Miracle-dz/UniFAR-FTUs huggingface dataset:
EpCAM aptamer activated 5-FU-loaded PLGA nanoparticles in CRC treatment; in vitro and in vivo study

Abstract In this study, epithelial cell adhesion molecule (EpCAM) aptamer-activated nanoparticles (Ap-NPs) were synthesised to enhance treatment efficiency in colorectal cancer (CRC). PLGA [poly(d, l-lactide-co-glycolide)] copolymer was fabricated by conjugation of COOH-PEG-NH2 to PLGA-COOH through an EDC/NHS-mediated chemistry. Afterwards, 5-fluorouracil-loaded (FU) nanoparticles were prepared using the water/oil/water double emulsion solvent evaporation method. The in vitro cytotoxicity of formulations was evaluated using the MTT assay in HCT-116, CT-26 and HEK-293 cell lines. For in vivo study, tumour-bearing BALB/c mice were established by subcutaneous injection of CT-26 cell line. The results indicated that fabricated AP-FU-NPs had 101 nm size with a spherical surface, relatively homogeneously and, satisfactory encapsulation efficiency (83.93%). In vitro experiments revealed that Ap-FU-NPs had a superior in vitro cytotoxicity than both FU-NPs and free 5-FU in CT-26 and HCT-116 cells but, were significantly low toxic against HEK-293 cells relative to free 5-FU. Furthermore, in vivo results showed no significant haemolytic effect, hepatic and renal injury, or weight loss. After treatment of various animal groups with formulations, notable tumour growth delay was observed following the order: Ap-FU-NPs < FU-NPs < 5-FU < PBS. The results suggest that AP-FU-NPs could be an effective and promising carrier for 5-FU delivery to the EpCAM overexpressing CRC cells. GRAPHICAL ABSTRACT The present study was carried out in the three steps summarised: (1) synthesis and characterisation. At first, PEG was conjugated to PLGA polymers by EDC/NHS chemistry method, then the resulting polymers were used to prepare PLGA-PEG NPs via the W/O/W technique. Finally, EpCAM Aptamers were attached to fabricated NPs. (2) In the second step cytotoxicity of formulated NPs was evaluated in vitro experiments in HEK-293, CT-26 and HCT-116 cell lines. (3) In the third step in vitro results further was investigated in CT-26 tumour-bearing BALB/c mice. ‘Created with BioRender.com’.
Efficacy of Dry Needling for Chronic Low Back Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Objective To evaluate the current evidence of the effectiveness of dry needling in patients with chronic low back pain (LBP). Methods PubMed, Medline, ScienceDirect, Web of Science, CINAHL and PEDro databases were searched until 2020. Study selection Randomised controlled trials (RCTs) that used dry needling as the main treatment and which included participants diagnosed with chronic LBP. Data extraction Two reviewers independently screened articles, scored methodologic quality, and extracted data. The primary outcomes were pain intensity and functional disability at post-intervention and follow-up. Results A total of 8 RCTs involving 414 patients were included in the meta-analysis. All trials examined the efficacy of DN in patients with chronic LBP. Results suggested that compared with other treatments, dry needling combined was more effective in alleviating the pain intensity of LBP post-intervention (standardised mean difference [SMD], -0.42; 95% confidence interval [CI], -0.79 to -0.05; P = .03) and at short- term (SMD -0.99, 95% CI -1.61 to -0.37, P = .002). Conclusion Current evidence showed that dry needling, especially if associated with other therapies, could be recommended to relieve the pain intensity of LBP at post-intervention and at short-term follow up. There is no evidence that dry needling alone or in combination improves disability at post-immediate or at short-term follow up. Registration This review was registered on PROSPERO (PROSPERO CRD42020215781) and was aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting systematic reviews that evaluate healthcare interventions.
Improved microbial genomes and gene catalog of the chicken gut from metagenomic sequencing of high-fidelity long reads

