Miracle-dz/UniFAR-FTUs huggingface dataset:
GelMA/PEDOT:PSS Composite Conductive Hydrogel-Based Generation and Protection of Cochlear Hair Cells through Multiple Signaling Pathways

Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, in which the patient has intact low-frequency hearing and profound high-frequency hearing pre-operatively. Therefore, the synergistic restoration of dysfunctional cochlear hair cells and the protection of hair cells from ototoxic insults have become a persistent target pursued for this hybrid system. In this study, we developed a composite GelMA/PEDOT:PSS conductive hydrogel that is suitable as a coating for the cochlear implant electrode for the potential local delivery of otoregenerative and otoprotective drugs. Various material characterization methods (e.g., 1H NMR spectroscopy, FT-IR, EIS, and SEM), experimental models (e.g., murine cochlear organoid and aminoglycoside-induced ototoxic HEI-OC1 cellular model), and biological analyses (e.g., confocal laser scanning microscopy, real time qPCR, flow cytometry, and bioinformatic sequencing) were used. The results demonstrated decent material properties of the hydrogel, such as mechanical (e.g., high tensile stress and Young’s modulus), electrochemical (e.g., low impedance and high conductivity), biocompatibility (e.g., satisfactory cochlear cell interaction and free of systemic toxicity), and biosafety (e.g., minimal hemolysis and cell death) features. In addition, the CDR medicinal cocktail sustainably released by the hydrogel not only promoted the expansion of the cochlear stem cells but also boosted the trans-differentiation from cochlear supporting cells into hair cells. Furthermore, hydrogel-based drug delivery protected the hair cells from oxidative stress and various forms of programmed cell death (e.g., apoptosis and ferroptosis). Finally, using large-scale sequencing, we enriched a complex network of signaling pathways that are potentially downstream to various metabolic processes and abundant metabolites. In conclusion, we present a conductive hydrogel-based local delivery of bifunctional drug cocktails, thereby serving as a potential solution to intracochlear therapy of bimodal auditory rehabilitation and diseases beyond.
Metabolic Rate and Egg Production in Japanese Quails Can Be Predicted by Assessing Growth Parameters of Laying Hens

Simple Summary Quails are becoming increasingly popular for their meat and eggs, and thus, the productivity of laying hens, and how that can be predicted, is of growing interest to quail producers. Because of this, we wanted to find out whether we could predict the performance of laying hens (typically expressed as the number of eggs produced multiplied by the egg weight—the so-called total egg mass) simply by looking at certain growth traits (i.e., body weight, surface area, and volume), as well as the metabolic rate among eight Japanese quail breeds. To succeed in this analysis, we developed a novel method for calculating the volume and surface area of a quail body. As a result, we derived a new mathematical formula called the metabolic index, which included the measurements of body weight, surface area, and volume. We discovered that the total egg mass in quails can be judged from these growth parameters, particularly when we examined the slope angles of the trend lines in the graphs pertaining to these parameters. Abstract The aim of the current study was to assess the female metabolic rate and test the hypothesis that there is a relationship between the egg productivity of Japanese quails from eight breeds and their morphometric, or growth, parameters. Parameters measured were body weight (B), volume (V), and surface area (S), as well as the metabolism level expressed by the ratio S/V. The collected egg performance traits were as follows: the number of eggs produced (N), the average egg weight (W), and the total egg mass (M) (i.e., N multiplied by W). To measure the S and V values, a novel technique was developed that takes into account the similarity of the quail’s body to an ellipsoid. An analysis of the relationships between productivity indicators allowed us to introduce a new index called the metabolic index, B·S/V, based on all three main growth parameters in quails. Using the values of this index, we were then able to judge indirectly the level of quails’ egg productivity. We went on to assess the N, W, and M values, not only depending on the size of the bird’s growth parameters but also according to the degree of their changes during quail growth. These changes were expressed as the slope angles of trend lines describing the growth process data. This approach produced more accurate results for predicting the egg productivity in terms of W and M.
Assessment of Preferences in Taking Painkillers among Students of Medicine, Dentistry, and Pharmacy: A Pilot Study

