Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenovirus-Derived Nano-Capsid Platforms for Targeted Delivery and Penetration of Macromolecules into Resistant and Metastatic Tumors

Simple Summary Many cancer therapeutics may have a robust effect on target molecules but lack the means of effective localization into tumor cells, thus displaying reduced therapeutic efficacy. Viruses bear naturally evolved machinery to ensure entry and localization of nucleic acid cargo into a cell. Utilizing and better understanding the mechanism of the penton base protein that contributes to the adenovirus cell entry machinery may improve the intracellular delivery of tumor targeting therapeutics. This review describes the progression of penton-base-derived cancer nanotherapeutic development and highlights essential requirements for robust delivery into a tumor cell. Abstract Macromolecular therapeutics such as nucleic acids, peptides, and proteins have the potential to overcome treatment barriers for cancer. For example, nucleic acid or peptide biologics may offer an alternative strategy for attacking otherwise undruggable therapeutic targets such as transcription factors and similar oncologic drivers. Delivery of biological therapeutics into tumor cells requires a robust system of cell penetration to access therapeutic targets within the cell interior. A highly effective means of accomplishing this may be borrowed from cell-penetrating pathogens such as viruses. In particular, the cell entry function of the adenovirus penton base capsid protein has been effective at penetrating tumor cells for the intracellular deposition of macromolecular therapies and membrane-impermeable drugs. Here, we provide an overview describing the evolution of tumor-targeted penton-base-derived nano-capsids as a framework for discussing the requirements for overcoming key barriers to macromolecular delivery. The development and pre-clinical testing of these proteins for therapeutic delivery has begun to also uncover the elusive mechanism underlying the membrane-penetrating function of the penton base. An understanding of this mechanism may unlock the potential for macromolecular therapeutics to be effectively delivered into cancer cells and to provide a treatment option for tumors resisting current clinical therapies.
Using a Smartphone-Based Colorimetric Device with Molecularly Imprinted Polymer for the Quantification of Tartrazine in Soda Drinks

The present study reports the development and application of a rapid, low-cost in-situ method for the quantification of tartrazine in carbonated beverages using a smartphone-based colorimetric device with molecularly imprinted polymer (MIP). The MIP was synthesized using the free radical precipitation method with acrylamide (AC) as the functional monomer, N,N′-methylenebisacrylamide (NMBA) as the cross linker, and potassium persulfate (KPS) as radical initiator. The smartphone (RadesPhone)-operated rapid analysis device proposed in this study has dimensions of 10 × 10 × 15 cm and is illuminated internally by light emitting diode (LED) lights with intensity of 170 lux. The analytical methodology involved the use of a smartphone camera to capture images of MIP at various tartrazine concentrations, and the subsequent application of the Image-J software to calculate the red, green, blue (RGB) color values and hue, saturation, value (HSV) values from these images. A multivariate calibration analysis of tartrazine in the range of 0 to 30 mg/L was performed, and the optimum working range was determined to be 0 to 20 mg/L using five principal components and a limit of detection (LOD) of 1.2 mg/L was obtained. Repeatability analysis of tartrazine solutions with concentrations of 4, 8, and 15 mg/L (n = 10) showed a coefficient of variation (% RSD) of less than 6%. The proposed technique was applied to the analysis of five Peruvian soda drinks and the results were compared with the UHPLC reference method. The proposed technique showed a relative error between 6% and 16% and % RSD lower than 6.3%. The results of this study demonstrate that the smartphone-based device is a suitable analytical tool that offers an on-site, cost-effective, and rapid alternative for the quantification of tartrazine in soda drinks. This color analysis device can be used in other molecularly imprinted polymer systems and offers a wide range of possibilities for the detection and quantification of compounds in various industrial and environmental matrices that generate a color change in the MIP matrix.
Graft-Derived Cell-Free DNA Quantification following Liver Transplantation Using Tissue-Specific DNA Methylation and Donor-Specific Genotyping Techniques: An Orthogonal Comparison Study

