Miracle-dz/UniFAR-FTUs huggingface dataset:
Precision Medicine and Melanoma: Multi-Omics Approaches to Monitoring the Immunotherapy Response

The treatment and management of patients with metastatic melanoma have evolved considerably in the “era” of personalized medicine. Melanoma was one of the first solid tumors to benefit from immunotherapy; life expectancy for patients in advanced stage of disease has improved. However, many progresses have yet to be made considering the (still) high number of patients who do not respond to therapies or who suffer adverse events. In this scenario, precision medicine appears fundamental to direct the most appropriate treatment to the single patient and to guide towards treatment decisions. The recent multi-omics analyses (genomics, transcriptomics, proteomics, metabolomics, radiomics, etc.) and the technological evolution of data interpretation have allowed to identify and understand several processes underlying the biology of cancer; therefore, improving the tumor clinical management. Specifically, these approaches have identified new pharmacological targets and potential biomarkers used to predict the response or adverse events to treatments. In this review, we will analyze and describe the most important omics approaches, by evaluating the methodological aspects and progress in melanoma precision medicine.
Guaranteed State Estimation Using a Bundle of Interval Observers with Adaptive Gains Applied to the Induction Machine

The scope of this paper is the design of an interval observer bundle for the guaranteed state estimation of an uncertain induction machine with linear, time-varying dynamics. These guarantees are of particular interest in the case of safety-critical systems. In many cases, interval observers provide large intervals for which the usability becomes impractical. Hence, based on a reduced-order hybrid interval observer structure, the guaranteed enclosure within intervals of the magnetizing current’s estimates is improved using a bundle of interval observers. One advantage of such an interval observer bundle is the possibility to reinitialize the interval observers at specified timesteps during runtime with smaller initial intervals, based on previously observed system states, resulting in decreasing interval widths. Thus, unstable observer dynamics are considered so as to take advantage of their transient behavior, whereby the overall stability of the interval estimation is maintained. An algorithm is presented to determine the parametrization of reduced-order interval observers. To this, an adaptive observer gain is introduced with which the system states are observed optimally by considering a minimal interval width at variable operating points. Furthermore, real-time capability and validation of the proposed methods are shown. The results are discussed with simulations as well as experimental data obtained with a test bench.
Super-Resolution STED Microscopy-Based Mobility Studies of the Viral Env Protein at HIV-1 Assembly Sites of Fully Infected T-Cells

The ongoing threat of human immunodeficiency virus (HIV-1) requires continued, detailed investigations of its replication cycle, especially when combined with the most physiologically relevant, fully infectious model systems. Here, we demonstrate the application of the combination of stimulated emission depletion (STED) super-resolution microscopy with beam-scanning fluorescence correlation spectroscopy (sSTED-FCS) as a powerful tool for the interrogation of the molecular dynamics of HIV-1 virus assembly on the cell plasma membrane in the context of a fully infectious virus. In this process, HIV-1 envelope glycoprotein (Env) becomes incorporated into the assembling virus by interacting with the nascent Gag structural protein lattice. Molecular dynamics measurements at these distinct cell surface sites require a guiding strategy, for which we have used a two-colour implementation of sSTED-FCS to simultaneously target individual HIV-1 assembly sites via the aggregated Gag signal. We then compare the molecular mobility of Env proteins at the inside and outside of the virus assembly area. Env mobility was shown to be highly reduced at the assembly sites, highlighting the distinct trapping of Env as well as the usefulness of our methodological approach to study the molecular mobility of specifically targeted sites at the plasma membrane, even under high-biosafety conditions.
Differentially Expressed Gene Patterns in Ascarid-Infected Chickens of Higher- or Lower-Performing Genotypes

