Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomics Analysis of Aqueous Humor and Rejected Graft in Pig-to-Non-Human Primate Corneal Xenotransplantation

Although pig-to-non-human primate (NHP) corneal xenotransplantation has shown long-term graft survival, xenogeneic antigen-related immune responses are still stronger than allogeneic antigen-associated responses. Therefore, there is an unmet need to investigate major rejection pathways in corneal xenotransplantation, even with immunosuppression. This study aimed to identify biomarkers in aqueous humor for predicting rejection and to investigate rejection-related pathways in grafts from NHPs transplanted with porcine corneas following the administration of steroids combined with tacrolimus/rituximab. NHPs who had received corneas from wild-type (WT) or α-1,3-galactosyltransferase gene-knockout (GTKO) pigs were divided into groups with or without rejection according to clinical examinations. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the proteomes of corneal tissues or aqueous humor. The biological functions of differentially expressed proteins (DEPs) were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathways and protein–protein interaction network analysis. Among the 66 DEPs in aqueous humor, complement proteins (C3, C5, and C9) and cholesterol metabolic proteins (APOA1 and APOA2) were related to xenogeneic rejection as biomarkers, and alternative pathways of the complement system seemed to be important in xenogeneic graft rejection. Among the 416 DEPs of the cornea, NF-κB1 and proteosomes (PSMD7, PSMA5, and PSMD3) seemed to be related to xenogeneic graft rejection. Additionally, oxidative phosphorylation and leukocyte activation-related pathways are involved in rejection. Overall, our proteomic approach highlights the important role of NF-κB1, proteosomes, oxidative phosphorylation, and leukocyte activation-related inflammation in the cornea and the relevance of complement pathways of the aqueous humor as a predictive biomarker of xenogeneic rejection.
Prognostic Evaluation of Metastasis-Related Lymphocyte/Monocyte Ratio in Stage Ⅰ-Ⅲ Breast Cancer Receiving Chemotherapy

Purpose This study aims to clarify the prognostic significance of metastasis-related indicators in peripheral blood in stage I-III breast cancer (BC). Methods The clinicopathological data of 938 breast cancer patients and 509 benign breast disease patients were retrospectively analyzed, and fasting blood samples were collected before treatment. Univariate and multivariate regression analyses were used to evaluate factors related to metastasis risk and prognosis. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to measure differences in survival between groups. Results Use the cut-off value (3.433) of LMR, the logistic regression analysis revealed that high carbohydrate antigen 153 (CA153), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), killer T cell level, and low lymphocyte to monocyte ratio (LMR) level were significantly associated with BC distant metastasis. In contrast, LMR>=3.433 (HR: 0.409, 95%CI: 0.193–0.867, P = 0.020), Th/Tc ratio >=1.946 (HR: 0.378, 95% CI: 0.158–0.904, P =0.029) is regarded as a protective factor in the multivariate cox analyses. LMR is an independent prognostic factor for DFS in HER2-negative BC patients. Conclusion Peripheral blood parameters play an important role in predicting distant metastasis and prognosis of BC patients. As a potential marker, LMR can predict the metastasis and prognosis of patients with stage I-III BC.
Comparison between current-based and flux/torque-based model predictive control methods for open-end winding induction motor drives

In automotive testing systems such as chassis dynamometers and engine dynamometers, effective and efficient control strategies are required to control the induction motor drives, so that fast torque response and low-torque ripples can be obtained. The fast torque response can be obtained by using model predictive control (MPC) due to its high bandwidth over a wide-speed range; and the torque ripple can be reduced by using open-end winding induction motor (OEWIM). Since MPC can be current based or flux/torque based, and can be linear and non-linear, it is necessary to evaluate the effectiveness of different MPC methods on the open-end winding drives. In this study, linear and non-linear current-based MPC methods and flux/torque-based MPC methods for OEWIM drive are derived and evaluated. The transient and steady-state responses of MPC methods are compared through simulation and experiment. The results show that linear MPC methods require less computation time, and under the same sampling frequency, linear MPC methods provide lower current ripple and better zero-sequence-current suppression than non-linear MPC methods. This study provides practical perception for MPC used on multi-level converters and MPC used for unbalanced situations.
Analysis of COVID-19 Collective Irrationalities Based on Epidemic Psychology

As the SARS-CoV-2 virus swept the world in late 2019, it has brought widespread fear, some suspicion, and degrees of stigma. In the shadow of the COVID-19 pandemics, a series of collective irrationalities such as panic buying, protest marches against vaccines, and pandemic stigma occurred. This phenomenon is inseparable from the spread of rumors about the epidemic. The advent of social media has radically changed the way we consume information and form opinions and made a flood of digital misinformation becoming ubiquitous. The diffusion of false rumors affects the public’s perception of reality and disrupts the prevention of the epidemic. This paper analyzes the COVID-19 collective irrationalities from epidemic psychology to provide a new reference view for overcoming psychological problems related to COVID-19.
Effective Diagnosis of Prostate Cancer Based on mRNAs From Urinary Exosomes

