Miracle-dz/UniFAR-FTUs huggingface dataset:
NK Cells in Myeloproliferative Neoplasms (MPN)

Simple Summary NK cells are important innate immune effectors that contribute substantially to tumor control, however the role of NK cells in haematological cancers is not as well understood. The aim of this review is to highlight the importance of the role of NK cells in the management of Ph+ Myeloproliferative Neoplasms, and emphasize the need and possible benefits of a more in-depth investigation into their role in classical MPNs and show potential strategies to harness the anti-tumoral capacities of NK cells. Abstract Myeloproliferative neoplasms (MPNs) comprise a heterogenous group of hematologic neoplasms which are divided into Philadelphia positive (Ph+), and Philadelphia negative (Ph−) or classical MPNs. A variety of immunological factors including inflammatory, as well as immunomodulatory processes, closely interact with the disease phenotypes in MPNs. NK cells are important innate immune effectors and substantially contribute to tumor control. Changes to the absolute and proportionate numbers of NK cell, as well as phenotypical and functional alterations are seen in MPNs. In addition to the disease itself, a variety of therapeutic options in MPNs may modify NK cell characteristics. Reports of suppressive effects of MPN treatment strategies on NK cell activity have led to intensive investigations into the respective compounds, to elucidate the possible negative effects of MPN therapy on control of the leukemic clones. We hereby review the available literature on NK cells in Ph+ and Ph− MPNs and summarize today’s knowledge on disease-related alterations in this cell compartment with particular focus on known therapy-associated changes. Furthermore, we critically evaluate conflicting data with possible implications for future projects. We also aim to highlight the relevance of full NK cell functionality for disease control in MPNs and the importance of considering specific changes related to therapy in order to avoid suppressive effects on immune surveillance.
The Hidden Treasures of Preoperative Blood Assessment in Oral Cancer: A Potential Source of Biomarkers

Simple Summary In this study, we assess the prognostic potential of immune and inflammatory elements determined preoperatively in the peripheral blood of patients with oral squamous cell carcinoma (OSCC). Preoperative plasma fibrinogen (Fib) and platelet-to-lymphocyte ratio (PLR) show strong correlations with patients’ outcomes. Analyzed together, in a new parameter named Fibrinogen-PLR Algorithm (FiPLA), predictive power increases significantly. Clinicians can use this new, easy, cost-effective, and globally available tool for risk stratification of patients with OSCC, as early as from the moment of diagnosis. Abstract (1) Background: Oral squamous cell carcinoma (OSCC) is a common malignancy, and the impact of immune and inflammatory mechanisms in its development and progression are of major interest. The aim of our study is to assess the prognostic potential of circulating immune and inflammatory elements determined preoperatively in patients with OSCC, as well as the development of a new compound parameter with predictive value. (2) Methods: We assessed preoperative fibrinogen (Fib) and the platelet-to-lymphocyte ratio (PLR) in 111 OSCC patients. Using a mathematic algorithm, we determined a composite parameter with cumulative information from Fib and PLR, named Fibrinogen-PLR Algorithm (FiPLA). Survival analysis, followed by bivariate and multivariate analyses, was subsequently conducted. (3) Results: Increased preoperative Fib and PLR levels were associated with poor outcome in OSCC (p = 0.0001 and p = 0.0015, respectively). Preoperative FiPLA values were also associated with poor patient survival (p < 0.0001). Multivariate analysis confirmed the independent prognostic role for FiPLA only (CI95% 1.232–67.770, p = 0.03), showing the superior predictive value of FiPLA compared to its individual components. (4) Conclusions: Preoperative assessments of circulating immune and inflammatory elements can provide high-quality prognostic information, and they represent valuable tools in clinical practice, facilitating the early risk stratification of patients with OSCC.
In Vitro and In Vivo Effects of SerpinA1 on the Modulation of Transthyretin Proteolysis