Simple Summary Nematode infections may increase mortality and welfare problems in laying hens. The two ascarid worms, Ascaridia galli and Heterakis gallinarum, are highly prevalent in laying hens kept in non-cage housing systems worldwide. The ability of a host to expel pathogens is a component of resistance to diseases. The molecular basis of differences between different host animals in their efficiency to expel worms is, however, not well understood. Therefore, we performed a detailed analysis of differentially expressed genes (DEGs) in two chicken genotypes (Lohmann Brown Plus (LB), Lohmann Dual (LD)), each with a lower or higher infection intensity level of A. galli and H. gallinarum. Our data showed significant upregulation of Guanylate Binding Protein 7 (GBP7) in LD hens. Gene ontology analysis revealed higher transcriptome activity related to “response to external stimulus” in LB hens, implying a higher stress response in this genotype. In contrast, LD hens showed higher transcriptomic expression of genes associated with a higher tolerance to infections. Abstract Here, we describe the first transcriptomic investigation of the peripheral blood of chickens exposed to Ascaridia galli and Heterakis gallinarum infections. We investigated differentially expressed gene (DEG) patterns in two chicken genotypes with either a higher (Lohmann Brown Plus, LB) or lower (Lohmann Dual, LD) laying performance level. The hens were experimentally coinfected with A. galli and H. gallinarum, and their worm burdens and infection parameters were determined six weeks post infection. Based on most representative infection parameters, the hens were clustered into lower- and higher-infection intensity classes. We identified a total of 78 DEGs contributing to infection-related phenotypic variation in the two genotypes. Our data showed significant upregulation of Guanylate Binding Protein 7 (GBP7) in LD hens, making it a promising candidate for tolerance to ascarid infections in chickens. Gene ontology analysis revealed higher transcriptome activity related to biological processes such as “response to external stimulus” in LB hens, implying a higher stress response in this genotype. In contrast, LD hens showed higher transcriptomic expression of genes related to ontology classes that are possibly associated with a higher tolerance to infections. These findings may help explain why lower-performing genotypes (i.e., LD) are less sensitive to infections in terms of maintaining their performance.
Effects of Dietary Protein Level on the Gut Microbiome and Nutrient Metabolism in Tilapia (Oreochromis niloticus)

Simple Summary Dietary protein is an important factor affecting aquaculture. In this study, the homeostasis of the gut microbiome and metabolic profile of the liver and serum of tilapia were analyzed, comparing those fed with different diets to evaluate the effect of diet on protein levels. As a result, there was no significant difference found in the diversity and richness of the gut microbiome but had differences in the microbial composition of the gut among different groups. As for the liver metabolome of the tilapia, the glucose content increased along with increased protein levels. As for serum metabolome, the levels of tyrosine, guanosine, and inosine were significantly different. In summary, diets with different protein levels can affect the composition of gut microbiota and glycolysis and amino acid metabolism in tilapia. These results may also help to improve the conditions of tilapia cultivation. Abstract Dietary protein is one of the most important nutritional factors in aquaculture. The aim of this study was to examine the effects of dietary protein levels on the gut microbiome and the liver and serum levels of metabolites in tilapia. Tilapia were fed a diet with a low (20%), moderate (30%), or high (40%) content of crude protein, and the homeostasis of the gut microbiome and metabolic profile of the liver and serum were analyzed. The results showed no significant differences in the diversity and richness of the gut microbiome among the groups; however, there were differences in the microbial composition of the gut. The metabolome analysis of liver samples revealed a difference in the glucose level among the groups, with the highest glucose level in fish fed a high protein diet. In addition, there were significant differences in the levels of tyrosine, guanosine, and inosine among the metabolome analysis of serum samples of these groups. In summary, diets with different protein levels could affect the composition of gut microbiota and the dynamic balance of microbial communities. Dietary protein content can also affect glycolysis and amino acid metabolism in tilapia.
Exploring the Loci Responsible for Awn Development in Rice through Comparative Analysis of All AA Genome Species

