Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Finishing Diet on Physico-Chemical and Lipolytic Parameters and Volatile Compounds Throughout the Manufacture of Dry-Cured Foal “Cecina”

The objective of this study was to investigate the effect of the finishing diet (1.5 kg vs. 3 kg of commercial feed) on the physico-chemical, colour, textural and lipolytic parameters and volatile compounds of dry-cured foal “cecina” throughout the manufacturing process. Ripening time significantly affected ( P <0.05) all the studied parameters. Finishing diet of foals did not affect ( P >0.05) its chemical composition. Considering physico-chemical parameters, some differences were found at several sample points. Higher red colour (a*) ( P <0.001) and lower total work (kg∙mm) ( P <0.05) were observed in the 3 kg “cecinas” group at the end of manufacturing process. TBAR´s reached their maximum values after post-salting stage, being these results significantly higher in “cecinas” from foals feed with 3 kg of concentrate. Free fatty acids (FFA) release was significantly higher in “cecinas” from the 3 kg group, especially due to the higher content of oleic and palmitic acid. Finally, the largest amount of volatile compounds was obtained in “cecinas” from the 3 kg group, however, hexanal content was significantly higher on 1.5 group.
The Relationship Between Mental Health and Psychosocial Stress of Reservoir Migrants in the Middle Route of China’s South-to-North Water Diversion Project (SNWDP): The Mediating Role of Social Support

Background: South–North Water Diversion Project (SNWDP) migrants were vulnerable to developing mental health problems due to post-migration stresses and lack of social support. However, the evidence on the mental health, psychosocial stress and social support of SNWDP migrants and their interrelationships are limited and inconclusive. We aimed to explore the mechanism of influence of social support on the relationship between mental health and social psychosocial stress of SNWDP migrants. Methods: We performed a cross-sectional analysis of the data of 983 SNWDP migrants. The mental health status, psychosocial stress and social support of the participants were evaluated by Symptom Checklist-90-Revised (SCL-90-R), Psychosocial Stress Survey for Groups (PSSG) and Social Support Rating Scale (SSRS). Multiple stepwise regression model was used to analyze the data. Results: Among the 983 individuals, the average SCL-90-R score was 1.47, the PSSG score was 30.50, and the SSRS score was 40.30. The SCL-90-R was positively correlated with PSSG ( r =0.483, P <0.001) and negatively correlated with SSRS ( r =−0.257, P <0.001), PSSG was negatively correlated with SSRS ( r =−0.516, P <0.001). Multiple regression analysis showed that PSSG and SSRS had significant effects on SCL-90-R prediction and that SSRS played a partial intermediary role in SCL-90-R and PSSG (46.87%). Conclusion: The SNWDP migrants performed a strong correlation between social support, mental health and psychosocial stress. Social support plays a part role in mediating mental health and psychosocial stress.
Regulation of the c fos Serum Response Element by C/EBP b

Serum response element binding protein (SRE BP) is a novel binding factor present in nuclear extracts of avian and NIH 3T3 ﬁbroblasts which speciﬁcally binds to the c fos SRE within a region overlapping and immediately 3 * to the CArG box. Site-directed mutagenesis combined with transfection experiments in NIH 3T3 cells showed that binding of both serum response factor (SRF) and SRE BP is necessary for maximal serum induction of the SRE. In this study, we have combined size fractionation of the SRE BP DNA binding activity with C/EBP b antibodies to demonstrate that homodimers and heterodimers of p35C/EBP b (a transactivator) and p20C/EBP b (a repressor) contribute to the SRE BP complex in NIH 3T3 cells. Transactivation of the SRE by p35C/EBP b is dependent on SRF binding but not ternary complex factor (TCF) formation. Both p35C/ EBP b and p20C/EBP b bind to SRF in vitro via a carboxy-terminal domain that probably does not include the leucine zipper. Moreover, SRE mutants which retain responsiveness to the TCF-independent signaling path- way bind SRE BP in vitro with afﬁnities that are nearly identical to that of the wild-type SRE, whereas mutant SRE.M, which is not responsive to the TCF-independent pathway, has a nearly 10-fold lower afﬁnity for SRE BP. We propose that C/EBP b may play a role in conjunction with SRF in the TCF-independent signaling pathway for SRE
An Essential Role of S -Adenosyl- L -Methionine: L Methionine S -Methyltransferase in Selenium Volatilization by Plants. Methylation of Selenomethionine to Selenium-Methyl- L - Selenium-Methionine, the Precursor of Volatile Selenium 1

