Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet).
Physical fitness and somatic structure in adolescent taekwondo athletes and untrained peers

Abstract Study aim: The purpose of the study was to assess the level of physical fitness (PF) and somatic structure in children training a Korean martial art (ITF taekwondo) and untrained peers and to determine the associations of children’s BMI with that of their parents. Material and methods: The research material consisted of data from 135 individuals, representing 45 child-mother-father triplets, including 22 triplets with children practicing taekwondo and 23 triplets with untrained children. The children had an average chronological age of 10.08 ± 1.35 years, whereas the age of mothers and fathers was 38.09 ± 4.56 years and 40.57 ± 4.70 years, respectively. Traits analyzed included those evaluated by selected physical fitness tests from the Eurofit Physical Fitness Test battery, body mass index (BMI), and waist-to-height ratio (WHtR) in children, and BMI in parents. Statistical analyses included the chi-square test, Mann-Whitney U test, and Spearman’s correlations, with a significance level set at α = 0.05. Results: The results showed no significant differences in the somatic structure, physical fitness, BMI, and WHtR in the children studied. However, a tendency was observed for children attending ITF taekwondo classes to be characterized by higher levels of physical fitness. Higher BMI was found in the parents of the trained children and positive correlations were found between the BMI of the trained children and their parents. Conclusions: Identifying and studying the effect size of PA determinants in adolescents, with a particular focus on the influence of parents, may be the key to improving the health of future generations.
Effects of acute taurine consumption on single bout of muscular endurance resistance exercise performance and recovery in resistance trained young male adults

Abstract Study aim: This study investigated the effect of taurine supplementation on exercise performance and recovery from resistance exercise. The study was conducted with a cross-over design in a double-blind manner. Material and methods: Ten resistance trained males (age 21.4 ± 2.01 years; BMI: 23.6 ± 2.5 kg/m²) ingested either a taurine (0.1g/kg) supplement or placebo (18 mg aspartame) prior to resistance exercise. Vertical jump, flexibility, balance, systolic blood pressure, diastolic blood pressure, heart rate (HR), maximal voluntary muscle contraction, speed, lactate, glucose and perceived soreness and strain were assessed. The subjects performed two exercise trials with 1 week wash out interval. Blood samples were collected at baseline and before each exercise (chest press, abdominal crunch and leg extension) to analyse plasma levels of lactate and glucose. Results: Paired-T test results showed statistically significant increment (p < 0.05) in total volume (kg × #repetitions), chest press volume and leg extension volume. Repeated measure ANOVA results demonstrated statistically significant differences (p < 0.05) in lactate and flexibility in trial and time, and in maximal voluntary isometric muscle contraction (MVIC) test in time, trial and trial × time in favour taurine group. No statistically significant differences were found in cardiovascular parameters, glucose, and balance parameters (p > 0.05). Conclusion: In conclusion, 0.1 g/kg of taurine consumption before resistance exercise could positively affect exercise performance by increasing exercise volume and reducing lactate levels.
Prevalence and Predictors of Palliative Care Utilization among Hospitalized Patients with Diffuse Large B-Cell Lymphoma

Objective: Research has shown that palliative care improves the quality of life of cancer patients; however, there is no literature on specific factors that predict its use in diffuse large b-cell lymphoma (DLBCL) patients. Therefore, the prevalence of palliative care utilization and predictors of palliative care utilization among patients with DLBCL were examined. Methods: Data from the National Inpatient Sample (NIS) collected between 2016 to 2018 were used for all analyses. Multivariable logistic regression models were used to examine the predictors of palliative care utilization among hospitalized patients with DLBCL. Descriptive analyses were used to explore the overall prevalence of palliative care receipt in this population. Results: Of the 41,789 hospitalizations, 7.1% of patients used palliative care during hospitalization, while 4.8% utilized palliative care and were discharged alive. DLBCL patients aged 70 and older had 1.3 times (95% CI: 1.14-1.41) higher odds of utilizing palliative care compared to those less than 70 years. Relative to Medicare/Medicaid patients, those with other types of insurance were 1.7 times (95% CI: 1.34-2.05) more likely to receive palliative care. Those who were either transferred to a facility/discharged with home health (AOR: 6.23; 95% CI: 5.21-7.44) or died during hospitalization (AOR: 45.17; 95% CI: 36.98-55.17) had higher odds of receiving palliative care when relative to those with a routine hospital discharge. Other associated factors were type of admission, length of stay, chemotherapy receipt, and number of comorbidities. Conclusions: The prevalence of palliative care utilization was low and factors predicting utilization in our population were identified. Our findings highlight the need to increase awareness among medical oncologists on the need to involve the palliative care team early in the management of hospitalized patients with DLBCL.
Annual Variation and Global Structures of The DE3 Tide