Background Novel non-invasive biomarkers are urgently required to improve the diagnostic sensitivity and specificity of prostate cancer (PCa). Therefore, the diagnostic value of following candidate genes (ERG, PCA3, ARV7, PSMA, CK19, and EpCAM) were estimated by testing mRNAs from urinary exosomes of patients with primary PCa. Methods Exosomes were obtained using size-exclusion chromatography (SEC), out of which RNAs were extracted, then analyzed by quantitative reverse transcription-polymerase chain reaction according to manufacturer’s protocol. Results The expression of urinary exosomal ERG, PCA3, PSMA, CK19, and EpCAM were significantly increased in patients with PCa compared with healthy males. In addition, the levels of urinary exosomal ERG, ARV7, and PSMA were intimately correlated with the Gleason score in PCa patients (P < 0.05). The receiver operating characteristic curves (ROCs) showed that urinary exosomal ERG, PCA3, PSMA, CK19, and EpCAM were able to distinguish patients with PCa from healthy individuals with the area under the curve (AUC) of 0.782, 0.783, 0.772, 0.731, and 0.739, respectively. Urinary exosomal PCA3 and PSMA distinguished PCa patients from healthy individuals with an AUC of 0.870. Combination of urinary exosomal PCA3, PSMA with serum PSA and PI-RADS achieved higher AUC compared with PSA alone (0.914 and 0.846, respectively). Kaplan-Meier curves demonstrated that PCA3, ARV7, and EpCAM were associated in androgen-deprivation therapy (ADT) failure time which is defined as from the initiation of ADT in hormone-sensitive stage to the development of castration-resistant prostate cancer. Conclusion These findings suggested that mRNAs from urinary exosomes have the potential in serving as novel and non-invasive indicators for PCa diagnosis and prediction.
Restricted Proliferation During Neurogenesis Contributes to Regionalisation of the Amphioxus Nervous System

The central nervous system of the cephalochordate amphioxus consists of a dorsal neural tube with an anterior brain. Two decades of gene expression analyses in developing amphioxus embryos have shown that, despite apparent morphological simplicity, the amphioxus neural tube is highly regionalised at the molecular level. However, little is known about the morphogenetic mechanisms regulating the spatiotemporal emergence of cell types at distinct sites of the neural axis and how their arrangements contribute to the overall neural architecture. In vertebrates, proliferation is key to provide appropriate cell numbers of specific types to particular areas of the nervous system as development proceeds, but in amphioxus proliferation has never been studied at this level of detail, nor in the specific context of neurogenesis. Here, we describe the dynamics of cell division during the formation of the central nervous system in amphioxus embryos, and identify specific regions of the nervous system that depend on proliferation of neuronal precursors at precise time-points for their maturation. By labelling proliferating cells in vivo at specific time points in development, and inhibiting cell division during neurulation, we demonstrate that localised proliferation in the anterior cerebral vesicle is required to establish the full cell type repertoire of the frontal eye complex and the putative hypothalamic region of the amphioxus brain, while posterior proliferating progenitors, which were found here to derive from the dorsal lip of the blastopore, contribute to elongation of the caudal floor plate. Between these proliferative domains, we find that trunk nervous system differentiation is independent from cell division, in which proliferation decreases during neurulation and resumes at the early larval stage. Taken together, our results highlight the importance of proliferation as a tightly controlled mechanism for shaping and regionalising the amphioxus neural axis during development, by addition of new cells fated to particular types, or by influencing tissue geometry.
Antigen–Antibody Complex-Guided Exploration of the Hotspots Conferring the Immune-Escaping Ability of the SARS-CoV-2 RBD

The COVID-19 pandemic resulting from the spread of SARS-CoV-2 spurred devastating health and economic crises around the world. Neutralizing antibodies and licensed vaccines were developed to combat COVID-19, but progress was slow. In addition, variants of the receptor-binding domain (RBD) of the spike protein confer resistance of SARS-CoV-2 to neutralizing antibodies, nullifying the possibility of human immunity. Therefore, investigations into the RBD mutations that disrupt neutralization through convalescent antibodies are urgently required. In this study, we comprehensively and systematically investigated the binding stability of RBD variants targeting convalescent antibodies and revealed that the RBD residues F456, F490, L452, L455, and K417 are immune-escaping hotspots, and E484, F486, and N501 are destabilizing residues. Our study also explored the possible modes of actions of emerging SARS-CoV-2 variants. All results are consistent with experimental observations of attenuated antibody neutralization and clinically emerging SARS-CoV-2 variants. We identified possible immune-escaping hotspots that could further promote resistance to convalescent antibodies. The results provide valuable information for developing and designing novel monoclonal antibody drugs to combat emerging SARS-CoV-2 variants.
Anti-Inflammatory Medicinal Plants of Bangladesh—A Pharmacological Evaluation