Selenium (Se) phytovolatilization, the process by which plants metabolize various inorganic or organic species of Se (e.g. selenate, selenite, and Se-methionine [Met]) into gaseous Se forms (e.g. dimethylselenide), is a potentially important means of removing Se from contaminated environments. Before attempting to genetically enhance the efficiency of Se phytovola- tilization, it is essential to elucidate the enzymatic pathway involved and to identify its rate-limiting steps. The present research tested the hypothesis that S- adenosyl- l -Met: l -Met S- methyltransferase (MMT) is the enzyme responsible for the methylation of Se-Met to Se-methyl Se-Met (SeMM). To this end, we identified and characterized an Arabidopsis T-DNA mutant knockout for MMT. The lack of MMT in the Arabidopsis T-DNA mutant plant resulted in an almost complete loss in its capacity for Se volatilization. Using chemical complementation with SeMM, the presumed enzymatic product of MMT, we restored the capacity of the MMT mutant to produce volatile Se. Overexpressing MMT from Arabidopsis in Escherichia coli , which is not known to have MMT activity, produced up to 10 times more volatile Se than the untransformed strain when both were supplied with Se-Met. Thus, our results provide in vivo evidence that MMT is the key enzyme catalyzing the methylation of Se-Met to SeMM.
Oridonin ameliorates depressive-like behaviors induced by chronic unpredictable mild stress in mice via TXNIP/NLRP3 signaling pathway

Purpose: To investigate the effect and mechanism of oridonin in chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors. Methods: CUMS was established using 6-week stress stimuli, including feed/water deprivation, night lighting, inverted light/dark cycle, and tail clamping. Depressive behaviors were analyzed using the sucrose preference test, forced swim test (FST), and tail suspension test (TST). Locomotor activity was analyzed using the open field test (OFT) while inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. The activation of the TXNIP/NLRP3 signaling pathway was evaluated by western blot. Results: Sucrose consumption of CUMS-treated mice was significantly decreased, while immobility times of the FST (control vs. CUMS, ~50 to 150 s; p < 0.01) and TST (Control vs. CUMS, ~50 to 130 s; p < 0.01) were increased; oridonin significantly reversed these effects. Spontaneous locomotor activities (crossing, rearing, and grooming) measured in the OFT were decreased after the CUMS procedure, and oridonin increased these activities (p < 0.01 vs. CUMS). Oridonin decreased the production of tumor necrosis factor alpha, interleukin (IL)-1 β , IL-6, and monocyte chemoattractant protein-1 in the hippocampus of CUMS-treated mice and significantly inhibited activation of the TXNIP/NLRP3 pathway induced by CUMS. Conclusion: Oridonin ameliorates depressive-like behaviors in mice induced by CUMS, partly via TXNIP/NLRP3 signaling pathway. Thus, the findings provide evidence for the potential application of oridonin in depression therapy.
ADHD‐associated PARK2 copy number variants: A pilot study on gene expression and effects of supplementary deprivation in patient‐derived cell lines

