Miracle-dz/UniFAR-FTUs huggingface dataset:
Attention-based Knowledge Graph Representation Learning for Predicting Drug-drug Interactions

Drug-drug interactions (DDIs) are known as the main cause of life-threatening adverse events, and their identification is a key task in drug development. Existing computational algorithms mainly solve this problem by using advanced representation learning techniques. Though effective, few of them are capable of performing their tasks on biomedical knowledge graphs (KGs) that provide more detailed information about drug attributes and drug-related triple facts. In this work, an attention-based KG representation learning framework, namely DDKG, is proposed to fully utilize the information of KGs for improved performance of DDI prediction. In particular, DDKG first initializes the representations of drugs with their embeddings derived from drug attributes with an encoder-decoder layer, and then learns the representations of drugs by recursively propagating and aggregating first-order neighboring information along top-ranked network paths determined by neighboring node embeddings and triple facts. Last, DDKG estimates the probability of being interacting for pairwise drugs with their representations in an end-to-end manner. To evaluate the effectiveness of DDKG, extensive experiments have been conducted on two practical datasets with different sizes, and the results demonstrate that DDKG is superior to state-of-the-art algorithms on the DDI prediction task in terms of different evaluation metrics across all datasets.
Identifying Phased Mutations and Complex Rearrangements in Human Prostate Cancer Cell Lines through Linked-Read Whole-Genome Sequencing

Abstract A limited number of cell lines have fueled the majority of preclinical prostate cancer research, but their genomes remain incompletely characterized. Here, we utilized whole-genome linked-read sequencing for comprehensive characterization of phased mutations and rearrangements in the most commonly used cell lines in prostate cancer research including PC3, LNCaP, DU145, CWR22Rv1, VCaP, LAPC4, MDA-PCa-2b, RWPE-1, and four derivative castrate-resistant (CR) cell lines LNCaP_Abl, LNCaP_C42b, VCaP-CR, and LAPC4-CR. Phasing of mutations allowed determination of “gene-level haplotype” to assess whether genes harbored heterozygous mutations in one or both alleles. Phased structural variant analysis allowed identification of complex rearrangement chains consistent with chromothripsis and chromoplexy. In addition, comparison of parental and derivative CR lines revealed previously known and novel genomic alterations associated with the CR phenotype. Implications: This study therefore comprehensively characterized phased genomic alterations in the commonly used prostate cancer cell lines, providing a useful resource for future prostate cancer research.
Effect of optimizing nitrogen and potassium application in Johnson nutrient solution on essential oil content of Peppermint in hydroponics culture

Mint (Mentha piperita) has extensive uses in food and drug technology. Mint essential oil is one of the most applicable essential oil at the world. Menthol, as peppermint essential oil, has anti-bacterial properties and is used in throat and mouth washing solutions. Also it has anti-inflammatory effect. In order to investigate different levels of nitrogen and potassium in Johnson solution on essence amount of peppermint (Mentha piperita) an experiment was carried out during 2006-2007 in mashhad weather condition. The treatments included N in five levels (105, 135, 165, 195 and 225 ppm) and k in three levels (138, 178 and 218 ppm) with three replications. The statistical design of the experiment was factorial based on completely randomized blocks design. Peppermint plants were grown in sand media under open-air soilless culture condition and the system was bag culture method. The results showed that the highest essential oil production was in N at 195 ppm and K at 218 ppm concentration. The optimal level of nitrogen and potassium for peppermint growing in open-air hydroponics according to the results was, respectively, at 195-225 and 178-218 ppm.
Heterogeneity of social cognitive performance in autism and schizophrenia

