Miracle-dz/UniFAR-FTUs huggingface dataset:
Psoralen inhibits the proliferation and promotes apoptosis through endoplasmic reticulum stress in human osteosarcoma cells.

INTRODUCTION . Psoralen is a main active component of Psoralea corylifolia Linn. (Leguminosae). Psoralen has been reported to show antitumor effects and activity to accelerate osteoblastic proliferation. Nevertheless, the antitumor mechanism of psoralen in osteosarcoma has never been elucidated. The current study is aimed to investigate the therapeutic function of psoralen in human osteosarcoma cells and its potential regulatory mechanism. MATERIAL AND METHODS Effects of psoralen (0-70 μg/mL) on the viability of two osteosarcoma cell lines cultured for 48 h was evaluated by MTT assays. The concentration of IC₁₀ (8 μg/mL for MG-63 cells and 9 μg/mL for U2OS cells) was regarded to be a non-cytotoxic dose selected as the working concentration in the subsequent experiments. Effects of psoralen on cell proliferation for 48 h was assessed by colony formation assays. Flow cytometry analyses were performed to measure cell cycle and apoptosis. RT-qPCR and Western blotting were carried out to assess RNA expression and protein levels of endoplasmic reticulum (ER) stress associated factors. RESULTS Psoralen inhibited osteosarcoma cell viability (IC₅₀ 25 μg/mL for MG-63 cells and IC₅₀ 40 μg/mL for U2OS cells) in a dose-dependent manner and growth inhibition rate reached the highest level when cells were treated with 70 μg/mL psoralen. Psoralen induced cell cycle arrest in the G0/G1 phase and promoted apoptosis of both MG-63 and U2OS cells. The treatment of psoralen resulted in an increase in ATF-6 and CHOP protein levels as well as a decrease in Bcl-2 protein level, indicating that cell apoptosis induced by psoralen was associated with ER stress. Treatment with 4-PBA, the ER stress inhibitor, attenuated the ability of psoralen to promote apoptosis of MG-63 and U2OS cells. CONCLUSIONS Psoralen showed growth-inhibitory effects in osteosarcoma cells, and induced apoptosis via the ER stress pathway, which might be a potential drug to suppress the development of osteosarcoma.
In silico and in vitro studies on inhibitors for SARS-CoV-2 non-structural proteins with dual herbal combination of Withania somnifera with five rasayana herbs

Abstract Being highly transmissible, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has affected millions of people causing devastating global impact and has also not slowed down even after vaccination. The emerges of new strains has made more concerns than the original one. We need a new therapeutic approach against the disease. Our comprehensive in silico study investigates dual herbal combinatorial methanolic extracts of W. somnifera (W) alone and with P. emblica (P) (W:P/1:4) , T. sinensis (T) (W:T/1:4), B. monnieri (B) (W:B/1:1), O. basilicum (O) (W:O/1:4), A. racemosus (A) (W:A/4:1) for potential four phytochemicals as ligands docked with eight COVID-19 Nonstructural proteins (nsp)—main protease (PDB ID:6LU7), papain-like protease (6WUU), helicase ADP (2XZL), N7-methyltransferase (5C8S), endoribonuclease (6WLC), 2’O-methyltransferase (6WVN), RNA dependent RNA polymerase (6M71), and 3Cprotease (6YNQ) along with Remdesivir and Hydroxychloroquine. Ligands from W:P/1:4 showed remarkable docking score (−9.01 kcal/mol) 6M71-(8E,11E,14E)-eicosa-8,11,14-trienoicacidmethylester (EIS) and (−9.99 kcal/mol) 6YNQ-N-[(E)-[4-[(2-methoxydibenzofuran-3-yl)amino]-4-oxobutan-2-ylidene]amino] 4nitrobenzamide (MET). Further, MD simulations were studied for 100 ns and showed the complexes were flexible, stable in the binding pockets of the receptors, and MM-PBSA analysis determined high binding energy of −129.673 ± 15.284 and −134.594 ± 7.085 for 6M71-EIS (Asn496, Lys577, Arg569) and 6YNQ-MET (Cys145, His41). Finally, in vitro JURKAT E6.1 cell lines treated with W:P/1:4 and W:O/1:4 methanolic extracts yielded 44.06 and 31.53 ng/mL levels for interferon alpha to counteract an external stimulus by establishing an antiviral state. Thus, nsp is targeted to design effective antiviral drugs for developing an effective therapeutic approach to combat viral RNA synthesis, processing, and suppression of host immunity. Communicated by Ramaswamy H. Sarma Graphical Abstract
Implication of metabolomics and transporter modulation based strategies to minimize multidrug resistance and enhance site-specific bioavailability: a needful consideration toward modern anticancer drug discovery

