Miracle-dz/UniFAR-FTUs huggingface dataset:
The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses

Simple Summary The main target of mesenchymal stem cell therapy in horses has long been the locomotor system, because these athletic animals commonly suffer from tendon and joint lesions. Originally, mesenchymal stem cells were thought to act by just differentiating into the cells of the injured tissue. However, these cells are also able to regulate and stimulate the body’s own repair mechanisms, opening the door to many applications in inflammatory and immune-mediated disorders in both animals and humans. In horses, beyond their traditional application in the musculoskeletal system, these cells have been studied for ophthalmologic pathologies such as corneal ulcers or immune-mediated processes, and for reproductive disorders such as endometritis/endometrosis. Their potential has been explored for equine pathologies very similar to those affecting people, such as asthma, metabolic syndrome, aberrant wound healing, or endotoxemia, as well as for equine-specific pathologies such as laminitis. Current evidence is still preliminary, and further research is needed to clarify different aspects, although research performed so far shows the promising potential of mesenchymal stem cells to treat a wide variety of equine pathologies, some of which are analogous to human disorders. Therefore, advancements in this path will be beneficial for both animals and people. Abstract The differentiation ability of mesenchymal stem cells (MSCs) initially raised interest for treating musculoskeletal injuries in horses, but MSC paracrine activity has widened their scope for inflammatory and immune-mediated pathologies in both equine and human medicine. Furthermore, the similar etiopathogenesis of some diseases in both species has advanced the concept of “One Medicine, One Health”. This article reviews the current knowledge on the use of MSCs for equine pathologies beyond the locomotor system, highlighting the value of the horse as translational model. Ophthalmologic and reproductive disorders are among the most studied for MSC application. Equine asthma, equine metabolic syndrome, and endotoxemia have been less explored but offer an interesting scenario for human translation. The use of MSCs in wounds also provides a potential model for humans because of the healing particularities in both species. High-burden equine-specific pathologies such as laminitis have been suggested to benefit from MSC-therapy, and MSC application in challenging disorders such as neurologic conditions has been proposed. The available data are preliminary, however, and require further development to translate results into the clinic. Nevertheless, current evidence indicates a significant potential of equine MSCs to enlarge their range of application, with particular interest in pathologies analogous to human conditions.
Establishment of a Potential Serum Biomarker Panel for the Diagnosis and Prognosis of Cholangiocarcinoma Using Decision Tree Algorithms

Potential biomarkers which include S100 calcium binding protein A9 (S100A9), mucin 5AC (MUC5AC), transforming growth factor β1 (TGF-β1), and angiopoietin-2 have previously been shown to be effective for cholangiocarcinoma (CCA) diagnosis. This study attempted to measure the sera levels of these biomarkers compared with carbohydrate antigen 19-9 (CA19-9). A total of 40 serum cases of CCA, gastrointestinal cancers (non-CCA), and healthy subjects were examined by using an enzyme-linked immunosorbent assay. The panel of biomarkers was evaluated for their accuracy in diagnosing CCA and subsequently used as inputs to construct the decision tree (DT) model as a basis for binary classification. The findings showed that serum levels of S100A9, MUC5AC, and TGF-β1 were dramatically enhanced in CCA patients. In addition, 95% sensitivity and 90% specificity for CCA differentiation from healthy cases, and 70% sensitivity and 83% specificity for CCA versus non-CCA cases was obtained by a panel incorporating all five candidate biomarkers. In CCA patients with low CA19-9 levels, S100A9 might well be a complementary marker for improved diagnostic accuracy. The high levels of TGF-β1 and angiopoietin-2 were both associated with severe tumor stages and metastasis, indicating that they could be used as a reliable prognostic biomarkers panel for CCA patients. Furthermore, the outcome of the CCA burden from the Classification and Regression Tree (CART) algorithm using serial CA19-9 and S100A9 showed high diagnostic efficiency. In conclusion, results have shown the efficacy of CCA diagnosis and prognosis of the novel CCA-biomarkers panel examined herein, which may prove be useful in clinical settings.
Design and In Vitro Evaluation of Splice-Switching Oligonucleotides Bearing Locked Nucleic Acids, Amido-Bridged Nucleic Acids, and Guanidine-Bridged Nucleic Acids

