Miracle-dz/UniFAR-FTUs huggingface dataset:
Level of Murine DDX3 RNA Helicase Determines Phenotype Changes of Hepatocytes In Vitro and In Vivo

DDX3 RNA helicase is intensively studied as a therapeutic target due to participation in the replication of some viruses and involvement in cancer progression. Here we used transcriptome analysis to estimate the primary response of hepatocytes to different levels of RNAi-mediated knockdown of DDX3 RNA helicase both in vitro and in vivo. We found that a strong reduction of DDX3 protein (>85%) led to similar changes in vitro and in vivo—deregulation of the cell cycle and Wnt and cadherin pathways. Also, we observed the appearance of dead hepatocytes in the healthy liver and a decrease of cell viability in vitro after prolonged treatment. However, more modest downregulation of the DDX3 protein (60–65%) showed discordant results in vitro and in vivo—similar changes in vitro as in the case of strong knockdown and a different phenotype in vivo. These results demonstrate that the level of DDX3 protein can dramatically influence the cell phenotype in vivo and the decrease of DDX3, for more than 85% leads to cell death in normal tissues, which should be taken into account during the drug development of DDX3 inhibitors.
Discovering Digital Tumor Signatures—Using Latent Code Representations to Manipulate and Classify Liver Lesions

Simple Summary We use a generative deep learning paradigm for the identification of digital signatures in radiological imaging data. The model is trained on a small inhouse data set and evaluated on publicly available data. Apart from using the learned signatures for the characterization of lesions, in analogy to radiomics features, we also demonstrate that by manipulating them we can create realistic synthetic CT image patches. This generation of synthetic data can be carried out at user-defined spatial locations. Moreover, the discrimination of liver lesions from normal liver tissue can be achieved with high accuracy, sensitivity, and specificity. Abstract Modern generative deep learning (DL) architectures allow for unsupervised learning of latent representations that can be exploited in several downstream tasks. Within the field of oncological medical imaging, we term these latent representations “digital tumor signatures” and hypothesize that they can be used, in analogy to radiomics features, to differentiate between lesions and normal liver tissue. Moreover, we conjecture that they can be used for the generation of synthetic data, specifically for the artificial insertion and removal of liver tumor lesions at user-defined spatial locations in CT images. Our approach utilizes an implicit autoencoder, an unsupervised model architecture that combines an autoencoder and two generative adversarial network (GAN)-like components. The model was trained on liver patches from 25 or 57 inhouse abdominal CT scans, depending on the experiment, demonstrating that only minimal data is required for synthetic image generation. The model was evaluated on a publicly available data set of 131 scans. We show that a PCA embedding of the latent representation captures the structure of the data, providing the foundation for the targeted insertion and removal of tumor lesions. To assess the quality of the synthetic images, we conducted two experiments with five radiologists. For experiment 1, only one rater and the ensemble-rater were marginally above the chance level in distinguishing real from synthetic data. For the second experiment, no rater was above the chance level. To illustrate that the “digital signatures” can also be used to differentiate lesion from normal tissue, we employed several machine learning methods. The best performing method, a LinearSVM, obtained 95% (97%) accuracy, 94% (95%) sensitivity, and 97% (99%) specificity, depending on if all data or only normal appearing patches were used for training of the implicit autoencoder. Overall, we demonstrate that the proposed unsupervised learning paradigm can be utilized for the removal and insertion of liver lesions at user defined spatial locations and that the digital signatures can be used to discriminate between lesions and normal liver tissue in abdominal CT scans.
Effect of Informed Conditions on Sensory Expectations and Actual Perceptions: A Case of Chocolate Brownies Containing Edible-Cricket Protein

