Miracle-dz/UniFAR-FTUs huggingface dataset:
Polyphenolic Natural Products Active In Silico against SARS-CoV-2 Spike Receptor Binding Domains and Non-Structural Proteins - A Review.

The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has been proven to be more severe than the previous coronavirus outbreaks due to the virus' high transmissibility. With the emergence of new variants, this global phenomenon took on a more dramatic turn with many countries recently experiencing higher surges of confirmed cases and deaths. On top of this, the inadequacy of effective treatment options for COVID-19 aggravated the problem. As a way to address the unavailability of target-specific viral therapeutics, computational strategies have been employed to hasten and systematize the search. The objective of this review is to provide initial data highlighting the utility of polyphenols as potential prophylaxis or treatment for COVID-19. In particular, presented here are virtually screened polyphenolic compounds which showed potential as either antagonists to viral entry and host cell recognition through binding with various receptor-binding regions of SARS-CoV-2 spike protein or as inhibitors of viral replication and post-translational modifications through binding with essential SARS-CoV-2 non-structural proteins.
The BDNF rs7934165 polymorphism is a biomarker of central obesity and cardiometabolic risk in Mexican women.

OBJECTIVE Brain-derived neurotrophic factor (BDNF) is a cornerstone in the hypothalamic regulation of food intake and energy homeostasis. Polymorphisms in the BDNF gene may thus contribute to obesity traits. The aim of this investigation was to analyze the association of rs6265 and rs7934165 BDNF polymorphisms in women from Northeast Mexico classified as obese or overweight using their BMI and waist-to-height ratio (WHtR). PATIENTS AND METHODS A total of 296 women were enrolled and further divided into normal weight and obese overweight groups according to their BMI status and WHtR classifications, which were low and high at < 0.50 and ≥ 0.50, respectively. Genotyping of BDNF rs6265 and rs7934165 polymorphisms was performed using a TaqMan assay. Distinct anthropometric, biochemical, clinical, and dietary parameters were obtained and used as covariates in the statistical analyses. RESULTS The rs6265-G allele and its homozygote state (GG) were the most prominent without statistically significant differences between groups (p = 0.412). The study of rs7934165 with BMI showed marginal associations. Moreover, the rs7934165-AA genotype was more frequent among individuals with a high WHtR than those with a low WHtR (43.4 vs. 25.2%, p = 0.01). This association was maintained after adjustments for age and caloric intake through logistic regression analysis (OR = 2.20, 95% CI = 1.15-4.18, p = 0.016). CONCLUSIONS The present study indicates that the BDNF-rs7934165-AA genotype is associated with a higher WHtR which is related to central obesity and its comorbidities. This suggests that this SNP could act as a potential biomarker for central obesity and cardiometabolic risk.
GRASP55 restricts early-stage autophagy and regulates spatial organization of the early secretory network

ABSTRACT There is great interest in understanding the cellular mechanisms controlling autophagy, a tightly regulated catabolic and stress-response pathway. Prior work has uncovered links between autophagy and the Golgi reassembly stacking protein of 55 kDa (GRASP55), but their precise interrelationship remains unclear. Intriguingly, both autophagy and GRASP55 have been functionally and spatially linked to the endoplasmic reticulum (ER)-Golgi interface, broaching this compartment as a site where GRASP55 and autophagy may intersect. Here, we uncover that loss of GRASP55 enhances LC3 puncta formation, indicating that GRASP55 restricts autophagosome formation. Additionally, using proximity-dependent biotinylation, we identify a GRASP55 proximal interactome highly associated with the ER-Golgi interface. Both nutrient starvation and loss of GRASP55 are associated with coalescence of early secretory pathway markers. In light of these findings, we propose that GRASP55 regulates spatial organization of the ER-Golgi interface, which suppresses early autophagosome formation.
HEXACO-60 Personality Trait Inventory: Psychometric characteristics in a sample of medical students from Serbia.