Abstract Background Due to the importance of chicken production and the remarkable influence of the gut microbiota on host health and growth, tens of thousands of metagenome-assembled genomes (MAGs) have been constructed for the chicken gut microbiome. However, due to the limitations of short-read sequencing and assembly technologies, most of these MAGs are far from complete, are of lower quality, and include contaminant reads. Results We generated 332 Gb of high-fidelity (HiFi) long reads from the 5 chicken intestinal compartments and assembled 461 and 337 microbial genomes, of which 53% and 55% are circular, at the species and strain levels, respectively. For the assembled microbial genomes, approximately 95% were regarded as complete according to the “RNA complete” criteria, which requires at least 1 full-length ribosomal RNA (rRNA) operon encoding all 3 types of rRNA (16S, 23S, and 5S) and at least 18 copies of full-length transfer RNA genes. In comparison with the short-read-derived chicken MAGs, 384 (83% of 461) and 89 (26% of 337) strain-level and species-level genomes in this study are novel, with no matches to previously reported sequences. At the gene level, one-third of the 2.5 million genes in the HiFi-derived gene catalog are novel and cannot be matched to the short-read-derived gene catalog. Moreover, the HiFi-derived genomes have much higher continuity and completeness, as well as lower contamination; the HiFi-derived gene catalog has a much higher ratio of complete gene structures. The dominant phylum in our HiFi-assembled genomes was Firmicutes (82.5%), and the foregut was highly enriched in 5 genera: Ligilactobacillus, Limosilactobacillus, Lactobacillus, Weissella, and Enterococcus, all of which belong to the order Lactobacillales. Using GTDB-Tk, all 337 species-level genomes were successfully classified at the order level; however, 2, 35, and 189 genomes could not be classified into any known family, genus, and species, respectively. Among these incompletely classified genomes, 9 and 49 may belong to novel genera and species, respectively, because their 16S rRNA genes have identities lower than 95% and 97% to any known 16S rRNA genes. Conclusions HiFi sequencing not only produced metagenome assemblies and gene structures with markedly improved quality but also recovered a substantial portion of novel genomes and genes that were missed in previous short-read-based metagenome studies. The novel genomes and species obtained in this study will facilitate gut microbiome and host–microbiota interaction studies, thereby contributing to the sustainable development of poultry resources.
Wilson loops in N=4 super Yang-Mills theory: Rotation in S 5

We study Wilson loops in $\mathcal{N}=4$ super Yang-Mills (SYM) theory which are nonconstant in the scalar $({\mathrm{S}}^{5})$ directions and open string solutions associated with them in the context of AdS conformal field theory correspondence. An interplay between Minkowskian and Euclidean pictures turns out to be nontrivial for time-dependent Wilson loops. We find that in the ${\mathrm{S}}^{5}$-rotating case there appears to be no direct open-string duals for the Minkowskian Wilson loops, and their expectation values should be obtained by analytic continuation from the Euclidean-space results. In the Euclidean case, we determine the dependence of the ``quark-antiquark'' potential on the rotation parameter $\ensuremath{\nu},$ both at weak coupling (i.e., in the 1-loop perturbative SYM theory) and at strong coupling (i.e., in the classical string theory in ${\mathrm{AdS}}_{5}\ifmmode\times\else\texttimes\fi{}{\mathrm{S}}^{5}). $
METTL3-mediated m6A modification stabilizes TERRA and maintains telomere stability

Abstract Telomeric repeat-containing RNA (TERRA) is a type of long non-coding RNA transcribed from telomeres, and it forms R-loops by invasion into telomeric DNA. Since either an excessive or inadequate number of R-loops leads to telomere instability, the TERRA levels need to be delicately modulated. In this study, we found that m6A modification presents on the subtelomeric regions of TERRA and stabilizes it, and the loss of METTL3 impacts telomere stability. Mechanically, the m6A modification on TERRA is catalyzed by METTL3, recognized and stabilized by the m6A reader YTHDC1. Knockdown of either METTL3 or YTHDC1 enhances TERRA degradation. The m6A-modified TERRA forms R-loops and promotes homologous recombination which is essential for the alternative lengthening of telomeres (ALT) pathway in cancer cells. METTL3 depletion leads to R-loop reduction, telomere shortening and instability. Altogether, these findings reveal that METTL3 protects telomeres by catalyzing m6A modification on TERRA, indicating that inhibition or deletion of METTL3 is potentially a new avenue for ALT cancer therapy.
Dynamics of Circumstellar Disks. II. Heating and Cooling

