Miracle-dz/UniFAR-FTUs huggingface dataset:
Child pain‐related injustice appraisals mediate the relationship between just‐world beliefs and pain‐related functioning

Research among adult and paediatric samples suggests that pain‐related injustice appraisals contribute to adverse pain‐related functioning. However, a singular focus on pain‐related injustice appraisals carries the risk of underestimating the role of broader concepts of justice. This study examined the unique roles of child pain‐related injustice appraisals and just‐world beliefs in understanding disability and physical, emotional, social and academic functioning, as well as the mediating role of injustice appraisals in the relationship between just‐world beliefs and functioning.
Pseudomonas Exotoxin A Based Toxins Targeting Epidermal Growth Factor Receptor for the Treatment of Prostate Cancer

The epidermal growth factor receptor (EGFR) was found to be a valuable target on prostate cancer (PCa) cells. However, EGFR inhibitors mostly failed in clinical studies with patients suffering from PCa. We therefore tested the targeted toxins EGF-PE40 and EGF-PE24mut consisting of the natural ligand EGF as binding domain and PE40, the natural toxin domain of Pseudomonas Exotoxin A, or PE24mut, the de-immunized variant thereof, as toxin domains. Both targeted toxins were expressed in the periplasm of E.coli and evoked an inhibition of protein biosynthesis in EGFR-expressing PCa cells. Concentration- and time-dependent killing of PCa cells was found with IC50 values after 48 and 72 h in the low nanomolar or picomolar range based on the induction of apoptosis. EGF-PE24mut was found to be about 11- to 120-fold less toxic than EGF-PE40. Both targeted toxins were more than 600 to 140,000-fold more cytotoxic than the EGFR inhibitor erlotinib. Due to their high and specific cytotoxicity, the EGF-based targeted toxins EGF-PE40 and EGF-PE24mut represent promising candidates for the future treatment of PCa.
An Immune Risk Score Predicts Survival of Patients with Acute Myeloid Leukemia Receiving Chemotherapy

Purpose: Prediction models for acute myeloid leukemia (AML) are useful, but have considerable inaccuracy and imprecision. No current model includes covariates related to immune cells in the AML microenvironment. Here, an immune risk score was explored to predict the survival of patients with AML. Experimental Design: We evaluated the predictive accuracy of several in silico algorithms for immune composition in AML based on a reference of multi-parameter flow cytometry. CIBERSORTx was chosen to enumerate immune cells from public datasets and develop an immune risk score for survival in a training cohort using least absolute shrinkage and selection operator Cox regression model. Results: Six flow cytometry–validated immune cell features were informative. The model had high predictive accuracy in the training and four external validation cohorts. Subjects in the training cohort with low scores had prolonged survival compared with subjects with high scores, with 5-year survival rates of 46% versus 19% (P < 0.001). Parallel survival rates in validation cohorts-1, -2, -3, and -4 were 46% versus 6% (P < 0.001), 44% versus 18% (P = 0.041), 44% versus 24% (P = 0.004), and 62% versus 32% (P < 0.001). Gene set enrichment analysis indicated significant enrichment of immune relation pathways in the low-score cohort. In multivariable analyses, high-risk score independently predicted shorter survival with HRs of 1.45 (P = 0.005), 2.12 (P = 0.004), 2.02 (P = 0.034), 1.66 (P = 0.019), and 1.59 (P = 0.001) in the training and validation cohorts, respectively. Conclusions: Our immune risk score complements current AML prediction models.
The Chemical Compositions of Essential Oils Derived from Cryptocarya alba and Laurelia sempervirens Possess Antioxidant, Antibacterial and Antitumoral Activity Potential

Cryptocarya alba (Peumo; CA) and Laurelia sempervirens (Laurel; LS) are herbs native to the Chilean highlands and have historically been used for medicinal purposes by the Huilliches people. In this work, the essential oils were extracted using hydrodistillation in Clevenger apparatus and analyzed by GC-MS to determine their composition. The antioxidant capacity (AC) was evaluated in vitro. The cytotoxicity was determined using cell line cultures both non tumoral and tumoral. The toxicity was determined using the nematode Caenorhabditis elegans. The antimicrobial activity was evaluated against 52 bacteria using the agar disc diffusion method and the minimum inhibitory concentrations (MICs) were determined. The principal compounds found in C. alba essential oil (CA_EO) were α-terpineol (24.96%) and eucalyptol (21.63%) and were isazafrol (91.9%) in L. sempervirens essential oil (LS_EO). Both EOs showed antioxidant capacity in vitro. Both EO showed antibacterial activity against bacteria using. LS_EO showed more inhibitory effect on these cell lines respect to CA_EO. Both EOs showed toxicity against the nematode C. elegans at 3.12–50 mg/mL. The essential oils of CA and LS have an important bioactive potential in their antioxidant, antibacterial and cytotoxicity activity. Both essential oils could possibly be used in the field of natural medicine, natural food preservation, cosmetics, sanitation and plaguicides among others.
Celecoxib Loaded In-Situ Provesicular Powder and Its In-Vitro Cytotoxic Effect for Cancer Therapy: Fabrication, Characterization, Optimization and Pharmacokinetic Evaluation