The 60-item HEXACO (HEXACO-60) Personality Trait Inventory may be strategically more important for researchers compared to the 100-item HEXACO. The aim of this study was to assess the psychometric properties of the 60-item HEXACO questionnaire in the Serbian language. This cross-sectional study, conducted at three of five Faculties of Medicine during the summer semester of the 2016/2017 academic year, included 617 students. Relevant data were collected by an anonymous questionnaire. Cronbach's α and McDonald's ω coefficients for the total scale were . 71 and . 72, respectively. Apart from Agreeableness, all other domains showed an adequate level of internal consistency (both Cronbach's α and McDonald's ω coefficients were >.70). Random data eigenvalues obtained on the parallel analysis had higher values than initial exploratory factor analysis eigenvalues up to the sixth factor. Accordingly, it was concluded that six factors should be extracted from the Serbian HEXACO-60. These factors corresponded in item distribution with the original ones. Based on the confirmatory factor analysis, using both 60 items and 24 facets, overall goodness of fit of the Serbian HEXACO-60 was acceptable. Moreover, there were no domains with completely invalid indices, as there were at least two indices that were acceptable for each domain. The Serbian version of the HEXACO-60 has acceptable psychometric properties. This shorter version with 60 items may be more suitable for brief surveys or when the time allocated to fill in a questionnaire is limited.
Impact of coinfection status and comorbidity on disease severity in adult emergency department patients with influenza B

Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B.
Self-consistent simulation studies on effect of methane concentration on microwave assisted H2-CH4 plasma at low pressure

Self-consistent simulations of low-pressure hydrogen-methane plasmas in a microwave-resonating chamber have been conducted. The dynamics of the plasma are dictated by the dominant ion species in the reactor, which is affected by the methane chemistry. Even small concentrations of methane have substantial effects on the plasma, and self-consistent simulations are necessary to capture the wave plasma interaction. In particular, the input power at which the transition between two different coupling regimes, namely a stable single plasma ball regime and a two ball unstable and undesirable plasma regime, takes place depending on the methane composition. The first experimental results show good agreement with the simulations.
Preoperative serum fibrinogen as a valuable predictor in the nomogram predicting overall survival of postoperative patients with gallbladder cancer.

Background Coagulation and fibrinolysis activation are frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis and worse long-term outcome. The specific aim of this study was to develop an effective prognostic nomogram to help make individualized estimates for patients with resected gallbladder cancer (GBC). Methods Patients with resected GBC who were diagnosed between 2006 and 2014 at Xinhua Hospital were selected. Model performance was measured by c-index and calibration curve. The results were further validated using bootstrap and a cohort of 38 patients from a branch hospital who underwent surgery from 2006 to 2014. Results Backward stepwise selection and Lasso were applied respectively to select predictors. T stage, N stage, and preoperative serum fibrinogen were included in the final model. Predictions correlated well with observed 1- and 3-year survival. The c-index for predicting survival was 0.74 (95% confidence interval, 0.70-0.78), which was statistically higher than that of the AJCC 7th system and Nevin system (P=0.04, 0.04, respectively). In the validation cohort, the nomogram performed better than the other two staging systems (c-index: 0.71 vs. 0.67 and 0.67). Conclusions The validated nomogram is a practical tool for predicting the overall survival (OS) of postoperative GBC patients. Preoperative serum fibrinogen levels were associated with tumor progression and may be an independent predictor for GBC patients.
2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages.