Our group previously developed a series of bridged nucleic acids (BNAs), including locked nucleic acids (LNAs), amido-bridged nucleic acids (AmNAs), and guanidine-bridged nucleic acids (GuNAs), to impart specific characteristics to oligonucleotides such as high-affinity binding and enhanced enzymatic resistance. In this study, we designed a series of LNA-, AmNA-, and GuNA-modified splice-switching oligonucleotides (SSOs) with different lengths and content modifications. We measured the melting temperature (Tm) of each designed SSO to investigate its binding affinity for RNA strands. We also investigated whether the single-stranded SSOs formed secondary structures using UV melting analysis without complementary RNA. As a result, the AmNA-modified SSOs showed almost the same Tm values as the LNA-modified SSOs, with decreased secondary structure formation in the former. In contrast, the GuNA-modified SSOs showed slightly lower Tm values than the LNA-modified SSOs, with no inhibition of secondary structures. We also evaluated the exon skipping activities of the BNAs in vitro at both the mRNA and protein expression levels. We found that both AmNA-modified SSOs and GuNA-modified SSOs showed higher exon skipping activities than LNA-modified SSOs but each class must be appropriately designed in terms of length and modification content.
MicroRNA Interference in Hepatic Host-Pathogen Interactions

The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host–pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens.
Metabolomics of Photosynthetically Active Tissues in White Grapes: Effects of Light Microclimate and Stress Mitigation Strategies

The effects of climate change are becoming a real concern for the viticulture sector, with impacts on both grapevine physiology and the quality of the fresh berries and wine. Short-term mitigation strategies, like foliar kaolin application and smart irrigation regimes, have been implemented to overcome these problems. We previously showed that these strategies also influence the photosynthetic activity of the berries themselves, specifically in the exocarp and seed. In the present work, we assessed the modulating effects of both canopy-light microclimate, kaolin and irrigation treatments on the metabolic profiles of the exocarp and seed, as well as the potential role of berry photosynthesis herein. Berries from the white variety Alvarinho were collected at two contrasting light microclimate positions within the vine canopy (HL—high light and LL—low light) from both irrigated and kaolin-treated plants, and their respective controls, at three fruit developmental stages (green, véraison and mature). Untargeted liquid chromatography mass spectrometry (LCMS) profiling of semi-polar extracts followed by multivariate statistical analysis indicate that both the light microclimate and irrigation influenced the level of a series of phenolic compounds, depending on the ripening stage of the berries. Moreover, untargeted gas chromatography mass spectrometry (GCMS) profiling of polar extracts show that amino acid and sugar levels were influenced mainly by the interaction of irrigation and kaolin treatments. The results reveal that both photosynthetically active berry tissues had a distinct metabolic profile in response to the local light microclimate, which suggests a specific role of photosynthesis in these tissues. A higher light intensity within the canopy mainly increased the supply of carbon precursors to the phenylpropanoid/flavonoid pathway, resulting in increased levels of phenolic compounds in the exocarp, while in seeds, light mostly influenced compounds related to carbon storage and seed development. In addition, our work provides new insights into the influence of abiotic stress mitigation strategies on the composition of exocarps and seeds, which are both important tissues for the quality of grape-derived products.
A Clinical Bridge between Family Caregivers and Older Adults: The Contribution of Patients’ Frailty and Optimism on Caregiver Burden

The association between caregiver burden and the physical frailty of older adults has been the object of previous studies. The contribution of patients’ dispositional optimism on caregiver burden is a poorly investigated topic. The present study aimed at investigating whether older adults’ multidimensional frailty and optimism might contribute to the burden of their family caregivers. The Caregiver Burden Inventory was used to measure the care-related burden of caregivers. The multidimensional frailty status of each patient was evaluated by calculating a frailty index, and the revised Life Orientation Test was used to evaluate patients’ dispositional optimism. The study involved eighty family caregivers (mean age 64.28 ± 8.6) and eighty older patients (mean age 80.45 ± 7.13). Our results showed that higher frailty status and lower levels of optimism among patients were significantly associated with higher levels of overall burden and higher burden related to the restriction of personal time among caregivers. Patients’ frailty was additionally associated with caregivers’ greater feelings of failure, physical stress, role conflicts, and embarrassment. Understanding the close connection between patient-related factors and the burden of caregivers appears to be an actual challenge with significant clinical, social, and public health implications.
Performance of the EWGSOP2 Cut-Points of Low Grip Strength for Identifying Sarcopenia and Frailty Phenotype: A Cross-Sectional Study in Older Inpatients

