Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization and Optimization of Injectable in situ Crosslinked Chitosan-Genipin Hydrogels.

In recent years, there has been an increased interest in injectable, in situ crosslinking hydrogels due to their minimally invasive application and ability to conform to their environment. Current in situ crosslinking chitosan hydrogels are either mechanically robust with poor biocompatibility and limited biodegradation due to toxic crosslinking agents or the hydrogels are mechanically weak and undergo biodegradation too rapidly due to insufficient crosslinking. Herein, we developed and characterized a thermally-driven, injectable chitosan-genipin hydrogel capable of in situ crosslinking at 37°C that is mechanically robust, biodegradable, and maintained high biocompatibility. The natural crosslinker genipin was utilized as a thermally-driven, non-toxic crosslinking agent. The chitosan-genipin hydrogel's crosslinking kinetics, injectability, viscoelasticity, swelling and pH response, and biocompatibility against human keratinocyte cells were characterized. The developed chitosan-genipin hydrogels were successfully crosslinked at 37°C, demonstrating temperature sensitivity. The hydrogels maintained a high percentage of swelling over several weeks before degrading in biologically relevant environments, demonstrating mechanical stability while remaining biodegradable. Long-term cell viability studies demonstrated the chitosan-genipin hydrogels have excellent biocompatibility over 7-days, including during the hydrogel crosslinking phase. Overall, our findings support the development of an injectable, in situ crosslinking chitosan-genipin hydrogel for minimally invasive biomedical applications. This article is protected by copyright. All rights reserved.
Sarcopenia‐defining parameters, but not sarcopenia, are associated with cognitive domains in middle‐aged and older European men

Previous research suggests that sarcopenia is associated with lower cognitive functioning. Evidence on the longitudinal relationship between cognition and sarcopenia, according to the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2), is scarce. This study aimed to investigate both cross‐sectional and longitudinal associations between sarcopenia and its defining parameters (muscle strength, muscle mass and physical performance) and cognitive performance in middle‐aged and older men.
Modelling, Simulation and Visualization of Heat Equation Dynamics

Aims/ objectives: To show modelling, simulation and visualization of the dynamics of heat equation in a rod. Other PDE models and Numerical approaches are also discussed. Study design: Cross-sectional study. This paper is simply about how to use MATLAB software to solve PDE model. Place and Duration of Study: Australia Methodology: A Class of PDE was uniquely modelled, simulated, and visualized using certain algorithm and MATLAB routine for Elliptic/Hyperbolic PDE. Different diagrams showing the nature of the solution are discussed. Results:The nature of the PDE governing heat dynamic in a rod are shown in the figures. Another PDE model is also presented. Conclusion: A simple demostration of numerical simulation of PDE governing the popular heat equation is presented. Three other PDE models are considered. The results herein can be adapted and applied to other more complex PDE models.
In Vivo Pharmacodynamic Profile of EVER206, a Novel Polymyxin Antimicrobial, against Gram-Negative Bacteria in the Murine Thigh Infection Model

