Miracle-dz/UniFAR-FTUs huggingface dataset:
Phospholipid-mimicking block, graft, and block-graft copolymers for phase-transition microbubbles as ultrasound contrast agents

Background: Lipid and polymer microbubbles (MBs) are widely used as ultrasound contrast agents in clinical diagnosis, and possess great potential in ultrasound-mediated therapy due to their drug loading function. However, overcoming the limitations of stability and echo enhancement of MBs are still a considerable challenge. Methods: A series novel block, graft and block-graft copolymers was proposed and prepared in this work, and these copolymers were used as shells to encapsulate perfluoropentane as ultrasound contrast agents. First, block, graft and block-graft copolymers with different topological structures were prepared. Then, these copolymers were prepared into block copolymer phase-transition MBs, graft copolymer phase-transition MBs, and block-graft copolymer phase-transition MBs, respectively. Finally, the dexamethasone was used for drug-loaded phase-transition microbubbles model to explore the potential of theranostic microbubbles. Results: Finally, these three resulting copolymer MBs with average size of 4–5 μm exhibited well enhancement of ultrasound imaging under the influence of different frequencies and mechanical index, and they exhibited a longer contrast-enhanced ultrasound imaging time and higher resistance to mechanical index compared with SonoVue in vitro and in vivo. In vitro drug release results also showed that these copolymer MBs could encapsulate dexamethasone drugs, and the drug release could be enhanced by ultrasonic triggering. These copolymer MBs were therapeutic MBs for targeted triggering drug release. Conclusion: Therefore, the feasibility of block, graft, and block-graft copolymers as ultrasonic contrast agents was verified, and their ultrasonic enhancement performance in vitro and in vivo was compared. The ultrasound contrast agents developed in this work have excellent development potential in comprehensive diagnosis and treatment.
Immediate Effects of (Simulated) Age-Related Hearing Loss on Cognitive Processing and Performance for the Backward-Digit-Span Task

The recall of auditorily presented sequences of digits in reverse order (also known as the Backward Digit Span, BDS) is considered to reflect a person’s information storage and processing abilities which have been linked to speech-in-noise intelligibility. However, especially in aging research and audiology, persons who are administered the BDS task are often affected by hearing loss (HL). If uncorrected, HL can have immediate assessment-format-related effects on cognitive-test performance and can result, in the long term, in neuroplastic changes impacting cognitive functioning. In the present study, an impairment-simulation approach, mimicking mild-to-moderate age-related HLs typical for persons aged 65, 75, and 85 years, was used in 19 young normal-hearing participants to evaluate the impact of HL on cognitive performance and the cognitive processes probed by the BDS task. Participants completed the BDS task in several listening conditions, as well as several commonly used visual tests of short-term and working memory. The results indicated that BDS performance was impaired by a simulated HL representing that of persons aged 75 years and above. In the normal-hearing condition, BDS performance correlated positively with both performance on tests of short-term memory and performance on tests of working memory. In the listening condition simulating moderate HL (as experienced by the average 85-year-old person), BDS performance only correlated with performance on working-memory tests. In conclusion, simulated (and, by extrapolation, actual) age-related HL negatively affects cognitive-test performance and may change the composition of the cognitive processes associated with the completion of a cognitive task.
Theory of the 1-point PDF for incompressible Navier-Stokes fluids