Autistic adults and those with schizophrenia (SCZ) demonstrate similar levels of reduced social cognitive performance at the group level, but it is unclear whether these patterns are relatively consistent or highly variable within and between the two conditions. Seventy‐two adults with SCZ (52 male, Mage = 28.2 years) and 94 with diagnoses on the autism spectrum (83 male, Mage = 24.2 years) without intellectual disability completed a comprehensive social cognitive battery. Latent profile analysis identified four homogeneous subgroups that were compared on their diagnosis, independent living skills, neurocognition, and symptomatology. Two groups showed normative performance across most social cognitive tasks but were differentiated by one having significantly higher hostility and blaming biases. Autistic participants were more likely to demonstrate fully normative performance (46.8%) than participants with SCZ, whereas normative performance in SCZ was more likely to co‐occur with increased hostility and blaming biases (36.1%). Approximately 43% of participants in the full sample were classified into the remaining two groups showing low or very low performance. These participants tended to perform worse on neurocognitive tests and have lower IQ and fewer independent living skills. The prevalence of low performance on social cognitive tasks was comparable across clinical groups. However, nearly half of autistic participants demonstrated normative social cognitive performance, challenging assumptions that reduced social cognitive performance is inherent to the condition. Subgrouping also revealed a meaningful distinction between the clinical groups: participants with SCZ were more likely to demonstrate hostility biases than autistic participants, even when social cognitive performance was otherwise in the typical range.
A systematic overview of electrode configuration in electric‐driven micropumps

Accurate manipulation of fluids in microfluidic devices is an important factor affecting their functions. Since the emergence of microfluidic technology to transport fluids in microchannels, the electric field has been utilized as an effective dynamic pumping mechanism. This review attempts to provide a fundamental insight of the various electric‐driven flows in microchannels and their working mechanisms as micropumps for microfluidic devices. Different electrokinetic mechanisms implemented in electrohydrodynamic‐, electroosmosis‐, electrothermal, and dielectrophoresis‐based micropumps are discussed. A detailed description of different mechanisms is presented to provide a comprehensive overview on the key parameters used in electric micropumps. Furthermore, electrode configurations and their shapes in different micropumps are explored and categorized to provide conclusive information for the selection of efficient, simple, and affordable strategies to transport fluids in microfluidic devices. In this paper, recent theoretical, numerical and experimental investigations are covered to provide a better insight both on the operational mechanisms and strategies for lab‐on‐chip applications.
A dominant function of LynB kinase in preventing autoimmunity

Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain lyn splicing and expression, generating single-isoform LynA knockout (LynAKO) or LynBKO mice. Autoimmune disease in total LynKO mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells. Expression of LynA or LynB alone uncoupled the developmental phenotype from the autoimmune disease: B cell transitional populations were restored, but myeloid cells and differentiated B cells were dysregulated. These changes were isoform-specific, sexually dimorphic, and distinct from the complete LynKO. Despite the apparent differences in disease etiology and penetrance, loss of either LynA or LynB had the potential to induce severe autoimmune disease with parallels to human systemic lupus erythematosus (SLE).
Janus‐like BxC/C Quantum Sheets with Z‐Scheme Mechanism Strengthen Tumor Photothermal‐Immunotherapy in NIR‐II Biowindow

Carbon dots (CDs) are one of the most popular photothermal agents (PTAs) as a noninvasive strategy for tumor treatment. However, because of the inherent dominant fluorescent emission, the CDs‐based PTAs hardly achieve a single photothermal conversion, which causes low photothermal conversion efficiency and poor photothermal performance. In this regard, finding a new CDs‐based material system to greatly restrain its fluorescence to enhance its photothermal conversion efficiency is highly required, however, it is still a grand challenge. Herein, a kind of Z‐scheme CDs‐based PTAs consisting of 2D ultrathin nonmetallic BxC/C Janus quantum sheets (BxC/C JQSs) is reported to greatly enhance the photothermal conversion efficiency. It is demonstrated that the heterogeneous growth of Z‐scheme BxC/C JQSs enables the NIR‐driven quick injection of hot electrons from C into the conjugated BxC, realizing a single conversion of light to heat, and resulting in a high photothermal conversion of 60.0% in NIR‐II. Furthermore, these new Z‐scheme BxC/C‐polyethylene glycol JQSs display outstanding biocompatibility and show effective tumor elimination outcome both in vitro and in vivo through the synergistic photothermal‐immunotherapy in the NIR‐II biowindow with undetectable harm to normal tissues.
Design and Development of Solid SMEDDS and Liquisolid Formulations of Lovastatin, for Improved Drug Dissolution and In vivo Effects—a Pharmacokinetic and Pharmacodynamic Assessment