The objective was to determine the magnitude of the EVER206 free-plasma area under the concentration time curve (fAUC)/MIC target associated with bacteriostasis and 1-log10 kill against clinically relevant Gram-negative bacteria in the murine thigh model. Twenty-seven clinical isolates (Pseudomonas aeruginosa, n = 10; Escherichia coli, n = 9; Klebsiella pneumoniae, n = 5; Enterobacter cloacae, n = 2; and Klebsiella aerogenes, n = 1) were tested. ABSTRACT The objective was to determine the magnitude of the EVER206 free-plasma area under the concentration time curve (fAUC)/MIC target associated with bacteriostasis and 1-log10 kill against clinically relevant Gram-negative bacteria in the murine thigh model. Twenty-seven clinical isolates (Pseudomonas aeruginosa, n = 10; Escherichia coli, n = 9; Klebsiella pneumoniae, n = 5; Enterobacter cloacae, n = 2; and Klebsiella aerogenes, n = 1) were tested. Mice were pretreated with cyclophosphamide (induce neutropenia) and uranyl nitrate (increase the exposure of test compound through predictable renal dysfunction). Two hours postinoculation, five doses of EVER206 were administered subcutaneously. EVER206 pharmacokinetics were determined in infected mice. Data were fit using maximum effect (Emax) models to elucidate the fAUC/MIC targets for stasis and 1-log10 bacterial kill (reported as mean [range] by species). EVER206 MICs (mg/L) ranged from 0.25 to 2 mg/L (P. aeruginosa), 0.06 to 2 mg/L (E. coli), 0.06 to 0.125 mg/L (E. cloacae), 0.06 mg/L (K. aerogenes), and 0.06 to 2 mg/L (K. pneumoniae). In vivo, the mean 0-h baseline bacterial burden was 5.57 ± 0.39 log10 CFU/thigh. Stasis was achieved in 9/10 P. aeruginosa (fAUC/MIC, 88.13 [50.33 to 129.74]), 9/9 E. coli (fAUC/MIC, 112.84 [19.19 to 279.38]), 2/2 E. cloacae (fAUC/MIC, 259.28 [124.08 to 394.47]), 0/1 K. aerogenes, and 4/5 K. pneumoniae (fAUC/MIC, 99.26 [62.3 to 144.43]) isolates tested. 1-log10 kill was achieved in 9/10 for P. aeruginosa (fAUC/MIC, 106.43 [55.22 to 152.08]), 3/9 for E. coli (fAUC/MIC, 258.96 [74.08 to 559.4]), and 1/2 for E. cloacae (fAUC/MIC, 255.33). Using the murine thigh model, the fAUC/MIC targets of EVER206 were assessed across a broad MIC distribution. Integrating these data with microbiologic and clinical exposure data will aid in determining the clinical dose of EVER206.
Head and neck tumor segmentation convolutional neural network robust to missing PET/CT modalities using channel dropout

Objective. Radiation therapy for head and neck (H&N) cancer relies on accurate segmentation of the primary tumor. A robust, accurate, and automated gross tumor volume segmentation method is warranted for H&N cancer therapeutic management. The purpose of this study is to develop a novel deep learning segmentation model for H&N cancer based on independent and combined CT and FDG-PET modalities. Approach. In this study, we developed a robust deep learning-based model leveraging information from both CT and PET. We implemented a 3D U-Net architecture with 5 levels of encoding and decoding, computing model loss through deep supervision. We used a channel dropout technique to emulate different combinations of input modalities. This technique prevents potential performance issues when only one modality is available, increasing model robustness. We implemented ensemble modeling by combining two types of convolutions with differing receptive fields, conventional and dilated, to improve capture of both fine details and global information. Main Results. Our proposed methods yielded promising results, with a Dice similarity coefficient (DSC) of 0.802 when deployed on combined CT and PET, DSC of 0.610 when deployed on CT, and DSC of 0.750 when deployed on PET. Significance. Application of a channel dropout method allowed for a single model to achieve high performance when deployed on either single modality images (CT or PET) or combined modality images (CT and PET). The presented segmentation techniques are clinically relevant to applications where images from a certain modality might not always be available.
Resistance of Klebsiella pneumoniae to Phage hvKpP3 Due to High-Molecular Weight Lipopolysaccharide Synthesis Failure

Multidrug-resistant (MDR) Klebsiella pneumoniae strains pose a particular threat to human health. Therefore, it is very important for us to isolate phage and overcome phage resistance. ABSTRACT The spread of multidrug resistant and hypervirulent Klebsiella pneumoniae has recently increased. Phages have been considered alternatives for treating infections caused by tenacious pathogens. Our study describes a novel lytic Klebsiella phage, hvKpP3, and we obtained spontaneous mutants, hvKpP3R and hvKpP3R15, of hvKpLS8 strain that showing strong resistance to the lytic phage hvKpP3. Sequencing analysis showed that nucleotide-deletion mutations of the glycosyltransferase gene (GT) and wcaJ genes, located in the lipopolysaccharide (LPS) gene cluster and the capsular polysaccharide (CPS) gene cluster, respectively, led to phage resistance. The wcaJ mutation confers the inhibition of phage adsorption by affecting the synthesis of hvKpP3R15 capsular polysaccharide, indicating that the capsule is the main adsorption receptor for bacteriophage hvKpP3. Interestingly, the phage-resistant mutant hvKpP3R has a loss-of-function mutation in GT, which is responsible for lipopolysaccharide biosynthesis. This results in the loss of high-molecular weight lipopolysaccharide (HMW-LPS), and alteration of the lipopolysaccharide structure of the bacterial cell wall confers resistance to phages. In conclusion, our study provides a detailed description of phage hvKpP3 and provides new insights into phage resistance in K. pneumoniae. IMPORTANCE Multidrug-resistant (MDR) Klebsiella pneumoniae strains pose a particular threat to human health. Therefore, it is very important for us to isolate phage and overcome phage resistance. In this study, we isolated a novel phage belonging to the Myoviridae family, hvKpP3, that exhibited high lytic activity against K2 hypervirulent K. pneumoniae. We demonstrated the excellent stability of phage hvKpP3 through in vitro and in vivo experiments, indicating its potential as a candidate for future clinical phage therapy. Furthermore, we identified that loss of function in the glycotransferase gene (GT) caused the failure of HMW-LPS synthesis, leading to phage resistance, which provides new insights into phage resistance in K. pneumoniae.
In vitro sepsis up‐regulates Nociceptin/Orphanin FQ receptor expression and function on human T‐ but not B‐cells

