Miracle-dz/UniFAR-FTUs huggingface dataset:
The Expression of Selected Wnt Pathway Members (FZD6, AXIN2 and β-Catenin) in Canine Oral Squamous Cell Carcinoma and Acanthomatous Ameloblastoma

Simple Summary The expression patterns of selected Wnt pathway molecules were analyzed in two of the most common canine oral neoplasia—canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA). We found an overlap of areas with high expression of FZD6 and SOX2 in COSCC, while cytokeratin expression was low in these areas, indicating the low differentiation status of these cells. In CAA, FZD6-positive areas expressed cytokeratin and exhibited features of squamous metaplasia. Moreover, the expression of β-catenin and AXIN2 was higher in both CAA and COSCC than in the healthy canine oral epithelium. This work uncovered the distinct expression patterns of Wnt molecules in both lesions, indicating the involvement of this pathway in the pathology of canine oral cancers, which presents opportunities for their usage for the prediction of cell behavior or in the development of new therapeutic approaches. Abstract The Wnt signaling pathway is well known to be involved in many types of human cancer; however, in veterinary medicine, the investigation of individual Wnt members’ expression, and their role in or association with oral tumor pathogenesis, is still underevaluated. We aim to determine the expression pattern of Frizzled-6 (FZD6) as one of the Wnt receptors in two of the most common canine oral neoplastic lesions—canine oral squamous cell carcinoma (COSCC) and canine acanthomatous ameloblastoma (CAA). While COSCC is a malignant tumor with aggressive biological behavior and a tendency to metastasize, CAA is a benign tumor with high local invasiveness. In CAA, the expression of FZD6 was mostly located in the center of the epithelial tumorous tissue, and cells exhibiting features of squamous metaplasia were strongly positive. In well-differentiated COSCC, FZD6 was expressed in the tumorous epithelium as well as the tumorous stroma. There was a negative correlation between cytokeratin expression and FZD6 expression in COSCC, where the central parts of the epithelial tumorous tissue were often FZD6-negative. The non-differentiated COSCC with low expression of cytokeratin exhibited a diffuse FZD6 signal. The invasive front with areas of tumor budding exhibited high FZD6 expression with a loss of cytokeratin expression. Moreover, the expression of β-catenin and AXIN2 was increased in comparison to gingiva. In conclusion, our study revealed significant differences in the expression patterns and the levels of FZD6 between COSCC and CAA, indicating the differential engagement of the Wnt pathway in these tumors.
The Differential Effects of the Amount of Training on Sensitivity of Distinct Actions to Reward Devaluation

Shifting between goal-directed and habitual behaviors is essential for daily functioning. An inability to do so is associated with various clinical conditions, such as obsessive–compulsive disorder (OCD). Here we developed a new behavioral model in mice allowing us to produce and examine the development of different behaviors under goal-directed or habitual control. By using overtraining of instrumental associations between two levers and two rewards, and later devaluating one of the rewards, we differentiate and explore the motivational control of behaviors within the task which consequentially promotes what seems like excessive irrational behavior. Using our model, we found that the ability of instrumental behavior, to adapt to a change in the value of a known reward, is a function of practice. Once an instrumental action was practiced extensively it becomes habitual and, thus, under S–R control and could not be amended, not even when resulting in a noxious outcome. However, direct consummatory or Pavlovian actions, such as licking or checking, responds immediately to the change in value. This imbalance could render an instrumental behavior excessive and unresponsive to changes in outcome while the direct change in consumption implies that the change was in fact registered. This could suggest a system that, when out of balance, can create excessive behaviors, not adapting to an acknowledged change.
Recent Research for Unobtrusive Atrial Fibrillation Detection Methods Based on Cardiac Dynamics Signals: A Survey

