Miracle-dz/UniFAR-FTUs huggingface dataset:
Arjunetin as a promising drug candidate against SARS-CoV-2: molecular dynamics simulation studies

Abstract Stem and bark of the tree Terminalia arjuna Wight & Arn. (Combretaceae) has been documented to exhibit therapeutic properties like cardiotonic, anticancer, antiviral, antibacterial, antifungal, hypercholesterolemia, hypolipidemic, and anti-coagulant. Our previous studies have shown that, ethanolic extract of T. arjuna bark exhibits radical scavenging anti-oxidant activity and also effectively inhibited catalase activity. In this study, oleanane triterpenoids type compounds viz., oleanolic acid, arjunolic acid, arjunolitin, arjunetin were isolated from ethanolic bark extract as bio-active compound and their structures were elucidated using 1H, 13C NMR, HR-ESIMS, IR. Of the various compounds, Arjunetin showed significant inhibition of catalase activity as compared to the other compounds. Based on the structural similarity between arjunetin and current antiviral drugs, we propose that arjunetin might exhibit antiviral activity. Molecular docking and molecular dynamics studies showed that arjunetin binds to the binds to key targets of SARS-CoV-2 namely, 3CLpro, PLpro, and RdRp) with a higher binding energy values (3CLpro, −8.4 kcal/mol; PLpro, −7.6 kcal/mol and RdRp, −8.1 kcal/mol) as compared with FDA approved protease inhibitor drugs to Lopinavir (3CLpro, −7.2 kcal/mole and PLpro −7.7 kcal/mole) and Remdesivir (RdRp −7.6 kcal/mole). To further investigate this, we performed 200–500 ns molecular dynamics simulation studies. The results transpired that the binding affinity of Arjunetin is higher than Remdesivir in the RNA binding cavity of RdRp. Based on structural similarity between arjunetin and Saikosaponin (a known antiviral agents) and based on our molecular docking and molecular dynamic simulation studies, we propose that arjunetin can be a promising drug candidate against Covid-19. Communicated by Ramaswamy H. Sarma Graphical Abstract
Liquid biopsy in esophageal cancer: a case report of false-positive circulating tumor DNA detection due to clonal hematopoiesis

Circulating tumor DNA (ctDNA) analysis is a promising non-invasive technique for active surveillance after chemoradiotherapy for locally advanced resectable esophageal carcinoma. In other malignancies false-positive results in ctDNA analysis have been reported due to clonal hematopoiesis. In this case, we present a 66-year-old male who had adenocarcinoma of the gastroesophageal junction for which he received neoadjuvant chemoradiotherapy and underwent a transhiatal esophagectomy. Postoperatively our patient received follow-up with ctDNA analysis using next generation sequencing (NGS) and droplet digital PCR (ddPCR). This case report illustrates a number of the current challenges in ctDNA diagnostics in esophageal carcinoma. Firstly, the TP53 c.524G>A; p.R175H mutation that was found in preoperative tumor biopsies became detectable in ctDNA only after distant metastases had already been confirmed by clinical symptoms and standard imaging- and biopsy techniques. Secondly our patient repeatedly had false-positive outcomes of ctDNA analysis. Genomic analysis of white blood cells revealed that the origin of these discordant mutations lies in clonal hematopoiesis. Failure to detect TP53 c.524G>A; p.R175H in cell-free DNA (cfDNA) is most likely due to the amount of ctDNA in the cfDNA fraction being below the limit of detection for NGS and ddPCR analyses. Clinicians should be aware of the possibility of finding mutations originating from clonal hematopoiesis when using ctDNA analysis during active surveillance for esophageal carcinoma. We recommend correlation of mutations in cfDNA with mutations in tumor biopsies.
SRI‐42127, a novel small molecule inhibitor of the RNA regulator HuR, potently attenuates glial activation in a model of lipopolysaccharide‐induced neuroinflammation

