Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-Tumor Potency of Short-Term Interleukin-15 Dendritic Cells Is Potentiated by In Situ Silencing of Programmed-Death Ligands

Dendritic cell (DC) vaccines have proven to be a valuable tool in cancer immune therapy. With several DC vaccines being currently tested in clinical trials, knowledge about their therapeutic value has been significantly increased in the past decade. Despite their established safety, it has become clear that objective clinical responses are not yet robust enough, requiring further optimization. Improvements of this advanced therapy medicinal product encompass, among others, regulating their immune stimulating capacity by in situ gene engineering, in addition to their implementation in combination therapy regimens. Previously, we have reported on a superior monocyte-derived DC preparation, including interleukin-15, pro-inflammatory cytokines and immunological danger signals in the culture process. These so-called IL-15 DCs have already proven to exhibit several favorable properties as cancer vaccine. Evolving research into mechanisms that could further modulate the immune response towards cancer, points to programmed death-1 as an important player that dampens anti-tumor immunity. Aiming at leveraging the immunogenicity of DC vaccines, we hypothesized that additional implementation of the inhibitory immune checkpoint molecules programmed death-ligand (PD-L)1 and PD-L2 in IL-15 DC vaccines would exhibit superior stimulatory potential. In this paper, we successfully implemented PD-L silencing at the monocyte stage in the 3-day IL-15 DC culture protocol resulting in substantial downregulation of both PD-L1 and PD-L2 to levels below 30%. Additionally, we validated that these DCs retain their specific characteristics, both at the level of phenotype and interferon gamma secretion. Evaluating their functional characteristics, we demonstrate that PD-L silencing does not affect the capacity to induce allogeneic proliferation. Ultimately designed to induce a durable tumor antigen-specific immune response, PD-L silenced IL-15 DCs were capable of surpassing PD-1-mediated inhibition by antigen-specific T cells. Further corroborating the superior potency of short-term IL-15 DCs, the combination of immune stimulatory components during DC differentiation and maturation with in situ checkpoint inhibition supports further clinical translation.
Multi-Omics Association Reveals the Effects of Intestinal Microbiome–Host Interactions on Fat Deposition in Broilers

Growing evidence indicates that gut microbiota factors cannot be viewed as independent in the occurrence of obesity. Because the gut microbiome is highly dimensional and complex, studies on interactions between gut microbiome and host in obesity are still rare. To explore the relationship of gut microbiome–host interactions with obesity, we performed multi-omics associations of gut metagenome, intestinal transcriptome, and host obesity phenotypes in divergently selected obese–lean broiler lines. Metagenomic shotgun sequencing generated a total of 450 gigabases of clean data from 80 intestinal segment contents of 20 broilers (10 of each line). The microbiome comparison showed that microbial diversity and composition in the duodenum, jejunum, ileum, and ceca were altered variously between the lean- and fat-line broilers. We identified two jejunal microbes (Escherichia coli and Candidatus Acetothermia bacterium) and four cecal microbes (Alistipes sp. CHKCI003, Ruminococcaceae bacterium CPB6, Clostridiales bacterium, and Anaeromassilibacillus sp. An200), which were significantly different between the two lines (FDR < 0.05). When comparing functional metagenome, the fat-line broilers had an intensive microbial metabolism in the duodenum and jejunum but degenerative microbial activities in the ileum and ceca. mRNA-sequencing identified a total of 1,667 differentially expressed genes (DEG) in the four intestinal compartments between the two lines (| log2FC| > 1.5 and FDR < 0.05). Multi-omics associations showed that the 14 microbial species with abundances that were significantly related with abdominal fat relevant traits (AFRT) also have significant correlations with 155 AFRT-correlated DEG (p < 0.05). These DEG were mainly involved in lipid metabolism, immune system, transport and catabolism, and cell growth-related pathways. The present study constructed a gut microbial gene catalog of the obese–lean broiler lines. Intestinal transcriptome and metagenome comparison between the two lines identified candidate DEG and differential microbes for obesity, respectively. Multi-omics associations suggest that abdominal fat deposition may be influenced by the interactions of specific gut microbiota abundance and the expression of host genes in the intestinal compartments in which the microbes reside. Our study explored the interactions between gut microbiome and host intestinal gene expression in lean and obese broilers, which may expand knowledge on the relationships between obesity and gut microbiome.
Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes to Predict the Cardiotoxicity Potential of Next Generation Nicotine Products