Introduction: Several recent studies have shown that the role of cyclooxygenase 2 (COX-2) in carcinogenesis has become more evident. It affects angiogenesis, apoptosis, and invasion, and plays a key role in the production of carcinogens. It has also been reported that COX-2 inhibitors such as celecoxib (CLX) might play an effective role in preventing cancer formation and progression. Formulation of CLX into nanovesicles is a promising technique to improve its bioavailability and anticancer efficacy. Aim: The aim of this study is to optimize and evaluate the anticancer efficacy of CLX-loaded in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles in-vitro and determine its pharmacokinetic parameters in-vivo. Methods: The novel provesicular powders were prepared by the slurry method and optimized by 32 full factorial design using the desirability function. Results: Small mean particle size was achieved by the formed vesicles with value of 351.7 ± 1.76 nm and high entrapment efficacy of CLX in the formed vesicles of 97.53 ± 0.84%. Solid state characterization of the optimized formulation showed that the powder was free flowing, showed no incompatibilities between drug and excipients and showed smooth texture. The cytotoxic study of the optimized formula on HCT-116, HepG-2, A-549, PC-3 and MCF-7 cell lines showed significant increase in activity of CLX compared to its free form. The pharmacokinetic study on albino rabbits after oral administration showed significant increase in the area under the curve (AUC)0–24 h and significantly higher oral relative bioavailability of the optimized formulation compared to Celebrex® 100 mg market product (p < 0.05). Conclusion: All findings of this study suggest the potential improvement of efficacy and bioavailability of CLX when formulated in the form of in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles for its repositioned use as an anticancer agent.
Knockout of the Glucocorticoid Receptor Impairs Reproduction in Female Zebrafish

The pleiotropic effects of glucocorticoids in metabolic, developmental, immune and stress response processes have been extensively investigated; conversely, their roles in reproduction are still less documented. It is well known that stress or long-lasting therapies can cause a strong increase in these hormones, negatively affecting reproduction. Moreover, the need of glucocorticoid (GC) homeostatic levels is highlighted by the reduced fertility reported in the zebrafish glucocorticoid receptor mutant (nr3c1ia30/ia30) line (hereafter named gr−/−). Starting from such evidence, in this study, we have investigated the role of glucocorticoid receptor (Gr) in the reproduction of female zebrafish. Key signals orchestrating the reproductive process at the brain, liver, and ovarian levels were analyzed using a multidisciplinary approach. An impairment of the kiss-GnRH system was observed at the central level in (gr−/−) mutants as compared to wild-type (wt) females while, in the liver, vitellogenin (vtg) mRNA transcription was not affected. Changes were instead observed in the ovary, particularly in maturing and fully grown follicles (classes III and IV), as documented by the mRNA levels of signals involved in oocyte maturation and ovulation. Follicles isolated from gr−/− females displayed a decreased level of signals involved in the acquisition of competence and maturation, causing a reduction in ovulation with respect to wt females. Fourier transform infrared imaging (FTIRI) analysis of gr−/− follicle cytoplasm showed major changes in macromolecule abundance and distribution with a clear alteration of oocyte composition. Finally, differences in the molecular structure of the zona radiata layer of gr−/− follicles are likely to contribute to the reduced fertilization rate observed in mutants.
Molecular Testing in CML between Old and New Methods: Are We at a Turning Point?

Molecular monitoring of minimal residual disease (MRD) and BCR-ABL1 kinase domain (KD) mutation testing have a well consolidated role in the routine management of chronic myeloid leukemia (CML) patients, as they provide precious information for therapeutic decision-making. Molecular response levels are used to define whether a patient has an “optimal”, “warning”, or “failure” response to tyrosine kinase inhibitor (TKI) therapy. Mutation status may be useful to decide whether TKI therapy should be changed and which alternative TKI (or TKIs) are most likely to be effective. Real-time quantitative polymerase chain reaction (RQ-qPCR) and Sanger sequencing are currently the gold standard for molecular response monitoring and mutation testing, respectively. However, in recent years, novel technologies such as digital PCR (dPCR) and next-generation sequencing (NGS) have been evaluated. Here, we critically describe the main features of these old and novel technologies, provide an overview of the recently published studies assessing the potential clinical value of dPCR and NGS, and discuss how the state of the art might evolve in the next years.
Polyetheretherketone and Its Composites for Bone Replacement and Regeneration

