Miracle-dz/UniFAR-FTUs huggingface dataset:
Decellularized Porcine Cartilage Scaffold; Validation of Decellularization and Evaluation of Biomarkers of Chondrogenesis

Osteoarthritis is a major concern in the United States and worldwide. Current non-surgical and surgical approaches alleviate pain but show little evidence of cartilage restoration. Cell-based treatments may hold promise for the regeneration of hyaline cartilage-like tissue at the site of injury or wear. Cell–cell and cell–matrix interactions have been shown to drive cell differentiation pathways. Biomaterials for clinically relevant applications can be generated from decellularized porcine auricular cartilage. This material may represent a suitable scaffold on which to seed and grow chondrocytes to create new cartilage. In this study, we used decellularization techniques to create an extracellular matrix scaffold that supports chondrocyte cell attachment and growth in tissue culture conditions. Results presented here evaluate the decellularization process histologically and molecularly. We identified new and novel biomarker profiles that may aid future cartilage decellularization efforts. Additionally, the resulting scaffold was characterized using scanning electron microscopy, fluorescence microscopy, and proteomics. Cellular response to the decellularized scaffold was evaluated by quantitative real-time PCR for gene expression analysis.
Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.
Reading Food Experiences from the Face: Effects of Familiarity and Branding of Soy Sauce on Facial Expressions and Video-Based RPPG Heart Rate

Food experiences are not only driven by the food’s intrinsic properties, such as its taste, texture, and aroma, but also by extrinsic properties such as visual brand information and the consumers’ previous experiences with the foods. Recent developments in automated facial expression analysis and heart rate detection based on skin color changes (remote photoplethysmography or RPPG) allow for the monitoring of food experiences based on video images of the face. RPPG offers the possibility of large-scale non-laboratory and web-based testing of food products. In this study, results from the video-based analysis were compared to the more conventional tests (scores of valence and arousal using Emojis and photoplethysmography heart rate (PPG)). Forty participants with varying degrees of familiarity with soy sauce were presented with samples of rice and three commercial soy sauces with and without brand information. The results showed that (1) liking and arousal were affected primarily by the specific tastes, but not by branding and familiarity. In contrast, facial expressions were affected by branding and familiarity, and to a lesser degree by specific tastes. (2) RPPG heart rate and PPG both showed effects of branding and familiarity. However, RPPG heart rate needs further development because it underestimated the heart rate compared to PPG and was less sensitive to changes over time and with activity (viewing of brand information and tasting). In conclusion, this study suggests that recording of facial expressions and heart rates may no longer be limited to laboratories but can be done remotely using video images, which offers opportunities for large-scale testing in consumer science.
Application of Deep Learning Networks to Segmentation of Surface of Railway Tracks

The article presents a vision system for detecting elements of railway track. Four types of fasteners, wooden and concrete sleepers, rails, and turnouts can be recognized by our system. In addition, it is possible to determine the degree of sleeper ballast coverage. Our system is also able to work when the track is moderately covered by snow. We used a Fully Convolutional Neural Network with 8 times upsampling (FCN-8) to detect railway track elements. In order to speed up training and improve performance of the model, a pre-trained deep convolutional neural network developed by Oxford’s Visual Geometry Group (VGG16) was used as a framework for our system. We also verified the invariance of our system to changes in brightness. To do this, we artificially varied the brightness of images. We performed two types of tests. In the first test, we changed the brightness by a constant value for the whole analyzed image. In the second test, we changed the brightness according to a predefined distribution corresponding to Gaussian function.
Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases

Epithelial cells exfoliated in human urine can include cells anywhere from the urinary tract and kidneys; however, podocytes and proximal tubular epithelial cells (PTECs) are by far the most relevant cell types for the study of genetic kidney diseases. When maintained in vitro, they have been proven extremely valuable for discovering disease mechanisms and for the development of new therapies. Furthermore, cultured patient cells can individually represent their human sources and their specific variants for personalized medicine studies, which are recently gaining much interest. In this review, we summarize the methodology for establishing human podocyte and PTEC cell lines from urine and highlight their importance as kidney disease cell models. We explore the well-established and recent techniques of cell isolation, quantification, immortalization and characterization, and we describe their current and future applications.
Rintatolimod Induces Antiviral Activities in Human Pancreatic Cancer Cells: Opening for an Anti-COVID-19 Opportunity in Cancer Patients?

