Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Myeloma Relapse Is Associated with Increased NFκB Pathway Activity and Upregulation of the Pro-Survival BCL-2 Protein BFL-1

Simple Summary Multiple myeloma (MM) is a blood cancer that is still incurable because patients become insensitive to available treatments. The cancerous cells in MM misuse a signaling route, called the NFκB pathway, to make MM more difficult to treat. In our study, we used a new method to measure NFκB pathway activity in cancer cells of MM patients at different stages of disease. We found that NFκB pathway activity remains unchanged during disease development, is independent of the life expectancy of MM patients, and does not predict how well the cancer cells will respond to treatment. However, the cancer cells that survive after treatment of MM patients do show higher NFκB pathway activity. In a subgroup of these patients, the cancer cells also showed higher BFL-1 gene expression. BFL-1 can enhance cancer cell survival after treatment and may therefore be a potential new candidate to target in these patients. Abstract Multiple myeloma (MM) is a hematological malignancy that is still considered incurable due to the development of therapy resistance and subsequent relapse of disease. MM plasma cells (PC) use NFκB signaling to stimulate cell growth and disease progression, and for protection against therapy-induced apoptosis. Amongst its diverse array of target genes, NFκB regulates the expression of pro-survival BCL-2 proteins BCL-XL, BFL-1, and BCL-2. A possible role for BFL-1 in MM is controversial, since BFL-1, encoded by BCL2A1, is downregulated when mature B cells differentiate into antibody-secreting PC. NFκB signaling can be activated by many factors in the bone marrow microenvironment and/or induced by genetic lesions in MM PC. We used the novel signal transduction pathway activity (STA) computational model to quantify the functional NFκB pathway output in primary MM PC from diverse patient subsets at multiple stages of disease. We found that NFκB pathway activity is not altered during disease development, is irrespective of patient prognosis, and does not predict therapy outcome. However, disease relapse after treatment resulted in increased NFκB pathway activity in surviving MM PC, which correlated with increased BCL2A1 expression in a subset of patients. This suggests that BFL-1 upregulation, in addition to BCL-XL and BCL-2, may render MM PC resistant to therapy-induced apoptosis, and that BFL-1 targeting could provide a new approach to reduce therapy resistance in a subset of relapsed/refractory MM patients.
Endogenous Biomarkers for SLC Transporter-Mediated Drug-Drug Interaction Evaluation

Membrane transporters play an important role in the absorption, distribution, metabolism, and excretion of xenobiotic substrates, as well as endogenous compounds. The evaluation of transporter-mediated drug-drug interactions (DDIs) is an important consideration during the drug development process and can guide the safe use of polypharmacy regimens in clinical practice. In recent years, several endogenous substrates of drug transporters have been identified as potential biomarkers for predicting changes in drug transport function and the potential for DDIs associated with drug candidates in early phases of drug development. These biomarker-driven investigations have been applied in both preclinical and clinical studies and proposed as a predictive strategy that can be supplanted in order to conduct prospective DDIs trials. Here we provide an overview of this rapidly emerging field, with particular emphasis on endogenous biomarkers recently proposed for clinically relevant uptake transporters.
Mitochondrial Heterogeneity in Metabolic Diseases

Simple Summary Often times mitochondria within a single cell are depicted as homogenous entities both morphologically and functionally. In normal and diseased states, mitochondria are heterogeneous and display distinct functional properties. In both cases, mitochondria exhibit differences in morphology, membrane potential, and mitochondrial calcium levels. However, the degree of heterogeneity is different during disease; or rather, heterogeneity at the physiological state stems from physically distinct mitochondrial subpopulations. Overall, mitochondrial heterogeneity is both beneficial and detrimental to the cellular system; protective in enabling cellular adaptation to biological stress or detrimental in inhibiting protective mechanisms. Abstract Mitochondria have distinct architectural features and biochemical functions consistent with cell-specific bioenergetic needs. However, as imaging and isolation techniques advance, heterogeneity amongst mitochondria has been observed to occur within the same cell. Moreover, mitochondrial heterogeneity is associated with functional differences in metabolic signaling, fuel utilization, and triglyceride synthesis. These phenotypic associations suggest that mitochondrial subpopulations and heterogeneity influence the risk of metabolic diseases. This review examines the current literature regarding mitochondrial heterogeneity in the pancreatic beta-cell and renal proximal tubules as they exist in the pathological and physiological states; specifically, pathological states of glucolipotoxicity, progression of type 2 diabetes, and kidney diseases. Emphasis will be placed on the benefits of balancing mitochondrial heterogeneity and how the disruption of balancing heterogeneity leads to impaired tissue function and disease onset.
Local Interleukin-12 Treatment Enhances the Efficacy of Radiation Therapy by Overcoming Radiation-Induced Immune Suppression