Fundamental aspects of fluid dynamics are related to construction of statistical models for incompressible Navier-Stokes fluids. The latter can be considered either deterministic or stochastic, respectively for regular or turbulent flows. In this work we claim that a possible statistical formulation of this type can be achieved by means of the 1-point (local) velocity-space probability density function (PDF, f1) to be determined in the framework of the so-called inverse kinetic theory (IKT). There are several important consequences of the theory. These include, in particular, the characterization of the initial PDF [for the statistical model {f1, }] . This is found to be generally non-Gaussian PDF, even in the case of flows which are regular at the initial time. Moreover, both for regular and turbulent flows, its time evolution is provided by a Liouville equation, while the corresponding Liouville operator is found to depend only on a finite number of velocity moments of the same PDF. Hence, its time evolution depends (functionally) solely on the same PDF. In addition, the statistical model here developed determines uniquely both the initial condition and the time evolution of f1. As a basic implication, the theory allows the exact construction of the corresponding statistical equation for the stochastic-averaged PDF and the unique representation of the multi-point PDF’s solely in terms of the 1-point PDF. As an example, the case of the reduced 2-point PDF’s, usually adopted for the statistical description of NS turbulence, is considered.
Multi-frame DVC for temporal image sequences

Digital volume correlation (DVC) is a 3D image-based technique for displacement and strain computation. Traditionally, both (digital image correlation) DIC and DVC are methods based on two individual time frames; the estimation of the displacement and strain field is done using one reference and one moving frame as input. However, dynamic experiments generate more than two temporal frames. Therefore, with classical DVC techniques, only a subset of the available data is used. In this study, we propose a novel DVC method that can rely on more than two frames for the displacement and strain computation. The proposed method aims to be as general as possible; there is no constraint regarding the nature or the rate of the displacement (e.g., cyclic or linear). The aim of this method is to impose a temporal regularization that improves the self-consistency of the algorithm. The multi-frame DVC improves the quality of the registration in challenging situations. As an example, we investigate the dissolution of a pharmaceutical tablet in water, which undergoes three processes: swelling, gel formation, and material erosion. The accuracy of the registration—quantified by the sum of square differences (SSD)—has improved by 23% on an average with respect to the classical two-frame method. Classical DVC methods fail in registering images with structures that change appearance through time, such as the tablet that, in contact with water, reacts chemically, changing phase and becoming a gel. Moreover, we proved that multi-frame DVC is more robust in registering images with severe but realistic motion artefacts. As an example for this case, we apply the method to a series of μ-CT datasets of aluminum foam during a compression experiment. As seen with the tablets, we are in a situation where the appearance of the structures in the images changes through time, but in this case it is because of motion artefacts. Finally, the use of more than two frames makes the method more robust against noisy images, with an average improvement of 35% in registration accuracy obtained using the three-frame DVC method compared to the classical two-frame DVC method.
Guidelines for treating child and adolescent obesity: A systematic review

Obesity is a chronic disease that compromises the physical and mental health of an increasing proportion of children globally. In high-income countries, prevalence of paediatric obesity is increasing faster in those from marginalised populations such as low-income households, suggesting the disease as one that is largely systemic. Appropriate treatment should be prioritised in these settings to prevent the development of complications and co-morbidities and manage those that already exist. An array of clinical practice guidelines are available for managing overweight and obesity in children and adolescents, but no systematic review has yet compared their quality or synthesised their recommendations. We aimed to narratively review clinical practice guidelines published in English for treating child and adolescent obesity, to identify the highest quality guidelines, and assess similarities, conflicts, and gaps in recommendations. We systematically searched academic databases and grey literature for guidelines published. We used the AGREE II tool to assess the quality, and identified nine high quality guidelines for inclusion in a narrative review of recommendations. Guidelines predominantly recommended the delivery of multi-component behaviour-change interventions aimed at improving nutrition and physical activity. Treatment outcomes were generally focussed on weight, with less emphasis on managing complications or improving quality-of-life. There was no evidence-based consensus on the best mode of delivery, setting, or treatment format. The guidelines rarely included recommendations for addressing the practical or social barriers to behaviour change, such as cooking skills or supervised physical activity. There is insufficient evidence to evaluate pharmaceutical and surgical interventions in children, and these were generally not recommended. It should be noted that this review addressed documents published in English only, and therefore the included guidelines were applicable predominantly to high-resource settings.
Association between arterial stiffness and left ventricular diastolic function: A large population-based cross-sectional study