Objective The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors. Methods Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses. Results The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ. Conclusion The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors via M1-polarized TAMs, and HPTA may be considered as a new therapeutic for amplifying the efficacy of local RT for non-targeted breast tumors. The graphical abstract was available in the web of www.besjournal. com.
Evolution of Bordetella pertussis over a 23-year period in France, 1996 to 2018

Background Bordetella pertussis is the main agent of whooping cough. Vaccination with acellular pertussis vaccines has been largely implemented in high-income countries. These vaccines contain 1 to 5 antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and/or fimbrial proteins (FIM2 and FIM3). Monitoring the emergence of B. pertussis isolates that might partially escape vaccine-induced immunity is an essential component of public health strategies to control whooping cough. Aim We aimed to investigate temporal trends of fimbriae serotypes and vaccine antigen-expression in B. pertussis over a 23-year period in France (1996–2018). Methods Isolates (n = 2,280) were collected through hospital surveillance, capturing one third of hospitalised paediatric pertussis cases. We assayed PT, FHA and PRN production by Western blot (n = 1,428) and fimbriae production by serotyping (n = 1,058). Molecular events underlying antigen deficiency were investigated by genomic sequencing. Results The proportion of PRN-deficient B. pertussis isolates has increased steadily from 0% (0/38) in 2003 to 48.4% (31/64) in 2018 (chi-squared test for trend, p < 0.0001), whereas only 5 PT-, 5 FHA- and 9 FIM-deficient isolates were found. Impairment of PRN production was predominantly due to IS481 insertion within the prn gene or a 22 kb genomic inversion involving the prn promoter sequence, indicative of convergent evolution. FIM2-expressing isolates have emerged since 2011 at the expense of FIM3. Conclusions B. pertussis is evolving through the rapid increase of PRN-deficient isolates and a recent shift from FIM3 to FIM2 expression. Excluding PRN, the loss of vaccine antigen expression by circulating B. pertussis isolates is epidemiologically insignificant.
Femoroacetabular impingement syndrome and labral injuries: grading the evidence on diagnosis and non-operative treatment—a statement paper commissioned by the Danish Society of Sports Physical Therapy (DSSF)

This statement summarises and appraises the evidence on diagnostic tests and clinical information, and non-operative treatment of femoroacetabular impingement (FAI) syndrome and labral injuries. We included studies based on the highest available level of evidence as judged by study design. We evaluated the certainty of evidence using the Grading of Recommendations Assessment Development and Evaluation framework. We found 29 studies reporting 23 clinical tests and 14 different forms of clinical information, respectively. Restricted internal hip rotation in 0° hip flexion with or without pain was best to rule in FAI syndrome (low diagnostic effectiveness; low quality of evidence; interpretation of evidence: may increase post-test probability slightly), whereas no pain in Flexion Adduction Internal Rotation test or no restricted range of motion in Flexion Abduction External Rotation test compared with the unaffected side were best to rule out (very low to high diagnostic effectiveness; very low to moderate quality of evidence; interpretation of evidence: very uncertain, but may reduce post-test probability slightly). No forms of clinical information were found useful for diagnosis. For treatment of FAI syndrome, 14 randomised controlled trials were found. Prescribed physiotherapy, consisting of hip strengthening, hip joint manual therapy techniques, functional activity-specific retraining and education showed a small to medium effect size compared with a combination of passive modalities, stretching and advice (very low to low quality of evidence; interpretation of evidence: very uncertain, but may slightly improve outcomes). Prescribed physiotherapy was, however, inferior to hip arthroscopy (small effect size; moderate quality of evidence; interpretation of evidence: hip arthroscopy probably increases outcome slightly). For both domains, the overall quality of evidence ranged from very low to moderate indicating that future research on diagnosis and treatment may alter the conclusions from this review.
Molecular simulations in drug delivery: Opportunities and challenges

