end-to-end workflow for the use of rapid WGS for diagnosis in critically ill children in a UK National Health Service (NHS) diagnostic setting. Methods We sought to establish a multidisciplinary Rapid Paediatric Sequencing team for case selection, trio WGS, rapid bioinformatics sequence analysis and a phased analysis and reporting system to prioritise genes with a high likelihood of being causal. Results Trio WGS in 24 critically ill children led to a molecular diagnosis in 10 (42%) through the identification of causative genetic variants. In 3 of these 10 individuals (30%), the diagnostic result had an immediate impact on the individual’s clinical management. For the last 14 trios, the shortest time taken to reach a provisional diagnosis was 4 days (median 8.5 days). Conclusion Rapid WGS can be used to diagnose and inform management of critically ill children within the constraints of an NHS clinical diagnostic setting. We provide a robust workflow that will inform and facilitate the rollout of rapid genome sequencing in the NHS and other healthcare systems globally.
High‐resolution echo‐planar spectroscopic imaging at ultra‐high field

MR spectroscopic imaging (MRSI) at ultra‐high field (≥7 T) benefits from improved sensitivity that allows the detection of low‐concentration metabolites in the brain. However, optimized acquisition techniques are required to overcome inherent limitations of MRSI at ultra‐high field. This work describes an optimized method for fast high‐resolution 1H‐MRSI of the brain at 7 T. The proposed acquisition sequence combines precise volume localization using semi‐localization by adiabatic selective refocusing, fast spatial encoding using high‐bandwidth symmetric echo‐planar spectroscopic imaging (EPSI), and robust water suppression with variable power and optimized relaxation delays. This showed improved robustness to B0 and B1+ inhomogeneities, eddy currents, nuisance signal contamination and system instabilities. Furthermore, a method for correction of phase inconsistencies in symmetric EPSI enabled high‐bandwidth measurements at 7 T. The proposed correction effectively removed spectral ghosting using a single‐shot water reference scan. This framework was tested in healthy volunteers at 7 T and spectral quality was compared with lower‐spatial‐resolution scans, measured at 3 T using the same methodology. A gain in the signal‐to‐noise ratio (SNR) per unit volume and unit time of 1.57 was achieved, keeping acquisition time short (5 min) and the specific absorption rate within the permitted limits. This SNR enhancement obtained at ultra‐high field enabled high‐resolution (0.25–0.375 mL) metabolite mapping of the brain within a clinically feasible scan time. The correlation of the reconstructed maps with anatomical structures was observed, showing the diagnostic potential of the technique.