Combustible cigarette smoking is an established risk factor for cardiovascular disease. By contrast, the cardiotoxicity potential of non-combustible next generation nicotine products (NGPs), which includes heated tobacco products (HTPs) and electronic vaping products (EVPs), and how this compares relative to combustible cigarettes is currently an area of scientific exploration. As such, there is a need for a rapid screening assay to assess this endpoint. The Cardio quickPredict is a metabolomics biomarker-based assay that uses human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to screen for potential structural and functional cardiac toxicants based on the changes of four metabolites, lactic acid, arachidonic acid, thymidine, and 2′-deoxycytidine. The study aims were to investigate the cardiotoxicity potential of NGPs compared to cigarettes, in addition to nicotine. To accomplish this, hiPSC-CM were exposed to smoke or aerosol bubbled PBS samples: reference cigarette (1R6F); three variants of HTP; and three EVP variants. The 1R6F bPBS was the most active, having cardiotoxic potential at 0.3–0.6% bPBS (0.4–0.9 μg/mL nicotine), followed by HTP, which displayed cardiotoxic potential at a 10 times higher concentration, 3.3% bPBS (4.1 μg/mL nicotine). Both 1R6F and HTP bPBS (at 10-fold higher concentration than 1R6F) affected all four predictive metabolites, whereas none of the EVP bPBS samples were active in the assay up to the maximal concentration tested (10% bPBS). Nicotine tested on its own was predicted to have cardiotoxic potential at concentrations greater than 80 μg/mL, which is higher than expected physiological levels associated with combustible cigarette smoking. The application of this rapid screening assay to NGP research and the associated findings adds to the weight-of-evidence indicating that NGPs have a tobacco harm reduction potential when compared to combustible cigarettes. Additionally, this technique was shown to be sensitive and robust for the assessment of different NGPs and may be considered as part of a larger overall scientific framework for NGP assessments.
Effects of Health Qigong Exercise on Lower Limb Motor Function in Parkinson's Disease

Purpose This study explored the effects of Health Qigong exercise on lower limb motor function in patients with Parkinson's disease (PD). Patients and Methods A total of 40 patients with PD were recruited and randomly allocated into the experimental group and the control group. The experimental group completed an intervention of Health Qigong exercise over 12 weeks, while the control group did not perform any regular physical activity. Data relating to gait, lower-limb joint range of motion, Timed Up and Go, as well as scores for motor function scale from the Unified Parkinson's Comprehensive Rating Scale III (UPCRS III) before and after the intervention were collected for Repeated Measure ANOVA. Results Compared to the control group, Health Qigong exercise improved the constant- and high-speed stride length and gait velocity of patients, but not constant- and high-speed stride frequency. Left and right hip flexion and extension range were improved as well as left and right knee flexion range. Finally, Timed Up and Go time became significantly slower and UPCRS III score significantly decreased. Conclusion Health Qigong exercise can improve walking ability and lower limb joint range of motion in patients with PD, lessen motor difficulties, and improve the quality of life. This non-pharmacological exercise intervention may be a useful adjustment treatment for PD.
Time-Series Generative Adversarial Network Approach of Deep Learning Improves Seizure Detection From the Human Thalamic SEEG