Background: The European Working Group on Sarcopenia has recently proposed revised cut-off values for the definition of low grip strength (EWGSOP2). We therefore compared performance of the EWGSOP2 cut-off definition of low grip strength with other internationally used cut-off points in a sample of older patients. Methods: We analyzed geriatric assessment data in a cross-sectional sample of 98 older patients admitted to a post-acute care hospital. First, we compared prevalence of sarcopenia and frailty phenotype in our sample using low grip strength cut-points from the EWGSOP2 and seven other internationally used consensus statements. Second, we calculated correlations between low grip strength and two independent surrogate outcomes (i.e., gait speed, and the clinical frailty scale) for the EWGSOP2 and the other seven cut-point definitions. Results: Prevalence of sarcopenia based on the EWGSOP2 grip strength cut-off values was significantly lower (10.2%) than five of the seven other cut-point definitions (e.g., 19.4% based on Sarcopenia Definitions and Outcomes Consortium (SDOC) criteria). Similarly, frailty phenotype prevalence was significantly lower based on EWGSOP2 cut-points (57.1%) as compared to SDOC (70.4%). The correlation coefficient of gait speed with low grip strength based on EWGSOP2 cut-points was lower (0.145) as compared to other criteria (e.g., SDOC 0.240). Conclusions: Sarcopenia and frailty phenotype were identified considerably less using the EWGSOP2 cut-points for low grip strength, potentially underestimating prevalence of sarcopenia and frailty phenotype in post-acute hospital patients.
Early Results of Kinesio Taping and Steroid Injections in Elbow Lateral Epicondylitis: A Randomized, Controlled Study

Background and objectives: This study prospectively compares early results of Kinesio tape (KT) as an alternative method for the treatment of lateral epicondylitis with those of corticosteroid injection and the rest-and-medication group (RMG). Materials and methods: Among the fifty patients (53 elbows), KT was applied to 20 patients (21 elbows), and corticosteroid injection (CSI) was applied to 15 patients (17 elbows). Fifteen patients were included in the RMG. Patients in the RMG were informed about their condition, and necessary warnings were given. No oral or topical treatments were recommended. If needed, paracetamol or nonsteroidal anti-inflammatory drugs (NSAIDs) were prescribed. Patients were classified according to the Nirschl scores and evaluated with visual analog scale (VAS); Quick Disability of Arm, Shoulder and Hand (QDASH); and the Turkish version of the Patient Related Elbow Evaluation (PREE-T). Results: Improvements in all scores were statistically significant in all groups at the end of the second week. At the end of the fourth week, there was also a statistically significant improvement in all three groups, but these improvements were not as high as they were in the first 2 weeks. There was a slight deterioration in the functional scores in the RMG and CSI groups, while the improvement in the KT group continued. In the KT group, the average QDASH score was 18.1 (4.5–35), the VAS score was 2 (1–3), the VAS score in resisted wrist extension was 4 (2–5) and the Nirschl score was 2 (1–3) at the fourth week. The KT group had significant superiority in these parameters over the RMG (p = 0.035, p = 0.035, p = 0.029, p = 0.035, respectively). However, there was no significant difference between the KT, the RMG and the CSI groups at the fourth week. Conclusions: CSI, KT and rest-and-medication treatments were all effective in terms of pain reduction and functional scores at the end of week 2, and the only treatment that continued to be effective in the final week was KT.
Durvalumab after Chemoradiotherapy for PD-L1 Expressing Inoperable Stage III NSCLC Leads to Significant Improvement of Local-Regional Control and Overall Survival in the Real-World Setting

Simple Summary Concurrent platinbased chemoradiotherapy followed by maintenance treatment with the PD-L1 inhibitor durvalumab is the new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with chemoradiotherapy to those treated with chemoradiotherapy and durvalumab (CRT-IO) in the real-world setting. Median follow-up for entire cohort was 33.1 months and median overall survival was 27.2 months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, local-regional-progression-free-survival, progression-free, and overall survival (PFS, OS) were significantly improved compared to the historical cohort of conventional chemoradiotherapy patients. This real-world analysis demonstrated that durvalumab after chemoradiotherapy (CRT) led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort. Abstract Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) in the real-world setting. The analysis was performed based on the retro- and prospectively collected data of 144 consecutive inoperable stage III NSCLC patients treated between 2011–2020. Local-regional-progression-free-survival (LRPFS—defined as progression in the mediastinum, hilum and/or supraclavicular region at both sites and the involved lung), progression-free survival (PFS), and overall survival (OS) were evaluated from the last day of thoracic radiotherapy (TRT). Median follow-up for the entire cohort was 33.1 months (range: 6.3–111.8) and median overall survival was 27.2 (95% CI: 19.5–34.9) months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, median PFS was not reached, LRPFS (p = 0.002), PFS (p = 0.018), and OS (p = 0.005) were significantly improved vs. the historical cohort of conventional CRT patients. After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume, and treatment mode, and exact matching for T-and N-stage, 22 CRT-IO patients were matched 1:2 to 44 CRT patients. Twelve-month LRPFS, PFS, and OS rates in the CRT-IO vs. CRT cohort were 78.9 vs. 45.5% (p = 0.002), 60.0 vs. 31.8% (p = 0.007), and 100 vs. 70.5% (p = 0.003), respectively. This real-world analysis demonstrated that durvalumab after CRT led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.
Strain Sensing Coatings for Large Composite Structures Based on 2D MXene Nanoparticles