We present a series of two-dimensional (r,ϕ) hydrodynamic simulations of marginally self-gravitating disks (MD/M* = 0.2, with M* = 0.5 M☉ and with disk radius RD = 50 and 100 AU) around protostars using a Smoothed Particle Hydrodynamic (SPH) code. We implement simple and approximate prescriptions for heating via dynamical processes in the disk. Cooling is implemented with a simple radiative cooling prescription, which does not assume that local heat dissipation exactly balances local heat generation. Instead, we compute the local vertical (z) temperature and density structure of the disk and obtain a "photosphere temperature," which is then used to cool that location as a blackbody. We synthesize spectral energy distributions (SEDs) for our simulations and compare them to fiducial SEDs derived from observed systems, in order to understand the contribution of dynamical evolution to the observable character of a system. We find that these simulations produce less distinct spiral structure than isothermally evolved systems, especially in approximately the inner radial third of the disk. Pattern amplitudes are similar to isothermally evolved systems farther from the star, but patterns do not collapse into condensed objects. We attribute the differences in morphology to increased efficiency for converting kinetic energy into thermal energy in our current simulations. Our simulations produce temperatures in the outer part of the disk that are very low (~10 K). The radial temperature distribution of the disk photosphere is well fitted to a power law with index q ~ 1.1. Far from the star, corresponding to colder parts of the disk and long-wavelength radiation, known internal heating processes (P dV work and shocks) are not responsible for generating a large fraction of the thermal energy contained in the disk matter. Therefore gravitational torques responsible for such shocks cannot transport mass and angular momentum efficiently in the outer disk. Within ~5-10 AU of the star, rapid breakup and reformation of spiral structure causes shocks, which provide sufficient dissipation to power a larger fraction of the near-infrared radiated energy output. In this region, the spatial and size distributions of grains can have marked consequences on the observed near-infrared SED of a given disk and can lead to increased emission and variability on ≲10 yr timescales. The inner disk heats to the destruction temperature of dust grains. Further temperature increases are prevented by efficient cooling when the hot disk midplane is exposed. When grains are vaporized in the midplane of a hot region of the disk, we show that they do not reform into a size distribution similar to that on which most opacity calculations are based. With rapid grain reformation into the original size distribution, the disk does not emit near-infrared photons. With a plausible modification of the opacity, it contributes much more.
How should clinicians assess acute dental pain?: A review

Pain is the most common complaint in the dental field and may have a significant impact on the patients’ quality of life. However, objective pain assessment is sometimes difficult, and medical and dental clinicians may encounter cases of pain in the head and neck region, making it difficult to establish differential diagnoses. This study aimed to review acute pain in clinical dentistry at each phase of dental procedures and discuss the current status and issues in the development of acute dental pain assessment methods in the future. Acute pain in clinical dentistry may differ in nature and modifying conditions of pain at each stage: before dental procedures, while visiting dentists, and during and after dental procedures. They are related to actual or potential tissue damage, and may be modified and aided by personal experiences, including psychological and social factors. With respect to the aging and multinational population and pandemic of infectious diseases, significant breakthroughs in the development of new pain scales without verbal descriptions are desirable. Furthermore, it is expected that a new pain scale that can be applied to acute pain in the head and neck regions, including the oral cavity, will be developed.
Characterization of a novel marine microbial uricase from Priestia flexa and evaluation of the effects of CMCS conjugation on its enzymatic properties

Abstract A novel uricase producing marine bacterium Priestia flexa alkaAU was isolated and identified. The 16S rDNA and the uricase coding gene were sequenced, analyzed and submitted to GenBank. The uricase from Priestia flexa alkaAU (PFU) was purified, determined to be 58.87 kDa, and conjugated with carboxymethyl chitosan (CMCS) by ionic gelation. CMCS conjugation had no effect on the optimum pH of PFU but decreased the optimum temperature by 10 °C. CMCS conjugation increased the specific activity of PFU by 53% at the human body temperature (37 °C) and small intestine’s pH (pH 6.8). Uricase thermostabilizing ability of CMCS was significant in the range of 37–80 °C but not at lower temperatures. For improvement of the pH stability of PFU, CMCS was more effective at pHs 3–5 than pHs 6–11. CMCS increased the half-life of PFU against artificial intestinal fluid by 1.5 folds, which demonstrated the potential capability of CMCS–PFU for oral administration.
Stochastic Method for Airfoil Self-Noise Computation in Frequency Domain

A stochastic Fourier method for the computation of synthetic solenoidal velocity uctuations is revised and applied to the problem of noise radiation from the trailing edge of a NACA 0012 airfoil. The method is used to compute the source term of the Howe’s acoustic analogy equation for an isentropic ow that is solved in frequency-domain using a FEM discretization. For each spectral component of the source term, a prescribed number of realizations of the synthetic source eld is generated by seeding the stochastic generator. The corresponding sound elds are then computed and nally averaged to track statistically converged noise spectra. For the present study, two-dimensional CFD/CAA computations are carried out and the linear system is solved using a direct method with multi-right-handside capabilities. Therefore, for each frequency, the computation of the dierent stochastic realizations is managed in a very ecient way. The self-noise spectra computed for an airfoil at dierent values of the free-stream velocity are compared with literature experimental data and semi-analytical predictions performed using the same RANS solutions. It is shown that the the CAA results are in good agreement with the semi-analytical results: both the free-stream velocity noise power law and the spectral content at each velocity compare quite well. Furthermore, a very good agreement between the CAA noise spectra and the measured ones is obtained for higher values of the free-stream velocity. Conversely, for lower velocities, the predicted noise levels, using both CAA and semi-analytical methods, are signicantly underestimated, in particular, in the high frequency regime. The cause of the disagreement can be inferred to the low-Reynolds behaviour of the employed RANS model.
[89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT to Predict Watchful Waiting Duration in Patients with Metastatic Clear-cell Renal Cell Carcinoma