Molecular simulations are promising tools for in silico design of drug delivery formulations, as they provide a prediction of formulation properties prior to synthesis thus minimizing the need for in vitro and in vivo experimentation. The detailed molecular insight obtained by these simulations is precious and often beyond the reach of sophisticated experimental facilities. Although initially limited to the prediction of single‐molecule behavior (e.g., drug orientation in a bilayer), gradual advances in computing speed and efficient simulation approaches have made it feasible to employ these methods for phenomena occurring at substantially large length and time scales (e.g., carrier‐drug complexation) with modest computational cost and resources. We present a nonmathematical review of molecular simulation methods and their applications in drug delivery, with special emphasis on the use of atomistic and coarse‐grained Monte Carlo (MC) and molecular dynamics (MD) methods and excluding the drug docking studies used in drug discovery. Current capabilities and problems associated with the use of these methods in the context of drug delivery are highlighted, along with a discussion of representative applications of molecular simulations in drug delivery. We conclude that while molecular simulations are expected to play a central role in the future of drug delivery field, we require a concerted effort of computational scientists, experimentalists, and industry personnel working on drug delivery to identify specific areas where these simulations can be especially useful.
Acute Decompensated Heart Failure and the Kidney: Physiological, Histological and Transcriptomic Responses to Development and Recovery

BACKGROUND Acute decompensated heart failure (ADHF) is associated with deterioration in renal function—an important risk factor for poor outcomes. Whether ADHF results in permanent kidney damage/dysfunction is unknown. METHODS AND RESULTS We investigated for the first time the renal responses to the development of, and recovery from, ADHF using an ovine model. ADHF development induced pronounced hemodynamic changes, neurohormonal activation, and decline in renal function, including decreased urine, sodium and urea excretion, and creatinine clearance. Following ADHF recovery (25 days), creatinine clearance reductions persisted. Kidney biopsies taken during ADHF and following recovery showed widespread mesangial cell prominence, early mild acute tubular injury, and medullary/interstitial fibrosis. Renal transcriptomes identified altered expression of 270 genes following ADHF development and 631 genes following recovery. A total of 47 genes remained altered post‐recovery. Pathway analysis suggested gene expression changes, driven by a network of inflammatory cytokines centered on IL‐1β (interleukin 1β), lead to repression of reno‐protective eNOS (endothelial nitric oxide synthase) signaling during ADHF development, and following recovery, activation of glomerulosclerosis and reno‐protective pathways and repression of proinflammatory/fibrotic pathways. A total of 31 dysregulated genes encoding proteins detectable in urine, serum, and plasma identified potential candidate markers for kidney repair (including CNGA3 [cyclic nucleotide gated channel subunit alpha 3] and OIT3 [oncoprotein induced transcript 3]) or long‐term renal impairment in ADHF (including ACTG2 [actin gamma 2, smooth muscle] and ANGPTL4 [angiopoietin like 4]). CONCLUSIONS In an ovine model, we provide the first direct evidence that an episode of ADHF leads to an immediate decline in kidney function that failed to fully resolve after ≈4 weeks and is associated with persistent functional/structural kidney injury. We identified molecular pathways underlying kidney injury and repair in ADHF and highlighted 31 novel candidate biomarkers for acute kidney injury in this setting.
Cardenolide, Potassium, and Pyrethroid Insecticide Combinations Reduce Growth and Survival of Monarch Butterfly Caterpillars (Lepidoptera: Nymphalidae)

