Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis And Characterization Of 3D-Printed Functionally Graded Synthesis And Characterization Of 3D-Printed Functionally Graded Porous Titanium Alloy Porous Titanium Alloy

This study aims to 3D print titanium alloy constructs incorporating gradient of porosities, from the fully dense core to the porous outer surface. Gradient porous specimens were prepared using selective laser melting (SLM). Fully dense specimens fabricated by SLM were used as the control group. Characterization of samples was done using X-ray tomography, uniaxial compression testing, and optical and scanning electron microscopes. The biocompatibility of fabricated samples was investigated using human periodontal ligament stem cells via assessment of cell attachment, viability, and proliferation by direct and indirect assays. The data were analyzed using ANOVA and Tukey’s post hoc test. Characterization of constructs reveals interconnected gradient porosities and higher contact angle in porous samples. The introduction of porosity leads to a significant decrease in compression strength. However, Young’s modulus of the samples with gradient porosity was more similar to the natural bone modulus. The surface microstructure consists of loosely bonded spherical particles. Biocompatibility of the dense and porous samples is appropriate. Although the porosity size led to a reduced cell proliferation rate in the gradient sample, the extract of the gradient sample results in more cell proliferation than the dense sample’s extract. The study demonstrates that a biocompatible functionally graded porous titanium structure can be well fabricated by SLM, and this structure leads to a good match of Young’s modulus to that of the bone. of cell attachment, viability, and proliferation by direct and indirect assays. The data were analyzed using ANOVA and Tukey's post hoc test. Characterization of constructs reveals interconnected gradient porosities and higher contact angle in porous samples. The introduction of porosity leads to a significant decrease in compression strength. However, Young's modulus of the samples with gradient porosity was more similar to the natural bone modulus. The surface microstructure consists of loosely bonded spherical particles. Biocompatibility of the dense and porous samples is appropriate. Although the porosity size led to a reduced cell proliferation rate in the gradient sample, the extract of the gradient sample results in more cell proliferation than the dense sample's extract. The study demonstrates that a biocompatible functionally graded porous titanium structure can be well fabricated by SLM, and this structure leads to a good match of Young's modulus to that of the bone.
A Combined Human in Silico and CRISPR/Cas9-Mediated in Vivo Zebrafish Based Approach to Provide Phenotypic Data for Supporting Early Target Validation

The clinical heterogeneity of heart failure has challenged our understanding of the underlying genetic mechanisms of this disease. In this respect, large-scale patient DNA sequencing studies have become an invaluable strategy for identifying potential genetic contributing factors. The complex aetiology of heart failure, however, also means that in vivo models are vital to understand the links between genetic perturbations and functional impacts as part of the process for validating potential new drug targets. Traditional approaches (e.g., genetically-modified mice) are optimal for assessing small numbers of genes, but less practical when multiple genes are identified. The zebrafish, in contrast, offers great potential for higher throughput in vivo gene functional assessment to aid target prioritisation, by providing more confidence in target relevance and facilitating gene selection for definitive loss of function studies undertaken in mice. Here we used whole-exome sequencing and bioinformatics on human patient data to identify 3 genes (API5, HSPB7, and LMO2) suggestively associated with heart failure that were also predicted to play a broader role in disease aetiology. The role of these genes in cardiovascular system development and function was then further investigated using in vivo CRISPR/Cas9-mediated gene mutation analysis in zebrafish. We observed multiple impacts in F0 knockout zebrafish embryos (crispants) following effective somatic mutation, including changes in ventricle size, pericardial oedema, and chamber malformation. In the case of lmo2, there was also a significant impact on cardiovascular function as well as an expected reduction in erythropoiesis. The data generated from both the human in silico and zebrafish in vivo assessments undertaken supports further investigation of the potential roles of API5, HSPB7, and LMO2 in human cardiovascular disease. The data presented also supports the use of human in silico genetic variant analysis, in combination with zebrafish crispant phenotyping, as a powerful approach for assessing gene function as part of an integrated multi-level drug target validation strategy.
Simulating Multi-Scale Pulmonary Vascular Function by Coupling Computational Fluid Dynamics With an Anatomic Network Model