Abstract Purpose: Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with <2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites [referred to as watch and wait (“W&W”) criteria]. The IMaging PAtients for Cancer drug SelecTion-Renal Cell Carcinoma study objective was to assess the predictive value of [18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT for WW duration in patients with mccRCC. Experimental Design: Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients. Results: The median WW time was 16.1 months [95% confidence interval (CI): 9.0–31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4–14.7; P < 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9–3.3; P = 0.13). Patients with “W&W criteria” had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9–3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the “W&W criteria” improved the prediction of WW duration (P < 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53). Conclusions: In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of the “W&W criteria” for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this.
High Isolation Improvement in a Compact UWB MIMO Antenna

A compact multiple-input-multiple-output (MIMO) antenna with very high isolation is proposed for ultrawide-band (UWB) applications. The antenna with a compact size of 30.1x20. 5 mm^2 (0.31${\lambda}_0$ x0.21${\lambda}_0$ ) consists of two planar-monopole antenna elements. It is found that isolation of more than 25 dB can be achieved between two parallel monopole antenna elements. For the low-frequency isolation, an efficient technique of bending the feed-line and applying a new protruded ground is introduced. To increase isolation, a design based on suppressing surface wave, near-field, and far-field coupling is applied. The simulation and measurement results of the proposed antenna with the good agreement are presented and show a bandwidth with S 11 < -10 dB, S 12 < -25 dB ranged from 3.1 to 10.6 GHz making the proposed antenna a good candidate for UWB MIMO systems.
Registry of Senior Australians (ROSA): integrating cross-sectoral information to evaluate quality and safety of care provided to older people

Purpose The Registry of Senior Australians (ROSA) was established to evaluate aged care experiences in Australia. In this manuscript, we describe the ROSA framework, the two ROSA cohorts, highlights from research findings, and future plans. Participants The South Australian ROSA Prospective Cohort (August 2018–June 2020) enrolled 26 605 participants, of which 59.2% (N=15 745) are women, with a median age of 83 (interquartile range (IQR) 77–88). The National ROSA Historical Cohort (January 2002–June 2020) includes 1 694 206 participants with an aged care eligibility assessment, of which 59.1% (N=1 001 705) are women and the median age is 78 (IQR 72–83). Findings to date Most research using the ROSA has focused on dementia, service accessibility, quality and safety of care, falls and injuries and quality use of medicines. The ROSA has also examined the experience of individuals with highly prevalent and understudied conditions in aged care settings (eg, eye and mental health) and aspects of services (eg, built environment) and innovation (eg, mobile radiological services) that can affect older people’s health. Important learnings from the ROSA’s development include the significant resources and multidisciplinary expertise required for establishing this platform. Between 2018 and 2022, 43 academic publications, eight reports of the Australian Government Royal Commission into Aged Care Quality and Safety, and several reports to state health authorities and professional societies have used the ROSA. Future plans Our plans include to: (1) continue delivering high-quality evidence to support the improvement of ageing and aged care services; (2) influence and improve the quality of research in and for the aged care sector; (3) expand scope to facilitate examining aims in more depth; (4) include future aged care sector data collections within the ROSA; (5) inform best practices and innovate how consumer engagement occurs in research; (6) monitor and evaluate the impact of the 2021 Australian Aged Care Reforms.
Gut microbiota composition as a candidate risk factor for dimethyl fumarate-induced lymphopenia in multiple sclerosis

ABSTRACT Mounting evidence points towards a pivotal role of gut microbiota in multiple sclerosis (MS) pathophysiology. Yet, whether disease-modifying treatments alter microbiota composition and whether microbiota shape treatment response and side-effects remain unclear. In this prospective observational pilot study, we assessed the effect of dimethyl fumarate (DMF) on gut microbiota and on host/microbial metabolomics in a cohort of 20 MS patients. Combining state-of-the-art microbial sequencing, metabolome mass spectrometry, and computational analysis, we identified longitudinal changes in gut microbiota composition under DMF-treatment and an increase in citric acid cycle metabolites. Notably, DMF-induced lymphopenia, a clinically relevant safety concern, was correlated with distinct baseline microbiome signatures in MS patients. We identified gastrointestinal microbiota as a key therapeutic target for metabolic properties of DMF. By characterizing gut microbial composition as a candidate risk factor for DMF-induced lymphopenia, we provide novel insights into the role of microbiota in mediating clinical side-effects.