In animal models of sepsis, increased activation of the Nociceptin/Orphanin FQ (N/OFQ) receptor NOP is associated with mortality and NOP antagonists improved survival. We have explored the role of the N/OFQ‐NOP system in freshly isolated volunteer human B‐ and T‐cells incubated with lipopolysaccharide (LPS) and peptidoglycan G (PepG) as a model of in vitro sepsis.
ON A GENERAL CLASS OF

The present paper is a study of a general class of polynomial L~a,/3;-y,o) ( x, y) of two variables which include as particular cases the polynomials L~a,/3) ( x, y) due to Ragab and L~,/3 ( x) due to Prabhakar and Rekha. Certain generating functions, a finite sum property, integral representations, Schliifli 's contour integral, fractional integrals, Laplace transform and a series relation for this general class of polynomial have been obtained.
How Do Different Self-Presentation Strategies Affect Bridging and Bonding Social Capital on SSNs? An Empirical Study of the WeChat Users in China

The goal of this study is to examine the relationship between online self-presentation strategies and social capital (bonding and bridging) on social networking sites (SNSs). An online survey was conducted using a WeChat user sample (aged 18-22 years; 202 males, 216 females). The results showed that, the supplication strategy was positively associated only with online bonding social capital; exemplification and ingratiation strategies were positively associated with both two types of online social capital; however, no significant relationship was found between self-promotion strategy and online social capital. Theoretical implications and limitations are discussed.
A verified and validated moving domain computational fluid dynamics solver with applications to cardiovascular flows

Computational fluid dynamics (CFD) in combination with patient‐specific medical images has been used to correlate flow phenotypes with disease initiation, progression and outcome, in search of a prospective clinical tool. A large number of CFD software packages are available, but are typically based on rigid domains and low‐order finite volume methods, and are often implemented in massive low‐level C++ libraries. Furthermore, only a handful of solvers have been appropriately verified and validated for their intended use. Our goal was to develop, verify and validate an open‐source CFD solver for moving domains, with applications to cardiovascular flows. The solver is an extension of the CFD solver Oasis, which is based on the finite element method and implemented using the FEniCS open source framework. The new solver, named OasisMove, extends Oasis by expressing the Navier–Stokes equations in the arbitrary Lagrangian–Eulerian formulation, which is suitable for handling moving domains. For code verification we used the method of manufactured solutions for a moving 2D vortex problem, and for validation we compared our results against existing high‐resolution simulations and laboratory experiments for two moving domain problems of varying complexity. Verification results showed that the L2 error followed the theoretical convergence rates. The temporal accuracy was second‐order, while the spatial accuracy was second‐ and third‐order using ℙ1/ℙ1 and ℙ2/ℙ1 finite elements, respectively. Validation results showed good agreement with existing benchmark results, by reproducing lift and drag coefficients with less than 1% error, and demonstrating the solver's ability to capture vortex patterns in transitional and turbulent‐like flow regimes. In conclusion, we have shown that OasisMove is an open‐source, accurate and reliable solver for cardiovascular flows in moving domains.
Elephant ‘selfies’: Evaluating the effectiveness of Instagram’s warning of the potential negative impacts of photo opportunities with wild animals