The function of the pulmonary circulation is truly multi-scale, with blood transported through vessels from centimeter to micron scale. There are scale-dependent mechanisms that govern the flow in the pulmonary vascular system. However, very few computational models of pulmonary hemodynamics capture the physics of pulmonary perfusion across the spatial scales of functional importance in the lung. Here we present a multi-scale model that incorporates the 3-dimensional (3D) complexities of pulmonary blood flow in the major vessels, coupled to an anatomically-based vascular network model incorporating the multiple contributing factors to capillary perfusion, including gravity. Using the model we demonstrate how we can predict the impact of vascular remodeling and occlusion on both macro-scale functional drivers (flow distribution between lungs, and wall shear stress) and micro-scale contributors to gas exchange. The model predicts interactions between 3D and 1D models that lead to a redistribution of blood between postures, both on a macro- and a micro-scale. This allows us to estimate the effect of posture on left and right pulmonary artery wall shear stress, with predictions varying by 0.75–1.35 dyne/cm2 between postures.
Pro-Arrhythmic Effects of Discontinuous Conduction at the Purkinje Fiber-Ventricle Junction Arising From Heart Failure-Induced Ionic Remodeling – Insights From Computational Modelling

Heart failure is associated with electrical remodeling of the electrical properties and kinetics of the ion channels and transporters that are responsible for cardiac action potentials. However, it is still unclear whether heart failure-induced ionic remodeling can affect the conduction of excitation waves at the Purkinje fiber-ventricle junction contributing to pro-arrhythmic effects of heart failure, as the complexity of the heart impedes a detailed experimental analysis. The aim of this study was to employ computational models to investigate the pro-arrhythmic effects of heart failure-induced ionic remodeling on the cardiac action potentials and excitation wave conduction at the Purkinje fiber-ventricle junction. Single cell models of canine Purkinje fiber and ventricular myocytes were developed for control and heart failure. These single cell models were then incorporated into one-dimensional strand and three-dimensional wedge models to investigate the effects of heart failure-induced remodeling on propagation of action potentials in Purkinje fiber and ventricular tissue and at the Purkinje fiber-ventricle junction. This revealed that heart failure-induced ionic remodeling of Purkinje fiber and ventricular tissue reduced conduction safety and increased tissue vulnerability to the genesis of the unidirectional conduction block. This was marked at the Purkinje fiber-ventricle junction, forming a potential substrate for the genesis of conduction failure that led to re-entry. This study provides new insights into proarrhythmic consequences of heart failure-induced ionic remodeling.
Inhibitory Effect of Andrographis paniculata Lactone on Staphylococcus aureus α-Hemolysin

We investigated the effect of andrographolide (AP) on the hemolytic capacity of Staphylococcus aureus (S. aureus) isolated from our region. AP is a labdane diterpenoid isolated from the stem and leaves of Andrographis paniculata. The hla gene from 234 S. aureus strains and the quality control standard strain ATCC29213 in dairy cows in some areas of Ningxia was analyzed. Evolutionary analysis, homology modeling, and functional enrichment annotation of α-hemolysin Hla detected from our region were performed through bioinformatics. The hemolytic ability of S. aureus isolates from the region was examined using the hemolysis test, and the effect of AP on S. aureus was quantified. Moreover, the effect of AP on the transcript levels of hla and genes highly related to hla (i.e., clfA and fnbA) was examined through fluorescence quantitative PCR. The mode of action of AP on the detected Hla was analyzed through molecular docking and dynamic simulation. The results showed that S. aureus in our region has a high rate of hla carriage. The hemolytic activity of strains NM98 and XF10 was significant, and ATCC29213 also exhibited some hemolytic activity. AP could inhibit the expression of Hla and its related proteins by downregulating hla, clfA, and fnbA transcript levels, which in turn attenuated the S. aureus hemolytic activity. Meanwhile, the AP molecule can form three hydrogen bonds with residues ASN105, SER106, and THR155 of Hla protein; bind with PRO103 through alkyl intermolecular forces; and form carbon hydrogen bonds with LYS154, reflecting that the AP molecule has a comparatively ideal theoretical binding activity with Hla protein. Among them, PRO103 and LYS154 are highly conserved in Hla protein molecules and play pivotal roles in the biological functions of Hla, and their binding may affect these functions. Their binding may also prevent the conformational transition of Hla from a monomer to an oligomer, thus inhibiting Hla hemolytic activity. This study offers a molecular basis for use of AP as an antivirulence drug and new ideas for developing novel drugs against S. aureus infection.
Monitoring Autophagy in Rice With GFP-ATG8 Marker Lines