Background: Graft-derived cell-free DNA (gdcfDNA) analysis has shown promise as a non-invasive tool for monitoring organ health following solid organ transplantation. A number of gdcfDNA analysis techniques have been described; however, the majority rely on sequencing or prior genotyping to detect donor-recipient mis-matched genetic polymorphisms. Differentially methylated regions of DNA can be used to identify the tissue-of-origin of cell-free DNA (cfDNA) fragments. In this study, we aimed to directly compare the performance of gdcfDNA monitoring using graft-specific DNA methylation analysis and donor-recipient genotyping techniques in a pilot cohort of clinical samples from patients post-liver transplantation. Results: 7 patients were recruited prior to LT, 3 developed early, biopsy-proven TCMR in the first 6 weeks post-LT. gdcfDNA was successfully quantified in all samples using both approaches. There was a high level of technical correlation between results using the two techniques (Spearman testing, rs = 0.87, p < 0.0001). gdcfDNA levels quantified using the genotyping approach were significantly greater across all timepoints in comparison to the tissue-specific DNA methylation-based approach: e.g., day 1 post-LT median 31,350 copies/mL (IQR 6731–64,058) vs. 4133 copies/mL (IQR 1100–8422), respectively. Qualitative trends in gdcfDNA levels for each patient were concordant between the two assays. Acute TCMR was preceded by significant elevations in gdcfDNA as quantified by both techniques. Elevations in gdcfDNA, using both techniques, were suggestive of TCMR in this pilot study with a 6- and 3-day lead-time prior to histological diagnosis in patients 1 and 2. Conclusions: Both the graft-specific methylation and genotyping techniques successfully quantified gdcfDNA in patients post-LT with statistically significant concordance. A direct comparison of these two techniques is not only important from a technical perspective for orthogonal validation, but significantly adds weight to the evidence that gdcfDNA monitoring reflects the underlying biology. Both techniques identified LT recipients who developed acute TCMR, with several days lead-time in comparison to conventional diagnostic workflows. Whilst the two assays performed comparably, gdcfDNA monitoring based on graft-specific DNA methylation patterns in cfDNA offers major practical advantages over the donor-recipient genotyping, and hence enhances the potential to translate this emerging technology into clinical practice.
Effect of Autumn Irrigation on Salt Leaching under Subsurface Drainage in an Arid Irrigation District

Non-growing season irrigation and farmland subsurface drainage play a crucial role in salt leaching and salinization control in arid irrigation areas. This study aimed to investigate the reduction of autumn irrigation quotas and drainage discharge while maintaining soil moisture retention and reducing soil salinization. Field experiments were conducted with different autumn irrigation quotas (160 mm for SD1, 180 mm for SD2, and 200 mm for SD3) combined with subsurface drainage (1.5 m drain depth and 45 m spacing). A control treatment (referred to as CK) without subsurface drainage received 200 mm of irrigation. The results showed that, after 31 days of autumn irrigation, the groundwater depth in all three subsurface drainage plots stabilized to 1.5 m, with the CK being 0.2–0.3 m shallower compared to the SD plots. The mean soil water content in the 0–150 cm soil layer of the SD1, SD2, SD3, and CK after autumn irrigation was 0.36, 0.39, 0.41, and 0.42 cm3cm−3, respectively. The combination of autumn irrigation and subsurface drainage significantly reduced the soil salt content. The mean desalination rates in the root zone (0–60 cm) soil layer were 57.5%, 53.7%, 51.9%, and 45.1% for the SD3, SD2, CK, and SD1, respectively. The mean desalination rate of 60–150 cm was not significantly different between the SD2 and SD3 (p > 0.05), and both were significantly higher than that of the SD1 and CK (p < 0.05). The drainage discharge was 31, 36, and 40 mm in the SD1, SD2 and SD3, respectively. The amount of salt discharge through the drain pipe increased with increasing irrigation quota, which was 1.22 t/ha, 1.41 t/ha, and 1.50 t/ha for the SD1, SD2, and SD3, respectively. Subsurface drainage is an effective way to prevent salt accumulation in the soil, and an autumn irrigation quota of 180 mm is recommended for leaching of salinity in the Hetao Irrigation District. These findings provide valuable insights into optimizing irrigation practices and managing soil salinization in arid regions.
Pharmaceutical Communication in Spain around the COVID-19 Crisis: A Scoping Review