Radiation therapy (RT) recruits myeloid cells, leading to an immunosuppressive microenvironment that impedes its efficacy against tumors. Combination of immunotherapy with RT is a potential approach to reversing the immunosuppressive condition and enhancing tumor control after RT. This study aimed to assess the effects of local interleukin-12 (IL-12) therapy on improving the efficacy of RT in a murine prostate cancer model. Combined treatment effectively shrunk the radioresistant tumors by inducing a T helper-1 immune response and influx of CD8+ T cells. It also delayed the radiation-induced vascular damage accompanied by increased α-smooth muscle actin-positive pericyte coverage and blood perfusion. Moreover, RT significantly reduced the IL-12-induced levels of alanine aminotransferase in blood. However, it did not further improve the IL-12-induced anti-tumor effect on distant tumors. Upregulated expression of T-cell exhaustion-associated genes was found in tumors treated with IL-12 only and combined treatment, suggesting that T-cell exhaustion is potentially correlated with tumor relapse in combined treatment. In conclusion, this study illustrated that combination of radiation and local IL-12 therapy enhanced the host immune response and promoted vascular maturation and function. Furthermore, combination treatment was associated with less systemic toxicity than IL-12 alone, providing a potential option for tumor therapy in clinical settings.
The Study of Growth and Performance in Local Chicken Breeds and Varieties: A Review of Methods and Scientific Transference

Simple Summary The present review evaluates twenty years (2001 to 2021) of the study of growth and performance in local chicken breeds worldwide. The assessment of methodological approaches and their constraints when intending to fit for data derived from often endangered autochthonous populations was performed. The evaluation of conditioning factors on the impact that publications reporting on research progresses in the field have on the scientific community and how such advances are valued suggests the need to seek new methodological alternatives or statistical strategies. Such strategies must meet the requirements of local populations which are characterized by reduced censuses, a lack of data structure, highly skewed sex ratios, and a large interbreed and variety variability. The sustainable conservation of these populations cannot be approached if scientific knowledge on their productive behaviour is not reinforced in a manner that allows distinctive products to be put on the market and be competitive. Abstract A review of the scientific advances in the study of the growth and performance in native chicken breeds and varieties over the past 20 years was performed. Understanding the growth patterns of native breeds can only be achieved if the constraints characterizing these populations are considered and treated accordingly. Contextually, the determination of researchers to use the same research methods and study designs applied in international commercial poultry populations conditions the accuracy of the model, variability capturing ability, and the observational or predictive performance when the data of the local population are fitted. Highly skewed sex ratios favouring females, an inappropriate census imbalance compensation and a lack of population structure render models that are regularly deemed effective as invalid to issue solid and sound conclusions. The wider the breed diversity is in a country, the higher the scientific attention paid to these populations. A detailed discussion of the most appropriate models and underlying reasons for their suitability and the reasons preventing the use of others in these populations is provided. Furthermore, the factors conditioning the scientific reception and impact of related publications used to transfer these results to the broad scientific public were evaluated to serve as guidance for the maximization of the success and dissemination of local breed information.
Design and Development of a Wearable Assistive Device Integrating a Fuzzy Decision Support System for Blind and Visually Impaired People

In this article, a new design of a wearable navigation support system for blind and visually impaired people (BVIP) is proposed. The proposed navigation system relies primarily on sensors, real-time processing boards, a fuzzy logic-based decision support system, and a user interface. It uses sensor data as inputs and provides the desired safety orientation to the BVIP. The user is informed about the decision based on a mixed voice–haptic interface. The navigation aid system contains two wearable obstacle detection systems managed by an embedded controller. The control system adopts the Robot Operating System (ROS) architecture supported by the Beagle Bone Black master board that meets the real-time constraints. The data acquisition and obstacle avoidance are carried out by several nodes managed by the ROS to finally deliver a mixed haptic–voice message for guidance of the BVIP. A fuzzy logic-based decision support system was implemented to help BVIP to choose a safe direction. The system has been applied to blindfolded persons and visually impaired persons. Both types of users found the system promising and pointed out its potential to become a good navigation aid in the future.
Behavioral Changes of Solitary Housed Female Pygmy Slow Lorises (Nycticebus pygmeaus) after Introduction into Group Enclosures