Simple Summary Specific treatment for COVID-19 infections in cancer patients is lacking while the demand for treatment is increasing. Therefore, we explored the effect of Rintatolimod, a Toll-like receptor 3 (TLR3) agonist, on human epithelial cancerous cells. Our results demonstrated that Rintatolimod stimulated an anti-viral effect by producing RNase L that blocks virus replication. Moreover, Rintatolimod activated the innate and the adaptive immune systems by activating a cascade of actions in human cancerous cells. We believe that Rintatolimod should be considered in the treatment regimens of cancer patients who suffer from SARS-CoV-2 infection. Abstract Severe acute respiratory virus-2 (SARS-CoV-2) has spread globally leading to a devastating loss of life. Large registry studies have begun to shed light on the epidemiological and clinical vulnerabilities of cancer patients who succumb to or endure poor outcomes of SARS-CoV-2. Specific treatment for COVID-19 infections in cancer patients is lacking while the demand for treatment is increasing. Therefore, we explored the effect of Rintatolimod (Ampligen®) (AIM ImmunoTech, Ocala, FL, USA), a Toll-like receptor 3 (TLR3) agonist, to treat uninfected human pancreatic cancer cells (HPACs). The direct effect of Rintatolimod was measured by targeted gene expression profiling and by proteomics measurements. Our results show that Rintatolimod induces an antiviral effect in HPACs by inducing RNase-L-dependent and independent pathways of the innate immune system. Treatment with Rintatolimod activated the interferon signaling pathway, leading to the overexpression of several cytokines and chemokines in epithelial cells. Furthermore, Rintatolimod treatment increased the expression of angiogenesis-related genes without promoting fibrosis, which is the main cause of death in patients with COVID-19. We conclude that Rintatolimod could be considered an early additional treatment option for cancer patients who are infected with SARS-CoV-2 to prevent the complicated severity of the disease.
Diversity of Rainbow Trout Blood B Cells Revealed by Single Cell RNA Sequencing

Simple Summary Although evolutionarily jawed fish constitute the first group of animals in which a complete adaptive immune system based on immunoglobulins (Igs) is present, many structural immune differences between fish and mammals predict important functional and phenotypical differences between B cells in these two animal groups. However, to date, very few tools are available to study B cell heterogeneity and functionality in fish. Hence, thus far, antibodies targeting the different Igs have been almost exclusively applied as tools to investigate B cell functionality in fish. In the current study, we used the newly developed 10× Genomics single cell RNA sequencing technology and used it to analyze the transcriptional pattern of single B cells from peripheral blood. The results obtained provide us with a transcriptional profile at single cell level of what seem to correspond to different B cell subsets or B cells in different stages of maturation or differentiation. The information provided will not only help us understand the biology of teleost B cells, but also provides us with a repertoire of potential markers that could be used in the future to differentiate trout B cell subsets. Abstract Single-cell sequencing technologies capable of providing us with immune information from dozens to thousands of individual cells simultaneously have revolutionized the field of immunology these past years. However, to date, most of these novel technologies have not been broadly applied to non-model organisms such as teleost fish. In this study, we used the 10× Genomics single cell RNA sequencing technology and used it to analyze for the first time in teleost fish the transcriptional pattern of single B cells from peripheral blood. The analysis of the data obtained in rainbow trout revealed ten distinct cell clusters that seem to be associated with different subsets and/or maturation/differentiation stages of circulating B cells. The potential characteristics and functions of these different B cell subpopulations are discussed on the basis of their transcriptomic profile. The results obtained provide us with valuable information to understand the biology of teleost B cells and offer us a repertoire of potential markers that could be used in the future to differentiate trout B cell subsets.
Functional Characterization of the Photosynthetic Machinery in Smicronix Galls on the Parasitic Plant Cuscuta campestris by JIP-Test