Currently, many consumers are reluctant to consume edible-cricket protein (ECP). Chocolate brownie (CB) formulations without (WO) and with (W) 6%w/w ECP (CBWO and CBW, respectively) were presented under two informed conditions: formulated without ECP (ECP−) and formulated with ECP+benefits (ECP+). CBWO− (CBWO presented with the “ECP−” claim), CBWO+ (CBWO presented with the “ECP+” claim), CBW− (CBW presented with the “ECP−” claim), and CBW+ (CBW presented with the “ECP+” claim) were evaluated by 210 consumers for expected and actual attribute liking, and after-tasting consumption and purchase intent. Multi-way ANOVA, principal component analysis, and agglomerative clustering examined liking. Cochran-Q tests compared actual-liking profiles, purchase and consumption intent. Before tasting, CBW− obtained the lowest appearance liking, flavor liking was higher for ECP− than for ECP+ for either formulation, and ECP+ decreased aroma and overall liking only for CBWO. After tasting, CBWO had higher liking than CBW (except for aroma) for either informed condition. Regardless of the formulation, ECP− and ECP+ had similar actual liking. Nevertheless, ECP+ prevented negative disconfirmation for both formulations while ECP− decreased texture liking (for CBWO) and all liking (for CBW) upon tasting. Females’ consumption intent was higher for CBWO regardless of the informed condition, but CBW+ achieved a similar purchase intent to CBWO− for both genders.
Proteomic Profiling of Tissue Exosomes Indicates Continuous Release of Malignant Exosomes in Urinary Bladder Cancer Patients, Even with Pathologically Undetectable Tumour

Simple Summary Urinary bladder cancer (UBC) has a high recurrence rate, and biomarkers for different treatment strategies are highly needed. This study investigated the release of nanovesicles called exosomes from urinary bladder tissue from tumour-proximal sites as well as tumour-distant sites in transurethrally resected (TUR-B) patients with or without preoperative neoadjuvant chemotherapy prior to ensuing radical cystectomy—all without remaining visible tumour after TUR-B. We show that cancer-promoting exosomes were detected from both sites, suggesting that the previous tumour has altered the whole bladder tissue into a cancer-supporting milieu. The exosomes may originate from remaining pathologically undetectable cancer cells or transformed epithelial cells, and the study supports the notion of exosomes as mediators of metastatic spread and as potential biomarkers. It also supports early and radical removal of the bladder in urinary bladder cancer patients. Abstract Invasive urothelial bladder cancer (UBC) has high recurrence rates even after radical cystectomy (RC). Exosomes are membrane-bound nanovesicles, which have been shown to contribute to carcinogenesis and metastasis. We previously showed that urinary exosomes display a malignant profile in UBC patients despite the absence of detectable tumour. Here, we investigated exosomes from sampling sites close to or distant from the former tumour, aiming to understand the effect of the tumour on the local milieu. Ten patients scheduled for cystectomy after transurethral bladder resection (TUR-B), without remaining detectable tumour, were included. Exosomes were isolated from tissue explants of both the previous tumour site and distant bladder tissue. Proteins were quantified by mass spectrometry in seven patients. Exosomes from the previous tumour site were enriched in inflammatory but not cancer-related pathways compared to distant tissue. However, the 69 most abundant proteins in tissue-derived exosomes regardless of site, 20 of which were also found in urinary exosomes from our previous study, were enriched for cancer-related metabolic pathways and associated with poor prognosis in an external mRNA dataset. The enrichment of cancer-related pathways in the most abundant proteins, regardless of sampling site, confirms our hypothesis that despite the absence of detectable tumour, the entire bladder releases exosomes that contribute to metastasis and highlights the need for early RC.
Histoplasmosis in Children; HIV/AIDS Not a Major Driver

The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, many cases of histoplasmosis were documented both in the pediatric and adult population. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939–2021). North America (n = 1231) had the highest number of cases, followed by South America (n = 135), Africa (n = 65), Asia (n = 26) and Europe (n = 4). Histoplasmosis was much more common in the non-HIV pediatric population (n = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies (n = 207), such as leukemias and lymphomas as well as their treatment, lung diseases (n = 7), environmental exposures and toxins (n = 224), autoimmune diseases (n = 12), organ transplants (n = 12), long-term steroid therapy (n = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors (n = 7) malnutrition (n = 12), histiocytosis (n = 3), hyperimmunoglobulin M and E syndromes (n = 15, 1.2%), pancytopaenias (n = 26), diabetes mellitus (n = 1) and T-cell deficiency (n = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions.
Detection of Silver Nanoparticles in Seawater Using Surface-Enhanced Raman Scattering