Abstract Induction of drug-metabolizing enzymes and efflux transporters (DMET) through activation of pregnane x receptor (PXR) is the primary factor involved in almost all bioavailability and drug resistance-related problems of anticancer drugs. PXR is a transcriptional regulator of many metabolizing enzymes and efflux transporters proteins like p-glycoprotein (p-gp), multidrug resistant protein 1 and 2 (MRP 1 and 2), and breast cancer resistant protein (BCRP), etc. Several anticancer drugs are potent activators of PXR receptors and can modulate the gene expression of DMET proteins. Involvement of anticancer drugs in transcriptional regulation of DMET can prompt increased metabolism and efflux of their own or other co-administered drugs, which leads to poor site-specific bioavailability and increased drug resistance. In this review, we have discussed several novel strategies to evade drug-induced PXR activation and p-gp efflux including assessment of PXR ligand and p-gp substrate at early stages of drug discovery. Additionally, we have critically discussed the chemical structure and drug delivery-based approaches to avoid PXR binding and inhibit the p-gp activity of the drugs at their target sites.
Efficient Prestimulus Network Integration of Fusiform Face Area Biases Face Perception during Binocular Rivalry

Abstract Ongoing fluctuations in neural excitability and connectivity influence whether or not a stimulus is seen. Do they also influence which stimulus is seen? We recorded magnetoencephalography data while 21 human participants viewed face or house stimuli, either one at a time or under bistable conditions induced through binocular rivalry. Multivariate pattern analysis revealed common neural substrates for rivalrous versus nonrivalrous stimuli with an additional delay of ∼36 msec for the bistable stimulus, and poststimulus signals were source-localized to the fusiform face area. Before stimulus onset followed by a face versus house report, fusiform face area showed stronger connectivity to primary visual cortex and to the rest of the cortex in the alpha frequency range (8–13 Hz), but there were no differences in local oscillatory alpha power. The prestimulus connectivity metrics predicted the accuracy of poststimulus decoding and the delay associated with rivalry disambiguation suggesting that perceptual content is shaped by ongoing neural network states.
Psychometric properties of the Brazilian short-version of the Northwick Park Neck Pain Questionnaire

Objective To translate, cross-culturally adapt and assess measurement properties of the translated version of the Northwick Park Neck Pain Questionnaire into Brazilian Portuguese. Design Cross-sectional study. Settings University healthcare facility and online. Participants People with chronic neck pain (n = 178). Interventions Not applicable. Main outcome measures Participants answered the translated version of Northwick Park Neck Pain Questionnaire, the Neck Disability Index, the Numerical Rating Scale for pain, the Tampa Scale for Kinesiophobia and the Pain Catastrophizing Scale. Seven to ten days after that, a subset of 84 participants answered the Northwick Park Neck Pain Questionnaire again. The structural (exploratory and confirmatory factor analyses) and construct validities, internal consistency, reliability and concordance were assessed. Level of significance was set at 5%. Results Participants’ (35.6 ± 13.5 years old) with symptoms duration of 54.4 ± 60.4 months scored 25.5 ± 14.0 on the Brazilian Northwick Park Neck Pain Questionnaire and 11.9 ± 5.8 on the Neck Disability Index. The structural analysis showed that the short version of the Northwick Park Neck Pain Questionnaire has an adequate structure to measure disability due to neck pain. Correlations with other questionnaires were between 0.268 and 0.678, Cronbach's alfa was 0.76, intraclass correlation coefficient was 0.96, standard error of measurement was 2.74 and minimal detectable change was 7.60. Conclusion The short version of the Northwick Park Neck Pain Questionnaire is valid and reliable to be used in patients with chronic neck pain, as it presented adequate measurement properties of structural and construct validity, reliability and concordance.
Measuring web-based service quality