The SABER/TIMED temperatures taken in 2002–2006 are used to delineate the tidal signals in the middle and upper atmosphere. Then the Hough mode decomposition is applied with the DE3 tide, and the overall features of the seasonal variations and the complete global structures of the tide are observed. Investigation results show that the tide is most prominent at 110 km with the maximal amplitude of > 9K, and exhibits significant seasonal variation with its maximum amplitude always occurring in July every year. Results from the Hough mode decomposition reveal that the tide is composed primarily of two leading propagating Hough modes, i.e., the (−3,3) and the (−3,4) modes, thus is equatorially trapped. Estimation of the mean amplitude of the Hough modes show that the (−3,3) mode and (−3,4) mode exhibit maxima at 110km and 90 km, respectively. The (−3,3) mode plays a predominant role in shaping the global latitude-height structure of the tide, e.g., the vertical scale of > 50km at the equator, and the annual course. Significant influence of the (−3,4) mode is found below 90km, where the tide exhibits anti-symmetric structure about the equator; meanwhile the tide at northern tropical latitudes exhibits smaller vertical wavelength of about 30 km.
Anisotropic Turbulence of Shear-Alfvén Waves

Weak turbulence of shear-Alfvén waves is considered in the limit of strongly anisotropic pulsations that are elongated along the external magnetic field. The kinetic equation thus derived agrees with the Galtier et al. formulation of the full three-dimensional helical case when taking the proper limit. This new approach allows for significant simplification, and, as a result, the applicability conditions for the weak turbulence theory are now more transparent. It thus provides an attractive theoretical framework for describing anisotropic MHD turbulence in astrophysical contexts where a strong magnetic field is present and for which shear-Alfvén waves are important.
Dynamic response of an elastic and viscoelastic full-space to a spherical source

The dynamic response due to a spherical source of radius a embedded in an elastic and viscoelastic full-space is investigated at a distance R from the source. Previous solutions to the elastic case are extended to incorporate realistic source pressure functions. The elastic solution is then cast in a scale independent form in order to generalize the application. The results show that the near-field of the spherical source may be defined by R/a 5) the particle velocity and displacement decrease as R −1 , and the risetime is independent of R. A non-constant Q model is developed to model viscoelastic attenuation and a complete analytical solution for wave propagation is obtained by cascading the separate mechanisms of geometric attenuation and viscoelastic attenuation. A comparison of our analytical model with the results of dynamic finite element modelling shows excellent agreement. This suggests that the method of cascading the separate transfer functions is a valid approach for wave propagation in viscoelastic media
Structures of trehalose-6-phosphate synthase, Tps1, from the fungal pathogen Cryptococcus neoformans: a target for novel antifungals

Invasive fungal diseases are a major threat to human health, resulting in more than 1.5 million deaths worldwide each year. Yet the arsenal of antifungal therapeutics remains limited and is in dire need of novel drugs that target additional fungal-specific biosynthetic pathways. One such pathway involves the biosynthesis of trehalose. Trehalose is a non-reducing disaccharide composed of two molecules of glucose that is required for pathogenic fungi, including Candida albicans and Cryptococcus neoformans, to survive in their human hosts. Trehalose biosynthesis is a two-step process in fungal pathogens. Trehalose-6-phosphate synthase (Tps1) converts UDP-glucose and glucose-6-phosphate to trehalose-6-phosphate (T6P). Subsequently, trehalose-6-phosphate phosphatase (Tps2) converts T6P to trehalose. The trehalose biosynthesis pathway has been identified as a top candidate for novel antifungal development based on quality, occurrence, specificity, and assay development. However, there are currently no known antifungal agents that target this pathway. As initial steps to develop Tps1 from Cryptococcus neoformans (CnTps1) as a drug target, we report the structures of full-length apo CnTps1 and CnTps1 in complex with uridine diphosphate (UDP) and glucose-6-phosphate (G6P). Both CnTps1 structures are tetramers and display D2 (222) molecular symmetry. Comparison of these two structures reveals significant movement towards the catalytic pocket by the N-terminus upon ligand binding and identifies key residues required for substrate-binding, which are conserved amongst other Tps1 enzymes, as well as residues that stabilize the tetramer. Intriguingly, an intrinsically disordered domain (IDD), encompassing residues M209 to I300, which is conserved amongst Cryptococcal species and closely related Basidiomycetes, extends from each subunit of the tetramer into the “solvent”but is not visible in the density maps. Although, activity assays revealed that the highly conserved IDD is not required for catalysis in vitro, we hypothesize that the IDD is required for C. neoformans Tps1-dependent thermotolerance and osmotic stress survival. Characterization of the substrate specificity of CnTps1 revealed that UDP-galactose, an epimer of UDP-glucose, is a very poor substrate and inhibitor of the enzyme and highlights the exquisite substrate specificity of Tps1. In toto, these studies expand our knowledge of trehalose biosynthesis in Cryptococcus and highlight the potential of developing antifungal therapeutics that disrupt the synthesis of this disaccharide or the formation of a functional tetramer and the use of cryo-EM in the structural characterization of CnTps1-ligand/drug complexes.
Damage-induced basal epithelial cell migration modulates the spatial organization of redox signaling and sensory neuron regeneration

Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue-scale ROS production and sustained sensory axon damage. Osmotic regulation induced by isotonic treatment was sufficient to limit keratinocyte movement, spatially-restrict ROS production and rescue sensory function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair.
Constitutively synergistic multiagent drug formulations targeting MERTK, FLT3, and BCL-2 for treatment of AML

Although high-dose, multi-agent chemotherapy has improved leukemia survival rates in recent years, treatment outcomes remain poor in high-risk subsets, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in infants. Development of new, more effective therapies for these patients is therefore an urgent, unmet clinical need. To address this challenge, we developed a nanoscale combination drug formulation that exploits ectopic expression of MERTK tyrosine kinase and dependency on BCL-2 family proteins for leukemia cell survival in pediatric AML and MLL-rearranged precursor B-cell ALL (infant ALL). In a novel, high-throughput combination drug screen, the MERTK/FLT3 inhibitor MRX-2843 synergized with venetoclax and other BCL-2 family protein inhibitors to reduce AML cell density in vitro. Neural network models based on drug exposure and target gene expression were used to identify a classifier predictive of drug synergy in AML. To maximize the therapeutic potential of these findings, we developed a combination monovalent liposomal drug formulation that maintains ratiometric drug synergy in cell-free assays and following intracellular delivery. The translational potential of these nanoscale drug formulations was confirmed in a genotypically diverse set of primary AML patient samples and both the magnitude and frequency of synergistic responses were not only maintained but were improved following drug formulation. Together, these findings demonstrate a systematic, generalizable approach to combination drug screening, formulation, and development that maximizes therapeutic potential, was effectively applied to develop a novel nanoscale combination therapy for treatment of AML, and could be extended to other drug combinations or diseases in the future.
BrainSuite BIDS App: Containerized Workflows for MRI Analysis

There has been a concerted effort by the neuroimaging community to establish standards for computational methods for data analysis that promote reproducibility and portability. In particular, the Brain Imaging Data Structure (BIDS) specifies a standard for storing imaging data, and the related BIDS App methodology provides a standard for implementing containerized processing environments that include all necessary dependencies to process BIDS datasets using image processing workflows. We present the BrainSuite BIDS App, which encapsulates the core MRI processing functionality of BrainSuite within the BIDS App framework. Specifically, the BrainSuite BIDS App implements a participant-level workflow comprising three pipelines and a corresponding set of group-level analysis workflows for processing the participant-level outputs. The BrainSuite Anatomical Pipeline (BAP) extracts cortical surface models from a T1-weighted (T1w) MRI. It then performs surface-constrained volumetric registration to align the T1w MRI to a labeled anatomical atlas, which is used to delineate anatomical regions of interest in the MRI brain volume and on the cortical surface models. The BrainSuite Diffusion Pipeline (BDP) processes diffusion-weighted imaging (DWI) data, with steps that include coregistering the DWI data to the T1w scan, correcting for geometric image distortion, and fitting diffusion models to the DWI data. The BrainSuite Functional Pipeline (BFP) performs fMRI processing using a combination of FSL, AFNI, and BrainSuite tools. BFP coregisters the fMRI data to the T1w image, then transforms the data to the anatomical atlas space and to the Human Connectome Project’s grayordinate space. Each of these outputs can then be processed during group-level analysis. The outputs of BAP and BDP are analyzed using the BrainSuite Statistics in R (bssr) toolbox, which provides functionality for hypothesis testing and statistical modeling. The outputs of BFP can be analyzed using atlas-based or atlas-free statistical methods during group-level processing. These analyses include the application of BrainSync, which synchronizes the time-series data temporally and enables comparison of resting-state or task-based fMRI data across scans. We also present the BrainSuite Dashboard quality control system, which provides a browser-based interface for reviewing the outputs of individual modules of the participant-level pipelines across a study in real-time as they are generated. BrainSuite Dashboard facilitates rapid review of intermediate results, enabling users to identify processing errors and make adjustments to processing parameters if necessary. The comprehensive functionality included in the BrainSuite BIDS App provides a mechanism for rapidly deploying the BrainSuite workflows into new environments to perform large-scale studies. We demonstrate the capabilities of the BrainSuite BIDS App using structural, diffusion, and functional MRI data from the Amsterdam Open MRI Collection’s Population Imaging of Psychology dataset.
A data-driven Boolean model explains memory subsets and evolution in CD8+ T cell exhaustion