Wild rice species have long awns at their seed tips, but this trait has been lost through rice domestication. Awn loss mitigates harvest and seed storage; further, awnlessness increases the grain number and, subsequently, improves grain yield in Asian cultivated rice, highlighting the contribution of the loss of awn to modern rice agriculture. Therefore, identifying the genes regulating awn development would facilitate the elucidation of a part of the domestication process in rice and increase our understanding of the complex mechanism in awn morphogenesis. To identify the novel loci regulating awn development and understand the conservation of genes in other wild rice relatives belonging to the AA genome group, we analyzed the chromosome segment substitution lines (CSSL). In this study, we compared a number of CSSL sets derived by crossing wild rice species in the AA genome group with the cultivated species Oryza sativa ssp. japonica. Two loci on chromosomes 7 and 11 were newly discovered to be responsible for awn development. We also found wild relatives that were used as donor parents of the CSSLs carrying the functional alleles responsible for awn elongation, REGULATOR OF AWN ELONGATION 1 (RAE1) and RAE2. To understand the conserveness of RAE1 and RAE2 in wild rice relatives, we analyzed RAE1 and RAE2 sequences of 175 accessions among diverse AA genome species retrieved from the sequence read archive (SRA) database. Comparative sequence analysis demonstrated that most wild rice AA genome species maintained functional RAE1 and RAE2, whereas most Asian rice cultivars have lost either or both functions. In addition, some different loss-of-function alleles of RAE1 and RAE2 were found in Asian cultivated species. These findings suggest that different combinations of dysfunctional alleles of RAE1 and RAE2 were selected after the speciation of O. sativa, and that two-step loss of function in RAE1 and RAE2 contributed to awnlessness in Asian cultivated rice.
Human Cadaveric Donor Cornea Derived Extra Cellular Matrix Microparticles for Minimally Invasive Healing/Regeneration of Corneal Wounds

Biological materials derived from extracellular matrix (ECM) proteins have garnered interest as their composition is very similar to that of native tissue. Herein, we report the use of human cornea derived decellularized ECM (dECM) microparticles dispersed in human fibrin sealant as an accessible therapeutic alternative for corneal anterior stromal reconstruction. dECM microparticles had good particle size distribution (≤10 µm) and retained the majority of corneal ECM components found in native tissue. Fibrin–dECM hydrogels exhibited compressive modulus of 70.83 ± 9.17 kPa matching that of native tissue, maximum burst pressure of 34.3 ± 3.7 kPa, and demonstrated a short crosslinking time of ~17 min. The fibrin–dECM hydrogels were found to be biodegradable, cytocompatible, non-mutagenic, non-sensitive, non-irritant, and supported the growth and maintained the phenotype of encapsulated human corneal stem cells (hCSCs) in vitro. In a rabbit model of anterior lamellar keratectomy, fibrin–dECM bio-adhesives promoted corneal re-epithelialization within 14 days, induced stromal tissue repair, and displayed integration with corneal tissues in vivo. Overall, our results suggest that the incorporation of cornea tissue-derived ECM microparticles in fibrin hydrogels is non-toxic, safe, and shows tremendous promise as a minimally invasive therapeutic approach for the treatment of superficial corneal epithelial wounds and anterior stromal injuries.
Modelling and Experimental Assessment of Inter-Personal Distancing Based on Shared GNSS Observables

In the last few years, all countries worldwide have fought the spread of SARS-CoV-2 (COVID-19) by exploiting Information and Communication Technologies (ICT) to perform contact tracing. In parallel, the pandemic has highlighted the relevance of mobility and social distancing among citizens. The monitoring of such aspects appeared prominent for reactive decision-making and the effective tracking of the infection chain. In parallel to the proximity sensing among people, indeed, the concept of social distancing has captured the attention to signal processing algorithms enabling short-to-medium range distance estimation to provide behavioral models in the emergency. By exploiting the availability of smart devices, the synergy between mobile network connectivity and Global Navigation Satellite Systems (GNSS), cooperative ranging approaches allow computing inter-personal distance measurements in outdoor environments through the exchange of light-weight navigation data among interconnected users. In this paper, a model for Inter-Agent Ranging (IAR) is provided and experimentally assessed to offer a naive collaborative distancing technique that leverages these features. Although the technique provides distance information, it does not imply the disclosure of the user’s locations being intrinsically prone to protect sensitive user data. A statistical error model is presented and validated through synthetic simulations and real, on-field experiments to support implementation in GNSS-equipped mobile devices. Accuracy and precision of IAR measurements are compared to other consolidated GNSS-based techniques showing comparable performance at lower complexity and computational effort.
Li2(BH4)(NH2) Nanoconfined in SBA-15 as Solid-State Electrolyte for Lithium Batteries