In this article, recent advances in the development, preparation, biocompatibility and mechanical properties of polyetheretherketone (PEEK) and its composites for hard and soft tissue engineering are reviewed. PEEK has been widely employed for fabricating spinal fusions due to its radiolucency, chemical stability and superior sterilization resistance at high temperatures. PEEK can also be tailored into patient-specific implants for treating orbital and craniofacial defects in combination with additive manufacturing process. However, PEEK is bioinert, lacking osseointegration after implantation. Accordingly, several approaches including surface roughening, thin film coating technology, and addition of bioactive hydroxyapatite (HA) micro-/nanofillers have been adopted to improve osseointegration performance. The elastic modulus of PEEK is 3.7–4.0 GPa, being considerably lower than that of human cortical bone ranging from 7–30 GPa. Thus, PEEK is not stiff enough to sustain applied stress in load-bearing orthopedic implants. Therefore, HA micro-/nanofillers, continuous and discontinuous carbon fibers are incorporated into PEEK for enhancing its stiffness for load-bearing applications. Among these, carbon fibers are more effective than HA micro-/nanofillers in providing additional stiffness and load-bearing capabilities. In particular, the tensile properties of PEEK composite with 30wt% short carbon fibers resemble those of cortical bone. Hydrophobic PEEK shows no degradation behavior, thus hampering its use for making porous bone scaffolds. PEEK can be blended with hydrophilic polymers such as polyglycolic acid and polyvinyl alcohol to produce biodegradable scaffolds for bone tissue engineering applications.
Synthesis, Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide

Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. 1H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA’s ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells.
The Application of Mucoadhesive Chitosan Nanoparticles in Nasal Drug Delivery

Mucosal delivery of antigens can induce both humoral and cellular immune responses. Particularly, the nasal cavity is a strongly inductive site for mucosal immunity among several administration routes, as it is generally the first point of contact for inhaled antigens. However, the delivery of antigens to the nasal cavity has some disadvantages such as rapid clearance and disposition of inhaled materials. For these reasons, remarkable efforts have been made to develop antigen delivery systems which suit the nasal route. The use of nanoparticles as delivery vehicles enables protection of the antigen from degradation and sustains the release of the loaded antigen, eventually resulting in improved vaccine and/or drug efficacy. Chitosan, which exhibits low toxicity, biodegradability, good cost performance, and strong mucoadhesive properties, is a useful material for nanoparticles. The present review provides an overview of the mucosal immune response induced by nanoparticles, recent advances in the use of nanoparticles, and nasal delivery systems with chitosan nanoparticles.
Recent Advances in Microswimmers for Biomedical Applications

Microswimmers are a rapidly developing research area attracting enormous attention because of their many potential applications with high societal value. A particularly promising target for cleverly engineered microswimmers is the field of biomedical applications, where many interesting examples have already been reported for e.g., cargo transport and drug delivery, artificial insemination, sensing, indirect manipulation of cells and other microscopic objects, imaging, and microsurgery. Pioneered only two decades ago, research studies on the use of microswimmers in biomedical applications are currently progressing at an incredibly fast pace. Given the recent nature of the research, there are currently no clinically approved microswimmer uses, and it is likely that several years will yet pass before any clinical uses can become a reality. Nevertheless, current research is laying the foundation for clinical translation, as more and more studies explore various strategies for developing biocompatible and biodegradable microswimmers fueled by in vivo-friendly means. The aim of this review is to provide a summary of the reported biomedical applications of microswimmers, with focus on the most recent advances. Finally, the main considerations and challenges for clinical translation and commercialization are discussed.
Multisectoral approach to achieve canine rabies controlled zone using Intervention Mapping: Preliminary results

Background Annually, in India, millions of dog bite cases occur; most of them are inflicted by a stray dog. There are over 25 million dogs in the country. The rate of stray dog vaccination is suboptimal in India. This study aims to develop an intervention strategy, using Intervention Mapping framework, tailored for the target community to achieve canine rabies controlled zone. Methodology This is an exploratory, cross-sectional study conducted at a tertiary care Medical Institute at Jodhpur, Rajasthan, India, from 2018–2019. The semi-structured, In-Depth Discussion was conducted with a multidisciplinary planning group comprising of members from veterinary, health, and administrative sectors. The In-Depth Discussion focused on knowledge regarding complete stray dog vaccination schedule, self-efficacy (to prevent dog bites), challenges, and barriers faced by residents to achieve canine rabies controlled zone. Further, discussion with veterinary stakeholders focused on challenges faced for rigorous implementation of stray dog vaccination and sterilization. Results In-Depth Discussion revealed the following challenges: Lack of participation by the study population for canine vaccination, incomplete knowledge about annual canine vaccination schedule, lack of understanding of dog gestures, lack of infrastructure and resources at veterinary hospitals. The majority of the dogs in the study area were stray dogs that were partially or non-vaccinated and non-sterilized. An intersectoral collaboration was achieved between the community members, veterinary stakeholders both private and Non-Governmental organisations, and heath sector. Following which 35 (76.0%) stray dogs were vaccinated, and 17 (35.4%) were sterilized with community support. Burden of dog bite cases also decreased. The stray dog density map was prepared, and community engagement activity on dog gestures was conducted. Conclusion The present study demonstrates the feasibility of achieving canine rabies controlled zone. When implemented in a phase-wise manner across all Medical and Residential complex, this strategy would ensure achieving canine rabies controlled zone through multi-stakeholder engagement.
Responses to Salt Stress in Portulaca: Insight into Its Tolerance Mechanisms