Since the birth of the internet, two-way communication via web-based exchanges has become increasingly popular in electronic transaction, publication, broadcasting, and other service applications. Based on an understanding of the attributes of the web-based service and its differences from traditional communication channels, this paper describes the development of a conceptual framework to measure the web-based service quality using the SERVQUAL model as a starting point. An online survey was conducted to collect web-based service quality information from an international customer's perspective. The results indicate a need to modify SERVQUAL to suit better the context of the web-based service. Several web-based service attributes and dimensions were identified. This information should be useful to web designers and service providers and in the management of web-based services.
A Semi-Automated Method for Measuring Biofilm Accumulation on the Teeth Using Quantitative Light-Induced Fluorescence in Dogs and Cats

Oral health conditions (eg, plaque, calculus, gingivitis) cause morbidity and pain in companion animals. Thus, developing technologies that can ameliorate the accumulation of oral biofilm, a critical factor in the progression of these conditions, is vital. Quantitative light-induced fluorescence (QLF) is a method to quantify oral substrate accumulation, and therefore, it can assess biofilm attenuation of different products. New software has recently been developed that automates aspects of the procedure. However, few QLF studies in companion animals have been performed. QLF was used to collect digital images of oral substrate accumulation on the teeth of dogs and cats to demonstrate the ability of QLF to discriminate between foods known to differentially inhibit oral substrate accumulation. Images were taken as a function of time and diet. Software developed by the Cytometry Laboratory, Purdue University quantified biofilm coverage. Intra- and intergrader reproducibility was also assessed, as was a comparison of the results of the QLF software with those of an experienced grader using undisclosed coverage-only metrics similar to those used for the Logan and Boyce index. Quantification of oral substrate accumulation using QLF-derived images demonstrated the ability to distinguish between dental diets known to differentially inhibit oral biofilm accumulation. Little variance in intra- and intergrader reproducibility was observed, and the comparison between the experienced Logan and Boyce grader and the QLF software yielded a concordance correlation coefficient of 0.89 (95% CI = 0.84, 0.92). These results show that QLF is a useful tool that allows the semi-automated quantification of the accumulation of oral biofilm in companion animals.
Neural activity during story listening is synchronized across individuals despite acoustic masking

Older people with hearing problems often experience difficulties understanding speech in the presence of background sound. As a result, they may disengage in social situations, which has been associated with negative psychosocial health outcomes. Measuring listening (dis-)engagement during challenging listening situations has received little attention thus far. We recruit young, normal-hearing human adults (both sexes) and investigate how speech intelligibility and engagement during naturalistic story listening is affected by the level of acoustic masking (12-talker babble) at different signal-to-noise ratios (SNRs). In Experiment 1, we observed that word-report scores were above 80% for all but the lowest SNR (-3 dB SNR) we tested, at which performance dropped to 54%. In Experiment 2, we calculated inter-subject correlation (ISC) using electroencephalography (EEG) data to identify dynamic spatial patterns of shared neural activity evoked by the stories. ISC has previously been used as a neural measure of participants’ engagement with naturalistic materials. Our results show that ISC was stable across all but the lowest SNRs, despite reduced speech intelligibility. Comparing ISC and intelligibility demonstrated that word-report performance declined more strongly with decreasing SNR compared to ISC. Our measure of neural engagement suggests that individuals remain engaged in story listening despite missing words due to background noise. Our work provides a potentially fruitful approach to investigate listener engagement with naturalistic, spoken stories that may be used to investigate (dis)engagement in older adults with hearing impairment.
Disclosing the Nature of Asymmetric Interface Magnetism in Co/Pt Multilayers.