Nanomaterials significantly contribute to the development of new solutions to improve consumer products properties. Silver nanoparticles (AgNPs) are one of the most used, and as human exposure to such NPs increases, there is a growing need for analytical methods to identify and quantify nanoparticles present in the environment. Here we designed a detection strategy for AgNPs in seawater using surface-enhanced Raman Scattering (SERS). Three commercial AgNPs coated with polyvinylpyrrolidone (PVP) were used to determine the relative impact of size (PVP-15nmAgNPs and PVP-100nmAgNPs) and aggregation degree (predefined Ag aggregates, PVP-50–80nmAgNPs) on the SERS-based detection method. The study of colloidal stability and dissolution of selected AgNPs into seawater was carried out by dynamic light scattering and UV-vis spectroscopy. We showed that PVP-15nmAgNPs and PVP-100nmAgNPs remained colloidally stable, while PVP-50–80nmAgNPs formed bigger aggregates. We demonstrated that the SERS-based method developed here have the capacity to detect and quantify single and aggregates of AgNPs in seawater. The size had almost no effect on the detection limit (2.15 ± 1.22 mg/L for PVP-15nmAgNPs vs. 1.51 ± 0.71 mg/L for PVP-100nmAgNPs), while aggregation caused an increase of 2.9-fold (6.08 ± 1.21 mg/L). Our results demonstrate the importance of understanding NPs transformation in seawater since this can influence the detection method performance.
Revictimization Patterns Among Unhoused Youth

Young people experiencing houselessness are at high risk for revictimization. As has been identified in other populations, symptoms of psychological distress may be an indirect pathway by which initial victimization may increase risk for later revictimization among youth experiencing houselessness. The current study used cross-sectional mediation analyses to examine the hypothesis that there would be an indirect effect of interpersonal victimization that occurred before young people left home on subsequent victimization while experiencing houselessness, through posttraumatic stress disorder (PTSD) and depression symptoms. Youth (N = 245) residing in a shelter provided responses during an in-person interview screening prior to participating in a larger clinical study. Relevant to the current study, youth reported victimization experiences before and after leaving home (Childhood Trauma and Juvenile Victimization Questionnaires, respectively), and PTSD and depression symptoms on the Mini International Neuropsychiatric Interview. Results replicated and extended previous findings determining high rates of victimization among houseless young people both before (92%) and after (75%) leaving home. Further, exposure to more types of childhood victimization significantly predicted likelihood of experiencing more types of victimization after leaving home. Significant indirect effects of childhood victimization risk on revictimization after leaving home were found, occurring through both PTSD and depression symptoms. Results are discussed in terms of existing theories of revictimization, with particular emphasis on the state-dependence theory of victimization. These findings have implications for intervention with young people experiencing houselessness, particularly with regard to addressing the consequences of childhood victimization and trauma-informed support systems.
ROBOTICALLY STEERABLE CATHETER FOR THE DIAGNOSIS AND TREATMENT OF CARDIAC DISORDERS

Now a day’s many people have been diagnosed with complex cardiac arrhythmia, resulting in hospitalization. The method for treating certain complex cardiac arrhythmias is known as catheter ablation. In this process, a tiny catheter is used to deliver energy to destroy small areas of heart muscle responsible for causing rapid or irregular heart rhythms. This required a manual technique in which physicians insert one end of the catheter with inadequate assurances that it reaches the desired site in the heart. Here the outcomes are less than optimal. This problem is overcome by the use of robotic catheters, which can be used by the physicians to manipulate the catheters with increased accuracy, precision and are able to accurately target only the desired area that are in need of treatment. A detailed study about the robotic steerable catheter has been discussed in this review journal.
AP-2α–Mediated Activation of E2F and EZH2 Drives Melanoma Metastasis