Students of pharmacy, medicine, and dentistry are important for shaping drug policy. The aim of this study is to assess and compare students preferences in taking painkillers. The study group consists of 382 students of pharmacy (28.8%), medicine (40.0%), and dentistry (30.1%). An anonymous questionnaire consisting of 17 questions was prepared using the Google Forms platform and distributed through social media. Ibuprofen was the most frequently preferred, regardless of the study major (57.8%). Pharmacy students expressed the least concern about the possible side effects of analgesics (17.5%). The fast onset of painkillers was more important for dental students (59.1%) and pharmacy students (44.7%), compared to medical students (39.22%). Medicine and pharmacy students indicated their studies to be their main source of information about painkillers compared to dentistry students (p = 0.001). There are no differences in pain severity regarding which analgesics are used among student groups (p = 0.547). Dental students experienced odontogenic pain less frequently (57.3%) than medical (79.7%) and pharmacy students (79.8%), (p = 0.000). Ketoprofen was the most frequently chosen prescription painkiller for odontogenic pain in all groups (49.4%). Gastrointestinal complaints were the most often reported side effects, regardless of the study major (87.1%). Choice of studies, gender, and year of study were the most important determinants of the choice of painkillers.
Single-Cell RNA Sequencing Reveals the Cellular Landscape of Longissimus Dorsi in a Newborn Suhuai Pig

The introduction of single-cell RNA sequencing (scRNA-seq) technology has spurred additional advancements in analyzing the cellular composition of tissues. The longissimus dorsi (LD) in pigs serves as the primary skeletal muscle for studying meat quality in the pig industry. However, the single-cell profile of porcine LD is still in its infancy stage. In this study, we profiled the transcriptomes of 16,018 cells in the LD of a newborn Suhuai pig at single-cell resolution. Subsequently, we constructed a cellular atlas of the LD, identifying 11 distinct cell populations, including endothelial cells (24.39%), myotubes (18.82%), fibro-adipogenic progenitors (FAPs, 18.11%), satellite cells (16.74%), myoblasts (3.99%), myocytes (5.74%), Schwann cells (3.81%), smooth muscle cells (3.22%), dendritic cells (2.99%), pericytes (1.86%), and neutrophils (0.33%). CellChat was employed to deduce the cell–cell interactions by evaluating the gene expression of receptor–ligand pairs across different cell types. The results show that FAPs and pericytes are the primary signal contributors in LD. In addition, we delineated the developmental trajectory of myogenic cells and examined alterations in the expression of various marker genes and molecular events throughout various stages of differentiation. Moreover, we found that FAPs can be divided into three subclusters (NR2F2-FAPs, LPL-FAPs, and TNMD-FAPs) according to their biological functions, suggesting that the FAPs could be associated with the differentiation of tendon cell. Taken together, we constructed the cellular atlas and cell communication network in LD of a newborn Suhuai pig, and analyzed the developmental trajectory of myogenic cells and the heterogeneity of FAPs subpopulation cells. This enhances our comprehension of the molecular features involved in skeletal muscle development and the meat quality control in pigs.
Biomarkers in Peripartum Cardiomyopathy—What We Know and What Is Still to Be Found

Peripartum cardiomyopathy (PPCM) is a form of heart failure, often severe, that occurs in previously healthy women at the end of their pregnancy or in the first few months after delivery. In PPCM, the recovery of heart function reaches 45–50%. However, the all-cause mortality in long-term observation remains high, reaching 20% irrespective of recovery status. The incidence of PPCM is increasing globally; therefore, effort is required to clarify the pathophysiological background of the disease, as well as to discover specific diagnostic and prognostic biomarkers. The etiology of the disease remains unclear, including oxidative stress; inflammation; hormonal disturbances; endothelial, microcirculatory, cardiomyocyte and extracellular matrix dysfunction; fibrosis; and genetic mutations. Currently, antiangiogenic 16-kDa prolactin (PRL), cleaved from standard 23-kDa PRL in the case of unbalanced oxidative stress, is recognized as the main trigger of the disease. In addition, 16-kDa PRL causes damage to cardiomyocytes, acting via microRNA-146a secreted from endothelial cells as a cause of the NF-κβ pathway. Bromocriptine, which inhibits the secretion of PRL from the pituitary gland, is now the only specific treatment for PPCM. Many different phenotypes of the disease, as well as cases of non-responders to bromocriptine treatment, indicate other pathophysiological pathways that need further investigation. Biomarkers in PPCM are not well established. There is a deficiency in specific diagnostic biomarkers. Pro-brain-type natriuretic peptide (BNP) and N-terminal BNP are the best, however unspecific, diagnostic biomarkers of heart failure at the moment. Therefore, more efforts should be engaged in investigating more specific biomolecules of a diagnostic and prognostic manner such as 16-kDa PRL, galectin-3, myeloperoxidase, or soluble Fms-like tyrosine kinase-1/placental growth factor ratio. In this review, we present the current state of knowledge and future directions of exploring PPCM pathophysiology, including microRNA and heat shock proteins, which may improve diagnosis, treatment monitoring, and the development of specific treatment strategies, and consequently improve patients’ prognosis and outcome.
Alloplastic Epidermal Skin Substitute in the Treatment of Burns