Nowadays, a wide number of applications based on magnetic materials rely on the properties arising at the interface between different layers in complex heterostructures engineered at the nanoscale. In ferromagnetic/heavy metal multilayers, such as the [Co/Pt]N and [Co/Pd]N systems, the magnetic proximity effect was demonstrated to be asymmetric, thus inducing a magnetic moment on the Pt (Pd) layer that is typically higher at the top Co/Pt(Pd) interface. In this work, advanced spectroscopic and imaging techniques were combined with theoretical approaches to clarify the origin of this asymmetry both in Co/Pt trilayers and, for the first time, in multilayer systems that are more relevant for practical applications. The different magnetic moment induced at the Co/Pt interfaces was correlated to the microstructural features that are in turn affected by the growth processes that induce a different intermixing during the film deposition, thus influencing the interface magnetic profile.
Sparse Triangular Decomposition for Computing Equilibria of Biological Dynamic Systems Based on Chordal Graphs

Many biological systems are modeled mathematically as dynamic systems in the form of polynomial or rational differential equations. In this paper we apply sparse triangular decomposition to compute the equilibria of biological dynamic systems by exploiting the inherent sparsity of parameter-free systems via the chordal graph and by constructing suitable elimination orderings for parametric systems using the newly introduced block chordal graph. Our experiments with parameter-free systems provide practical information on suitable algorithms for chordal completion and verify the performance gains of sparse triangular decomposition against the ordinary one in the settings of computation of the equilibria. Then we establish full characterizations of block chordal graphs and propose algorithms for testing block chordality and constructing minimal block chordal completions. Based on these results, which are of their own merits in graph theory, we present a new algorithm of sparse triangular decomposition for parametric systems and apply it to detect the equilibria of parametric biological dynamic systems, with remarkable speedups against ordinary triangular decomposition verified by the experiments.
Prolongation of QTc interval due to increased parity and great grand multiparity

Abstract Women are more prone to cardiac arrhythmias. Increased exposure to sex hormones may alter the ventricular repolarisation of the heart as the parity number increases. In this study, we aim to investigate the effect of parity number to electrocardiographic parameters. A total of 205 adult women were included for the study. Nulliparous (NP), primiparous (PP), multiparous (MP), grand multiparous (GMP) and great grand multiparous (GGMP) women constituted the study population. Increased parity has positive correlation with QTc interval (p=.000, r = 0.303). GGMP has significantly higher QTc compared to NP, PP, MP and GMP (p=.001, p=.000, p=.004 and p=.007, respectively). GGMP and parity have explanatory power on QTc (p=.019 and p=.020, respectively). Parity and GGMP affect cardiac repolarisation and prolong the QTc interval most probably due to repeated exposure to sex hormones. This study showed that GGMP and parity are independent risk factors for QTc interval prolongation. Impact Statement What is already known on this subject? Increased exposure to sex hormones may alter the ventricular repolarisation of the heart as the parity number increases. Previous studies showed that increased parity (up to 7) deteriorates ventricular diastolic functions, prolongs QTc interval and these conditions cause cardiovascular diseases. What do the results of this study add? In this study, we added great grand multiparity (10 or more parity) (GGMP) group that have never been studied before. We found that GGMP has much more impact on QTc prolongation than fewer parity groups and this result shows us that GGMP deteriorates ventricular functions more. What are the implications of these findings for clinical practice and/or further research? These results show us that women should be discouraged from having more delivery. Also, women with a pregnancy history of five and more (grand multiparity) should be evaluated with an electrocardiography and a cardiology consultation should be performed before re-conception. In the future, larger prospective studies are needed on this subject. In addition, other electrocardiographic parameters (QRS-T angle and Tpe/QTc in electrocardiography, etc.) that related with diastolic functions should be evaluated for comparison of GGMP and non-GGMP populations in future studies.
A comparison of medical therapy and ablation for atrial fibrillation in patients with heart failure

ABSTRACT Introduction Atrial fibrillation and heart failure frequently co-exist and the combination is associated with a worse prognosis than either condition alone. A number of pharmacological agents and invasive procedures have been shown to benefit this complex patient group. Objective In this review, we compare different therapeutic approaches to atrial fibrillation and heart failure, including pharmacotherapy, left atrial catheter ablation and pace-and-ablate. Expert opinion Left atrial catheter ablation is an efficacious option for restoring sinus rhythm and is most likely to provide benefit to those in whom durable sinus rhythm can be expected, and whose life expectancy is not significantly reduced by other pathologies or advanced age. A pace-and-ablate approach, particularly with physiological pacing, may provide more benefit to those with low chance of maintaining sinus rhythm. Both invasive options generally outperform pharmacotherapy, although it is important to individualize the approach for each patient through shared decision-making.
The Method and Practices of the Submarine Pipelines Detection Using Magnetometers