Glial activation with the production of pro‐inflammatory mediators is a major driver of disease progression in neurological processes ranging from acute traumatic injury to chronic neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. Posttranscriptional regulation is a major gateway for glial activation as many mRNAs encoding pro‐inflammatory mediators contain adenine‐ and uridine‐rich elements (ARE) in the 3′ untranslated region which govern their expression. We have previously shown that HuR, an RNA regulator that binds to AREs, plays a major positive role in regulating inflammatory cytokine production in glia. HuR is predominantly nuclear in localization but translocates to the cytoplasm to exert a positive regulatory effect on RNA stability and translational efficiency. Homodimerization of HuR is necessary for translocation and we have developed a small molecule inhibitor, SRI‐42127, that blocks this process. Here we show that SRI‐42127 suppressed HuR translocation in LPS‐activated glia in vitro and in vivo and significantly attenuated the production of pro‐inflammatory mediators including IL1β, IL‐6, TNF‐α, iNOS, CXCL1, and CCL2. Cytokines typically associated with anti‐inflammatory effects including TGF‐β1, IL‐10, YM1, and Arg1 were either unaffected or minimally affected. SRI‐42127 suppressed microglial activation in vivo and attenuated the recruitment/chemotaxis of neutrophils and monocytes. RNA kinetic studies and luciferase studies indicated that SRI‐42127 has inhibitory effects both on mRNA stability and gene promoter activation. In summary, our findings underscore HuR's critical role in promoting glial activation and the potential for SRI‐42127 and other HuR inhibitors for treating neurological diseases driven by this activation.
The seductive allure of the brain: Dualism and lay perceptions of neuroscience

ABSTRACT Laypeople prefer brain explanations of behavior (Weisberg, Keil, Goodstein, Rawson, & Gray, 2008). We suggest that this preference arises from ‘intuitive Dualism’. For the Dualist, mentalistic causation elicits a mind-body dissonance, as it suggests that the immaterial mind affects the body. Brain causation attributes behavior to the body, so it alleviates the dissonance, hence, preferred. We thus predict stronger brain preference for epistemic traits – those perceived as least material, even when no explanation is required. To test this prediction, participants diagnosed clinical conditions using matched brain- and behavioral tests. Experiments 1-2 showed that epistemic traits elicited stronger preference for brain tests. Experiment 3 confirmed that epistemic traits are perceived as immaterial. Experiment 4 showed that, the less material the trait seems, the stronger the surprise (possibly, dissonance) and brain preference. Results offer new insights into public perception of science, the role of intuitive Dualism, and the seductive allure of neuroscience.
Myrtle (Myrtus communis L.) fruit syrup for gastroesophageal reflux disease in children: A double‐blind randomized clinical trial

This double‐blind study was designed to evaluate the efficacy of a syrup made from Myrtus communis L. fruit on children with gastroesophageal reflux disease. Children aged 1–7 years old, diagnosed with gastroesophageal reflux disease (GERD), were randomly allocated to either intervention group (omeprazole and “myrtle fruit syrup”) or control group (omeprazole and placebo syrup). GERD symptom questionnaire for young children (GSQ‐YC) was filled out for each patient at zeroth and eighth week, and also 4 weeks after cessation of intervention. No statistically significant difference between two groups in terms of GERD score was reported neither in 8th nor in 12th week assessments. During the 4 weeks of the drug‐free period, patients in myrtle group did not experience a large shift in GERD score, while patients in placebo syrup group experienced an increase of as much as 19.4. However, this difference was not statistically significant, although it could be significant clinically. For achieving more conclusive results, more studies are needed. The symptom “refusal to eat” in the intervention group was less than in placebo group after 8 weeks (p = .018) and at the end of the study (p = .042). So myrtle fruit syrup may be considered for children with low appetite.
Young age increases the risk of lymph node positivity but improves prognosis in patients with bladder cancer treated via cystectomy: a population-based study

Background Age and lymph node positivity are significant prognostic indicators in patients with bladder cancer. This study aimed to investigate the impact of age on lymph node positivity and bladder cancer outcomes. Methods Patients with bladder cancer who underwent cystectomy with at least one lymph node examined between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Cochran-Armitage trend tests and logistic regression analyses were used to evaluate the association between age and lymph node positivity in all T stages. Multivariate Cox regression analysis was used to analyze the effect of age on overall survival (OS) and cancer-specific survival (CSS). Results Overall, 13,251 patients were identified, 648 of whom were under 50 years of age (4.89%). Lymph node positivity was negatively associated with increasing age in each stage except in non-invasive-muscular bladder cancer. In the multivariable analysis, age was an independent prognostic factor for OS and CSS in both the overall cohort and the lymph node positivity group. Conclusions In patients with bladder cancer undergoing cystectomy, young age at diagnosis is associated with a higher risk of lymph node positivity and superior outcomes. These findings may guide clinicians in selecting suitable treatments, determining the aggressiveness of lymph node involvement, and predicting survival outcomes in patients of different ages.
Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

Introduction Uncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America. Research design and methods Oral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan. Results The prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m2), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm2), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group. Conclusions Beta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ. Trial registration number NCT00001853.
Effect of lactic acid bacteria and yeast supplementation on anti-nutritional factors and chemical composition of fermented total mixed ration containing cottonseed meal or rapeseed meal