The goal of burn wound treatment is to ensure rapid epithelialization in superficial burns and the process of rebuilding the lost skin in deep burns. Topical treatment plays an important role. One of the innovations in the field of synthetic materials dedicated to the treatment of burns is epidermal skin substitutes. Since the introduction of Suprathel®, the alloplastic epidermal substitute, many research results have been published in which the authors investigated the properties and use of this substitute in the treatment of wounds of various origins, including burn wounds. Burn wounds cause both physical and psychological discomfort, which is why ensuring comfort during treatment is extremely important. Alloplastic epidermal substitute, due to its biodegradability, plasticity, no need to remove the dressing until healing, and the associated reduction in pain, is an alternative for treating burns, especially in children.
Extended cost-effectiveness analysis of interventions to improve uptake of diabetes services in South Africa

Abstract The rising prevalence of diabetes in South Africa (SA), coupled with significant levels of unmet need for diagnosis and treatment, results in high rates of diabetes-associated complications. Income status is a determinant of utilization of diagnosis and treatment services, with transport costs and loss of wages being key barriers to care. A conditional cash transfer (CCT) programme, targeted to compensate for such costs, may improve service utilization. We applied extended cost-effectiveness analysis (ECEA) methods and used a Markov model to compare the costs, health benefits and financial risk protection (FRP) attributes of a CCT programme. A population was simulated, drawing from SA-specific data, which transitioned yearly through various health states, based on specific probabilities obtained from local data, over a 45-year time horizon. Costs and disability-adjusted life years (DALYs) were applied to each health state. Three CCT programme strategies were simulated and compared to a ‘no programme’ scenario: (1) covering diagnosis services only; (2) covering treatment services only; (3) covering both diagnosis and treatment services. Cost-effectiveness was reported as incremental net monetary benefit (INMB) using a cost-effectiveness threshold of USD3015 per DALY for SA, while FRP outcomes were reported as catastrophic health expenditure (CHE) cases averted. Distributions of the outcomes were reported by income quintile and sex. Covering both diagnosis and treatment services for the bottom two quintiles resulted in the greatest INMB (USD22 per person) and the greatest CHE cases averted. There were greater FRP benefits for women compared to men. A CCT programme covering diabetes diagnosis and treatment services was found to be cost-effective, when provided to the poorest 40% of the SA population. ECEA provides a useful platform for including equity considerations to inform priority setting and implementation policies in SA.
Evaluation of the Therapeutic Effects of Harmine on Anaplastic Thyroid Cancer Cells

Anaplastic thyroid carcinoma (ATC) is an extremely difficult disease to tackle, with an overall patient survival of only a few months. The currently used therapeutic drugs, such as kinase inhibitors or immune checkpoint inhibitors, can prolong patient survival but fail to eradicate the tumor. In addition, the onset of drug resistance and adverse side-effects over time drastically reduce the chances of treatment. We recently showed that Twist1, a transcription factor involved in the epithelial mesenchymal transition (EMT), was strongly upregulated in ATC, and we wondered whether it might represent a therapeutic target in ATC patients. To investigate this hypothesis, the effects of harmine, a β-carboline alkaloid shown to induce degradation of the Twist1 protein and to possess antitumoral activity in different cancer types, were evaluated on two ATC-derived cell lines, BHT-101 and CAL-62. The results obtained demonstrated that, in both cell lines, harmine reduced the level of Twist1 protein and reverted the EMT, as suggested by the augmentation of E-cadherin and decrease in fibronectin expression. The drug also inhibited cell proliferation and migration in a dose-dependent manner and significantly reduced the anchorage-independent growth of both ATC cell lines. Harmine was also capable of inducing apoptosis in BHT-101 cells, but not in CAL-62 ones. Finally, the activation of PI3K/Akt signaling, but not that of the MAPK, was drastically reduced in treated cells. Overall, these in vitro data suggest that harmine could represent a new therapeutic option for ATC treatment.
Investigating the Health Implications of Whey Protein Consumption: A Narrative Review of Risks, Adverse Effects, and Associated Health Issues

This narrative review critically examines the current research on the health implications of whey protein (WP) supplementation, with a focus on potential risks and adverse effects. WP, commonly consumed for muscle building and weight loss, has been associated with various health concerns. Our comprehensive analysis involved a thorough search of multiple databases, resulting in the inclusion of 21 preclinical and human studies that collectively offer a detailed overview of WP’s health impacts. The review reveals significant findings, such as WP’s potential link to liver and kidney damage, alterations in gut microbiota, increased acne incidence, impacts on bone mass, and emotional and behavioural changes. These findings underscore the complexity of WP’s effects on human health, indicating both beneficial and detrimental outcomes in relation to different posologies in a variety of settings. Our study suggests caution for the protein intake in situations of hepatic and renal compromised functions, as well as in acne susceptibility, while possible beneficial effects can be achieved for the intestinal microbiota, humoral and behavioural level, and finally bone and muscle mass in elderly. We emphasizes the importance of balanced WP consumption and call for more in-depth research to understand its long-term health effects. Health professionals and individuals considering WP supplementation should be aware of these potential risks and approach its use with informed caution.
Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