Background The association between arterial stiffness and left ventricular (LV) diastolic function has been demonstrated in several studies, but the samples size in those studies was small. This study aims to verify this issue in a large number of study subjects. Methods A total of 7,013 consecutive participants (mean age 60.6 years and 43.3% female) who underwent both baPWV and transthoracic echocardiography were retrospectively analyzed. Subjects with significant cardiac structural abnormalities were excluded. Results There were significant correlations of baPWV with septal e′ velocity (r = – 0.408; P < 0.001), septal E/e′ (r = 0.349; P < 0.001), left atrial volume index (LAVI) (r = 0.122; P < 0.001) and maximal velocity of tricuspid valve regurgitation (TR Vmax) (r = 0.322; P < 0.001). The baPWV values increased proportionally with an increase in the number of LV diastolic indices meeting LV diastolic dysfunction criteria (P-for-trend < 0.001). In multivariable analyses with adjustment for confounding effects of various clinical covariates, higher baPWV was independently associated with septal e′ < 7 (odds ratio [OR], 1.30; 95% confidence interval [CI] 1.20–1.60; P < 0.001), septal E/e′ ≥ 15 (OR, 1.46; 95% CI, 1.21–1.78; P < 0.001), and TR Vmax > 2.8 m/s (OR, 1.60; 95% CI, 1.23–2.09; P < 0.001) but not with LAVI ≥ 34 mL/m2 (OR, 0.89; 95% CI, 0.76–1.03; P = 0.123). Conclusions Increased arterial stiffness, as measured by baPWV, was associated with abnormal diastolic function parameters in a large number of study participants, providing strong evidence to the existing data about ventricular-vascular coupling.
Editorial: Emotional intelligence: Current research and future perspectives on mental health and individual differences

COPYRIGHT © 2022 Mancini, Biolcati, Joseph, Trombini and Andrei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Emotional intelligence: Current research and future perspectives on mental health and individual di erences
Genomic analyses of the scorpion mud turtle (Kinosternon scorpioides) (Linnaeus, 1766) in insular and continental Colombia: Evidence for multiple conservation and taxonomic units

The turtle genus Kinosternon is widespread with at least 25 species distributed from Mexico to northern Argentina. The taxonomy of this genus is controversial and requires a full revision using both morphological and molecular approaches. In this study, we did a genomic analysis on the species Kinosternon scorpioides distributed in insular and continental Colombia in order to define conservation units. Total DNA was extracted from 24 tissue samples and RADseq genotyping analysis was done. In addition, the intron R35 was amplified and sequenced for a subset of samples. A total of 35,507 SNPs combined with 1,047 bp of the intron were used for spatiotemporal colonization pattern reconstruction and phylogenetic analyses. In addition, SNPs were used for population structure inferences and allele frequency-based analyses. Reciprocal monophyly, significant differences in allele frequencies (Fst = 0.32 - 0.78), and evidence of reproductive isolation (no admixture/geneflow), indicate long-term divergence between groups (2-8 MYA), possibly due to geographical barriers. Four Evolutionarily Significant Units (ESUs) were defined within our samples. One ESU was represented by the insular subspecies K. scorpioides albogulare, found on San Andrés island, and three ESUs were defined for the subspecies K. s. scorpioides in continental Colombia: one trans-Andean, found in northwestern Colombia (Caribbean region) and two cis-Andean, found in eastern and southeastern Colombia in the Orinoco and Amazon regions, respectively. Colonization of this species occurred from an ancestral area on South of Central America region (~ 8.43 MYA), followed by an establishing of current populations on San Andrés Island and then, in the continent. First, in the Colombian Caribbean, next, in the Orinoco, and more recently, in the Amazon. We hypothesize that the emergence of the Panamá Isthmus, as well as the final uplift of the North Eastern Andes and Vaupes Arch, were key event leading to the differentiation of these ESUs. For management and conservation purposes, each of these ESUs should be considered as a separate management unit. A full revision of the taxonomy of the genus Kinosternon is warranted.
Population pharmacokinetics of mycophenolate mofetil in pediatric patients early after liver transplantation