Transthyretin (TTR) proteolysis has been recognized as a complementary mechanism contributing to transthyretin-related amyloidosis (ATTR amyloidosis). Accordingly, amyloid deposits can be composed mainly of full-length TTR or contain a mixture of both cleaved and full-length TTR, particularly in the heart. The fragmentation pattern at Lys48 suggests the involvement of a serine protease, such as plasmin. The most common TTR variant, TTR V30M, is susceptible to plasmin-mediated proteolysis, and the presence of TTR fragments facilitates TTR amyloidogenesis. Recent studies revealed that the serine protease inhibitor, SerpinA1, was differentially expressed in hepatocyte-like cells (HLCs) from ATTR patients. In this work, we evaluated the effects of SerpinA1 on in vitro and in vivo modulation of TTR V30M proteolysis, aggregation, and deposition. We found that plasmin-mediated TTR proteolysis and aggregation are partially inhibited by SerpinA1. Furthermore, in vivo downregulation of SerpinA1 increased TTR levels in mice plasma and deposition in the cardiac tissue of older animals. The presence of TTR fragments was observed in the heart of young and old mice but not in other tissues following SerpinA1 knockdown. Increased proteolytic activity, particularly plasmin activity, was detected in mice plasmas. Overall, our results indicate that SerpinA1 modulates TTR proteolysis and aggregation in vitro and in vivo.
Analysis of Hazard Rate of Municipalities in Slovakia in Terms of COVID-19

The coronavirus became a phenomenon in 2020, which is making an unwanted but wide space for the study of various scientific disciplines. The COVID-19 pandemic situation which has reached almost the whole civilized world by its consequences thus offers a unique possibility to analyze the graphic space and the human activities inside it. The aim of this study is to predict and identify the potential rate of threat on the example of COVID-19 in Slovakia through an established model. This model consisted of an assessment of the partial phenomena of exposure, vulnerability, and overall risk. The statistical data used to evaluate these phenomena concerned individual cities in Slovakia. These represent the smallest administrative unit. Indirect methods based on the point method were applied in the paper. The spreading and transfer of the disease was influenced much more by the exposure presented by traffic availability, especially, but also the concentration of inhabitants in the selected locations (shops, cemeteries, and others). In the results, our modeling confirmed the regions with the highest intensity, especially in the districts (Bratislava, Košice, Prešov, and Nitra). The selection of the data and method used in this study together with the results reached and presented may serve as an appropriate tool for the support of decision-making of other measures for the future.
External Marginal Gap Variation and Residual Fracture Resistance of Composite and Lithium-Silicate CAD/CAM Overlays after Cyclic Fatigue over Endodontically-Treated Molars

The purpose of this in vitro study was to evaluate the external marginal gap variation with a 3D quantitative method and the residual fracture resistance after cyclic fatigue in endodontically treated molars restored with overlays of different materials, with and without fiber posts-supported buildups. Forty-eight human maxillary molars were selected, endodontically treated, prepared with standardized MOD cavities and randomly allocated into 6 study groups considering the “core strategy” (build-up with composite resin; build-up with composite resin supported by a fiber post); and the “restorative material” of the indirect adhesive overlay (GrandioBlocks, Voco; Cerasmart, GC; CeltraDuo, Dentsply). All procedures were executed according with manufacturers guidelines. Micro-CT analysis prior and after cyclic fatigue were executed, followed by scanning electron microscope analysis and fracture resistance test. The Two-Way ANOVA analysis showed that interfacial gap progression was significantly influenced by the “core strategy” (p < 0.01) but not of “restorative material” (p = 0.59). Concerning fracture resistance, “restorative material” was statistically significant (p < 0.01), while “core strategy” (p = 0.63) and the interaction (p = 0.84) were not. In conclusion, the fiber post presence within the build-up promoted a lower interfacial gap opening after fatigue, evaluated through micro-CT scans. In terms of fracture resistance, teeth restored with Cerasmart and Celtra Duo were statistically similar, but superior to GrandioBlocks.
Fungal Biotransformation of 2′-Methylflavanone and 2′-Methylflavone as a Method to Obtain Glycosylated Derivatives