Members of the genus Cuscuta are generally considered to be non-photosynthetic, stem-holoparasitic flowering plants. Under certain circumstances, at least some members of the genus are capable of limited photosynthesis. The galls of the Smicronyx weevils formed on Cuscuta campestris are particularly rich in chlorophylls compared to the stem of the parasitic plant. In the present study, we aimed to characterize the photosynthetic activity in the inner and outer gall cortices in comparison to the non-photosynthetic stems and a reference plant (Arabidopsis thaliana). The recorded prompt chlorophyll fluorescence transients were analyzed using JIP test. Detailed analysis of the chlorophyll fluorescence confirmed the presence of actively functioning photosynthetic machinery, especially in the inner cortex of the galls. This photosynthesis, induced by the insect larvae, did not reach the levels of the photosynthetic activity in Arabidopsis thaliana plants. Thylakoid protein complexes were identified by separation with two-dimensional Blue Native/SDS PAGE. It appeared that some of the complexes presented in A. thaliana are missing in C. campestris. We hypothesize that the insect-triggered transition from non-photosynthetic to photosynthetic tissue in the gall is driven by the increased requirements for nutrients related to the larval nutrition.
Comparison of Modern In Vitro Permeability Methods with the Aim of Investigation Nasal Dosage Forms

Nowadays, the intranasal route has become a reliable alternative route for drug administration to the systemic circulation or central nervous system. However, there are no official in vitro diffusion and dissolution tests especially for the investigation of nasal formulations. Our main goal was to study and compare a well-known and a lesser-known in vitro permeability investigation method, in order to ascertain which was suitable for the determination of drug permeability through the nasal mucosa from different formulations. The vertical diffusion cell (Franz cell) was compared with the horizontal diffusion model (Side-Bi-Side). Raw and nanonized meloxicam containing nasal dosage forms (spray, gel and powder) were tested and compared. It was found that the Side-Bi-Side cell was suitable for the investigation of spray and powder forms. In contrast, the gel was not measurable on the Side-Bi-Side cell; due to its high viscosity, a uniform distribution of the active substance could not be ensured in the donor phase. The Franz cell, designed for the analysis of semi-solid formulations, was desirable for the investigation of nasal gels. It can be concluded that the application of a horizontal cell is recommended for liquid and solid nasal preparations, while the vertical one should be used for semi-solid formulations.
The Cost-Effectiveness of Expanding Vaccination with a Cell-Based Influenza Vaccine to Low Risk Adults Aged 50 to 64 Years in the United Kingdom

Background: In response to COVID-19, the UK National Health Service (NHS) extended influenza vaccination in 50- to 64-year-olds from at-risk only to all in this age group for the 2020/21 season. The objective of this research is to determine the cost-effectiveness of continuing to vaccinate all with a quadrivalent cell-based vaccine (QIVc) compared to returning to an at-risk only policy after the pandemic resolves. Methods: A dynamic transmission model, calibrated to match infection data from the UK, was used to estimate the clinical and economic impact of vaccination across 10 influenza seasons. The base case effectiveness of QIVc was 63.9% and the list price was GBP 9.94. Results: Vaccinating 50% of all 50- to 64-year-olds with QIVc reduced the average annual number of clinical infections (−682,000), hospitalizations (−5800) and deaths (−740) in the UK. The base case incremental cost per quality-adjusted life-year gained (ICER) of all compared to at-risk only was GBP6000 (NHS perspective). When the cost of lost productivity was considered, vaccinating all 50- to 64-year-olds with QIVc became cost-saving. Conclusion: Vaccinating all 50- to 64-year-olds with QIVc is likely to be cost-effective. The NHS should consider continuing this policy in future seasons.
Precision Medicine in Oncology: A Review of Multi-Tumor Actionable Molecular Targets with an Emphasis on Non-Small Cell Lung Cancer

Precision medicine is essential for the modern care of a patient with cancer. Comprehensive molecular profiling of the tumor itself is necessary to determine the presence or absence of certain targetable abnormalities or biomarkers. In particular, lung cancer is a disease for which targetable genomic alterations will soon guide therapy in the majority of cases. In this comprehensive review of solid tumor-based biomarkers, we describe the genomic alterations for which targeted agents have been approved by the United States Food and Drug Administration (FDA). While focusing on alterations leading to approvals in a tumor-agnostic fashion (MSI-h, TMB-h, NTRK) and on those alterations with approvals in multiple malignancies (BRAF, ERBB2, RET, BRCA, PD-L1), we also describe several biomarkers or indications that are likely to lead to an approved drug in the near future (e.g., KRAS G12C, PD-L1 amplification, HER2 overexpression in colon cancer, HER2 mutations in lung cancer). Finally, we detail the current landscape of additional actionable alterations (EGFR, ALK, ROS1, MET) in lung cancer, a biomarker-rich malignancy that has greatly benefitted from the precision oncology revolution.
Roseabol A, a New Peptaibol from the Fungus Clonostachys rosea