Abstract The monarch butterfly, Danaus plexippus L. , has evolved to be insensitive to milkweed cardenolides via genetic modifications of Na+/K+-ATPase. There is concern for insecticide exposures near agriculture, with little information on monarch caterpillar toxicology. It is unclear how cardenolide insensitivity may affect the sensitivity of monarch caterpillars to pyrethroid insecticides. Additionally, potassium fertilizers may affect monarch caterpillar physiology and cardenolide sequestration. Here, we investigated the growth, survival, and development of caterpillars exposed to the cardenolide ouabain, bifenthrin, and potassium chloride (KCl) alone and in combination. Caterpillars were either exposed to 1) ouabain from third- to fifth-instar stage, 2) KCl at fifth-instar stage, 3) KCl and bifenthrin at fifth-instar stage, or 4) combinations of ouabain at third-instar stage + KCl + bifenthrin at fifth-instar stage. Caterpillar weight, diet consumption, frass, and survival were recorded for the duration of the experiments. It was observed that 1–3 mg ouabain/g diet increased body weight and diet consumption, whereas 50 mg KCl/g diet decreased body weight and diet consumption. Caterpillars feeding on KCl and treated with 0.2 µg/µl bifenthrin consumed significantly less diet compared to individuals provided untreated diet. However, there was no effect on survival or body weight. Combinations of KCl + ouabain did not significantly affect caterpillar survival or body weight following treatment with 0.1 µg/µl bifenthrin. At the concentrations tested, there were no effects observed for bifenthrin sensitivity with increasing cardenolide or KCl concentrations. Further studies are warranted to understand how milkweed-specific cardenolides, at increasing concentrations, and agrochemical inputs can affect monarch caterpillar physiology near agricultural landscapes.
Neural functional connectivity changes to psychosocial stress in young adults with bipolar disorder and preliminary associations with clinical trajectories

Stress‐related mechanisms are implicated in the pathophysiology of bipolar disorder and may contribute to heterogeneity in illness course. Yet, there is a lack of study investigating the neural mechanisms underlying the stress response in this condition. This study investigated changes in amygdala activation and functional connectivity in response to acute psychosocial stress in young adults with bipolar disorder and explored relations with clinical phenotype and prospective mood symptoms.
Additively Manufactured Deformation‐Recoverable and Broadband Sound‐Absorbing Microlattice Inspired by the Concept of Traditional Perforated Panels

Noise pollution is a highly detrimental daily health hazard. Sound absorbers, such as the traditionally used perforated panels, find widespread applications. Nonetheless, modern product designs call for material novelties with enhanced performance and multifunctionality. The advent of additive manufacturing has brought about the possibilities of functional materials design to be based on structures rather than chemistry. With this in mind, herein, the traditional concept of perforated panels is revisited and is incorporated with additive manufacturing for the development of a novel microlattice‐based sound absorber with additional impact resistance multifunctionality. The structurally optimized microlattice presents excellent broadband absorption with an averaged experimental absorption coefficient of 0.77 across a broad frequency range from 1000 to 6300 Hz. Extensive simulation and experiments reveal absorption mechanisms to be based on viscous flow, thermal and structural damping dissipations while broadband capabilities to be on multiple resonance modes working in tandem. High deformation recovery up to 30% strain is also possible from the strut‐based design and viscoelasticity of the base material. Overall, the excellent properties of the microlattice overcome tradeoffs commonly found in conventional absorbers. Additionally, this work aims to present a new paradigm: revisiting old concepts for the developments of novel materials using contemporary methods.
Deep learning: an efficient method for plasmonic design of geometric nanoparticles

Plasmons of noble metal nanoparticles have played an important role in energy transfer research, biomedical sensing, drug preparation and photocatalysis in recent years. The scattering spectra of nanoparticles are dramatically affected by numerous complex parameters, such as morphology, material, and volumes, making the parameters design a necessary step before the experiment. However, the plasmonic design is limited by several difficulties, such as the high degree of freedom, expensive trial and error costs. Herein, a plasmonic design method based on dual strategy deep learning is proposed, which can provide the design proposals according to the required spectrum. To make the model closer to the real experimental situation, the boundary element method was used to build a scattering spectra dataset of geometric nanoparticles (>1200 000 samples). Driven by the above data, the artificial intelligence (AI) model learns the relationship between spectral features and design parameters. Then, the performance statistics of the model were implemented from multiple dimensions, and a high design precision of over 90% was achieved in testing cases (testing samples >120 000). Moreover, to verify the realizability of the proposed model, the scattering spectra of nanoparticles designed by AI were constructed using a dark-field microscope system. The experimental results showed that the deviation between the target and the actual spectra was very small and within the acceptable range. This proves the realizability of the AI model proposed in this paper, and sheds light on the application of AI in plasmonic design.