Climate change and its detrimental effects on agricultural production, freshwater availability and biodiversity accentuated the need for more stress-tolerant varieties of crops. This requires unraveling the underlying pathways that convey tolerance to abiotic stress in wild relatives of food crops, industrial crops and ornamentals, whose tolerance was not eroded by crop cycles. In this work we try to demonstrate the feasibility of such strategy applying and investigating the effects of saline stress in different species and cultivars of Portulaca. We attempted to unravel the main mechanisms of stress tolerance in this genus and to identify genotypes with higher tolerance, a procedure that could be used as an early detection method for other ornamental and minor crops. To investigate these mechanisms, six-week-old seedlings were subjected to saline stress for 5 weeks with increasing salt concentrations (up to 400 mM NaCl). Several growth parameters and biochemical stress markers were determined in treated and control plants, such as photosynthetic pigments, monovalent ions (Na+, K+ and Cl−), different osmolytes (proline and soluble sugars), oxidative stress markers (malondialdehyde—a by-product of membrane lipid peroxidation—MDA) and non-enzymatic antioxidants (total phenolic compounds and total flavonoids). The applied salt stress inhibited plant growth, degraded photosynthetic pigments, increased concentrations of specific osmolytes in both leaves and roots, but did not induce significant oxidative stress, as demonstrated by only small fluctuations in MDA levels. All Portulaca genotypes analyzed were found to be Na+ and Cl− includers, accumulating high amounts of these ions under saline stress conditions, but P. grandiflora proved to be more salt tolerant, showing only a small reduction under growth stress, an increased flower production and the lowest reduction in K+/Na+ rate in its leaves.
Multi-Omics Integration Highlights the Role of Ubiquitination in CCl4-Induced Liver Fibrosis

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in chronic liver disease. Ubiquitination is a post-translational modification that is crucial for a plethora of physiological processes. Even though the ubiquitin system has been implicated in several human diseases, the role of ubiquitination in liver fibrosis remains poorly understood. Here, multi-omics approaches were used to address this. Untargeted metabolomics showed that carbon tetrachloride (CCl4)-induced liver fibrosis promotes changes in the hepatic metabolome, specifically in glycerophospholipids and sphingolipids. Gene ontology analysis of public deposited gene array-based data and validation in our mouse model showed that the biological process “protein polyubiquitination” is enriched after CCl4-induced liver fibrosis. Finally, by using transgenic mice expressing biotinylated ubiquitin (bioUb mice), the ubiquitinated proteome was isolated and characterized by mass spectrometry in order to unravel the hepatic ubiquitinated proteome fingerprint in CCl4-induced liver fibrosis. Under these conditions, ubiquitination appears to be involved in the regulation of cell death and survival, cell function, lipid metabolism, and DNA repair. Finally, ubiquitination of proliferating cell nuclear antigen (PCNA) is induced during CCl4-induced liver fibrosis and associated with the DNA damage response (DDR). Overall, hepatic ubiquitome profiling can highlight new therapeutic targets for the clinical management of liver fibrosis.
Electroosmotic Flow of Non-Newtonian Fluid in Porous Polymer Membrane at High Zeta Potentials

To help in the efficient design of fluid flow in electroosmotic pumps, electroosmotic flow of non-Newtonian fluid through porous polymer membrane at high zeta potentials is studied by mainly evaluating the total flow rate at different physical parameters. Non-Newtonian fluid is represented by the power-law model and the porous polymer membrane is considered as arrays of straight cylindrical pores. The electroosmotic flow of non-Newtonian fluid through a single pore is studied by solving the complete Poisson–Boltzmann equation and the modified Cauchy momentum equation. Then assuming the pore size distribution on porous polymer membrane obeys Gaussian distribution, the performance of electroosmotic pump operating non-Newtonian fluid is evaluated by computing the total flow rate of electroosmotic flow through porous polymer membrane as a function of flow behavior index, geometric parameters of porous membrane, electrolyte concentration, applied voltage, and zeta potential. It is found that enhancing zeta potential and bulk concentration rather than the applied voltage can also significantly improve the total flow rate in porous polymer membrane, especially in the case of shear thinning fluid.