Lovastatin (Lov) is a lipid-lowering agent, with 5% bioavailability (BA) due to extensive first pass metabolism and poor solubility. To enhance dissolution and in vivo effects, Lov solid self microemulsifying drug delivery system (SMEDDS) and liquisolid systems were developed and evaluated to select superior one. Solubilities were determined in oils, surfactants, and cosurfactants. Ternary phase diagrams were constructed and selected the one which showed maximum emulsion zone. In vitro dissolution, DSC, SEM and PXRD studies were used to characterize the developed formulations. In vivo studies were conducted on optimal formulations in wistar rats. Based on solubilities, Capmul PG8 and Capmul MCM were preferred as oils, Labrasol and Transcutol P as surfactant and cosurfactant. Here, Syloid XDP carrier showed better adsorption capacity among others, hence was used in optimal solid SMEDDS (SX) and liquisolid (LS) formulations. Dissolution study results showed significant improvement in release when compared to pure drug. DSC, SEM, and PXRD results indicated the loss of drug crystallinity in optimal formulations. In pharmacokinetic (PK) study, SX and LS showed 2.57 and 1.43 fold improvements in AUC, when compared to that of coarse suspension (CS). In pharmacodynamic (PD) study, hyperlipidemia was induced by Triton X-100. CS and LS treatments showed a decline in hyperlipidemic levels at 4 h. But, SX-treated group showed early onset of decline at 2 h. Further, the duration of anti-hyperlipidemia was at least 12 h extra when compared to CS and LS. This study confirmed the superiority of SX over LS in PK and PD effects.
MiR‐708‐5p/Pit‐1 axis mediates high phosphate‐induced calcification in vascular smooth muscle cells via Wnt8b/β‐catenin pathway

Recently, the underlying mechanism of vascular calcification (VC) has been partially elucidated. However, it is still high incidence, and no effective treatment has been found. This study aims at figuring out the underlying mechanisms of microRNA‐708‐5p (miR‐708‐5p)/sodium‐phosphate transporter 1 (Pit‐1) axis in high phosphate (HP)‐induced VC of T/G HA‐VSMCs. Alizarin Red S staining was used to evaluate calcium salt deposition, and the activity of alkaline phosphatase (ALP) was determined by measuring the absorbance at 405 nm. RT‐qPCR and Western blot were performed to assess the levels of miR‐708‐5p and Pit‐1, the levels of ALP, Pit‐1, β‐catenin, glycogen synthesis kinase 3 β (GSK3β), and p‐GSK3β proteins, respectively. The interaction between miR‐708‐5p and Pit‐1 was validated by luciferase reporter assay. Our findings illustrated that miR‐708‐5p was downregulated and Pit‐1was upregulated in HP‐induced VC. MiR‐708‐5p mimics inhibited HP‐induced VC. Further experiments demonstrated that miR‐708‐5p targets Pit‐1. In addition, miR‐708‐5p inactivates the Wnt8b/β‐catenin pathway via targeting Pit‐1 to reduce HP‐induced VC. MiR‐708‐5p has a crucial effect on VC via targeting Pit‐1 and inhibiting Wnt8b/β‐catenin pathway, it may serve as a new target for VC treatment.
Effects of anxiety on sedation among pediatric patients undergoing esophagogastroduodenoscopy