This paper addresses the scientific production of pharmaceutical communication in Spain around the COVID-19 crisis, in which information overload, amplified by the digital media, evidenced the relevance of communication in the digital society. The research observes the evolution and characteristics of such studies, identifying scientific fields and disciplines related to communication, thematic lines, agents and publics. To this end, it proposes an exploratory review study adjusted to the PRISMA protocol with a search strategy including three databases (Scopus, WOS and Dialnet) and whose filtration produced a final population of 56 publications on Spanish pharmaceutical communication between 2018 and 2022. The results point to a greater production of scientific papers around the year of the pandemic. These papers were published by university institutions in health sciences journals, although differences in authorship by gender were detected. Most of them are empirical papers, with a predominance of mixed content analyses. The field of public relations stands out, but terminological confusion was also detected. This leads to a reflection on its causes and solutions in favour of the transparency and accountability in pharmaceutical communication.
Induction of Reactive Bone Stromal Fibroblasts in 3D Models of Prostate Cancer Bone Metastases

Simple Summary When prostate cancer cells spread to other parts of the body (metastasise), they frequently migrate to the bone. Here they encounter a microenvironment that differs greatly from that in the primary tumour (prostate), namely interactions with bone-specific cells, including fibroblasts. To better understand the contribution of these fibroblasts to tumour progression, it is the aim of the current paper to propagate a biologically relevant fibroblast population that mimics the cellular and molecular profile of fibroblasts as found in the metastatic bone environment in the body. Using three-dimensional (3D) cell culture models, we were able to transform normal fibroblast cells into fibroblasts that express modified protein and gene profiles similar to those found in fibroblasts in the metastatic bone environment in the body. The exploitation of these engineered 3D models could help further unravel the novel biology regulating metastatic growth and the role fibroblasts play in the colonisation process. Elucidation of these processes has the potential to aid in the development of therapies not currently available for late-stage cancers. Abstract A dynamic interplay between prostate cancer (PCa) cells and reactive bone stroma modulates the growth of metastases within the bone microenvironment. Of the stromal cells, metastasis-associated fibroblasts (MAFs) are known to contribute but are the least studied cell type in PCa tumour progression. It is the aim of the current study to establish a biologically relevant 3D in vitro model that mimics the cellular and molecular profiles of MAFs found in vivo. Using 3D in vitro cell culture models, the bone-derived fibroblast cell line, HS-5, was treated with conditioned media from metastatic-derived PCa cell lines, PC3 and MDA-PCa 2b, or mouse-derived fibroblasts 3T3. Two corresponding reactive cell lines were propagated: HS5-PC3 and HS5-MDA, and evaluated for alterations in morphology, phenotype, cellular behaviour, plus protein and genomic profiles. HS5-PC3 and HS5-MDA displayed distinct alterations in expression levels of N-Cadherin, non-functional E-Cadherin, alpha-smooth muscle actin (α-SMA), Tenascin C, and vimentin, along with transforming growth factor receptor expression (TGF β R1 and R2), consistent with subpopulations of MAFs reported in vivo. Transcriptomic analysis revealed a reversion of HS5-PC3 towards a metastatic phenotype with an upregulation in pathways known to regulate cancer invasion, proliferation, and angiogenesis. The exploitation of these engineered 3D models could help further unravel the novel biology regulating metastatic growth and the role fibroblasts play in the colonisation process.
The Lost and Found: Unraveling the Functions of Orphan Genes

