Miracle-dz/UniFAR-FTUs huggingface dataset:
Four Unusual Cases of Congenital Forelimb Malformations in Dogs

Simple Summary Congenital limb defects are sporadically encountered in dogs during normal clinical practice. Literature concerning their diagnosis and management in canine species is poor. Sometimes, the diagnosis and description of congenital limb abnormalities are complicated by the concurrent presence of different malformations in the same limb and the lack of widely accepted classification schemes. In order to improve the knowledge about congenital limb anomalies in dogs, this report describes the clinical and radiographic findings in four dogs affected by unusual congenital forelimb defects, underlying also the importance of reviewing current terminology. Abstract Four dogs were presented with thoracic limb deformity. After clinical and radiographic examinations, a diagnosis of congenital malformations was performed for each of them. In one case, a deformity involving both the radial and ulnar side of the distal limb was observed. Based on clinical and radiological evaluations, a diagnosis of postaxial terminal longitudinal ulnar hemimelia was performed. The term ectrodactyly was used to refer different malformations characterized by skin and soft tissue separation of the distal forelimb observed in two dogs. Simple complete uncomplicated syndactyly of the right forelimb, and complex incomplete uncomplicated syndactyly of the left forelimb were diagnosed in the fourth case. To the authors’ knowledge, ectrodactyly and simple complete uncomplicated syndactyly are very uncommon anomalies in companion animals and have been rarely documented. Moreover, postaxial terminal longitudinal ulnar hemimelia has still not been reported in dogs.
Cardiac Hypertrophy Changes Compartmentation of cAMP in Non-Raft Membrane Microdomains

3′,5′-Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger which plays critical roles in cardiac function and disease. In adult mouse ventricular myocytes (AMVMs), several distinct functionally relevant microdomains with tightly compartmentalized cAMP signaling have been described. At least two types of microdomains reside in AMVM plasma membrane which are associated with caveolin-rich raft and non-raft sarcolemma, each with distinct cAMP dynamics and their differential regulation by receptors and cAMP degrading enzymes phosphodiesterases (PDEs). However, it is still unclear how cardiac disease such as hypertrophy leading to heart failure affects cAMP signals specifically in the non-raft membrane microdomains. To answer this question, we generated a novel transgenic mouse line expressing a highly sensitive Förster resonance energy transfer (FRET)-based biosensor E1-CAAX targeted to non-lipid raft membrane microdomains of AMVMs and subjected these mice to pressure overload induced cardiac hypertrophy. We could detect specific changes in PDE3-dependent compartmentation of β-adrenergic receptor induced cAMP in non-raft membrane microdomains which were clearly different from those occurring in caveolin-rich sarcolemma. This indicates differential regulation and distinct responses of these membrane microdomains to cardiac remodeling.
Clindamycin-Based 3D-Printed and Electrospun Coatings for Treatment of Implant-Related Infections

This study presents the development and characterisation of two novel bioactive coatings deposited on TiAlV and AISI 316LVM substrates. The coatings were prepared using 3D printing and electrospinning. The 3D-printed coating consisted of the cellulose nanofibril suspension, alginate, and carboxymethylcellulose (CMC), while CMC and polyethylene oxide were used to prepare the electrospun coating. Both coatings were loaded with the antibiotic clindamycin (CLIN), which is a bacteriostatic lincosamide known for its activity against streptococci, staphylococci, pneumococci, Bacteroides species, and other anaerobes. Initial characterisation of the coatings was performed by attenuated total reflectance Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and atomic force microscopy. Furthermore, the contact angle measurements, swelling rate, and biodegradability of the coatings were investigated. The released concentration of CLIN in PBS (pH = 7.4 at 25 °C) was determined by UV-VIS spectrophotometry. The coatings’ biocompatibility was determined using an MTT (3(4,5 dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay using an osteoblast cell culture (hFOB 1.19, ATCC CRL 11372).
Direct Electrochemical Determination of Glyphosate at Copper Phthalocyanine/Multiwalled Carbon Nanotube Film Electrodes

A copper phthalocyanine/multiwalled carbon nanotube film-modified glassy carbon electrode has been used for the determination of the herbicide glyphosate (Gly) at � 50 mV vs. SCE by electrochemical oxidation using differential pulse voltammetry (DPV). Cyclic voltammetry and electrochemical impedance spectroscopy showed that Gly is adsorbed on the metallic centre of the copper phthalocyanine molecule, with formation of Gly-copper ion complexes. An analytical method was developed using DPV in pH 7.4 phosphate buffer solution, without any pretreatment steps: Gly was determined in the concentration range of 0.83 –9.90 mmol L � 1 , with detection limit 12.2 nmol L � 1 (2.02 m gL � 1
The Determinants of Health-Related Quality of Life in a Sample of Primary School Children: A Cross-Sectional Analysis