Wildlife tourist attractions offering opportunities to observe, touch, and interact with wild animals, are visited by millions of people every year. Wildlife tourism has considerable economic value in many countries and can have positive impacts on wild animal populations (e.g. through habitat protection); it can also have negative impacts on population conservation and individual welfare (due to, e.g. habitat encroachment, disturbance, or disease). The recent phenomenon of ‘wildlife selfies’ shared on social media may seem harmless but can involve animals illegally or unsustainably captured from the wild, kept in poor conditions, or subject to cruel treatment. To address this issue, Instagram introduced a pop-up alert system that is triggered when users search for wild animal selfie hashtags (e.g. #elephantselfie), warning of the potential negative impacts of wildlife selfies on wild animals. Using elephant selfies as a case study, we found that Instagram’s alert was triggered by only 2% of 244 elephant selfie-related hashtags tested. By comparing three pairs of similar hashtags (one of each pair that triggered the warning and one that did not), we were unable to detect a consistent difference in the type of post using each of the hashtags, the popularity of posts, or the sentiment of viewer comments. The warning is not shown when posting an image, or if a post is viewed directly by a follower, only if the post is encountered via a hashtag search. Currently, what is portrayed on social media appears to be inconsistent with apparent recent shifts in social acceptibilty regarding tourism, particularly as concerns direct contact between tourists and elephants. Instagram’s wildlife selfie initiative was commendable but given its apparent lack of effect, we urge Instagram and other social platforms to do more to prevent harmful content from being posted on their platforms and to promote fair, ethical and sustainable interactions between wild animals and people.
The influence of early-life animal exposure on the risk of childhood atopic dermatitis, asthma and allergic rhinoconjunctivitis: findings from the Danish National Birth Cohort

Abstract Background Early-life animal exposure has been associated with both protective and harmful effects on asthma and allergic disease. We aimed to explore factors that may modify associations of early-life animal exposure with asthma and allergic disease, so as to better understand these differences in findings. Methods We used data from ≤84 478 children from the Danish National Birth Cohort recruited during pregnancy between 1996 and 2002, and linked registry data up to the child’s 13th birthday. Adjusted Cox models were used to examine associations of early-life cat, dog, rabbit, rodent, bird and livestock exposure with atopic dermatitis, asthma and allergic rhinoconjunctivitis overall, and by source of exposure (domestic or occupation), parental history of asthma or allergy, maternal education level and timing of exposure. Results Overall, associations between animal exposure and the three outcomes of interest were weak. However, dog exposure was associated with marginally lower risk of atopic dermatitis and asthma [adjusted hazard ratio (aHR) = 0.81, 95% CI: 0.70–0.94 and 0.88, 95% CI: 0.82–0.94, respectively], whereas prenatal domestic bird exposure was associated with slightly increased risk of asthma (aHR = 1.18, 95% CI: 1.05–1.32). Source of exposure, parental history of asthma or allergy and timing of exposure modified associations. Early-life animal exposure did not appear to increase the risk of allergic rhinoconjunctivitis (aHR range = 0.88, 95% CI: 0.81–0.95 to 1.00, 95% CI: 0.91–1.10). Conclusions The overall weak associations observed between animal exposure and atopic dermatitis, asthma and allergic rhinoconjunctivitis were modified by type of animal, source of exposure, parental history of asthma or allergy and timing of exposure, suggesting that these factors should be considered when assessing the risks associated with early-life animal exposure.
Risk factors for acute kidney injury in COVID-19 patients: an updated systematic review and meta-analysis

Abstract Objectives Acute kidney injury (AKI) is associated with increased mortality among coronavirus disease 2019 (COVID-19) patients. This meta-analysis aimed to identify risk factors for the development of AKI in patients with COVID-19. Methods A systematic literature search was conducted in PubMed and EMBASE from 1 December 2019 to 1 January 2023. Due to significant study heterogeneity, meta-analyses were conducted using random-effects models. Meta-regression and sensitivity analysis were also performed. Results A total of 153,600 COVID-19 patients from 39 studies were included, and 28,003 patients developed AKI. By meta-analysis, we discovered that age, male sex, obesity, black race, invasive ventilation, and the use of diuretics, steroids and vasopressors, in addition to comorbidities such as hypertension, congestive heart failure, chronic kidney disease, acute respiratory distress syndrome, and diabetes, were significant risk factors for COVID-19-associated AKI. Conclusions Early detection of these risk factors is essential to reduce the incidence of AKI and improve the prognosis of COVID-19 patients.
Mutant Prevention Concentration, Frequency of Spontaneous Mutant Selection, and Mutant Selection Window—a New Approach to the In Vitro Determination of the Antimicrobial Potency of Compounds