Recent studies show an association of Parkin RBR E3 ubiquitin protein ligase (PARK2) copy number variations (CNVs) with attention deficit hyperactivity disorder (ADHD). The aim of our pilot study to investigate gene expression associated with PARK2 CNVs in human‐derived cellular models. We investigated gene expression in fibroblasts, hiPSC and dopaminergic neurons (DNs) of ADHD PARK2 deletion and duplication carriers by qRT PCR compared with healthy and ADHD cell lines without PARK2 CNVs. The selected 10 genes of interest were associated with oxidative stress response (TP53, NQO1, and NFE2L2), ubiquitin pathway (UBE3A, UBB, UBC, and ATXN3) and with a function in mitochondrial quality control (PINK1, MFN2, and ATG5). Additionally, an exploratory RNA bulk sequencing analysis in DNs was conducted. Nutrient deprivation as a supplementary deprivation stress paradigm was used to enhance potential genotype effects. At baseline, in fibroblasts, hiPSC, and DNs, there was no significant difference in gene expression after correction for multiple testing. After nutrient deprivation in fibroblasts NAD(P)H‐quinone‐dehydrogenase 1 (NQO1) expression was significantly increased in PARK2 CNV carriers. In a multivariate analysis, ubiquitin C (UBC) was significantly upregulated in fibroblasts of PARK2 CNV carriers. RNA sequencing analysis of DNs showed the strongest significant differential regulation in Neurontin (NNAT) at baseline and after nutrient deprivation. Our preliminary results suggest differential gene expression in pathways associated with oxidative stress, ubiquitine‐proteasome, immunity, inflammation, cell growth, and differentiation, excitation/inhibition modulation, and energy metabolism in PARK2 CNV carriers compared to wildtype healthy controls and ADHD patients.
Preclinical and Phase 1 Assessment of Antisense Oligonucleotide Bepirovirsen in Hepatitis B Virus–Transgenic Mice and Healthy Human Volunteers: Support for Clinical Dose Selection and Evaluation of Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses

Dose‐dependent reductions in hepatitis B virus (HBV) RNA, DNA, and viral proteins following bepirovirsen administration were observed in HepG2.2. 15 cells. In HBV‐transgenic mice treated at 50 mg/kg/wk, hepatic HBV RNA and DNA were reduced by 90% and 99%, respectively. Subsequently, a phase 1 first‐in‐human study assessed pharmacokinetics and tolerability of single (75–450 mg) and multiple (150–450 mg on days 1, 4, 8, 11, 15, and 22) subcutaneous bepirovirsen doses in 96 healthy volunteers. Bepirovirsen at all dose levels was rapidly absorbed (maximum plasma concentration 3–8 hours after dosing), rapidly distributed to peripheral tissues, and slowly eliminated (median plasma terminal half‐life: 22.5–24.6 days across cohorts). Plasma exposure (dose‐proportional at 150–450 mg) and concentration‐time profiles were similar following the first and sixth doses, suggesting little to no plasma accumulation (steady state achieved by day 22). Renal elimination of full‐length bepirovirsen accounted for <2% of the total dose. Across the single and multiple dose cohorts, 197 treatment‐emergent adverse events were reported, with 99% and 65% classified as mild in severity and local injection site reactions, respectively. In conclusion, bepirovirsen showed an acceptable safety profile in humans with observed pharmacokinetics consistent with the chemical class, warranting further evaluation of bepirovirsen in chronic HBV infection.
Air Quality in Welding Workshops and Its Health Implication on Welders in Port Harcourt

Health is associated with the well being of an individual, which measures the extent to which a person is able to perform work and still remain in an optimal productive state. According to World Health Organization [1], health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. Health can be threatened by a lot of risk factors depending on the kind of occupation and the level of exposure. The International Standards Organization (2009) identified risk as the potential that a chosen action or activity will lead to a loss. It also identified that every human endeavors carries some level of risk but that risk levels differ due to the type of occupation that is been carried out. Health and wellbeing are affected by different factors, and ill health, disability, disease or death has been identified as risk factors [2]. Risk factors as they posits, are noted on individual basis, while in practice there operate holistically and not in isolation since there co exist and are seen to have an interaction with one another. With recent trends in globalization, development and innovations, the industrial sector plays an important role in the achievement of industrialization which is the driving force on any nation’s economy. In the process of production, welding plays an important role of providing the technology of joining, especially in the still manufacturing industries where it accounts for value creation, the production and manufacturing of ships, building bridges as well as offshore and onshore foundations for oil drilling operations (Cheng et al. 2015). The construction industry as put forth by Pinto, Nunes and Ribeiro [3] is a high employment generating sectors in many countries of the world. They stated that in the construction industry there is diversity of activities which workers perform and Abstract
Urinary metabotypes of newborns with perinatal asphyxia undergoing therapeutic hypothermia