Background: Health-related quality of life (HRQoL) in childhood is a multidimensional construct with many sub dimensions of subjective experience, including physical activity (PA), psychological well-being, social interaction, and school performance, that represents a fundamental health outcome to assess a child’s physical and psycho-social functioning. Our study aims to explore the potential predictors of children’s health-related quality of life, using a convenience sample from the Imola Active Break Study (I-MOVE), considering demographic, anthropometric measures, PA level measured by Actigraph accelerometers, parent-reported/self-reported HRQoL, and body image. Methods: A cross-sectional analysis was conducted among 151 primary school children in Italy. HRQoL was assessed using the Italian version 4.0 of the Paediatric Quality of Life (PedsQL) questionnaire. Results: Children who spent more time partaking in moderate PA were associated with a higher total PedsQL score (p < 0.03). Mother’s body mass index (BMI) was the only variable statistically significant associated with the physical health domain of PedsQL. Parent’s proxy-report perception concerning children’s psychosocial health was statistically relevant. The children’s gender, age, and BMI had no association with any of the HRQoL outcomes. Discussion: Parent proxy-report psychosocial health and mother’s BMI should be considered as predictors of HRQoL for the psychosocial and physical domain. PA should be implemented in order to improve the HRQoL of primary school children.
Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis

Simple Summary Head and neck cancer is the sixth most frequent type of cancer, with more than 600,000 new cases/year, and it is responsible for around 300,000 deaths/year. Substance P (SP) is a peptide of the tachykinin family whose functions are related to a large number of physiological mechanisms in humans. The implications of SP in human carcinogenesis have recently been reported through the stimulation of its receptor NK-1R, or directly through the effects derived from the constitutive activation of NK-1R. With this background, we have shown, through a systematic review and meta-analysis, evidence that the upregulation of SP and NK-1R are oncogenic events involved in head and neck carcinogenesis, probably acting in the early stages of malignization. Our findings also highlight translational opportunities for SP/NK-1R as potential therapeutic targets in head and neck cancer. Abstract The objective of our study has been, through a systematic review and meta-analysis, to increase the scientific evidence on the implications of SP and its receptor NK-1R in head and neck carcinogenesis. We searched studies published before May-2020 without date and publication language restrictions (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. A total 16 studies and 1308 cases met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same scientific rigor, finding the greatest risk of bias in the study confounding and prognostic factors measurement domains. Quantitative evaluation showed a greater SP/NK-1R overexpression in malignant head and neck lesions compared to benign lesions (p = 0.02), and that expression was observed in malignant salivary gland pathology. Likewise, we found a higher overexpression of NK-1R compared to SP (p = 0.02). In conclusion, the results of this systematic review and meta-analysis show evidence that the upregulation of SP and NK-1R are oncogenic events involved in head and neck carcinogenesis, probably acting in the early stages of malignization. In addition, there is evidence of a greater relevance of the upregulation of the NK-1R receptor compared to SP, which highlights the interest in deepening the development of targeted therapies on the receptor. Future studies assessing the relationships between SP/NK-1R among subjects with head and neck tumors could consider the recommendations given in this systematic review and meta-analysis to improve and standardize future research.
Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (≥8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors.
Hydrogen Sulfide—Clues from Evolution and Implication for Neonatal Respiratory Diseases

Reactive oxygen species (ROS) have been the focus of redox research in the realm of oxidative neonatal respiratory diseases such as bronchopulmonary dysplasia (BPD). Over the years, nitric oxide (NO) and carbon monoxide (CO) have been identified as important gaseous signaling molecules involved in modulating the redox homeostasis in the developing lung. While animal data targeting aspects of these redox pathways have been promising in treating and/or preventing experimental models of neonatal lung disease, none are particularly effective in human neonatal clinical trials. In recent years, hydrogen sulfide (H2S) has emerged as a novel gasotransmitter involved in a magnitude of cellular signaling pathways and functions. The importance of H2S signaling may lie in the fact that early life-forms evolved in a nearly anoxic, sulfur-rich environment and were dependent on H2S for energy. Recent studies have demonstrated an important role of H2S and its synthesizing enzymes in lung development, which normally takes place in a relatively hypoxic intrauterine environment. In this review, we look at clues from evolution and explore the important role that the H2S signaling pathway may play in oxidative neonatal respiratory diseases and discuss future opportunities to explore this phenomenon in the context of neonatal chronic lung disease.
DHA and Its Metabolites Have a Protective Role against Methylmercury-Induced Neurotoxicity in Mouse Primary Neuron and SH-SY5Y Cells