Objective This study aimed to determine the appropriate supplementation level of lactic acid bacteria (LAB; Lactobacillus plantarum and Bacillus clausii), yeast (Saccharomyces cariocanus and Wickerhamomyces anomalus) for degrading free gossypol and glucosinolate in the fermented total mixed ration (TMR) containing cottonseed meal (CSM) or rapeseed meal (RSM), to improve the utilization efficiency of these protein sources. Methods For LAB, L. plantarum or B. clausii was inoculated at 1.0×108, 1.0×109, 1.0×1010, and 1.0×1011 colony-forming unit (CFU)/kg dry matter (DM), respectively. For yeast, S. cariocanus or W. anomalus was inoculated at 5×106, 5×107, 5×108, and 5×109 CFU/kg DM, respectively. The TMR had 50% moisture and was incubated at 30°C for 48 h. After fermentation, the chemical compositions, and the contents of free gossypol and glucosinolate were determined. Results The results showed that the concentration of free gossypol content was reduced (p<0.05), while that of the crude protein content was increased (p<0.05) in the TMR containing CSM inoculated by B. clausii (1×109 CFU/kg DM) or S. cariocanus (5×109 CFU/kg DM). Similarly, the content of glucosinolate was lowered (p<0.05) and the crude protein content was increased (p<0.05) in TMR containing RSM inoculated with B. clausii (1×1010 CFU/kg DM) or S. cariocanus (5×109 CFU/g DM). Conclusion This study confirmed that inclusion of B. clausii with 1.0×109 or 1.0×1010 CFU/kg DM, or S. cariocanus (5×109 CFU/kg DM) to TMR containing CSM/RSM improved the nutritional value and decreased the contents of anti-nutritional factors.
The antimuscarinic agent biperiden selectively impairs recognition of abstract figures without affecting the processing of non‐words

The present study investigated the effects of biperiden, a muscarinic type 1 antagonist, on the recognition performance of pre‐experimentally unfamiliar abstract figures and non‐words in healthy young volunteers. The aim was to examine whether 4 mg biperiden could model the recognition memory impairment seen in healthy aging.
Genetic variants of the growth differentiation factor 8 affect body conformation traits in Chinese Dabieshan cattle

Objective The growth differentiation factor 8 (GDF8) gene plays a key role in bone formation, resorption, and skeletal muscle development in mammals. Here, we studied the genetic variants of GDF8 and their contribution to body conformation traits in Chinese Dabieshan cattle. Methods Single nucleotide polymorphisms (SNPs) were identified in the bovine GDF8 gene by DNA sequencing. Phylogenetic analysis, motif analysis, and genetic diversity analysis were conducted using bioinformatics software. Association analysis between five SNPs, haplotype combinations, and body conformation traits was conducted in 380 individuals. Results The GDF8 was highly conserved in seven species, and the GDF8 sequence of cattle was most similar to the sequences of sheep and goat based on the phylogenetic analysis. The motif analysis showed that there were 12 significant motifs in GDF8. Genetic diversity analysis indicated that the polymorphism information content of the five studied SNPs was within 0.25 to 0.5. Haplotype analysis revealed a total of 12 different haplotypes and those with a frequency of <0.05 were excluded. Linkage disequilibrium analysis showed a strong linkage (r2>0.330) between the following SNPs: g.5070C>A, g.5076T>C, and g.5148A>C. Association analysis indicated these five SNPs were associated with some of the body conformation traits (p<0.05), and the animals with haplotype combination H1H1 (-GGGG CCTTAA-) had greater wither height, hip height, heart girth, abdominal girth, and pin bone width than the other (p<0.05) Dabieshan cattle. Conclusion Overall, our results indicate that the genetic variants of GDF8 affected the body conformation traits of Chinese Dabieshan cattle, and the GDF8 gene could make a strong candidate gene in Dabieshan cattle breeding programs.
Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species

Staphylococcus aureus is a human commensal organism and opportunist pathogen, causing potentially fatal disease. The presence of non-pathogenic microflora or their components, at the point of infection, dramatically increases S. aureus pathogenicity, a process termed augmentation. Augmentation is associated with macrophage interaction but by a hitherto unknown mechanism. Here, we demonstrate a breadth of cross-kingdom microorganisms can augment S. aureus disease and that pathogenesis of Enterococcus faecalis can also be augmented. Co-administration of augmenting material also forms an efficacious vaccine model for S. aureus. In vitro, augmenting material protects S. aureus directly from reactive oxygen species (ROS), which correlates with in vivo studies where augmentation restores full virulence to the ROS-susceptible, attenuated mutant katA ahpC. At the cellular level, augmentation increases bacterial survival within macrophages via amelioration of ROS, leading to proliferation and escape. We have defined the molecular basis for augmentation that represents an important aspect of the initiation of infection.
Physicochemical properties of reduced-salt cured pork loin as affected by different freezing temperature and storage periods