Objective: To investigate the factors influencing the pharmacokinetics of mycophenolate mofetil (MMF) in pediatric patients after liver transplantation, and to establish a population pharmacokinetics model, which can provide a reference for clinical dosage adjustment. Methods: A prospective study in a single center was performed on pediatric patients who were administrated with mycophenolate mofetil dispersible tablets (MMFdt) for at least 4 days after liver transplantation continuously. Blood samples were collected in ethylene diamine tetraacetic acid anticoagulant tubes before dosing and 0.5, 1, 2, 4, 8, and 12 h after the morning intake of MMFdt. The concentrations of mycophenolic acid (MPA) in plasma were assayed with a validated reverse-phase high-performance liquid chromatography method. UGT1A8 518C > G, UGT1A9 -275T > A, UGT1A9 -2152C > T, UGT2B7 211G > T, SLC O 1B1 521T > C polymorphism were determined by Sanger sequencing. Nonlinear mixed effects modeling was used to establish the population pharmacokinetics (PPK) model. The predictability and stability of the model were internally evaluated by the goodness of fit plots, visual prediction check, normalized prediction errors, and bootstraps. Results: A two-compartment model with first-order absorption and first-order elimination was established with 115 MPA concentrations from 20 pediatric patients. The final model were: CL/F (L/h) = 14.8×(WT/7.5)0.75×(DOSE/11.16)0.452×е0. 06, Ka (h−1) = 2.02×(WT/7.5)−0.25, Vc/F (L) = 6.01×(WT/7.5), Vp/F (L) = 269 (fixed), Q/F (L/h) = 15.4×(WT/7.5)0.75×е1. 39. Where CL/F was the apparent clearance rate, Ka was the absorption rate constant, Vc/F was the apparent distribution volume of the central compartment, Vp/F was the apparent distribution volume of the peripheral compartment, Q/F was the atrioventricular clearance rate, WT was the body weight of the subject, and DOSE was the MMFdt administered dose. The model indicated there was large inter-individual variability in CL/F and Q/F after multiple dosing of MMFdt. Internal evaluation results showed that the final model had good stability and prediction performance. Conclusion: A stable and predictive population pharmacokinetic model of MMFdt in pediatric patients after the early stage of liver transplantation was established. The pediatric patient’s weight and the dose of MMFdt can be a reference to adjust the MMFdt dose.
Nramp: Deprive and conquer?

Solute carriers 11 (Slc11) evolved from bacterial permease (MntH) to eukaryotic antibacterial defense (Nramp) while continuously mediating proton (H+)-dependent manganese (Mn2+) import. Also, Nramp horizontal gene transfer (HGT) toward bacteria led to mntH polyphyly. Prior demonstration that evolutionary rate-shifts distinguishing Slc11 from outgroup carriers dictate catalytic specificity suggested that resolving Slc11 family tree may provide a function-aware phylogenetic framework. Hence, MntH C (MC) subgroups resulted from HGTs of prototype Nramp (pNs) parologs while archetype Nramp (aNs) correlated with phagocytosis. PHI-Blast based taxonomic profiling confirmed MntH B phylogroup is confined to anaerobic bacteria vs. MntH A (MA)’s broad distribution; suggested niche-related spread of MC subgroups; established that MA-variant MH, which carries ‘eukaryotic signature’ marks, predominates in archaea. Slc11 phylogeny shows MH is sister to Nramp. Site-specific analysis of Slc11 charge network known to interact with the protonmotive force demonstrates sequential rate-shifts that recapitulate Slc11 evolution. 3D mapping of similarly coevolved sites across Slc11 hydrophobic core revealed successive targeting of discrete areas. The data imply that pN HGT could advantage recipient bacteria for H+-dependent Mn2+ acquisition and Alphafold 3D models suggest conformational divergence among MC subgroups. It is proposed that Slc11 originated as a bacterial stress resistance function allowing Mn2+-dependent persistence in conditions adverse for growth, and that archaeal MH could contribute to eukaryogenesis as a Mn2+ sequestering defense perhaps favoring intracellular growth-competent bacteria.
Anti-SRP immune-mediated necrotizing myopathy: A critical review of current concepts