A new 11 amino acid linear peptide named roseabol A (1) and the known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic acid (2) were isolated from the fungus Clonostachys rosea. Combined NMR and MS analysis revealed that roseabol A (1) contained amino acid residues characteristic of the peptaibol family of peptides such as isovaline, α-aminoisobutyric acid, hydroxyproline, leucinol, and an N-terminal isovaleric acid moiety. The amino acid sequence was established by a combination of NMR studies and tandem MS fragmentation analyses, and the absolute configurations of the constituent amino acids of 1 were determined by the advanced Marfey’s method. Compound 2 showed inhibitory activity against Merkel cell carcinoma, a rare and difficult-to-treat type of skin cancer, with an IC50 value of 16.5 μM.
Usefulness of Imaging Response Assessment after Irreversible Electroporation of Localized Pancreatic Cancer—Results from a Prospective Cohort

Simple Summary Irreversible electroporation (IRE) is a novel therapy that is being studied for the treatment of nonmetastatic pancreatic cancer. The current methods for evaluating the treatment response after IRE have been adapted from the Response Evaluation Criteria in Solid Tumors (RECIST). However, it is uncertain whether these methods are appropriate, because the methods have not been validated. The aim of the current study was to evaluate the correlation between survival time and the most commonly used imaging assessment methods on FDG-PET/CT scans. We confirmed that the Response Evaluation Criteria in Solid Tumors (RECIST) are correlated with survival, when applied as intended. However, no correlation was found when the often-used lesion-level method was used. FDG-PET-derived data did not provide any benefit over conventional CT data. Several novel methods for lesion-level analysis were explored. Abstract (1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.
Early Life Wheeze and Risk Factors for Asthma—A Revisit at Age 7 in the GEWAC-Cohort

One third of all toddlers are in need of medical care because of acute wheeze and many of these children have persistent asthma at school age. Our aims were to assess risk factors for and the prevalence of asthma at age 7 in a cohort of children suffering from an acute wheezing episode as toddlers. A total of 113 children, included during an acute wheezing episode (cases), and 54 healthy controls were followed prospectively from early pre-school age to 7 years. The protocol included questionnaires, ACT, FeNO, nasopharyngeal virus samples, blood sampling for cell count, vitamin D levels, and IgE to food and airborne allergens. The prevalence of asthma at age 7 was 70.8% among cases and 1.9% among controls (p < 0.001). Acute wheeze caused by rhinovirus (RV) infection at inclusion was more common among cases with asthma at age 7 compared to cases without asthma (p = 0.011) and this association remained significant following adjustment for infection with other viruses (OR 3.8, 95% CI 1.4–10.5). Cases with asthma at age 7 had been admitted to hospital more often (p = 0.024) and spent more days admitted (p = 0.01) during the year following inclusion compared to cases without asthma. RV infection stands out as the main associated factor for wheeze evolving to persistent asthma. Cases who developed asthma also had an increased need of hospital time and care for wheeze during the year after inclusion.
Daptomycin versus Glycopeptides for the Treatment of Enterococcus faecium Bacteraemia: A Cohort Study

Background: Ampicillin resistant and glycopeptide susceptible Enterococcus faecium bloodstream infection (GSEF-BSI) incidence has risen. However, the treatment of choice remains unknown. Daptomycin use for the treatment of enterococcal infections has increased, despite effectiveness and safety concerns. The objective was to compare the effectiveness and safety of daptomycin and glycopeptides in the treatment of GSEF-BSI. Methods: This was a single-centre, retrospective observational cohort study performed at Hospital del Mar (Barcelona, Spain), from January 2006–May 2018. The primary outcome was clinical cure at the end of the therapy, and secondary outcomes included 14-day, 30-day, in-hospital mortality, and length of stay. Results: From a total of 192 patients with GSEF-BSI, 54 (28.1%) were treated with glycopeptides and 17 (8.9%) with daptomycin. Patients treated with daptomycin presented a lower clinical cure than patients treated with glycopeptides (58.8% vs. 83.3%, RR 0.416 (95% CI 0.189–0.915)). After controlling for confounding variables by means of multivariate analysis the significative difference was confirmed (aOR 4.313, 95% CI, 1.053–17.660). The need for treatment discontinuation due to adverse events was similar. Conclusions: Patients with GSEF-BSI treated with glycopeptides showed a higher clinical cure than those treated with daptomycin.