The consumption of fish now involves a risk of methylmercury (MeHg) exposure but also provides the benefit of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) such as docosahexaenoic acid (DHA). Some epidemiological studies have suggested that the intake of DHA can alleviate the neurotoxicity of MeHg, but the underlying mechanism is not known. Herein, we observed that pretreatment with 0.1–1 µM DHA suppressed MeHg-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells and mouse primary neuronal cells. These effects of DHA were canceled in the presence of the retinoid X receptor (RXR) antagonist UVI3003. An RXR agonist, bexarotene, suppressed the cytotoxicity of MeHg. DHA also suppressed the MeHg-induced production of reactive oxygen species (ROS) via an induction of antioxidant genes (catalase and SOD1). Pretreatment with DHA did not change the incorporation of MeHg. We showed previously that in the brain, the intake of DHA increased the level of 19,20-DHDP, which is the metabolite produced by cytochrome P450 and soluble epoxide hydrolase from DHA. In the present study, we observed that 19,20-DHDP also suppressed neurotoxicity from MeHg. These results indicate that DHA and its metabolites have a protective role in MeHg-induced neurotoxicity.
Trends in Articular Cartilage Tissue Engineering: 3D Mesenchymal Stem Cell Sheets as Candidates for Engineered Hyaline-Like Cartilage

Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction and restoration of limited mobility, current treatments do not reliably regenerate native hyaline cartilage or halt cartilage degeneration at these defect sites. Novel therapeutics aimed at addressing limitations of current clinical cartilage regeneration therapies increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, and available cell sources that express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing allogeneic MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs for direct and immediate replacement of hyaline cartilage, improve local site tissue integration, and optimize treatment outcomes. Among emerging tissue engineering technologies, advancements in cell sheet tissue engineering offer promising capabilities for achieving both in vitro hyaline-like differentiation and effective transplantation, based on controlled 3D cellular interactions and retained cellular adhesion molecules. This review focuses on 3D MSC-based tissue engineering approaches for fabricating “ready-to-use” hyaline-like cartilage constructs for future rapid in vivo regenerative cartilage therapies. We highlight current approaches and future directions regarding development of MSC-derived cartilage therapies, emphasizing cell sheet tissue engineering, with specific focus on regulating 3D cellular interactions for controlled chondrogenic differentiation and post-differentiation transplantation capabilities.
Total Laryngectomy—Still Cutting-Edge?

Simple Summary Complete removal of the larynx (total laryngectomy) offers a curative approach for advanced laryngeal and pharyngeal cancer. If the operation is performed after radiotherapy wound healing problems have to be taken into account which can be managed by adapted reconstructive techniques. Laryngectomy results in the loss of voice which can be managed e.g., by using a voice prosthesis with a significant increase in quality of life. Total laryngectomy still represents a relevant surgical procedure in modern head and neck oncology. Abstract Surgical removal of the larynx (total laryngectomy) offers a curative approach to patients with advanced laryngeal and hypopharyngeal (squamous cell) cancer without distant metastases. Particularly in T4a carcinoma, laryngectomy seems prognostically superior to primary radio(chemo)therapy. Further relevant indications for laryngectomy include massive laryngeal dysfunction associated with aspiration and recurrence after radio(chemo)therapy, resulting in salvage surgery. The surgical procedure including neck dissection is highly standardised and safe. The resulting aphonia can be compensated by functional rehabilitation (e.g., voice prosthesis) associated with a significant quality of life improvement. This article presents an overview of indications, preoperative diagnostics, surgical procedures, including new developments (robotics), possible complications, the choice of adjuvant treatment, alternative therapeutic approaches, rehabilitation and prognosis. In summary, total laryngectomy still represents a relevant surgical procedure in modern head and neck oncology.
Fetal Megalencephaly with Cortical Dysplasia at 18 Gestational Weeks Related to Paternal UPD Mosaicism with PTEN Mutation