Real-time strain monitoring of large composite structures such as wind turbine blades requires scalable, easily processable and lightweight sensors. In this study, a new type of strain-sensing coating based on 2D MXene nanoparticles was developed. A Ti3C2Tz MXene was prepared from Ti3AlC2 MAX phase using hydrochloric acid and lithium fluoride etching. Epoxy and glass fibre–reinforced composites were spray-coated using an MXene water solution. The morphology of the MXenes and the roughness of the substrate were characterised using optical microscopy and scanning electron microscopy. MXene coatings were first investigated under various ambient conditions. The coating experienced no significant change in electrical resistance due to temperature variation but was responsive to the 301–365 nm UV spectrum. In addition, the coating adhesion properties, electrical resistance stability over time and sensitivity to roughness were also analysed in this study. The electromechanical response of the MXene coating was investigated under tensile loading and cyclic loading conditions. The gauge factor at a strain of 4% was 10.88. After 21,650 loading cycles, the MXene coating experienced a 16.25% increase in permanent resistance, but the response to loading was more stable. This work provides novel findings on electrical resistance sensitivity to roughness and electromechanical behaviour under cyclic loading, necessary for further development of MXene-based nanocoatings. The advantages of MXene coatings for large composite structures are processability, scalability, lightweight and adhesion properties.
Using Specified Risk Materials-Based Peptides for Oil Sands Fluid Fine Tailings Management

Fluid fine tailings are produced in huge quantities by Canada’s mined oil sands industry. Due to the high colloidal stability of the contained fine solids, settling of fluid fine tailings can take hundreds of years, making the entrapped water unavailable and posing challenges to public health and the environment. This study focuses on developing value-added aggregation agents from specified risk materials (SRM), a waste protein stream from slaughterhouse industries, to achieve an improved separation of fluid fine tailings into free water and solids. Settling results using synthetic kaolinite slurries demonstrated that, though not as effective as hydrolyzed polyacrylamide, a commercial flocculant, the use of SRM-derived peptides enabled a 2-3-fold faster initial settling rate than the blank control. The pH of synthetic kaolinite tailings was observed to be slightly reduced with increasing peptides dosage in the test range (10–50 kg/ton). The experiments on diluted fluid fine tailings (as a representation of real oil sands tailings) demonstrated an optimum peptides dosage of 14 kg/ton, which resulted in a 4-fold faster initial settling rate compared to the untreated tailings. Overall, this study demonstrates the novelty and feasibility of using SRM-peptides to address intractable oil sands fluid tailings.
Cuticle Hydrocarbons Show Plastic Variation under Desiccation in Saline Aquatic Beetles

Simple Summary Desiccation resistance and physiological plasticity are key traits for species persistence in the context of aridification under global change. One of the main mechanisms of desiccation resistance in insects is the control of cuticular transpiration through changes in the quantity and composition of epicuticular hydrocarbons (CHCs), which have been well studied in terrestrial insects. Our study provides novel information regarding the capacity to cope with desiccation stress through plastic changes in the composition of cuticle hydrocarbons in aquatic insects from saline intermittent streams. We demonstrate that the plasticity of CHCs is an effective mechanism to regulate water loss rate under desiccation stress in the most saline-tolerant species studied. These traits, so far largely unexplored in aquatic insects, are relevant to understanding different biochemical adaptations to deal with drought stress in inland saline waters in an evolutionary and ecological context. Abstract In the context of aridification in Mediterranean regions, desiccation resistance and physiological plasticity will be key traits for the persistence of aquatic insects exposed to increasing desiccation stress. Control of cuticular transpiration through changes in the quantity and composition of epicuticular hydrocarbons (CHCs) is one of the main mechanisms of desiccation resistance in insects, but it remains largely unexplored in aquatic ones. We studied acclimation responses to desiccation in adults of two endemic water beetles from distant lineages living in Mediterranean intermittent saline streams: Enochrus jesusarribasi (Hydrophilidae) and Nebrioporus baeticus (Dytiscidae). Cuticular water loss and CHC composition were measured in specimens exposed to a prior non-lethal desiccation stress, allowed to recover and exposed to a subsequent desiccation treatment. E. jesusarribasi showed a beneficial acclimation response to desiccation: pre-desiccated individuals reduced cuticular water loss rate in a subsequent exposure by increasing the relative abundance of cuticular methyl-branched compounds, longer chain alkanes and branched alkanes. In contrast, N. baeticus lacked acclimation capacity for controlling water loss and therefore may have a lower physiological capacity to cope with increasing aridity. These results are relevant to understanding biochemical adaptations to drought stress in inland waters in an evolutionary and ecological context.