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It tends to cause multiple cardiac conditions, such as cerebral artery blockage, stroke, and heart failure. The morbidity and mortality of AF have been progressively increasing over the past few decades, which has raised widespread concern about unobtrusive AF detection in routine life. The up-to-date non-invasive AF detection methods include electrocardiogram (ECG) signals and cardiac dynamics signals, such as the ballistocardiogram (BCG) signal, the seismocardiogram (SCG) signal and the photoplethysmogram (PPG) signal. Cardiac dynamics signals can be collected by cushions, mattresses, fabrics, or even cameras, which is more suitable for long-term monitoring. Therefore, methods for AF detection by cardiac dynamics signals bring about extensive attention for recent research. This paper reviews the current unobtrusive AF detection methods based on the three cardiac dynamics signals, summarized as data acquisition and preprocessing, feature extraction and selection, classification and diagnosis. In addition, the drawbacks and limitations of the existing methods are analyzed, and the challenges in future work are discussed.
Structural and Functional Modulation of Perineuronal Nets: In Search of Important Players with Highlight on Tenascins

The extracellular matrix (ECM) of the brain plays a crucial role in providing optimal conditions for neuronal function. Interactions between neurons and a specialized form of ECM, perineuronal nets (PNN), are considered a key mechanism for the regulation of brain plasticity. Such an assembly of interconnected structural and regulatory molecules has a prominent role in the control of synaptic plasticity. In this review, we discuss novel ways of studying the interplay between PNN and its regulatory components, particularly tenascins, in the processes of synaptic plasticity, mechanotransduction, and neurogenesis. Since enhanced neuronal activity promotes PNN degradation, it is possible to study PNN remodeling as a dynamical change in the expression and organization of its constituents that is reflected in its ultrastructure. The discovery of these subtle modifications is enabled by the development of super-resolution microscopy and advanced methods of image analysis.
8a, a New Acridine Antiproliferative and Pro-Apoptotic Agent Targeting HDAC1/DNMT1

Epigenetic therapy using histone deacetylase (HDAC) inhibitors has become an attractive project in new drug development. However, DNA methylation and histone acetylation are important epigenetic ways to regulate the occurrence and development of leukemia. Given previous studies, N-(2-aminophenyl)benzamide acridine (8a), as a histone deacetylase 1 (HDAC1) inhibitor, induces apoptosis and shows significant anti-proliferative activity against histiocytic lymphoma U937 cells. HDAC1 plays a role in the nucleus, which we confirmed by finding that 8a entered the nucleus. Subsequently, we verified that 8a mainly passes through the endogenous (mitochondrial) pathway to induce cell apoptosis. From the protein interaction data, we found that 8a also affected the expression of DNA methyltransferase 1 (DNMT1). Therefore, an experiment was performed to assess the binding of 8a to DNMT1 at the molecular and cellular levels. We found that the binding strength of 8a to DNMT1 enhanced in a dose-dependent manner. Additionally, 8a inhibits the expression of DNMT1 mRNA and its protein. These findings suggested that the anti-proliferative and pro-apoptotic activities of 8a against leukemia cells were achieved by targeting HDAC1 and DNMT1.
Evaluation of Oropharyngeal pH-Monitoring in the Assessment of Laryngopharyngeal Reflux

Background: Laryngopharyngeal reflux (LPR) is a prevalent disorder. The aim of the present retrospective cohort study was to evaluate oropharyngeal pH-monitoring using a novel scoring system for LPR. Methods: In a total of 180 consecutive patients with possible LPR, reflux symptom index (RSI), reflux finding score (RFS), oropharyngeal pH-monitoring and transnasal esophagoscopy were carried out for further investigation. Results: In our series, 99 (55%) patients had severe LPR, 29 (16%) cases presented with moderate and 23 (13%) with mild severity, 9 (5%) subjects revealed neutral values, and 7 (4%) individuals were alkaline, while 13 (7%) patients had no LPR. In detecting LPR, the sensitivity, specificity and accuracy of oropharyngeal pH-monitoring was 95%, 93% and 94%, respectively. Conclusion: Oropharyngeal pH-monitoring is a reliable tool in the assessment of LPR, but the pH graphs have to be precisely analyzed and interpreted in context with other validated diagnostic tests.
Discovery and Characterization of Actively Replicating DNA and Retro-Transcribing Viruses in Lower Vertebrate Hosts Based on RNA Sequencing