The analysis of antimicrobial activity is usually MIC- and minimal bactericidal concentration (MBC)-focused, though also crucial are resistance-related parameters, e.g., the frequency of spontaneous mutant selection (FSMS), the mutant prevention concentration (MPC), and the mutant selection window (MSW). In vitro-determined MPCs, however, are sometimes variable, poorly repeatable, and not always reproducible in vivo. We propose a new approach to the in vitro determination of MSWs, along with novel parameters: MPC-D, MSW-D (for dominant mutants, i.e., selected with a high frequency, without a fitness loss), and MPC-F, MSW-F (for inferior mutants, i.e., with an impaired fitness). ABSTRACT The analysis of antimicrobial activity is usually MIC- and minimal bactericidal concentration (MBC)-focused, though also crucial are resistance-related parameters, e.g., the frequency of spontaneous mutant selection (FSMS), the mutant prevention concentration (MPC), and the mutant selection window (MSW). In vitro-determined MPCs, however, are sometimes variable, poorly repeatable, and not always reproducible in vivo. We propose a new approach to the in vitro determination of MSWs, along with novel parameters: MPC-D, MSW-D (for dominant mutants, i.e., selected with a high frequency, without a fitness loss), and MPC-F, MSW-F (for inferior mutants, i.e., with an impaired fitness). We also propose a new method for preparing the high-density inoculum (>1011 CFU/mL). In this study, the MPC and MPC-D (limited by FSMS of <10−10) of ciprofloxacin, linezolid, and novel benzosiloxaborole (No37) were determined for Staphylococcus aureus ATCC 29213 using the standard agar method, while the MPC-D and MPC-F were determined by the novel broth method. Regardless of the method, MSWs1010 of linezolid and No37 were the same. However, MSWs1010 of ciprofloxacin in the broth method was narrower than in the agar method. In the broth method, the 24-h incubation of ~1010 CFU in a drug-containing broth differentiates the mutants that can dominate the cell population from those that can only be selected under exposure. We consider MPC-Ds in the agar method to be less variable and more repeatable than MPCs. Meanwhile, the broth method may decrease discrepancies between in vitro and in vivo MSWs. The proposed approaches may help establish MPC-D-related resistance-restricting therapies.
Associations of habitual physical activity and carotid-femoral pulse wave velocity; a systematic review and meta-analysis of observational studies

The aim of this review was to understand the association between habitual physical activity (hPA) and carotid-femoral pulse wave velocity (cfPWV) in an ostensibly healthy adult population. Searches were performed in MEDLINE Web of Science, SPORTDiscus and CINAHL databases published up to 01/01/2022 (PROSPERO, Registration No: CRD42017067159). Observational English-language studies assessing the relationship between cfPWV and hPA (measured via self-report or device-based measures) were considered for inclusion in a narrative synthesis. Studies were excluded if studying specific disease. Studies were further included in pooled analyses where a standardised association statistic for continuous hPA and cfPWV was available. 29 studies were included in narrative synthesis, of which 18 studies provided sufficient data for pooled analyses, totalling 15,573 participants. A weak, significant, negative correlation between hPA and cfPWV was observed; partial r = -0.08 95%CI [-0.15, -0.01]; P = 0.045. Heterogeneity was high (I2 = 94.5% P<0.001). Results did not differ across sub-group analyses, however the high heterogeneity within pooled analyses was largely explained by studies utilizing self-reports of PA exposures, being of poor methodological quality or providing only univariate analyses. Overall this systematic review identified a weak negative beneficial association between hPA and cfPWV suggesting that higher levels of hPA benefit vascular health even amongst an asymptomatic population. However, the variation in PA metrics reported (restricting ability to complete meta-analysis), and the heterogeneity within pooled analyses suggests that findings should be interpreted with a degree of caution. The development of methods to precisely quantify day-to-day movement behaviours should support future high-quality research in this field.