We investigated whether the severity of anxiety among children undergoing endoscopy could affect sedation. We prospectively recruited patients under 18 years of age who were scheduled to undergo esophagogastroduodenoscopy (EGD). Baseline anxiety was evaluated using the Spence Children’s Anxiety Scale (SCAS). Our analysis considered the type and dose of sedative drugs, degree of sedation, and complications associated with sedation according to the scale score. The mean total SCAS T-scores and each subscale score were significantly higher in the 6–12-year age group. The mean T-score among patients who exhibited irritability during EGD was higher than that among other patients, with significant differences in the Total, Obsessive Disorder, Panic Agoraphobia and General Anxiety subscales. The midazolam doses of children exhibiting irritability were more likely to need higher (p = 0.006). Other sedation-related complications were not associated with the T-scores in each subscale. Total sleep time was not associated with any T-score subscales. Anxiety levels were significantly higher among 6–12-year-olds and children exhibiting irritability. Anxiety was often associated with irritability, difficulties achieving adequate sedation during EGD, and additional sedative drug administration. We recommend higher doses or more potent drugs to facilitate endoscopy for children with high anxiety levels.
EEG frequency tagging evidence of social interaction recognition

Abstract Previous neuroscience studies have provided important insights into the neural processing of third-party social interaction recognition. Unfortunately, however, the methods they used are limited by a high susceptibility to noise. Electroencephalogram (EEG) frequency tagging is a promising technique to overcome this limitation, as it is known for its high signal-to-noise ratio. So far, EEG frequency tagging has mainly been used with simplistic stimuli (e.g. faces), but more complex stimuli are needed to study social interaction recognition. It therefore remains unknown whether this technique could be exploited to study third-party social interaction recognition. To address this question, we first created and validated a wide variety of stimuli that depict social scenes with and without social interaction, after which we used these stimuli in an EEG frequency tagging experiment. As hypothesized, we found enhanced neural responses to social scenes with social interaction compared to social scenes without social interaction. This effect appeared laterally at occipitoparietal electrodes and strongest over the right hemisphere. Hence, we find that EEG frequency tagging can measure the process of inferring social interaction from varying contextual information. EEG frequency tagging is particularly valuable for research into populations that require a high signal-to-noise ratio like infants, young children and clinical populations.
Pharmacology, safety, efficacy and clinical uses of the COX‐2 inhibitor robenacoxib

Abstract Robenacoxib is a veterinary‐approved non‐steroidal anti‐inflammatory drug (NSAID) of the coxib group. It possesses anti‐hyperalgesic, anti‐inflammatory and anti‐pyretic properties. Robenacoxib inhibits the cyclooxygenase (COX)‐2 isoform of COX selectively (in vitro IC50 ratios COX‐1:COX‐2, 129:1 in dogs, 32:1 in cats). At registered dosages (2 mg/kg subcutaneously in dogs and cats, 1–4 mg/kg orally in dogs and 1–2.4 mg/kg orally in cats), robenacoxib produces significant inhibition of COX‐2 whilst sparing COX‐1. The pharmacokinetic (PK) profile of robenacoxib is characterized by a high degree of binding to plasma proteins (>98%) and moderate volume of distribution (at steady state, 240 ml/kg in dogs and 190 ml/kg in cats). In consequence, the terminal half‐life in blood (<2 h) is short, despite moderate body clearance (0.81 L/kg/h) in dogs and low clearance (0.44 L/kg/h) in cats. Excretion is principally in the bile (65% in dogs and 72% in cats). Robenacoxib concentrates in inflamed tissues, and clinical efficacy is achieved with once‐daily dosing, despite the short blood terminal half‐life. In dogs, no relevant breed differences in robenacoxib PK have been detected. Robenacoxib has a wide safety margin; in healthy laboratory animals daily oral doses 20‐fold (dog, 1 month), eight‐fold (cat, 6 weeks) and five‐fold (dog, 6 months) higher than recommended clinical doses were well tolerated. Clinical efficacy and safety have been demonstrated in orthopaedic and soft tissue surgery, and in musculoskeletal disorders in dogs and cats.
Classification of antiseizure drugs in cultured neuronal networks using multielectrode arrays and unsupervised learning

Antiseizure drugs (ASDs) modulate synaptic and ion channel function to prevent abnormal hypersynchronous or excitatory activity arising in neuronal networks, but the relationship between ASDs with respect to their impact on network activity is poorly defined. In this study, we first investigated whether different ASD classes exert differential impact upon network activity, and we then sought to classify ASDs according to their impact on network activity.
Exploring the misalignment on the value of further research between payers and manufacturers. A case study on a novel total artificial heart