Orphan Genes (OGs) are a mysterious class of genes that have recently gained significant attention. Despite lacking a clear evolutionary history, they are found in nearly all living organisms, from bacteria to humans, and they play important roles in diverse biological processes. The discovery of OGs was first made through comparative genomics followed by the identification of unique genes across different species. OGs tend to be more prevalent in species with larger genomes, such as plants and animals, and their evolutionary origins remain unclear but potentially arise from gene duplication, horizontal gene transfer (HGT), or de novo origination. Although their precise function is not well understood, OGs have been implicated in crucial biological processes such as development, metabolism, and stress responses. To better understand their significance, researchers are using a variety of approaches, including transcriptomics, functional genomics, and molecular biology. This review offers a comprehensive overview of the current knowledge of OGs in all domains of life, highlighting the possible role of dark transcriptomics in their evolution. More research is needed to fully comprehend the role of OGs in biology and their impact on various biological processes.
The cobra maneuver as a minimum time problem

The Cobra maneuver is envisioned as a pursuerevader problem in which the evader is to become the pursuer and attack the other aircraft. It is formulated as a minimum time problem and solved numerically for several sets of final conditions. If the final relative distance and flight path angle are prescribed, the minimum time maneuver looks like the Cobra maneuver, but the final speed is below the stall speed. If the final speed is also prescribed, the minimum time maneuver differs somewhat from the Cobra maneuver. Three-degree-of-freedom equations of motion and an F-16 model are used.
Underwater Transmitter Localization Based on TDOA and FDOA Considering the Unknown Time-Varying Emission Frequency

This article considers locating a noncooperative underwater transmitter utilizing multiple receivers, such that each receiver can measure the frequency difference of arrival (FDOA) as well as the time difference of arrival (TDOA) of the transmitter’s sound. This article considers the case where the unknown emission frequency of the transmitter changes as time goes. This article addresses hybrid TDOA-FDOA localization, under the assumption that the transmitter’s maximum speed is known in advance. To the best of our knowledge, this article is unique in tackling hybrid TDOA-FDOA localization, considering the case where the unknown emission frequency changes as time goes on. Under MATLAB simulations, this article shows that the proposed hybrid localization method is comparable to the ideal case, where the time-varying emission frequency is known in advance. Furthermore, we show that the proposed localization approach outperforms the case where the emission frequency is estimated as a wrong value.
Ultrasonic Levitation. Establishment of Levitation Theory and Clarification of Levitation Characteristics.

Objects weighing a few kilograms and having a large flat surface can be levirated near an ultrasonic vibration surface. A gap of minimal thickness is formed between the object and the vibration surface, and the acoustic radiation pressure in the gap is considered to be the root cause of generation of the levitation force. The purpose of this study is to clarify the mechanism and the characteristics of the ultrasonic levitation. In this work, several experiments are performed and the sound pressure in the gap is analyzed theoretically to grasp the essentials of the phenomenon. Through the experimental and the theoretical studies, the acoustic radiation pressure in the gap is analyzed using the fluid dynamics method, and a theory of ultrasonic levitation is established. Then the main factors of the levitation phenomenon are presented theoretically. The analytical results based on our theory agree well with the experimental ones.
Youth Adoption of Innovative Digital Marketing and Cross-Cultural Disparities

This paper aims to explore Youth’s attitudes towards digital marketing utility perception and its effect on behavioral patterns in a cross-cultural perspective. The unified theory of acceptance and use of technology (UTAUT 2) model was adopted together with three new variables from the reasoned action theory and the 5S Internet marketing model to propose a theoretical model on Youth’s digital marketing adoption. A survey was conducted in Italy (N = 165) and Lebanon (N = 150), and PLS analysis was implemented for the empirical testing of the proposed research model. In the Italian sample, Hedonic motivation, social influence, facilitating conditions, and efficiency significantly predicted the behavioral intention of digital marketing which, in turn, was significantly related to use behavior. Subsequently, in the Lebanese sample, the subjective norms of hedonic motivation, social influence, experience and habit predicted behavioral intention, which was positively related with use behavior. The results led to the conclusion that national cultures still play an important role in affecting digital marketing adoption among younger generations, especially in less industrialized and technologically developed countries. Therefore, companies should keep this aspect in mind when innovating and developing digital marketing strategies targeting this generation.
The Application of Design Thinking in Developing a Deep Learning Algorithm for Hip Fracture Detection