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the “HIE” group), and 32 did not (the “no HIE” group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the “HIE” and “no HIE” groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA.
Porcn as a novel therapeutic target in cancer therapy:  A review

Wingless‐related integration site (Wnt) signaling is one of the main oncogenic pathways in different malignancies. Therefore, targeting this pathway has been considered an exciting strategy in cancer treatment. Porcn is among the central enzymes in this pathway that has recently been considered for cancer‐targeted therapy. As a membrane‐bound O‐acyltransferase, Porcn plays a critical role in wnt ligand palmitoylation and its subsequent secretion. In addition to Porcn's role in stem cell signaling and differentiation, recent findings have shown its role in developing and progressing colorectal, pancreatic, liver, head, and neck cancers. Developed small molecule inhibitors have also opened a promising window toward cancer treatment strategies. In this review, the structure and biological role of Porcn in different cancer‐related signaling pathways and inhibitors used for inhibiting this enzyme are discussed.
Adherence to referrals from preschool vision screening and identification of barriers for non-adherence in Israel

ABSTRACT Clinical Relevance Preschool vision screening is essential for the early detection and treatment of eye and vision problems. Background The rate of parental adherence to referrals for comprehensive examination was assessed and factors and potential barriers associated with adherence were identified. Methods In a prospective cohort study design, parents were offered to bring their 3–6 year old aged children to free-of-charge vision screening tests at community-based Mother Child Health Centers. Children with abnormal findings were referred to an ophthalmologist examination. Parents were interviewed three to six months after the referral to evaluate adherence and barriers. Barriers were organised into a conceptual framework of parental predisposing and health system factors. Adherence and barriers were assessed by sex, age, ethnic group and socio-economic-status. Results Altogether 1283 children (mean age 4.5 ± 0.6 years, 47.8% girls) were screened in the Jerusalem district, Israel. The ethnic groups, Jewish (ultra-Orthodox 51.4%, secular/religious 33.2%) and Arab (15.4%), were similar by age and sex, but not by socio-economic status. The overall referral rate was 23.0% (N = 295). Referral rate was not associated with demographic factors. Overall, 54.3% (N = 160) of parents adhered to the referral to bring the child for a full eye examination. Adherence did not differ with sex, ethnicity or socio-economic-status. Parents of 5-6-year-old children were significantly more likely to adhere than parents of younger children. Of parents who did not adhere, 79.3% were attributed to predisposing factors, 16.3% to system factors and 4.4% to other reasons. Conclusions Only half the parents proceeded with the recommended full eye examination. Parents of older children were more likely to adhere to referral. In contrast with vaccinations provided by Mother Child Health Centers, adherence to vision screening did not vary based on ethnicity or socio-economic factors. Since most barriers were associated with predisposing factors of parents, interventions to improve adherence should include parental education.
Deep Neural Network for the Prediction of KRAS Genotype in Rectal Cancer.