Abstract Payers and manufacturers can disagree on the appropriate level of evidence that is required for new medical devices, resulting in high societal costs due to decisions taken with sub‐optimal information. A cost‐effectiveness model of a hypothetical total artificial heart was built using data from the literature and the (simulated) results of a pivotal study. The expected value of perfect information (EVPI) was calculated from both the payer and manufacturer perspectives, using net monetary benefit and the company's return on investment respectively. A function was also defined, linking effectiveness to market shares. Additional constraints such as a minimum clinical difference or maximum budget impact were introduced into the company's decisions to simulate additional barriers to adoption. The difference in the EVPI between manufacturers and payers varied greatly depending on the underlying decision rules and constraints. The manufacturer's EVPI depends on the probability of being reimbursed, the uncertainty on the (cost‐)effectiveness of the technology, as well as other parameters relating to initial investments, operating costs and market dynamics. The use of Value of information for both perspectives can outline potential misalignments and can be particularly useful to inform early dialogs between manufacturers and payers, or negotiations on conditional reimbursement schemes.
Increasing creative self‐efficacy: Developing the confidence of biochemistry undergraduates to innovate

Biochemistry graduates need to be creative, however assessing creativity requires the production of novelty, judged by or against that of peers. A related phenomenon is ‘creative self‐efficacy’ (CSE) – one's self‐belief in producing creative outcomes. CSE is a contributor to creativity, but is more easily assessed, and thus more amenable for targeting pedagogically. To investigate interactions between student CSE and the learning environment, a biochemistry laboratory exercise was deployed within a ‘creative’ module, wherein students created their own experimental protocols. Students completed questionnaires at the beginning and end of the module. Compared to ‘control’ modules lacking overtly creative activities, the creative module significantly increased students' perceptions of their own creativity and whether their studies had increased their creativity. Students' confidence in meeting degree learning outcomes (for instance the ability to work productively in a laboratory), and motivation to study, were also significantly increased. Marks attained from the creative exercise correlated with students' CSE, but surprisingly, students' expected marks correlated negatively with their CSE, implying they had a poor understanding of the relationship between creativity and success. Our results suggest that the learning environment can positively affect students' CSE, promoting academic attainment of learning outcomes, motivation, and their confidence as biochemists.
An Integrative QbD Approach for the Development and Optimization of Controlled Release Compressed Coated Formulation of Water-Soluble Drugs

Controlled release dosage forms maintain regulated pharmacokinetic profile of drug substance within its therapeutic window by ensuring constant plasma concentrations. Controlled release formulations not only increase the therapeutic efficacy of drug substances but also reduce their dose-related side effects. Present investigation was conducted to develop, optimize, and validate compressed coated controlled release tablet formulation for highly water-soluble drug substances which have no rate-controlling factor towards its release from dosage form. Drug dispersed waxy core tablet, press coated within the swellable hydrophilic polymeric barrier layer, was developed and optimized via quality by design approach (QbD) using Box-Behnken design. The optimized formulation was characterized and validated using in vitro quality control parameters. Attributes identified under SUPAC guidelines, such as drug release rates at 30 min, 6 h, and 12 h, were considered as the critical quality attributes (CQAs) that significantly affected efficiency of the compressed coated controlled release tablets. CQAs screened using risk assessment and Pareto chart analyses were used for optimizing controlled release dosage form. Findings revealed that tablets containing drug to wax ratio of 1:1, hydrophilic swellable polymer concentration of 200 mg, and prepared using compression pressure of 6.5 kg/cm2 exhibited the highest desirability indices in terms of controlling the release rate of drug substance. Optimized formulation was also evaluated for swelling rate, erosion rate, and other post-compression parameters, including release kinetics. Fickian diffusion-based zero-order controlled release of BCS class I drug substance was achieved through the developed dosage form.