Seizure detection algorithms are often optimized to detect seizures from the epileptogenic cortex. However, in non-localizable epilepsies, the thalamus is frequently targeted for neuromodulation. Developing a reliable seizure detection algorithm from thalamic SEEG may facilitate the translation of closed-loop neuromodulation. Deep learning algorithms promise reliable seizure detectors, but the major impediment is the lack of larger samples of curated ictal thalamic SEEG needed for training classifiers. We aimed to investigate if synthetic data generated by temporal Generative Adversarial Networks (TGAN) can inflate the sample size to improve the performance of a deep learning classifier of ictal and interictal states from limited samples of thalamic SEEG. Thalamic SEEG from 13 patients (84 seizures) was obtained during stereo EEG evaluation for epilepsy surgery. Overall, TGAN generated synthetic data augmented the performance of the bidirectional Long-Short Term Memory (BiLSTM) performance in classifying thalamic ictal and baseline states. Adding synthetic data improved the accuracy of the detection model by 18.5%. Importantly, this approach can be applied to classify electrographic seizure onset patterns or develop patient-specific seizure detectors from implanted neuromodulation devices.
IL-13 and IL-33 Serum Levels Are Increased in Systemic Sclerosis Patients With Interstitial Lung Disease

Objective Systemic sclerosis (SSc) mortality is extremely variable in its internal organ involvement. Pulmonary fibrosis occurs in up to 30% of the cases. Animal models provide evidence that IL-33 is able to induce both cutaneous and pulmonary fibrosis via increased IL-13 and in SSc patients the levels of IL-33 correlate with skin fibrosis. Our aim was to test whether both IL-33 and IL-13 are higher in patients with diffuse SSc and interstitial lung disease (SSc-ILD) compared to SSc patients without ILD and healthy controls. Methods Serum levels of IL-13 and IL-33 were measured in 30 SSc patients with diffuse disease and 30 healthy controls by enzyme-linked immunosorbent assay. The extent of pulmonary fibrosis was assessed according to HRCT Warrick score. Pulmonary function tests included lung diffusion capacity for carbon monoxide, forced vital capacity and total lung capacity. Results Both IL-13 and IL-33 levels were increased in SSc patients compared to controls and significantly associated each other. DLco, FVC and TLC scores were inversely associated with IL-33 and IL-13 levels. Both IL-33 and IL-13 levels were significantly associated with the Warrick severity score and higher in the group of SSc patients with reduced pulmonary function compared to SSc patients with normal pulmonary function tests. Conclusion The IL-13/IL-33 axis needs to be further explored in longitudinal studies of SSc-ILD patients to assess its validity as a biomarker and future treatment target, as does downstream mediator ST2.
Focus on Hyperparasites: Biotic and Abiotic Traits Affecting the Prevalence of Parasitic Microfungi on Bat Ectoparasites

The tritrophic association of bats, bat flies, and Laboulbeniales microfungi is a remarkably understudied system that may reveal patterns applicable to community ecology theory of (hyper)parasites. Laboulbeniales are biotrophic microfungi, exclusively associated with arthropods, with several species that are specialized on bat flies, which themselves are permanent ectoparasites of bats. Several hypotheses were tested on biotic and abiotic traits that may influence the presence and prevalence of hyperparasitic Laboulbeniales fungi on bat flies, based on southeastern European data. We found a wide distribution of fungal infection on bat flies, with underground-dwelling bats hosting more Laboulbeniales-infected flies compared to crevice-dwelling species. Bat host behavior, sociality, roost selection (underground versus crevice), bat fly sex, and season all have significant effects on the prevalence of fungal infection. Laboulbeniales infections are more common on bat flies that are infecting bat species with dense and long-lasting colonies (Miniopterus schreibersii, Myotis myotis, Myotis blythii), which roost primarily in underground sites. Inside these sites, elevated temperature and humidity may enhance the development and transmission of Laboulbeniales fungi. Sexual differences in bat hosts’ behavior also have an effect on fungal infection risk, with densely roosting female bat hosts harboring more Laboulbeniales-infected bat flies.
Numerical Simulation of Stainless Steel Powder Feeding in a Coaxial Nozzle for High Powder Efficiency in Laser Direct Energy Deposition