Simple Summary Most pygmy slow lorises confiscated in the illegal pet trade cannot be released back into the wild and end up in captivity for the rest of their lives. In the wild, their home ranges are large relative to their body size and they maintain a fairly solitary lifestyle compared to other primates. With the aim of improving their captive wellbeing, we tested to see whether female–female group pairings were in the animals’ best interest by looking at their behaviors before and after being moved to social housing in a larger enriched enclosure. With one nesting site per animal and ample space to avoid each other, all females opted to nest in pairs, not alone, and spent their time socially engaged in affiliative behaviors. We found that female pygmy slow lorises are more social than often assumed and that housing them with conspecifics is probably beneficial to their well-being in captivity. Abstract Pygmy slow lorises (Nycticebus pygmaeus) are threatened with extinction in the wild. Their nocturnal lifestyle and small size make them difficult to study in their natural habitat, but increasing evidence suggests that they are more social than previously thought. Our study was designed to assess the sociability of pygmy slow lorises by transferring six adult females from solo cages into environmentally enriched group home cages at the Japan Monkey Centre’s Slow Loris Conservation Centre. Two females were paired to create one group, while the other four were placed together in a second group. We compared their social interactions, activity budgets, and postural behaviors before and after social housing was initiated. We found that all-female slow loris groups had a high degree of sociality, preferred to stay close to each other, nested together every night, and spent less time in locomotion and more time grooming than when living alone. These results suggest that female pygmy slow lorises actively seek companions when available. The captive housing of all-female groups of lorises could lead to better husbandry practices and improved animal welfare by allowing them to have conspecific companions. We conclude that isosexual groups of pygmy slow lorises should be preferred over single housing when possible.
Ports Digitalization Level Evaluation

Currently, seaports are actively searching for methods and ways to improve their operational efficiency. Digitalization is considered as one of the main directions of current ports’ development. Ports’ digitalization levels are varied and may depend on different factors, including port size, traditions, turnover and handled cargo type, etc. Ports often face decision-making challenges related to assessment of their digitization level and choice of development directions. The article aims to develop a methodology to evaluate ports’ digitalization level. A marketing research tool was used to collect the data needed for the analysis. A mathematical model allowing simulations is proposed and a case study of 30 ports located in the Baltic, North and Mediterranean Seas regions is explored. Based on conducted calculations, a ranking of analysed ports considering their digitalization level was created. The ports were compared within groups of small, medium-sized and large ports. It was estimated that the digitalization level in small and medium-sized ports is about 30% lower than the level of large seaports. The research results may be of interest to seaports striving to assess their level of digitalization and choose the best digital improvement solutions.
Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry

The use of mesenchymal stem cells (MSCs) for regenerative purposes has become common in a large variety of diseases. In the dental and maxillofacial field, there are emerging clinical needs that could benefit from MSC-based therapeutic approaches. Even though MSCs can be isolated from different tissues, such as bone marrow, adipose tissue, etc., and are known for their multilineage differentiation, their different anatomical origin can affect the capability to differentiate into a specific tissue. For instance, MSCs isolated from the oral cavity might be more effective than adipose-derived stem cells (ASCs) for the treatment of dental defects. Indeed, in the oral cavity, there are different sources of MSCs that have been individually proposed as promising candidates for tissue engineering protocols. The therapeutic strategy based on MSCs can be direct, by using cells as components of the tissue to be regenerated, or indirect, aimed at delivering local growth factors, cytokines, and chemokines produced by the MSCs. Here, the authors outline the major sources of mesenchymal stem cells attainable from the oral cavity and discuss their possible usage in some of the most compelling therapeutic frontiers, such as periodontal disease and dental pulp regeneration.
Genetic Characterization of the Tetracycline-Resistance Gene tet(X) Carried by Two Epilithonimonas Strains Isolated from Farmed Diseased Rainbow Trout, Oncorhynchus mykiss in Chile