AP-2α drives melanoma metastasis by upregulating E2F pathway genes including EZH2 through inhibition of the NuRD repression complex, serving as a biomarker to predict responsiveness to EZH2 inhibitors. In melanoma metastasis, the role of the AP-2α transcription factor, which is encoded by TFAP2A, is controversial as some findings have suggested tumor suppressor activity while other studies have shown high TFAP2A expression in node-positive melanoma associated with poor prognosis. Here we demonstrate that AP-2α facilitates melanoma metastasis through transcriptional activation of genes within the E2F pathway including EZH2. A BioID screen found that AP-2α interacts with members of the nucleosome remodeling and deacetylase (NuRD) complex. Loss of AP-2α removed activating chromatin marks in the promoters of EZH2 and other E2F target genes through activation of the NuRD repression complex. In melanoma cells, treatment with tazemetostat, an FDA-approved and highly specific EZH2 inhibitor, substantially reduced anchorage-independent colony formation and demonstrated heritable antimetastatic effects, which were dependent on AP-2α. Single-cell RNA sequencing analysis of a metastatic melanoma mouse model revealed hyperexpansion of Tfap2aHigh/E2F-activated cell populations in transformed melanoma relative to progenitor melanocyte stem cells. These findings demonstrate that melanoma metastasis is driven by the AP-2α/EZH2 pathway and suggest that AP-2α expression can be used as a biomarker to predict responsiveness to EZH2 inhibitors for the treatment of advanced melanomas. Significance: AP-2α drives melanoma metastasis by upregulating E2F pathway genes including EZH2 through inhibition of the NuRD repression complex, serving as a biomarker to predict responsiveness to EZH2 inhibitors. Graphical Abstract
Polymer-Peptide Modified Gold Nanorods to Improve Cell Conjugation and Cell Labelling for Stem Cells Photoacoustic Imaging

The use of gold nanorods (GNRs) as a contrast agent in bioimaging and cell tracking has numerous advantages, primarily due to the unique optical properties of gold nanorods which allow for the use of infrared regions when imaging. Owing to their unique geometry, Au NRs exhibit surface plasmon modes in the near-infrared wavelength range, which is ideal for carrying out optical measurements in biological fluids and tissue. Gold nanorod functionalization is essential, since the Cetyltrimethyl ammonium bromide CTAB gold nanorods are toxic, and for further in vitro and in vivo experiments the nanorods should be functionalized to become optically stable and biocompatible. In the present study, gold nanorods with an longitudinal surface plasmon resonance (LSPR) position around 800 nm were synthesized in order to be used for photoacoustic imaging applications for stem cell tracking. The gold nanorods were functionalized using both thiolated poly (ethylene glycol) (PEG) to stabilize the gold nanorods surface and a CALNN–TAT peptide sequence. Both ligands were attached to the gold nanorods through an Au–sulfur bond. CALNN–TAT is known as a cell penetrating peptide which ensures endocytosis of the gold nanorods inside the mesenchymal stem cells of mice (MSCD1). Surface modifications of gold nanorods were achieved using optical spectroscopy (UV–VIS), electron microscopy (TEM), zeta-potential, and FTIR. Gold nanorods were incubated in MSCD1 in order to achieve a cellular uptake that was characterized by a transmission electron microscope (TEM). For photoacoustic imaging, Multi-Spectral Optoacoustic Tomography (MSOT) was used. The results demonstrated good cellular uptake for PEG–CALNN–TAT GNRs and the successful use of modified gold nanorods as both a contrast agent in photoacoustic imaging and as a novel tracking bioimaging technique.
Fullerene-Attached Polymeric Homogeneous/Heterogeneous Photoactivators for Visible-Light-Induced CuAAC Click Reactions

In this work, a visible-light-induced copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction via an electron transfer reaction employing fullerene (C60) containing linear polystyrene and network polymer as homogeneous and heterogeneous activators, PS-C60 and Gel-C60, respectively, is described. Various low molar mass organic and polymeric azide and alkyne compounds are used to conduct the click reaction, and almost quantitative yields are attained. Compared to the bare C60, the polymers with C60 units exhibited a much higher promoting effect to catalyze CuAAC reactions.
Validation of a Low-Cost Electrocardiography (ECG) System for Psychophysiological Research