(1) Background: Design thinking is a problem-solving approach that has been applied in various sectors, including healthcare and medical education. While deep learning (DL) algorithms can assist in clinical practice, integrating them into clinical scenarios can be challenging. This study aimed to use design thinking steps to develop a DL algorithm that accelerates deployment in clinical practice and improves its performance to meet clinical requirements. (2) Methods: We applied the design thinking process to interview clinical doctors and gain insights to develop and modify the DL algorithm to meet clinical scenarios. We also compared the DL performance of the algorithm before and after the integration of design thinking. (3) Results: After empathizing with clinical doctors and defining their needs, we identified the unmet need of five trauma surgeons as “how to reduce the misdiagnosis of femoral fracture by pelvic plain film (PXR) at initial emergency visiting”. We collected 4235 PXRs from our hospital, of which 2146 had a hip fracture (51%) from 2008 to 2016. We developed hip fracture DL detection models based on the Xception convolutional neural network by using these images. By incorporating design thinking, we improved the diagnostic accuracy from 0.91 (0.84–0.96) to 0.95 (0.93–0.97), the sensitivity from 0.97 (0.89–1.00) to 0.97 (0.94–0.99), and the specificity from 0.84 (0.71–0.93) to 0.93(0.990–0.97). (4) Conclusions: In summary, this study demonstrates that design thinking can ensure that DL solutions developed for trauma care are user-centered and meet the needs of patients and healthcare providers.
Hydrodynamic analysis of multi-body floating system in waves: from rigid to flexible structures

The hydrodynamic problem for multi-body systems in waves has complexity in both wave structure interaction and coupled dynamics with interconnection. A consistent approach is developed for calculating the dynamic response of multi-body floating systems. This method is based on multi-rigid-body hydrodynamics and Euler-beam bending theory and can be used to deal with rigid or flexible multi-body floating systems in both frequency and time domain. Within the framework of this consistent approach, a stiffness approximation method is proposed to calculate the natural frequency and corresponding oscillation mode of a hinged multi-module structure. This is significant for both traditional multi-body floating system (for the purpose of structural safety) and wave energy converters (for the purpose of power efficiency). The hydroelasticity theory proposed by Lu et al. (2016), which is used to deal with continuous flexible structures with cross section of simple shapes, is extended to be applicable for multi-module flexible structures with cross section of arbitrary shapes and varied geometric features in longitudinal direction. Finally, an effective strategy is established to analyse in time domain the dynamic response of a hinged multi-module flexible structure with moving point loads on the upper surface in waves, representative of vehicles moving on a floating bridge or airport.
Corporate Social Responsibility and the Willingness to Eco-Innovate among Chilean Firms

Adopting social responsibility can be a key strategy for firms to mitigate the impact of production on the environment, contributing to a more sustainable business model. Based on the triple bottom line perspective, we analyze the effect of Corporate Social Responsibility (CSR) on the willingness to allocate resources to eco-innovation among companies in a developing country. Firm-level data from the Fifth Longitudinal Survey of Chilean Firms are used to estimate a binary probit model for the willingness to eco-innovate and a Heckman sample-selection model for total expenditures and investment in eco-innovation. Results confirm that legal regulations and R&D efforts are drivers of eco-innovation among Chilean firms. Larger-sized and export-oriented firms also exhibit a higher willingness to eco-innovate. The main findings show a positive influence of CSR policy on the willingness to eco-innovate and on the resulting resource allocation decision. Interestingly, the evidence reveals that while financial and environmental CSR dimensions only affect the probability of adopting eco-innovation, the social CSR dimension also increases the amount firms spend on eco-innovation. This result suggests that social CSR may act as a complement to other CSR dimensions. These results are robust when controlling for firm-level specific effects under sample-selection models.