T cells play a key role in a variety of immune responses, including infection and cancer. Upon stimulation, naïve CD8+ T cells proliferate and differentiate into a variety of memory and effector cell types; however, failure to clear antigens causes prolonged stimulation of CD8+ T cells, ultimately leading to T cell exhaustion (TCE). The functional and phenotypic changes that occur during CD8+ T cell differentiation are well characterized, but the underlying gene expression state changes are not completely understood. Here, we utilize a previously published data-driven Boolean model of gene regulatory interactions shown to mediate TCE. Our network analysis and modeling reveal the final gene expression states that correspond to TCE, along with the sequence of gene expression patterns that give rise to those final states. With a model that predicts the changes in gene expression that lead to TCE, we could evaluate strategies to inhibit the exhausted state. Overall, we demonstrate that a common pathway model of CD8+ T cell gene regulatory interactions can provide insights into the transcriptional changes underlying the evolution of cell states in TCE.
A rapid genome-wide analysis of isolated giant viruses only using MinION sequencing

Following the discovery of Acanthamoeba polyphaga mimivirus, diverse giant viruses have been isolated. However, only a small fraction of these isolates has been completely sequenced, limiting our understanding of the genomic diversity of giant viruses. MinION is a portable and low-cost long-read sequencer that can be readily used in a laboratory. Although MinION provides highly error-prone reads that require correction through additional short-read sequencing, recent studies assembled high-quality microbial genomes only using MinION sequencing. Here, we evaluated the accuracy of MinION-only genome assemblies for giant viruses by re-sequencing a prototype marseillevirus. Assembled genomes presented over 99.98% identity to the reference genome with a few gaps, demonstrating a high accuracy of the MinION-only assembly. As a proof of concept, we de novo assembled five newly isolated viruses. Average nucleotide identities to their closest known relatives suggest that the isolates represent new species of marseillevirus, pithovirus, and mimivirus. Assembly of subsampled reads demonstrated that their taxonomy and genomic composition could be analyzed at the 50× sequencing coverage. We also identified a pithovirus gene whose homologues were detected only in metagenome-derived relatives. Collectively, we propose that MinION-only assembly is an effective approach to rapidly perform a genome-wide analysis of isolated giant viruses.
The origin and structural evolution of de novo genes in Drosophila

Although previously thought to be unlikely, recent studies have shown that de novo gene origination from previously non-genic sequences is a relatively common mechanism for gene innovation in many species and taxa. These young genes provide a unique set of candidates to study the structural and functional origination of proteins. However, our understanding of their protein structures and how these structures originate and evolve are still limited, due to a lack of systematic studies. Here, we combined high-quality base-level whole genome alignments, bioinformatic analysis, and computational structure modeling to study the origination, evolution, and protein structure of lineage-specific de novo genes. We identified 555 de novo gene candidates in D. melanogaster that originated within the Drosophilinae lineage. We found a gradual shift in sequence composition, evolutionary rates, and expression patterns with their gene ages, which indicates possible gradual shifts or adaptations of their functions. Surprisingly, we found little overall protein structural changes for de novo genes in the Drosophilinae lineage. Using Alphafold2, ESMFold, and molecular dynamics, we identified a number of de novo gene candidates with protein products that are potentially well-folded, many of which are more likely to contain transmembrane and signal proteins compared to other annotated protein-coding genes. Using ancestral sequence reconstruction, we found that most potentially well-folded proteins are often born folded. Interestingly, we observed one case where disordered ancestral proteins become ordered within a relatively short evolutionary time. Single-cell RNA-seq analysis in testis showed that although most de novo genes are enriched in spermatocytes, several young de novo genes are biased in the early spermatogenesis stage, indicating potentially important but less emphasized roles of early germline cells in the de novo gene origination in testis. This study provides a systematic overview of the origin, evolution, and structural changes of Drosophilinae-specific de novo genes.