Along with the economic development,the submarine pipeline engineering has been expanded rapidly in recent years.During the route survey,in order to ensure the safety of the submarine pipelines which have been paved before,we must detect the well and truly positions of the intersections between the new and old submarine pipeline routes,then the safeguards can be carried out.The retrospect of the submarine pipelines detection using magnetometers is introduced briefly in this paper firstly,and the operational principle and method such as information prepared and survey lines arrangement are explained,namely in general,the magnetic detecting lines of the submarine pipeline should plumb the route direction existent already,3~5 detecting lines are perfect,which distributing to both sides of the intersections,and the central line had better thrill through the intersection.1km length is designed for every line,and the space between lines is 200m in general.The characters of survey apparatus,including magnetometer,position system,echosounder,are elaborated and available types are list.In order to improve the survey precision,we can reduce the vessel speed and increase the weight near the magnetic sensor.In combination with the detection practice in the AAG-Asia America Gateway project,this paper discusses the survey procedure,data process and analysis,giving a suit of magnetic survey achievement charts.The engineering practice show that the magnetic detection is effective method for the submarine pipeline engineering.We suggest that the magnetic detection be one of the effective ways for the submarine pipeline engineering.
Results of a Phase II Study on the Use of Neoadjuvant Chemotherapy (FOLFIRINOX or GEM/nab-PTX) for Borderline-resectable Pancreatic Cancer (NUPAT-01)

Objective: Given the frequent adverse events with multidrug chemotherapy, not only the survival benefit but also the feasibility of using neoadjuvant chemotherapy to treat pancreatic cancer need to be clarified. Summary of Background Data: Although the development of multidrug chemotherapy regimens has improved the survival outcomes of patients with unresectable pancreatic cancer, the benefits of these treatments in the neo-adjuvant setting remain controversial. Methods: Patients with borderline-resectable pancreatic cancer were enrolled and randomly assigned to receive neoadjuvant chemotherapy with either FOLFIRINOX or gemcitabine with nab-paclitaxel (GEM/nab-PTX). After the completion of chemotherapy, patients underwent surgical resection when feasible. This study (NUPAT-01) was a randomized phase II trial, and the primary endpoint was the R0 resection rate. Results: Fifty-one patients were enrolled in this study [FOLFIRINOX (n = 26) and GEM/nab-PTX (n = 25)]. A total of 84.3% (n = 43/51) of the patients eventually underwent surgery, and R0 resection was achieved in 67.4% (n = 33/ 51) of the patients. Adverse events (grade >3) due to neoadjuvant treatment were observed in 45.1% of the patients (n = 23/51), and major surgical complications occurred in 30.0% (n = 13/43), with no mortality noted. The intention-to-treat analysis showed that the 3-year overall survival rate was 54.7%, with a median survival time of 39.4 months, and a significant difference in overall survival was not observed between the FOLFIRINOX and GEM/nab-PTX groups. Conclusions: These results indicate that neoadjuvant chemotherapy with FOLFIRINOX or GEM/nab-PTX is feasible and well tolerated, achieving an R0 resection rate of 67.4%. The survival of patients was even found to be favorable in the intention-to-treat analysis.
Biomarkers indicating tissue thyroid hormone status: ready to be implemented yet?

Currently, thyroid hormone status is predominantly determined by the measurement of serum thyroid stimulating hormone and free thyroxine. Although it is assumed that serum thyroid hormone concentrations within the reference range represent euthyroidism, it is unknown whether this reflects euthyroidism in all tissues (e.g. brain, muscle, bone, liver). To date, no serum marker has been established for clinical use that represents TH status within tissues accurately. However, several biomarkers have been investigated and innovative techniques have been used to unravel new biomarkers. This review provides an overview of proposed serum biomarkers that reflect tissue TH status in humans. Furthermore, we discuss the feasibility of these serum markers in clinical practice.