Autophagy is a conserved intracellular trafficking pathway for bulk degradation and recycling of cellular components in eukaryotes. The hallmark of autophagy is the formation of double-membraned vesicles termed autophagosomes, which selectively or non-selectively pack up various macromolecules and organelles and deliver these cargoes into the vacuole/lysosome. Like all other membrane trafficking pathways, the observation of autophagy is largely dependent on marker lines. ATG8/LC3 is the only autophagy-related (ATG) protein that, through a covalent bond to phosphatidylethanolamine (PE), associates tightly with the isolation membrane/pre-autophagosomal structure (PAS), the growing phagophore, the mature autophagosome, and the autophagic bodies. Therefore, fluorescent protein (FP)-tagged ATG8 had been widely used for monitoring autophagosome formation and autophagic flux. In rice (Oryza sativa), FP-OsATG8 driven by Cauliflower mosaic virus (CaMV) 35S promoter had been used for imaging autophagosome and autophagic bodies. Here, we constructed three vectors carrying GFP-OsATG8a, driven by 35S, ubiquitin, and the endogenous ATG8a promoter, individually. Then, we compared them for their suitability in monitoring autophagy, by observing GFP-ATG8a puncta formation in transiently transformed rice protoplasts, and by tracking the autophagic flux with GFP-ATG8 cleavage assay in rice stable transgenic lines. GFP-Trap immunoprecipitation and mass spectrometry were also performed with the three marker lines to show that they can be used reliably for proteomic studies. We found out that the ubiquitin promoter is the best for protoplast imaging. Transgenic rice seedlings of the three marker lines showed comparable performance in autophagic flux measurement using the GFP-ATG8 cleavage assay. Surprisingly, the levels of GFP-ATG8a transcripts and protein contents were similar in all marker lines, indicating post-transcriptional regulation of the transgene expression by a yet unknown mechanism. These marker lines can serve as useful tools for autophagy studies in rice.
Type 1 Insulin-Like Growth Factor Receptor Nuclear Localization in High-Grade Glioma Cells Enhances Motility, Metabolism, and In Vivo Tumorigenesis

Gliomas are the most frequent solid tumors in children. Among these, high-grade gliomas are less common in children than in adults, though they are similar in their aggressive clinical behavior. In adults, glioblastoma is the most lethal tumor of the central nervous system. Insulin-like growth factor 1 receptor (IGF1R) plays an important role in cancer biology, and its nuclear localization has been described as an adverse prognostic factor in different tumors. Previously, we have demonstrated that, in pediatric gliomas, IGF1R nuclear localization is significantly associated with high-grade tumors, worst clinical outcome, and increased risk of death. Herein we explore the role of IGF1R intracellular localization by comparing two glioblastoma cell lines that differ only in their IGF1R capacity to translocate to the nucleus. In vitro, IGF1R nuclear localization enhances glioblastoma cell motility and metabolism without affecting their proliferation. In vivo, IGF1R has the capacity to translocate to the nucleus and allows not only a higher proliferation rate and the earlier development of tumors but also renders the cells sensitive to OSI906 therapy. With this work, we provide evidence supporting the implications of the presence of IGF1R in the nucleus of glioma cells and a potential therapeutic opportunity for patients harboring gliomas with IGF1R nuclear localization.
Plant Consumption by Early-Middle Neolithic Peoples in Guangxi, South China: Archaeobotanical Evidence From the Dingsishan Site