Aspirin, other antiplatelet agents, and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases. A concomitant proton pump inhibitor (PPI) treatment is often prescribed in these patients, as gastrointestinal complications are relatively frequent. On the other hand, a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs; in particular, it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel, due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism. Previously, the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged. In contrast, it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel, new P2Y12 receptor antagonists. Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids, or non-steroidal anti-inflammatory drugs, and Helicobacter pylori (H. pylori) infection. In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding, PPIs could be recommended, even if their usefulness deserves further data. H. pylori infection should always be investigated and treated in patients with a history of peptic ulcer disease (with or without complication) treated with antithrombotic drugs. The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors, anticoagulants, and PPIs, discussing consequent clinical implications.
Management of ANCA-associated vasculitis: Current trends and future prospects

: The antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are a spectrum of heterogeneous autoimmune diseases characterized by necrotizing small vessel vasculitis and the presence of ANCA. These chronic multisystem disorders may be life-threatening if there is major organ involvement, such as acute renal failure or pulmonary hemorrhage, and require significant initial immunosuppression and long-term maintenance treatment. Long-established protocols using cyclophosphamide and prednisolone have resulted in dramatically improved outcomes for patients since the 1970s. Subsequently, international collaboration has contributed to a growing evidence base and consensus in the management of these rare disorders. Modifications to traditional treatment protocols by the use of azathioprine or methotrexate rather than cyclophosphamide, and the introduction of newer agents, such as rituximab, has maintained outcomes whilst decreasing toxicity. However, the treatment limitations of incomplete efficacy, infection, and cumulative toxicity persist. These issues have continued to drive the search for safer and more effective modulation of the immune system using targeted immunotherapy. This review will explore the current evidence base for management of ANCA-associated vasculitis and future treatment prospects.
Venous Thromboembolism in Patients Hospitalized for COVID-19 in a Non-Intensive Care Unit

Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may contribute to venous thromboembolism (VTE) with adverse effects on the course of COVID-19. The purpose of this study was to investigate an incidence and risk factors for VTE in patients hospitalized for COVID-19 in a non-intensive care unit (non-ICU). Consecutive adult patients with COVID-19 hospitalized from November 2021 to March 2022 in the isolation non-ICU at our center were included in the study. Incidence of VTE including pulmonary embolism (PE) and deep vein thrombosis (DVT), clinical characteristics, and D-dimer plasma levels during the hospitalization were retrospectively evaluated. Among the 181 patients (aged 68.8 ± 16.2 years, 44% females, 39% Delta SARS-CoV-2 variant, 61% Omicron SARS-CoV-2 variant), VTE occurred in 29 patients (VTE group, 16% of the entire cohort). Of them, PE and DVT were diagnosed in 15 (8.3% of the entire cohort) and 14 (7.7%) patients, respectively. No significant differences in clinical characteristics were observed between the VTE and non-VTE groups. On admission, median D-dimer was elevated in both groups, more for VTE group (1549 ng/mL in VTE vs. 1111 ng/mL in non-VTE, p = 0.09). Median maximum D-dimer was higher in the VTE than in the non-VTE group (5724 ng/mL vs. 2200 ng/mL, p < 0.005). In the univariate analysis, systemic arterial hypertension and the need for oxygen therapy were predictors of VTE during hospitalization for COVID-19 (odds ratio 2.59 and 2.43, respectively, p < 0.05). No significant associations were found between VTE risk and other analyzed factors; however, VTE was more likely to occur in patients with a history of VTE, neurological disorders, chronic pulmonary or kidney disease, atrial fibrillation, obesity, and Delta variant infection. Thromboprophylaxis (83.4% of the entire cohort) and anticoagulant treatment (16.6%) were not associated with a decreased VTE risk. The incidence of VTE in patients hospitalized in non-ICU for COVID-19 was high despite the common use of thromboprophylaxis or anticoagulant treatment. A diagnosis of arterial hypertension and the need for oxygen therapy were associated with an increased VTE risk. Continuous D-dimer monitoring is required for the early detection of VTE.
Coronary Artery Surgery: Past, Present, and Future

Coronary artery bypass grafting (CABG) is the most commonly performed and studied major cardiac operation worldwide. An understanding of the evolution of CABG, including the early days of cardiac surgery, the first bypass operation, continuous improvements in techniques, and streamlining of the operation, is important to inform current trends and future innovations. This article will examine how CABG evolved (from techniques to conduits), describe current trends in the field, and explore what lies on the horizon for the future of CABG.