Purpose of review This review aims to describe clinical and histological features, treatment, and prognosis in patients with anti-signal recognition particle (SRP) autoantibodies positive immune-mediated necrotizing myopathy (SRP-IMNM) based on previous findings. Previous findings Anti-SRP autoantibodies are specific in IMNM. Humoral autoimmune and inflammatory responses are the main autoimmune characteristics of SRP-IMNM. SRP-IMNM is clinically characterized by acute or subacute, moderately severe, symmetrical proximal weakness. Younger patients with SRP-IMNM tend to have more severe clinical symptoms. Patients with SRP-IMNM may be vulnerable to cardiac involvement, which ought to be regularly monitored and cardiac magnetic resonance imaging is the recommended detection method. The pathological features of SRP-IMNM are patchy or diffuse myonecrosis and myoregeneration accompanied by a paucity of inflammatory infiltrates. Endoplasmic reticulum stress-induced autophagy pathway and necroptosis are activated in skeletal muscle of SRP-IMNM. Treatment of refractory SRP-IMNM encounters resistance and warrants further investigation. Summary Anti-SRP autoantibodies define a unique population of IMNM patients. The immune and non-immune pathophysiological mechanisms are involved in SRP-IMNM.
Dual inhibition of BET and HAT/p300 suppresses colorectal cancer via DR5- and p53/PUMA-mediated cell death

Background Colorectal cancer (CRC) frequently has a dysregulated epigenome causing aberrant up-regulation of oncogenes such as c-MYC. Bromodomain and extra-terminal domain (BET) proteins and histone acetyltransferases (HAT) are epigenetic regulatory proteins that create and maintain epigenetic states supporting oncogenesis. BET inhibitors and HAT inhibitors are currently being investigated as cancer therapeutics due to their ability to suppress cancer-promoting epigenetic modifiers. Due to the extensive molecular crosstalk between BET proteins and HAT proteins, we hypothesized that dual inhibition of BET and HAT could more potently inhibit CRC cells than inhibition of each individual protein. Methods We investigated the activity and mechanisms of a dual BET and HAT inhibitor, NEO2734, in CRC cell lines and mouse xenografts. MTS, flow cytometry, and microscopy were used to assess cell viability. qPCR, Western blotting, and immunofluorescent staining were used to assess mechanisms of action. Results We found that NEO2734 more potently suppresses CRC cell growth than first generation BET inhibitors, regardless of the status of common CRC driver mutations. We previously showed that BET inhibitors upregulate DR5 to induce extrinsic apoptosis. In the current study, we show that NEO2734 treatment induces CRC cell apoptosis via both the intrinsic and extrinsic apoptosis pathways. NEO2734 increases p53 expression and subsequently increased expression of the p53-upregulated mediator of apoptosis (PUMA), which is a critical mechanism for activating intrinsic apoptosis. We demonstrate that inhibition of either the intrinsic or extrinsic branches of apoptosis partially rescues CRC cells from NEO2734 treatment, while the dual inhibition of both branches of apoptosis more strongly rescues CRC cells from NEO2734 treatment. Finally, we show that NEO2734 monotherapy is able to suppress tumor growth in CRC xenografts by inducing apoptosis. Conclusions Our study demonstrates NEO2734 potently suppresses CRC cells in vitro and in vivo by simultaneously upregulating PUMA and DR5 to induce cell death. Further studies of NEO2734 for treating CRC are warranted.