Background and Objective: The reliability of low-cost mobile systems for recording Electrocardiographic (ECG) data is mostly unknown, posing questions regarding the quality of the recorded data and the validity of the extracted physiological parameters. The present study compared the BITalino toolkit with an established medical-grade ECG system (BrainAmp-ExG). Methods: Participants underwent simultaneous ECG recordings with the two instruments while watching pleasant and unpleasant pictures of the “International Affective Picture System” (IAPS). Common ECG parameters were extracted and compared between the two systems. The Intraclass Correlation Coefficients (ICCs) and the Bland–Altman Limits of Agreement (LoA) method served as criteria for measurement agreement. Results: All but one parameter showed an excellent agreement (>80%) between both devices in the ICC analysis. No criteria for Bland–Altman LoA and bias were found in the literature regarding ECG parameters. Conclusion: The results of the ICC and Bland–Altman methods demonstrate that the BITalino system can be considered as an equivalent recording device for stationary ECG recordings in psychophysiological experiments.
In Vitro Antiplatelet Activity of Mulberroside C through the Up-Regulation of Cyclic Nucleotide Signaling Pathways and Down-Regulation of Phosphoproteins

Physiological agonists trigger signaling cascades, called “inside-out signaling”, and activated platelets facilitate adhesion, shape change, granule release, and structural change of glycoprotein IIb/IIIa (αIIb/β3). Activated αIIb/β3 interacts with fibrinogen and begins second signaling cascades called “outside-in signaling”. These two signaling pathways can lead to hemostasis or thrombosis. Thrombosis can occur in arterial and venous blood vessels and is a major medical problem. Platelet-mediated thrombosis is a major cause of cardiovascular disease (CVD). Therefore, controlling platelet activity is important for platelet-mediated thrombosis and cardiovascular diseases. In this study, focus on Morus Alba Linn, a popular medicinal plant, to inhibit the function of platelets and found the containing component mulberroside C. We examine the effect of mulberroside C on the regulation of phosphoproteins, platelet-activating factors, and binding molecules. Agonist-induced human platelet aggregation is dose-dependently inhibited by mulberroside C without cytotoxicity, and it decreased Ca2+ mobilization and p-selectin expression through the upregulation of inositol 1, 4, 5-triphosphate receptor I (Ser1756), and downregulation of extracellular signal-regulated kinase (ERK). In addition, mulberroside C inhibited thromboxane A2 production, fibrinogen binding, and clot retraction. Our results show antiplatelet effects and antithrombus formation of mulberroside C in human platelets. Thus, we confirm that mulberroside C could be a potential phytochemical for the prevention of thrombosis-mediated CVDs.
Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment

Simple Summary The tumor microenvironment is characterized by increased tissue stiffness, low (acidic) pH, and elevated temperature, all of which contribute to the development of cancer. Improving our in vitro models of cancer, therefore, requires the development of cell culture platforms that can mimic these microenvironmental properties. Here, we study a new biomaterial composed of short amino acid chains that self-assemble into a fibrous hydrogel network. This material enables simultaneous and independent tuning of substrate rigidity, extracellular pH, and temperature, allowing us to mimic both healthy tissues and the tumor microenvironment. We used this platform to study the effect of these conditions on pancreatic cancer cells and found that high substrate rigidity and low pH promote proliferation and survival of cancer cells and activate important signaling pathways associated with cancer progression. Abstract The tumor microenvironment plays a critical role in modulating cancer cell migration, metabolism, and malignancy, thus, highlighting the need to develop in vitro culture systems that can recapitulate its abnormal properties. While a variety of stiffness-tunable biomaterials, reviewed here, have been developed to mimic the rigidity of the tumor extracellular matrix, culture systems that can recapitulate the broader extracellular context of the tumor microenvironment (including pH and temperature) remain comparably unexplored, partially due to the difficulty in independently tuning these parameters. Here, we investigate a self-assembled polypeptide network hydrogel as a cell culture platform and demonstrate that the culture parameters, including the substrate stiffness, extracellular pH and temperature, can be independently controlled. We then use this biomaterial as a cell culture substrate to assess the effect of stiffness, pH and temperature on Suit2 cells, a pancreatic cancer cell line, and demonstrate that these microenvironmental factors can regulate two critical transcription factors in cancer: yes-associated protein 1 (YAP) and hypoxia inducible factor (HIF-1A).