Inflammatory diseases are considered major threats to human health worldwide. In Bangladesh, a number of medicinal plants have been used in traditional medicine from time immemorial in the treatment of diverse diseases, including inflammatory disorders. This assignment aims at providing the status of the medicinal plants of Bangladesh which are traditionally used in the management of inflammatory disorders and are investigated for their anti-inflammatory prospects using different preclinical studies and future research directions. The information of medicinal plants assembled in this review was obtained from a literature search of electronic databases such as Google Scholar, PubMed, Scopus, Web of Science and ScienceDirect up to December, 2020 from publications on plants investigated for their anti-inflammatory activities, in which the place of plant sample collection was identified as Bangladesh. Keywords for primary searches were “anti-inflammatory,” “Bangladeshi,” and “medicinal plants. ” Criteria followed to include plant species were plants that showed significant anti-inflammatory activities in 1) two or more sets of experiments in a single report, 2) same or different sets of experiments in two or more reports, and, 3) plants which are traditionally used in the treatment of inflammation and inflammatory disorders. In this study, 48 species of medicinal plants have been reviewed which have been used in traditional healing practices to manage inflammatory disorders in Bangladesh. The mechanistic pathways of the in vivo and in vitro study models used for the evaluation of anti-inflammatory properties of plant samples have been discussed. Selected plants were described in further detail for their habitat, anti-inflammatory studies conducted in countries other than Bangladesh, and anti-inflammatory active constituents isolated from these plants if any. Medicinal plants of Bangladesh have immense significance for anti-inflammatory activity and have potential to contribute toward the discovery and development of novel therapeutic approaches to combat diseases associated with inflammation. However, the plants reviewed in this article had chiefly undergone preliminary screening and require substantial investigations including identification of active molecules, understanding the mechanism of action, and evaluation for safety and efficacy to be followed by the formulation of safe and effective drug products.
Nanoparticles for Inducing Antigen-Specific T Cell Tolerance in Autoimmune Diseases

Autoimmune diseases affect many people worldwide. Current treatment modalities focus on the reduction of disease symptoms using anti-inflammatory drugs which can lead to side effects due to systemic immune suppression. Restoration of immune tolerance by down-regulating auto-reactive cells in an antigen-specific manner is currently the “holy grail” for the treatment of autoimmune diseases. A promising strategy is the use of nanoparticles that can deliver antigens to antigen-presenting cells which in turn can enhance antigen-specific regulatory T cells. In this review, we highlight some promising cell targets (e.g. liver sinusoidal endothelial cells and splenic marginal zone macrophages) for exploiting natural immune tolerance processes, and several strategies by which antigen-carrying nanoparticles can target these cells. We also discuss how nanoparticles carrying immunomodulators may be able to activate tolerance in other antigen-presenting cell types. Finally, we discuss some important aspects that must be taken into account when translating data from animal studies to patients.
Mxi1-0 Promotes Hypoxic Pulmonary Hypertension Via ERK/c-Myc-dependent Proliferation of Arterial Smooth Muscle Cells

Background: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality, and so far patients have failed to benefit from therapeutics clinically available. Max interacting protein 1–0 (Mxi1-0) is one of the functional isoforms of Mxi1. Although it also binds to Max, Mxi1-0, unlike other Mxi1 isoforms, cannot antagonize the oncoprotein c-Myc because of its unique proline rich domain (PRD). While Mxi1-0 was reported to promote cell proliferation via largely uncharacterized mechanisms, it is unknown whether and how it plays a role in the pathogenesis of HPH. Methods: GEO database was used to screen for genes involved in HPH development, and the candidate players were validated through examination of gene expression in clinical HPH specimens. The effect of candidate gene knockdown or overexpression on cultured pulmonary arterial cells, e.g., pulmonary arterial smooth muscle cells (PASMCs), was then investigated. The signal pathway(s) underlying the regulatory role of the candidate gene in HPH pathogenesis was probed, and the outcome of targeting the aforementioned signaling was evaluated using an HPH rat model. Results: Mxi1 was significantly upregulated in the PASMCs of HPH patients. As the main effector isoform responding to hypoxia, Mxi1-0 functions in HPH to promote PASMCs proliferation. Mechanistically, Mxi1-0 improved the expression of the proto-oncogene c-Myc via activation of the MEK/ERK pathway. Consistently, both a MEK inhibitor, PD98059, and a c-Myc inhibitor, 10058F4, could counteract Mxi1-0-induced PASMCs proliferation. In addition, targeting the MEK/ERK signaling significantly suppressed the development of HPH in rats. Conclusion: Mxi1-0 potentiates HPH pathogenesis through MEK/ERK/c-Myc-mediated proliferation of PASMCs, suggesting its applicability in targeted treatment and prognostic assessment of clinical HPH.
Aspectos da apropriação de práticas do design da experiência do usuário por pequenas e médias empresas de tecnologias de informação