The phosphatase and tensin homolog (PTEN) gene is a tumor-suppressor gene located on 10q22-23. Since the introduction of molecular genetics in prenatal diagnostics, various birth defects associated with gene mutations have been diagnosed. However, no reports on fetal cases related to PTEN mutation have been found, so far. We encountered a rare case of fetal PTEN mutation. Fetal macrocephaly was noted at 16 weeks. At 18 and 20 weeks, neurosonography revealed megalencephaly with an asymmetrical structure and multifocal polygyria. The head circumference (HC) was +6.2 SD at 18 weeks and +8.1 SD at 20 weeks. The parents opted for pregnancy termination, and the male fetus was delivered at 21 weeks, with HC +9.3 SD. Single-nucleotide polymorphism (SNP) array for amniotic cells showed paternal uniparental disomy (UPD) 10q mosaicism, and the mosaic ratio was calculated as 56% from B-allele frequency. Exome sequencing revealed the pathogenic PTEN mutation with mosaicism. The heterozygous PTEN mutation may not cause early manifestations from the fetal period, and an abnormal phenotype may appear after birth. This may be the reason why fetal defects associated with PTEN mutation are not detected. Since this case had homozygous and heterozygous mutations, survival was possible, exhibiting an incredibly huge head with cortical dysplasia from early pregnancy.
Unveiling Carbon Dioxide and Ethanol Diffusion in Carbonated Water-Ethanol Mixtures by Molecular Dynamics Simulations

The diffusion of carbon dioxide (CO2) and ethanol (EtOH) is a fundamental transport process behind the formation and growth of CO2 bubbles in sparkling beverages and the release of organoleptic compounds at the liquid free surface. In the present study, CO2 and EtOH diffusion coefficients are computed from molecular dynamics (MD) simulations and compared with experimental values derived from the Stokes-Einstein (SE) relation on the basis of viscometry experiments and hydrodynamic radii deduced from former nuclear magnetic resonance (NMR) measurements. These diffusion coefficients steadily increase with temperature and decrease as the concentration of ethanol rises. The agreement between theory and experiment is suitable for CO2. Theoretical EtOH diffusion coefficients tend to overestimate slightly experimental values, although the agreement can be improved by changing the hydrodynamic radius used to evaluate experimental diffusion coefficients. This apparent disagreement should not rely on limitations of the MD simulations nor on the approximations made to evaluate theoretical diffusion coefficients. Improvement of the molecular models, as well as additional NMR measurements on sparkling beverages at several temperatures and ethanol concentrations, would help solve this issue.
Patient Perceptions of a Group-Based Lifestyle Intervention for Overweight Women with Urinary Incontinence: A Qualitative Descriptive Study

Urinary incontinence (UI) affects many women and impacts quality of life. Group-based interventions may be an effective and efficient method for providing UI care; however, interventions must be acceptable to patients to have an impact. This study aimed to explore patients’ perceptions of an exercise training and healthy eating group program (ATHENA) for overweight and obese women with UI. This qualitative descriptive study involved semi-structured interviews with a subset of participants sampled from a feasibility study of ATHENA. The ATHENA intervention was co-developed with end-users and implemented in Women’s Health Physiotherapy services at an Australian hospital. Interviews were recorded, transcribed and analysed thematically. Eleven female patients participated (mean ± SD age 54.2 ± 9.9 years; body mass index 30.5 ± 3.25 kg/m2). Participants found ATHENA highly acceptable, with three themes emerging from interviews: (1) Participants’ journey of change through ATHENA, describing the shifts in knowledge, attitudes, behaviours and symptoms participants experienced; (2) High satisfaction with ATHENA, including educational content, exercise components and delivery style; and (3) Group setting integral to ATHENA’s success, with participants providing support, building friendships, and facilitating each other’s learning. Overall, ATHENA was acceptable to participants, who provided each other with peer support; an unexpected moderator to ATHENA’s success.
Change in Exercise Performance and Markers of Acute Kidney Injury Following Heat Acclimation with Permissive Dehydration

Implementing permissive dehydration (DEH) during short-term heat acclimation (HA) may accelerate adaptations to the heat. However, HA with DEH may augment risk for acute kidney injury (AKI). This study investigated the effect of HA with permissive DEH on time-trial performance and markers of AKI. Fourteen moderately trained men (age and VO2max = 25 ± 0.5 yr and 51.6 ± 1.8 mL·kg−1·min−1) were randomly assigned to DEH or euhydration (EUH). Time-trial performance and VO2max were assessed in a temperate environment before and after 7 d of HA. Heat acclimation consisted of 90 min of cycling in an environmental chamber (40 °C, 35% RH). Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were assessed pre- and post-exercise on day 1 and day 7 of HA. Following HA, VO2max did not change in either group (p = 0.099); however, time-trial performance significantly improved (3%, p < 0.01) with no difference between groups (p = 0.485). Compared to pre-exercise, NGAL was not significantly different following day 1 and 7 of HA (p = 0.113) with no difference between groups (p = 0.667). There was a significant increase in KIM-1 following day 1 and 7 of HA (p = 0.002) with no difference between groups (p = 0.307). Heat acclimation paired with permissive DEH does not amplify improvements in VO2max or time-trial performance in a temperate environment versus EUH and does not increase markers of AKI.