Solid electrolytes with high Li-ion conductivity and electrochemical stability are very important for developing high-performance all-solid-state batteries. In this work, Li2(BH4)(NH2) is nanoconfined in the mesoporous silica molecule sieve (SBA-15) using a melting–infiltration approach. This electrolyte exhibits excellent Li-ion conduction properties, achieving a Li-ion conductivity of 5.0 × 10−3 S cm−1 at 55 °C, an electrochemical stability window of 0 to 3.2 V and a Li-ion transference number of 0.97. In addition, this electrolyte can enable the stable cycling of Li|Li2(BH4)(NH2)@SBA-15|TiS2 cells, which exhibit a reversible specific capacity of 150 mAh g−1 with a Coulombic efficiency of 96% after 55 cycles.
Comparison of the Effect of Resistance and Balance Training on Isokinetic Eversion Strength, Dynamic Balance, Hop Test, and Ankle Score in Ankle Sprain

Ankle sprain is a commonly recurring sports injury. This study aimed to compare the rehabilitation effects of resistance and balance training programs in patients with recurrent ankle sprain. Patients with recurrent lateral ankle sprain completed a home-based rehabilitation program comprising resistance training (RT; n = 27) or balance training (BT; n = 27). RT consisted of exercises using elastic tube bands, and BT consisted mainly of exercises performed using a variety of balance tools. Exercises were performed for 6 weeks, twice a day for 20 min, 5 days per week. Isokinetic eversion strength, Y-Balance test and hop tests, and foot and ankle outcome score (FAOS) were evaluated. Both RT and BT significantly improved strength and dynamic balance (p < 0.05). Compared to RT, BT also significantly improved the outcome of the crossover hop test (p = 0.008). The changes reflected group and time in pain (p = 0.022), sports (p = 0.027), and quality of life (p = 0.033) of FAOS were significantly greater in BT than RT.
Modification of Bacteriophages to Increase Their Association with Lung Epithelium Cells In Vitro

There is currently a renaissance in research on bacteriophages as alternatives to antibiotics. Phage specificity to their bacterial host, in addition to a plethora of other advantages, makes them ideal candidates for a broad range of applications, including bacterial detection, drug delivery, and phage therapy in particular. One issue obstructing phage efficiency in phage therapy settings is their poor localization to the site of infection in the human body. Here, we engineered phage T7 with lung tissue targeting homing peptides. We then used in vitro studies to demonstrate that the engineered T7 phages had a more significant association with the lung epithelium cells than wild-type T7. In addition, we showed that, in general, there was a trend of increased association of engineered phages with the lung epithelium cells but not mouse fibroblast cells, allowing for targeted tissue specificity. These results indicate that appending phages with homing peptides would potentially allow for greater phage concentrations and greater efficacy at the infection site.
Development of an Electrostatic Comb-Driven MEMS Scanning Mirror for Two-Dimensional Raster Scanning

Microelectromechanical System (MEMS)-based scanning mirrors are important optical devices that have been employed in many fields as a low-cost and miniaturized solution. In recent years, the rapid development of Light Detection and Ranging (LiDAR) has led to opportunities and challenges for MEMS scanners. In this work, we propose a 2D electrostatically actuated micro raster scanner with relatively large aperture. The 2D scanner combines a resonant scanning axis driven by an in-plane comb and a quasistatic scanning axis driven by a vertical comb, which is achieved by raising the moving comb finger above the fixed comb finger through the residual stress gradient. The analytic formula for the resonant axis frequency, based on the mechanical coupling of two oscillation modes, is derived and compared with finite element simulation. A prototype is designed, fabricated, and tested, and an overall optical Field-of-View (FoV) of about 60° × 4° is achieved. Finally, some possibilities for further improvement or optimization are discussed.
Complementary Feeding and Overweight in European Preschoolers: The ToyBox-Study