Direct energy deposition (DED) is an efficient manufacturing process for the fabrication of complex parts and repair of worn-out turbine blades. In DED, all the injected powder is not going to melt and solidify due to spattering, reflection, ejection, effect of inert gas, and turbulence around the melt pool. In this study, through numerical simulation, the effect of powder size and inert gas flow under coaxial nozzle was analyzed. The number of particle participation in the melt pool by the effect of inert gas and the size of powder particles were analyzed. The powder particle sizes considered for the study were 50–60, 60–70, 70–80, 80–90, 90–100, and 45–90 µm. Argon and helium gases were used as carrier gas and shielding gas, respectively. According to gas–solid multiphase simulation, the convergence distance of the powder flow and powder participation focal point was analyzed through numerical simulation. The simulated results showed that using argon gas as a carrier gas produced high powder efficiency compared to helium gas. The focal point is forming at 11.86 mm, approximately 12 mm from the nozzle exit, which occurred for 60–70-µm particle size. The powder particle participation efficiency obtained was 64.1% using argon gas as carrier gas.
Targeted Deletion of Centrin in Leishmania braziliensis Using CRISPR-Cas9-Based Editing

Leishmania braziliensis is the main causative agent of Tegumentary Leishmaniasis in the Americas. However, difficulties related to genome manipulation, experimental infection, and parasite growth have so far limited studies with this species. CRISPR-Cas9-based technology has made genome editing more accessible, and here we have successfully employed the LeishGEdit approach to attenuate L. braziliensis. We generated a transgenic cell line expressing Cas9 and T7 RNA polymerase, which was employed for the targeted deletion of centrin, a calcium-binding cytoskeletal protein involved in the centrosome duplication in eukaryotes. Centrin-deficient Leishmania exhibit growth arrest at the amastigote stage. Whole-genome sequencing of centrin-deficient L. braziliensis (LbCen−/−) did not indicate the presence of off-target mutations. In vitro, the growth rates of LbCen−/− and wild-type promastigotes were similar, but axenic and intracellular LbCen−/− amastigotes showed a multinucleated phenotype with impaired survival following macrophage infection. Upon inoculation into BALB/c mice, LbCen−/− were detected at an early time point but failed to induce lesion formation, contrary to control animals, infected with wild-type L. braziliensis. A significantly lower parasite burden was also observed in mice inoculated with LbCen−/−, differently from control mice. Given that centrin-deficient Leishmania sp. have become candidates for vaccine development, we propose that LbCen−/− can be further explored for the purposes of immunoprophylaxis against American Tegumentary Leishmaniasis.
Deep Learning and Simulation for the Estimation of Red Blood Cell Flux With Optical Coherence Tomography

We present a deep learning and simulation-based method to measure cortical capillary red blood cell (RBC) flux using Optical Coherence Tomography (OCT). This method is more accurate than the traditional peak-counting method and avoids any user parametrization, such as a threshold choice. We used data that was simultaneously acquired using OCT and two-photon microscopy to uncover the distribution of parameters governing the height, width, and inter-peak time of peaks in OCT intensity associated with the passage of RBCs. This allowed us to simulate thousands of time-series examples for different flux values and signal-to-noise ratios, which we then used to train a 1D convolutional neural network (CNN). The trained CNN enabled robust measurement of RBC flux across the entire network of hundreds of capillaries.
Cross-Cultural Study of the Attitudes of Russian and Chinese Consumers Toward Electric Vehicles