In a previous study, a metatranscriptomics survey of RNA viruses in several important lower vertebrate host groups revealed huge viral diversity, transforming the understanding of the evolution of vertebrate-associated RNA virus groups. However, the diversity of the DNA and retro-transcribing viruses in these host groups was left uncharacterized. Given that RNA sequencing is capable of revealing viruses undergoing active transcription and replication, we collected previously generated datasets associated with lower vertebrate hosts, and searched them for DNA and retro-transcribing viruses. Our results revealed the complete genome, or “core gene sets”, of 18 vertebrate-associated DNA and retro-transcribing viruses in cartilaginous fishes, ray-finned fishes, and amphibians, many of which had high abundance levels, and some of which showed systemic infections in multiple organs, suggesting active transcription or acute infection within the host. Furthermore, these new findings recharacterized the evolutionary history in the families Hepadnaviridae, Papillomaviridae, and Alloherpesviridae, confirming long-term virus–host codivergence relationships for these virus groups. Collectively, our results revealed reliable and sufficient information within metatranscriptomics sequencing to characterize not only RNA viruses, but also DNA and retro-transcribing viruses, and therefore established a key methodology that will help us to understand the composition and evolution of the total “infectome” within a diverse range of vertebrate hosts.
Flow-Through Electrochemical Biosensor for the Detection of Listeria monocytogenes Using Oligonucleotides

Consumption of food contaminated by Listeria monocytogenes can result in Listeriosis, an illness with hospitalization rates of 94% and mortality rates up to 30%. As a result, U.S. regulatory agencies governing food safety retain zero-tolerance policies for L. monocytogenes. However, detection at such low concentrations often requires strategies such as increasing sample size or culture enrichment. A novel flow-through immunoelectrochemical biosensor has been developed for Escherichia coli O157:H7 detection in 1 L volumes without enrichment. The current work further augments this biosensor’s capabilities to (1) include detection of L. monocytogenes and (2) accommodate genetic detection to help overcome limitations based upon antibody availability and address specificity errors in phenotypic assays. Herein, the conjugation scheme for oligo attachment and the conditions necessary for genetic detection are laid forth while results of the present study demonstrate the sensor’s ability to distinguish L. monocytogenes DNA from L. innocua with a limit of detection of ~2 × 104 cells/mL, which agrees with prior studies. Total time for this assay can be constrained to <2.5 h because a timely culture enrichment period is not necessary. Furthermore, the electrochemical detection assay can be performed with hand-held electronics, allowing this platform to be adopted for near-line monitoring systems.
Elucidating the Fitness of a Dead-End Trap Crop Strategy against the Tomato Fruitworm, Helicoverpa armigera