Objective The objective of this study was to evaluate functional properties of reduced-salt pork meat products made of pre-rigor pork loin treated by different freezing temperatures (−30°C and −70°C) during storage. Methods Pre-rigor cured pork loin with 1.0% added salt was compared to post-rigor muscle added with 1.5% salt for pH, color (L*, a*, b*), cooking loss (CL), expressible moisture, warner-Bratzler shear value, thiobarbituric acid reactive substances (TBARS), and volatile basic nitrogen (VBN). Results Pre-rigor cured pork loins had higher pH and temperature than post-rigor ones as raw meat (p<0.05). pH values were higher for pre-rigor pork loins than those of post-rigor pork loins (p<0.05). Color values did not different among treatments (p>0.05). No color differences were observed during storage period after cooking (p>0.05). The CL (%) of pre-rigor cured pork loins was the lowest when frozen at −70°C. The TBARS and VBN increased from 8 weeks of storage (p<0.05), but no further changed thereafter (p>0.05). Pre-rigor cured pork loins added with 1.0% salt showed similar characteristics to post-rigor pork loins added with 1.5% salt. Conclusion Cured pork loins could be produced using pre-rigor muscle added with 1/3 of the original salt level (1.5%) and could be stored for up to 4 wks of frozen storage, regardless of a frozen temperature of −30°C or −70°C without detrimental effects.
Gambling behaviors during COVID-19: a narrative review

Abstract The COVID-19 pandemic has ushered the world into unforeseen circumstances, prompting the authorities to impose restrictions and cut back various events including many gambling avenues. Professional sports have been postponed, land casinos are closed, and social distancing has shut home games down. The present narrative overview has addressed the following changes in gambling behavior since the start of the pandemic: - a) Change in the number of gamblers and intensity of gambling b) differences among various types of gambling modalities (land-based, horse betting, casino, online). and transitioning between them. c) Psychosocial effects on gamblers owing to the shutdown of gambling avenues in the early phase of COVID-19 lockdown. It alludes to several survey studies conducted so far in Northern Europe (Sweden, UK, Italy), North America (Canada, USA), and Australia on the potential impact of the SARS-Cov2 pandemic on gambling figures. Problem Gambling Severity Index (PGSI) scale is used by most of the studies to demonstrate the severity among gamblers i.e., low-risk, high-risk, and problem gamblers respectively. The majority of studies are based on self-reported questionnaires, few tracked data from online gambling operators, and one study used revenue-based taxation of land-based and online gambling as its information source. The decline in the overall gambling activity attributable to the situational changes was predominant in a majority of surveys. The impact of the COVID-19 pandemic on gambling is diverse – possibly causing a reduction in current or future problems in some, but also promoting increased problematic gambling in others.
The recording of mental health consultations by patients: clinical, ethical and legal considerations

Summary The topic of patients recording healthcare consultations has been previously debated in the literature, but little consideration has been given to the risks and benefits of such recordings in the context of mental health assessments and treatment. This issue is of growing importance given the increasing use of technology in healthcare and the recent increase in online healthcare services, largely accelerated by the COVID-19 pandemic. We discuss the clinical, ethical and legal considerations relevant to audio or visual recordings of mental health consultations by patients, with reference to existing UK guidance and the inclusion of a patient's perspective.
Impact of a 10,000-m Cold-Water Swim on Norwegian Naval Special Forces Recruits.

BACKGROUND Special Operation Forces (SOF) operate regularly in extreme environmental conditions that may affect tactical and physical performance. The main aims of the present study were to elucidate the impact of a long cold-water swim on SOF recruits' dexterity, performance, and reaction time. MATERIAL AND METHODS Eleven recruits from Norwegian Naval Special Operation Command (NORNAVSOC) that were participating in a 10,000-m open water swim with a dry suit in 5°C cold water volunteered to participate in this study. The exercise was part of their training. Grip strength, lower body power, and dexterity were measured before, immediately after, and 24 hours after the swim. In addition, core and skin temperatures were measured continuously during the swim and until 45 minutes after the swim. RESULTS After the swim, moderate to large reductions in core temperature, lower body power, and reaction time were observed. Moreover, very large to extremely large reductions in skin temperature, grip strength, and dexterity were also observed. CONCLUSION These results demonstrate that exposure to a 10,000-m swim in 5°C water using standard equipment led to a significant drop in the recruits' temperature and performance. These findings could have a meaningful impact on the planning of training, operations, and gear used for SOF.