BACKGROUND KRAS mutation can alter the treatment plan after resection of colorectal cancer. Despite its importance, the KRAS status of several patients remains unchecked because of the high cost and limited resources. This study developed a deep neural network (DNN) to predict the KRAS genotype using hematoxylin and eosin (H&E)-stained histopathological images. STUDY DESIGN Three DNNs were created (KRAS_Mob, KRAS_Shuff, and KRAS_Ince) using the structural backbone of the MobileNet, ShuffleNet, and Inception networks, respectively. The Cancer Genome Atlas was screened to extract 49,684 image tiles that were used for deep learning and internal validation. An independent cohort of 43,032 image tiles was used for external validation. The performance was compared with humans, and a virtual cost-saving analysis was done. RESULTS The KRAS_Mob network (area under the receiver operating curve [AUC] 0.8, 95% CI 0.71 to 0.89) was the best-performing model for predicting the KRAS genotype, followed by the KRAS_Shuff (AUC 0.73, 95% CI 0.62 to 0.84) and KRAS_Ince (AUC 0.71, 95% CI 0.6 to 0.82) networks. Combing the KRAS_Mob and KRAS_Shuff networks as a double prediction approach showed improved performance. KRAS_Mob network accuracy surpassed that of two independent pathologists (AUC 0.79 [95% CI 0.64 to 0.93], 0.51 [95% CI 0.34 to 0.69], and 0.51 (95% CI 0.34 to 0.69]; p < 0.001 for all comparisons). CONCLUSION The DNN has the potential to predict the KRAS genotype directly from H&E-stained histopathological slide images. As an algorithmic screening method to prioritize patients for laboratory confirmation, such a model might possibly reduce the number of patients screened, resulting in significant test-related time and economic savings.
Effects of 10 add‐on HF‐rTMS treatment sessions on alcohol use and craving among detoxified inpatients with alcohol use disorder: a randomized sham‐controlled clinical trial

Abstract Background and aims Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF‐rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add‐on sessions of HF‐rTMS over the right dorsolateral pre‐frontal cortex (DLPFC) on alcohol use and craving. Design Single‐center, single blind sham‐controlled parallel‐group RCT (n = 80), with 3 and 6 months follow‐up. Setting Clinical treatment center in Amsterdam, the Netherlands. Participants Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years). Intervention Ten sessions of active or sham HF‐rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work‐days. Measurements The primary outcome measure is the number of abstinent days over 6‐month follow‐up (FU). Secondary outcome measures are craving over 6‐month FU (alcohol urge questionnaire and obsessive‐compulsive drinking scale), time to first relapse over 6‐month FU and grams of alcohol consumed over 6‐month FU. Additional outcome measures: full abstinence over 6‐month FU and treatment success over 12‐month FU. Findings HF‐rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578–3.547]. Moreover, HF‐rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/−0.53, 95% CI mixed‐effects model = −9.14 to 2.07/−1.44 to 2.40). Conclusions There was no clear evidence that high‐frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre‐frontal cortex treatment has a long‐term positive effect on alcohol use or craving as add‐on treatment for alcohol use disorder. High treatment response at 6‐month follow‐up could have limited the possibility to find an effect.
Overexpression of the FERONIA receptor kinase MdMRLK2 confers apple drought tolerance by regulating energy metabolism and free amino acids production.

Drought is a major abiotic stress limiting the growth and production of apple trees worldwide. The receptor-like kinase FERONIA is involved in plant growth, development, and stress responses, however, the function of FERONIA in apple under drought stress remains unclear. Here, the FERONIA receptor kinase gene MdMRLK2 from apple (Malus domestica) was shown to encode a plasma membrane-localized transmembrane protein and was significantly induced by abscisic acid and drought treatments. 35S::MdMRLK2 apple plants showed less photosystem damage and higher photosynthetic rates compared with wild-type (WT) plants, after seven days withholding water. 35S::MdMRLK2 apple plants also had enhanced energy levels, activated caspase activity and more free amino acids, than the WT, under drought conditions. By performing yeast two-hybrid screening, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and MdCYS4, a member of cystatin, were identified as MdMRLK2 interaction partners. Moreover, under drought conditions, the 35S::MdMRLK2 apple plants were characterized by higher abscisic acid (ABA) content. Overall, these findings demonstrated that MdMRLK2 regulates apple drought tolerance, probably via regulating levels of energetic matters, free amino acids and ABA.