The Dingsishan Site, located in Nanning City, Guangxi Zhuang Autonomous Region, is one of the most important Neolithic archaeological sites in the Lingnan region of China’s southeastern seaboard. Plant microfossil remains recovered from excavated artifacts and human teeth suggest that the site’s ancient inhabitants practiced a subsistence system based on foraging. Wild plant food resources dominated their vegetal diet. Starch granules extracted from residue samples represent various taxa, including plant roots and tubers, aquatic plant fruits, beans, and wild cereals, defining the primary vegetal diet of Dingsishan’s Neolithic occupants. In addition, residue samples from shell artifacts yielded starch granules and phytolith remains, providing significant clues as to the function of these tools. We also identified millet starch granules from Dingsishan Cultural Phases 3-4 (ca. 7,000–6000 BP), albeit in extremely low quantities. Holocene paleoecological conditions in the Lingnan area provided diverse and plentiful wild food resources, allowing the relatively late emergence of agriculture. Our study suggests that Middle Neolithic human groups in the Yong River drainage consumed various plants, and their subsistence pattern was relatively stable through the four Cultural Phases identified at Dingsishan. Our conclusions enhance understanding the diversity of plant food resources exploited by foraging societies and interpretations of differences in patterns of agricultural origins in different ecological regions of China.
A Positive Legacy of Trauma? The Role of Perceived Social Support on Mental Health Among Earthquake Survivors During the COVID-19 Outbreak

Background People with prior experience of severe trauma may be particularly vulnerable in the face of the COVID-19 pandemic. However, little is known about mental health problems among prior trauma survivors during the pandemic outbreak. Methods A total of 362 Wenchuan earthquake survivors were assessed using Patient Health Questionnaire, Generalized Anxiety Disorder Scale, as well as Multidimensional Scale of Perceived Social Support, as part of an online survey between February 3 and 10, 2020. Results Our results showed that 6.6 and 4.7% of the participants experienced depression and anxiety during the COVID-19 outbreak, respectively. Perceived social support was negatively associated with depressive and anxiety symptoms. Earthquake exposure has no direct effect on current depressive and anxiety symptoms, but it would moderate the direct relationship between perceived social support and psychological symptoms. Conclusions Our findings suggested that trauma exposure may lead to salutogenic outcomes. The protective effect of perceived social support on psychological symptoms was greater in people with a higher level of trauma exposure than in a lower one.
Feeding Strategies of Mangrove Leaf-Eating Crabs for Meeting Their Nitrogen Needs on a Low-Nutrient Diet

Sesarmid crabs play an important role in mangrove biogeochemical processes due to their leaf-eating and burrowing activities. How leaf-eating mangrove crabs meet their nitrogen (N) needs remains a puzzle, as N-poor leaf litter (<1% dry weight) cannot support the growth of most macrofauna. Several strategies for overcoming this challenge have been proposed, but the actual mechanisms remain unknown. We identified two categories of leaf-eating crabs according to their feeding habits (1): species active outside their burrows during low tide - we hypothesize that they meet their N needs through consuming the microphytobenthos (MPB) (hypothesis H1); and (2) species spending most of their time inside burrows - we hypothesize that they meet their N needs through N-fixation by associated microbes (H2). To test H1, we conducted a series of feeding experiments on the sesarmid crab Parasesarma affine (model species for category 1) with 13C- and 15N-enriched MPB and mangrove leaves. P. affine relied mainly on mangrove leaves as their C source and MPB as their N source, supporting H1. Two feeding experiments on Neosarmatium smithi (model species for category 2) showed that N limitation could be ameliorated by selecting seasonally available higher-quality food items such as floral parts, or by supplements from the associated nitrogen-fixing bacteria, as identified by genomic analysis. The strategy by which leaf-eating crabs meet their N needs may make significant contribution both to the growth of crabs and to their ecosystem functions of regulating the cycling of significant nutrient elements. The stoichiometric regulations by leaf-eating crabs to meet their N needs, such as food selection, can enhance trophic efficiency and nutrient transfer rate at the community level and ultimately increase nutrient turnover rate at the ecosystem level.
Genetical, Morphological, Behavioral, and Ecological Traits Support the Existence of Three Brazilian Species of the Anastrepha fraterculus Complex of Cryptic Species