Simple Summary The tomato fruitworm, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae), is a destructive polyphagous insect pest of tomatoes and its control largely depends on chemical pesticides. However, indiscriminate use of chemical pesticides has resulted in the development of resistance and posed serious environmental problems. Alternatively, in search of environmentally friendly pest management techniques, the use of trap crops has recently gained more attention. In this study, we compared different accessions of S. viarum to investigate which of them have the highest potential as a dead-end trap crop for H. armigera. Results from the laboratory experiment showed a significant variation among the S. viarum accessions in terms of H. armigera oviposition, and exhibited a higher level of resistance against H. armigera larvae compared to the tomato plants. Under the semi-field condition, trap cropping of S. viarum significantly reduces the total egg-laying of H. armigera on tomato. This study provides important information about the abilities of S. viarum plants to influence the life parameter of H. armigera and highlighted the possibilities to use S. viarum as a dead-end trap crop for the management of H. armigera. However, the efficacy of S. viarum needs to be tested under large, open-field conditions. Abstract Solanum viarum has been proposed as a potential dead-end trap crop for the management of Helicoverpa armigera because of its unsuitability for larval growth and survival despite being overwhelmingly preferred for oviposition. This study delved into the different S. viarum accessions for ovipositional preference and non-suitability for larval growth and survival of H. armigera. Besides, foliage trichomes, acylsugars, and phenolic content of S. viarum plants were assessed and compared with tomato. Since there is no significant variation in the ovipositional preference and larval performance of H. armigera, our result revealed that all those evaluated accessions of S. viarum have the potential to be used as a dead-end trap crop for the management of H. armigera. However, significant variation among the S. viarum accessions in terms of H. armigera oviposition was also evident in a no-choice experiment. Because of high-density glandular trichomes, acylsugars, and phenolic content, S. viarum significantly impaired H. armigera larval growth and survival compared to the tomato. Hence, our study elucidated that the S. viarum plant fits with the criteria for dead-end trap crop, and has the potential as a dead-end trap crop for the H. armigera, which needs to be tested under large, open-field conditions.
Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

Simple Summary Multiple myeloma is a cancer of immunoglobulin-secreting cells that accumulate in the bone marrow. Mesenchymal stromal cells are important components of the bone marrow microenvironment interacting with myeloma cells and having a pivotal role in the progression of the disease. Here we first review studies that have highlighted structural and functional differences between mesenchymal stromal cells derived from healthy donors and myeloma patients, and propose a model for the transition from the normal to the myeloma-condition of these cells. Next, we underscore the contribution of mesenchymal stromal cells to the promotion of myeloma growth and survival, development of drug resistance, dissemination and homing, myeloma bone disease, and the establishment of a pro-inflammatory and immunosuppressive microenvironment. It appears as if as a result of myeloma-mesenchymal stromal cell cross-talk, mesenchymal stromal cells in myeloma patients have converted into active contributors to the pathophysiology of the disease. Abstract Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structural and functional abnormalities have been found when characterizing MSCs derived from myeloma patients (MM-MSCs) and comparing them to those from healthy donors (HD-MSCs). Other studies have identified differences in genomic, mRNA, microRNA, histone modification, and DNA methylation profiles. We discuss these distinctive features shaping MM-MSCs and propose a model for the transition from HD-MSCs to MM-MSCs as a consequence of the interaction with myeloma cells. Finally, we review the contribution of MM-MSCs to several aspects of myeloma pathology, specifically to myeloma growth and survival, drug resistance, dissemination and homing, myeloma bone disease, and the induction of a pro-inflammatory and immunosuppressive microenvironment.
Feeding System Resizes the Effects of DGAT1 Polymorphism on Milk Traits and Fatty Acids Composition in Modicana Cows