The main objective of this study was to characterize the tet(X) genes, which encode a monooxygenase that catalyzes the degradation of tetracycline antibiotics, carried by the resistant strains FP105 and FP233-J200, using whole-genome sequencing analysis. The isolates were recovered from fin lesion and kidney samples of diseased rainbow trout Oncorhynchus mykiss, during two Flavobacteriosis outbreaks occurring in freshwater farms located in Southern Chile. The strains were identified as Epilithonimonas spp. by using biochemical tests and by genome comparison analysis using the PATRIC bioinformatics platform and exhibited a minimum inhibitory concentration (MIC) of oxytetracycline of 128 µg/mL. The tet(X) genes were located on small contigs of the FP105 and FP233-J200 genomes. The sequences obtained for the tet(X) genes and their genetic environment were compared with the genomes available in the GenBank database of strains of the Chryseobacterium clade belonging to the Flavobacterium family, isolated from fish and carrying the tet(X) gene. The Tet(X) proteins synthesized by the Chilean Epilithonimonas strains showed a high amino acid similarity (range from 84% to 100%), with the available sequences found in strains belonging to the genus Chryseobacterium and Flavobacterium isolated from fish. An identical neighborhood of tet(X) genes from both Chilean strains was observed. The genetic environment of tet(X) observed in the two strains of Epilithonimonas studied was characterized by the upstream location of a sequence encoding a hypothetical protein and a downstream located alpha/beta hydrolase-encoding gene, similar to the observed in some of the tet(X) genes carried by Chryseobacterium and Flavobacterium strains isolated from fish, but the produced proteins exhibited a low amino acid identity (25–27%) when compared to these synthesized by the Chilean strains. This study reports for the first time the carriage of the tet(X) gene by the Epilithonimonas genus and their detection in fish pathogenic bacteria isolated from farmed salmonids in Chile, thus limiting the use of therapies based on oxytetracycline, the antimicrobial most widely used in Chilean freshwater salmonid farming. This results suggest that pathogenic strains of the Chryseobacterium clade occurring in Chilean salmonid farms may serve as important reservoirs of tet(X) genes.
The Antifouling and Drag-Reduction Performance of Alumina Reinforced Polydimethylsiloxane Coatings Containing Phenylmethylsilicone Oil

Fouling-release coatings reinforced with micro-alumina and nano-alumina were prepared based on polydimethylsiloxane (PDMS) containing phenylmethylsilicone oil. The surface properties, mechanical properties, leaching behavior of silicone oil, anti-fouling and drag-reduction performance of the coating were studied. The results show that the addition of alumina can significantly improve the tensile strength, elastic modulus and Shore’s hardness of the coating. The adhesion experiments of marine bacteria and Navicula Tenera show that the addition of alumina can reduce the antifouling performance of the coating, which is related to the stripping mode of fouling organisms. The fouling organisms leave the coating surface by shearing, and the energy required for shearing is proportional to the elastic modulus of the coating. At 800–1400 rpm, the addition of alumina will reduce the drag reduction performance of the coating, which is related to the drag reduction mechanism of PDMS. PDMS counteracts part of the resistance by surface deformation. The larger the elastic modulus is, the more difficult the surface deformation is. The experiment of silicone oil leaching shows that the increase of alumina addition amount and the decrease of particle size will inhibit the leaching of silicone oil.
Improved YOLO Based Detection Algorithm for Floating Debris in Waterway

Various floating debris in the waterway can be used as one kind of visual index to measure the water quality. The traditional image processing method is difficult to meet the requirements of real-time monitoring of floating debris in the waterway due to the complexity of the environment, such as reflection of sunlight, obstacles of water plants, a large difference between the near and far target scale, and so on. To address these issues, an improved YOLOv5s (FMA-YOLOv5s) algorithm by adding a feature map attention (FMA) layer at the end of the backbone is proposed. The mosaic data augmentation is applied to enhance the detection effect of small targets in training. A data expansion method is introduced to expand the training dataset from 1920 to 4800, which fuses the labeled target objects extracted from the original training dataset and the background images of the clean river surface in the actual scene. The comparisons of accuracy and rapidity of six models of this algorithm are completed. The experiment proves that it meets the standards of real-time object detection.
African Swine Fever in Wild Boar (Poland 2020): Passive and Active Surveillance Analysis and Further Perspectives

African swine fever (ASF) is a fatal hemorrhagic disease of wild boar and domestic pigs which has been present in Poland since 2014. By 2020, the ASF virus (ASFV) spread across Central, Eastern and Western Europe (including Germany), and Asian countries (including China, Vietnam, and South Korea). The national ASF eradication and prevention program includes continuous passive (wild boar found dead and road-killed wild boar) and active (hunted wild boar) surveillance. The main goal of this study was to analyze the dynamic of the spread of ASF in the wild boar population across the territory of Poland in 2020. In that year in Poland, in total 6191 ASF-positive wild boar were declared. Most of them were confirmed in a group of animals found dead. The conducted statistical analysis indicates that the highest chance of obtaining an ASF-positive result in wild boar was during the winter months, from January to March, and in December 2020. Despite the biosecurity measures implemented by holdings of domestic pigs, the disease also occurred in 109 pig farms. The role of ASF surveillance in the wild boar population is crucial to apply more effective and tailored measures of disease control and eradication. The most essential measures to maintain sustainable production of domestic pigs in Poland include effective management of the wild boar population, along with strict implementation of biosecurity measures by domestic pig producers.