Complementary feeding (CF) should start between 4–6 months of age to ensure infants’ growth but is also linked to childhood obesity. This study aimed to investigate the association of the timing of CF, breastfeeding and overweight in preschool children. Infant-feeding practices were self-reported in 2012 via a validated questionnaire by >7500 parents from six European countries participating in the ToyBox-study. The proportion of children who received breast milk and CF at 4–6 months was 51.2%. There was a positive association between timing of solid food (SF) introduction and duration of breastfeeding, as well as socioeconomic status and a negative association with smoking throughout pregnancy (p < 0.005). No significant risk to become overweight was observed among preschoolers who were introduced to SF at 1–3 months of age compared to those introduced at 4–6 months regardless of the type of milk feeding. Similarly, no significant association was observed between the early introduction of SF and risk for overweight in preschoolers who were breastfed for ≥4 months or were formula-fed. The study did not identify any significant association between the timing of introducing SF and obesity in childhood. It is likely that other factors than timing of SF introduction may have impact on childhood obesity.
Assessment of Agreement between Two Difference Prostate-Specific Antigen Assay Modalities

Simple Summary Prostate-specific antigen is a biomarker for prostate cancer. If the level of prostate-specific antigen is high, a prostate biopsy is needed to diagnose prostate cancer. However, the definite level of prostate-specific antigen that requires prostate biopsy has not been established. Currently, there are many kinds of assay modalities that have been used for prostate-specific antigen testing. This study was conducted under the hypothesis that there will be differences between different assay modalities; therefore, there is no definite prostate-specific antigen level for prostate biopsy. In our study, the level of prostate-specific antigens was measured in one blood sample per patient, with two different assay modalities in 4810 patients. As a result, we confirmed that the overall agreement between the two modalities is excellent, but the agreement is slightly different in some ranges that may give clinical significance. Accordingly, the conformity between each assay modality should be secured in the future, and the threshold for the level of prostate-specific antigens for biopsy by each assay modality should be independently determined. Abstract There is controversy over the usefulness of prostate-specific antigen (PSA) as a prostate cancer (PCa) biomarker. This controversy arises when there are differences in the results of PSA assay modalities. In this study, which aimed to evaluate a proper validation between the two PSA assay modalities, the agreement between the results of the two modalities was analyzed. PSA examinations were conducted using two PSA assay modalities in 4810 patients. The intra-class correlation coefficient (ICC) and weighted kappa analysis were used to evaluate the agreement between the two assay modalities. A linear regression was performed to evaluate the association between the two assay modalities. According to ICC values (ICC: 0.999, p < 0.001) and weighted kappa analysis values (kappa: 0.951, alpha’s standard error (ASE): 0.001, p < 0.0001), the agreement between the assay modalities was rated as excellent. However, the strength of agreement was poor in the following PSA sub-groups: 0.05–0.1 ng/mL (ICC: 0.281, p = 0.0860); 0.15–0.2 ng/mL (ICC: 0.288, p = 0.0036); 1.5–2.0 ng/mL (ICC: 0.360, p = 0.0860); and 2.0–2.5 ng/mL (ICC: 0.303, p = 0.0868). In linear regression analysis, when modality B PSA yielded a value of 0.2 ng/mL, the expected value for modality A was 0.258 ng/mL (95% CI: 0.255–0.260), and when modality B PSA yielded a value of 4 ng/mL, the expected value for modality A was 3.192 ng/mL (95% CI: 3.150–3.235). The difference in the PSA values between the two PSA assay modalities is confirmed, and this difference may be clinically meaningful.