Simple Summary Genetic selection for single-locus polymorphisms could offer suitable opportunities to rapidly improve milk traits in local unselected cattle breeds characterized by low production levels. Since these hardy breeds are generally raised in traditional extensive and semi-intensive systems, which make wide use of grazing resources, the interactive effect between genotype and feeding system is worthy of investigation. In Modicana cattle breed, milk composition and fatty acid profile were influenced by both genetic polymorphisms at the DGAT1 K232A locus and feeding systems. The milk from homozygous AA cows was associated with a more favorable fatty acid composition due to a lower percentage of total saturated fatty acids, saturated to unsaturated ratio, atherogenic index, and a greater presence of oleic acid and total unsaturated fatty acids. Our finding confirmed the important role of pasture feeding on milk composition: the high nutritional and healthy value of milk obtained in extensive systems by pasture-fed cows. The interaction between the two experimental factors also appears to play a role: in our experimental condition, it seems that high pasture feeding can resize the effect of the DGAT1 genotype on milk traits and fatty acid composition in Modicana cows. Abstract The interaction between genetic polymorphism and feeding system on milk traits and fatty acid composition was investigated in Modicana cows. Two DGAT1 K232A genotypes (AK and AA) and two feeding regimes, extensive system (EX) with 8 h of grazing without concentrate (EX) and semi-intensive systems (SI) with 2 h of grazing with concentrate, were investigated. DGAT1 genotype did not influence milk yield and composition. The feeding system affected milk composition: protein was significantly higher in SI and lactose in the EX system. A significant genotype × feeding system interaction was observed: the protein and casein levels of AK cows were higher in the SI compared to the EX system. Milk fatty acids profile, total saturated to total unsaturated fatty acids, n-6 to n-3 ratios, and atherogenic index were affected by the feeding system, improving the healthy properties of milk from animals reared in the extensive system. DGAT1 genotype influenced the fatty acid composition: milk from AA cows had a more favorable fatty acid composition due to lower total saturated fatty acids, saturated to unsaturated ratio, atherogenic index, and higher levels of oleic acid and total unsaturated fatty acids. Furthermore, an interaction genotype x feeding system was observed: the AK milk was richer in short-chain FAs (C4:0–C8:0) and C10:0 only in the EX but not in the SI system. Our data suggest that a high amount of green forage in the diet of Modicana cows can resize the effect of the DGAT1 genotype on milk traits and fatty acids composition.
Informal faculty development in health professions education: Identifying opportunities in everyday practice

Abstract Introduction Faculty development (FD) supports health professions educators to develop knowledge, skills, and expertise. Whilst formal FD is a focus in the health professions education (HPE) literature, little is known about how FD occurs informally. We sought to identify opportunities and constraints for informal FD amongst health professions educators in the academic (university) setting and understand how they engage with these opportunities. Methods This exploratory study was conducted in one Australian university. Interviews and focus groups were conducted with undergraduate and postgraduate teachers and assessors (teachers) (n = 10); teaching team and program leaders (mid-level leaders) (n = 8); and senior (university-level) leaders (n = 2). We analysed data thematically and applied situated cognition theory. Results We identified three everyday educational practices that provide opportunities for informal FD in the academic setting: (1) applying evidence to; (2) evaluating; and (3) sharing, educational practice. Engaging with these opportunities was shaped by individuals’ motivation and proactivity to engage in professional learning (effectivities) and organisational culture and structures (constraints). Conclusion Applying evidence to, evaluating, and sharing educational practice provide valuable contexts for ongoing learning in the academic setting. Assisting educators and organisations to recognise and leverage these ‘in situ’ FD opportunities is vital in fostering a continuous learning culture.
The Putative Roles and Functions of Indel, Repetition and Duplication Events in Alphavirus Non-Structural Protein 3 Hypervariable Domain (nsP3 HVD) in Evolution, Viability and Re-Emergence

Alphavirus non-structural proteins 1–4 (nsP1, nsP2, nsP3, and nsP4) are known to be crucial for alphavirus RNA replication and translation. To date, nsP3 has been demonstrated to mediate many virus–host protein–protein interactions in several fundamental alphavirus mechanisms, particularly during the early stages of replication. However, the molecular pathways and proteins networks underlying these mechanisms remain poorly described. This is due to the low genetic sequence homology of the nsP3 protein among the alphavirus species, especially at its 3′ C-terminal domain, the hypervariable domain (HVD). Moreover, the nsP3 HVD is almost or completely intrinsically disordered and has a poor ability to form secondary structures. Evolution in the nsP3 HVD region allows the alphavirus to adapt to vertebrate and insect hosts. This review focuses on the putative roles and functions of indel, repetition, and duplication events that have occurred in the alphavirus nsP3 HVD, including characterization of the differences and their implications for specificity in the context of virus–host interactions in fundamental alphavirus mechanisms, which have thus directly facilitated the evolution, adaptation, viability, and re-emergence of these viruses.