Within the Neotropical genus Anastrepha, the nominal species Anastrepha fraterculus is widely distributed from Mexico through northern Argentina. Currently it is believed to comprises a complex of at least eight cryptic species—known as the Anastrepha fraterculus complex (AF complex)—three of which occur in Brazil: A. sp.1 aff. fraterculus, A. sp.2 aff. fraterculus, and A. sp.3 aff. fraterculus. In this study, we present the results of a broad integrated analysis of multiple biological attributes in samples of the three species collected in sympatric areas. Analyses of the mitotic chromosomes confirm that all of them differ in sex chromosomes, and that the relative frequency of the distinct karyotypes is associated with variation in altitude. In these sympatric areas, a single female hybrid karyotype was detected within a significant sample of individuals. Population samples were analyzed for the ribosomal transcribed spacer ITS1, confirming that the three species have specific sequence types. Observations of reproductive behavior under laboratory conditions revealed that A. sp.1 and A. sp.2 mate early in the morning, while A. sp.3 mates in the middle of the day. A bimodal distribution of mating time was observed in the laboratory for hybrids, obtained between A. sp.1 and A. sp.3. In a mating choice experiment, most of the mating pairs were homospecific. In addition, through a list of the most frequent hosts associated with geographical occurrence, a bioclimatic model of their potential distribution was generated. The set of data allowed for the construction of explanatory hypothesis about the observed geographical pattern and the differential use of host fruits. Morphometric analyses of wings clearly demonstrated differences among the three species, for both males and females. Based on a wing image of the A. fraterculus (Wiedemann, 1830) type specimen, the morphometric analysis indicated that the type specimen would correspond to a male of A. sp.2 aff. fraterculus. The information provided by this report is not only useful for taxonomic purposes, but also reveals aspects to be considered in any reconstruction of an evolutionary scenario of the Anastrepha fraterculus complex.
Weakly Supervised Skull Stripping of Magnetic Resonance Imaging of Brain Tumor Patients

Automatic brain tumor segmentation is particularly challenging on magnetic resonance imaging (MRI) with marked pathologies, such as brain tumors, which usually cause large displacement, abnormal appearance, and deformation of brain tissue. Despite an abundance of previous literature on learning-based methodologies for MRI segmentation, few works have focused on tackling MRI skull stripping of brain tumor patient data. This gap in literature can be associated with the lack of publicly available data (due to concerns about patient identification) and the labor-intensive nature of generating ground truth labels for model training. In this retrospective study, we assessed the performance of Dense-Vnet in skull stripping brain tumor patient MRI trained on our large multi-institutional brain tumor patient dataset. Our data included pretreatment MRI of 668 patients from our in-house institutional review board–approved multi-institutional brain tumor repository. Because of the absence of ground truth, we used imperfect automatically generated training labels using SPM12 software. We trained the network using common MRI sequences in oncology: T1-weighted with gadolinium contrast, T2-weighted fluid-attenuated inversion recovery, or both. We measured model performance against 30 independent brain tumor test cases with available manual brain masks. All images were harmonized for voxel spacing and volumetric dimensions before model training. Model training was performed using the modularly structured deep learning platform NiftyNet that is tailored toward simplifying medical image analysis. Our proposed approach showed the success of a weakly supervised deep learning approach in MRI brain extraction even in the presence of pathology. Our best model achieved an average Dice score, sensitivity, and specificity of, respectively, 94.5, 96.4, and 98.5% on the multi-institutional independent brain tumor test set. To further contextualize our results within existing literature on healthy brain segmentation, we tested the model against healthy subjects from the benchmark LBPA40 dataset. For this dataset, the model achieved an average Dice score, sensitivity, and specificity of 96.2, 96.6, and 99.2%, which are, although comparable to other publications, slightly lower than the performance of models trained on healthy patients. We associate this drop in performance with the use of brain tumor data for model training and its influence on brain appearance.