The definition of strategies or models that describe objectives and best practices to follow are relevant references in establishing development processes for companies of different sizes. The increasing adoption of Agile methods and also increasing the importance of the inclusion of the experience design practices in the development process in agile methods have attracted interest from the scientific community because few models and strategies prescribe how this adoption can be carried out together. For small and medium-sized companies, the challenges are greater, because the scenarios that act are facing several constraints on the budget, material, and human resources. This thesis aims to propose a strategy for incorporating the experience design practices in the software development cycle, in small and medium-sized businesses software industry to adopt agile methodologies, from the observation of restrictions and potentialities of the suggested practices in literature. We adopted a qualitative paradigm form of research to observe, analyze and interpret the practices of the subject in an attempt to understand the phenomenon investigated. A field study involved thirty professionals who analyzed practices suggested in the literature in their work context and evaluated the proposed strategy. The results suggest that a strategy for the selection, adoption, training and monitoring practices, techniques and forms to suit smaller organizations artifacts can promote inclusion and appropriation of these practices in the establishment of the organization process, noting the resource constraints in the context studied. In the end, it was possible to propose a strategy to guide and facilitate the appropriation of practices for small and medium-sized organizations. The main contribution of this thesis is, therefore, a strategy to improvements in the process of design experience appropriation in the scenario of agile methodologies in small and medium enterprises of information technology.
Editorial: Spatial Navigation and Neurodevelopmental Disorders

Department of Human Neuroscience, Section of Child and Adolescents Neuropsychiatry, Sapienza University of Rome, Rome, Italy, Department of Psychology, University Sapienza of Rome, Rome, Italy, Cognitive and Motor Rehabilitation and Neuroimaging Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Rome, Italy, Neuropaediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Combining Biocontrol Agent With Plant Nutrients for Integrated Control of Tomato Early Blight Through the Modulation of Physio-Chemical Attributes and Key Antioxidants

Early blight (EB) is one of the major fungal diseases caused by Alternaria solani that is responsible for destructive tomato production around the globe. Biocontrol agent/s can be adequately implemented in an integrated management framework by using it in combination with vital plant nutrients, e.g., nitrogen, phosphorus, and potassium (NPK) and zinc (Zn). The current study was aimed to assess the integrated effect of a biocontrol agent Bacillus subtilis (BS-01) and the selective plant nutrients (NPK and Zn) on EB disease management and tomato crop performance. A field experiment was conducted for the off-season tomato production (under walk-in tunnels) in Punjab, Pakistan. The trial was set in a randomized complete block design (RCBD) and comprised nine treatments of a biocontrol agent (BS-01) either alone or in combination with the plant nutrients, viz., NPK (64:46:50 kg acre–1) and Zn (10 kg acre–1) as sustainable disease managing approach against EB. In addition, the biocontrol efficacy of B. subtilis (BS-01) on a fungal load of A. solani was estimated by quantitative PCR assays, where the foliar application of BS-01 on tomato plants either alone or in combination with the plant nutrients was done as a preventive measure. Our results revealed that the interactive effect of BS-01 with plant nutrients conferred significantly a varying degree of resilience in the infected tomato plants against EB by effectively modifying the content of total chlorophyll, carotenoids, and total phenolics along with the activities of antioxidant enzymes (SOD, CAT, POX, PPO, and PAL). In addition, the integrative effect of BS-01 and plant nutrients proved significantly effective in reducing pathogen load on inoculated tomato foliage, displaying the desired level of protection against A. solani infection. Besides, the complementary interaction of BS-01 + Zn + NPK worked synergistically to improve crop productivity by providing the highest marketable yield (21.61 tons acre–1) and net profit (361,363 Pakistani rupees acre–1). This integrated approach is put forward as a way to reduce the fungicide doses to control EB that would act as a sustainable plant protection strategy to generate profitable tomato production.
Designing the ESM—Who Profits, Who Pays?

The European Stability Mechanism (ESM) is the permanent crisis prevention mechanism of the euro area. It was established in 2012 under considerable time pressure in an environment dominated by the financial crisis in the euro area. We analyze the costs of the current (suboptimal) design of the EMS and evaluate an alternative asset-backed securities (ABS) structure under different scenarios. Our simulation results indicate that switching to an ABS structure could lower EMS refunding costs by up to 2% with respect to our benchmark scenario. Moreover, the advantages of an ABS structure are found to be strongest in the mostly likely type of future crisis, namely, medium-sized requests for financial support from EMS members under economic stress accompanied by the unwillingness or inability of other EMS countries to provide new capital to the EMS.