Aim The article presents the results of a study of psychological factors of consumer loyalty concerning electric vehicles. An electric scooter was used as an example of an electric vehicle. The study involved a total of 165 people in China and 150 people in Russia. The study aimed to compare the psychological characteristics of Russian and Chinese consumers based on their attitudes toward an innovative product such as the electric scooter. Hypotheses (1) The identity of Russian and Chinese consumers and the perceived individuality of the product (electric scooter) differ significantly; (2) The proximity of the consumer's identity and the image of the product (electric scooter) enhances the positive attitude toward the product; (3) Risk strategies of consumer behavior of Chinese and Russians differ. Methods The questionnaire included the scales: (1) “Measuring brand personality” by J. Aaker, (2) “Measuring consumer identity” elaborated by Morozova and Antononva, (3) The risk behavior scale by Vasilenko, Tkachenko. Results (1) The first hypothesis was confirmed: there were revealed differences in the consumer behavior of the respondents of these two groups concerning in their self-perception, as well as in the perception of electric scooters. The Russians perceive an electric scooter as energetic, young, extravagant, modern, and unusual; the Chinese are down-to-earth, family-oriented, real. (2) The hypothesis that the correlation of the consumer's identity and the individuality of the product is one of the psychological factors that determine the consumer's loyalty to a product is also confirmed. (3) The Chinese consumers' identity is more close to the product individuality and their loyalty to the product is higher. (4) Risk strategies of consumer behavior of Chinese and Russians significantly differ in terms of satisfaction with choosing of vehicle, the frequency of its use, and the importance of family approval of the choice of vehicle. The results can be used in the marketing strategy development. From the scientifical perspective, these results contribute to an understanding of the consumer loyalty mechanisms associated with consumer identity.
Leukocytes in Cerebral Thrombus Respond to Large-Vessel Occlusion in a Time-Dependent Manner and the Association of NETs With Collateral Flow

Thrombus components are dynamically influenced by local blood flow and blood immune cells. After a large-vessel occlusion stroke, changes in the cerebral thrombus are unclear. Here we assessed a total of 206 cerebral thrombi from patients with ischemic stroke undergoing endovascular thrombectomy. The thrombi were categorized by time to reperfusion of <4 h (T4), 4–8 h (T4–8), and >8 h (T8). The cellular compositions in thrombus were analyzed, and relevant clinical features were compared. Both white blood cells and neutrophils were increased and then decreased in thrombus with time to reperfusion, which were positively correlated with those in peripheral blood. The neutrophil extracellular trap (NET) content in thrombus was correlated with the degree of neurological impairment of patients. Moreover, with prolonged time to reperfusion, the patients showed a trend of better collateral grade, which was associated with a lower NET content in the thrombus. In conclusion, the present results reveal the relationship between time-related endovascular immune response and clinical symptoms post-stroke from the perspective of thrombus and peripheral blood. The time-related pathological changes of cerebral thrombus may not be the direct cause for the difficulty in thrombolysis and thrombectomy. A low NET content in thrombi indicates excellent collateral flow, which suggests that treatments targeting NETs in thrombi might be beneficial for early neurological protection.
Deep Learning With Radiomics for Disease Diagnosis and Treatment: Challenges and Potential

The high-throughput extraction of quantitative imaging features from medical images for the purpose of radiomic analysis, i.e., radiomics in a broad sense, is a rapidly developing and emerging research field that has been attracting increasing interest, particularly in multimodality and multi-omics studies. In this context, the quantitative analysis of multidimensional data plays an essential role in assessing the spatio-temporal characteristics of different tissues and organs and their microenvironment. Herein, recent developments in this method, including manually defined features, data acquisition and preprocessing, lesion segmentation, feature extraction, feature selection and dimension reduction, statistical analysis, and model construction, are reviewed. In addition, deep learning-based techniques for automatic segmentation and radiomic analysis are being analyzed to address limitations such as rigorous workflow, manual/semi-automatic lesion annotation, and inadequate feature criteria, and multicenter validation. Furthermore, a summary of the current state-of-the-art applications of this technology in disease diagnosis, treatment response, and prognosis prediction from the perspective of radiology images, multimodality images, histopathology images, and three-dimensional dose distribution data, particularly in oncology, is presented. The potential and value of radiomics in diagnostic and therapeutic strategies are also further analyzed, and for the first time, the advances and challenges associated with dosiomics in radiotherapy are summarized, highlighting the latest progress in radiomics. Finally, a robust framework for radiomic analysis is presented and challenges and recommendations for future development are discussed, including but not limited to the factors that affect model stability (medical big data and multitype data and expert knowledge in medical), limitations of data-driven processes (reproducibility and interpretability of studies, different treatment alternatives for various institutions, and prospective researches and clinical trials), and thoughts on future directions (the capability to achieve clinical applications and open platform for radiomics analysis).