Methylated flavonoids are promising pharmaceutical agents due to their improved metabolic stability and increased activity compared to unmethylated forms. The biotransformation in cultures of entomopathogenic filamentous fungi is a valuable method to obtain glycosylated flavones and flavanones with increased aqueous solubility and bioavailability. In the present study, we combined chemical synthesis and biotransformation to obtain methylated and glycosylated flavonoid derivatives. In the first step, we synthesized 2′-methylflavanone and 2′-methylflavone. Afterwards, both compounds were biotransformed in the cultures of two strains of entomopathogenic filamentous fungi Beauveria bassiana KCH J1.5 and Isaria fumosorosea KCH J2. We determined the structures of biotransformation products based on NMR spectroscopy. Biotransformations of 2′-methyflavanone in the culture of B. bassiana KCH J1.5 resulted in three glycosylated flavanones: 2′-methylflavanone 6-O-β-d-(4″-O-methyl)-glucopyranoside, 3′-hydroxy-2′-methylflavanone 6-O-β-d-(4″-O-methyl)-glucopyranoside, and 2-(2′-methylphenyl)-chromane 4-O-β-d-(4″-O-methyl)-glucopyranoside, whereas in the culture of I. fumosorosea KCH J2, two other products were obtained: 2′-methylflavanone 3′-O-β-d-(4″-O-methyl)-glucopyranoside and 2-methylbenzoic acid 4-O-β-d-(4′-O-methyl)-glucopyranoside. 2′-Methylflavone was effectively biotransformed only by I. fumosorosea KCH J2 into three derivatives: 2′-methylflavone 3′-O-β-d-(4″-O-methyl)-glucopyranoside, 2′-methylflavone 4′-O-β-d-(4″-O-methyl)-glucopyranoside, and 2′-methylflavone 5′-O-β-d-(4″-O-methyl)-glucopyranoside. All obtained glycosylated flavonoids have not been described in the literature until now and need further research on their biological activity and pharmacological efficacy as potential drugs.
Vitamin K-Dependent Proteins in Skeletal Development and Disease

Vitamin K and Vitamin K-dependent proteins (VKDPs) are best known for their pivotal role in blood coagulation. Of the 14 VKPDs identified in humans to date, 6 play also important roles in skeletal biology and disease. Thus, osteocalcin, also termed bone Gla-protein, is the most abundant non-collagenous protein in bone. Matrix Gla protein and Ucma/GRP on the other hand are highly abundant in cartilage. Furthermore, periostin, protein S, and growth arrest specific 6 protein (GAS 6) are expressed in skeletal tissues. The roles for these VKDPs are diverse but include the control of calcification and turnover of bone and cartilage. Vitamin K plays an important role in osteoporosis and serum osteocalcin levels are recognized as a promising marker for osteoporosis. On the other hand, matrix Gla protein and Ucma/GRP are associated with osteoarthritis. This review focuses on the roles of these three VKDPs, osteocalcin, matrix Gla protein and Ucma/GRP, in skeletal development and disease but will also summarize the roles the other skeletal VKDPs (periostin, protein S and GAS6) in skeletal biology.
The Containment Scouts: First Insights into an Initiative to Increase the Public Health Workforce for Contact Tracing during the COVID-19 Pandemic in Germany

The COVID-19 pandemic in Germany has demanded a substantially larger public health workforce to perform contact tracing and contact management of COVID-19 cases, in line with recommendations of the World Health Organization (WHO). In response, the Robert Koch Institute (RKI) established the national “Containment Scout Initiative” (CSI) to support the local health authorities with a short-term workforce solution. It is part of a range of measures for strengthening the public health system in order to limit the spread of SARS-CoV-2 in Germany. The CSI is an example of how solutions to address critical health system capacity issues can be implemented quickly. It also demonstrates that medical or health-related backgrounds may not be necessary to support health authorities with pandemic-specific tasks and fulfil accurate contact tracing. However, it is a short-term solution and cannot compensate for the lack of existing qualified staff as well as other deficits that exist within the public health sector in Germany. This article describes the structure and process of the first phase of this initiative in order to support health policymakers, public health practitioners, and researchers considering innovative and flexible approaches for addressing urgent workforce capacity issues.
Cognitive Remediation in Virtual Environments for Patients with Schizophrenia and Major Depressive Disorder: A Feasibility Study

Standard approaches to cognitive remediation can suffer from limited skill transferability to patients’ life. Complex virtual environments (VEs) enable us to create ecologically valid remediation scenarios while preserving laboratory conditions. Nevertheless, the feasibility and efficacy of these programs in psychiatric patients are still unknown. Our aim was to compare the feasibility and efficacy of a novel rehabilitation program, designed in complex VEs, with standard paper–pencil treatment in patients with schizophrenia and major depressive disorder. We recruited 35 participants to complete a VE rehabilitation program and standard treatment in a crossover pilot study. Twenty-eight participants completed at least one program, 22 were diagnosed with schizophrenia and 6 with major depressive disorder. Participant’s performance in the representative VE training task significantly improved in terms of maximum achieved difficulty (p ≤ 0.001), speed (p < 0.001) and efficacy (p ≤ 0.001) but not in item performance measure. Neither the standard treatment nor the VE program led to improvement in standardized cognitive measures. Participants perceived both programs as enjoyable and beneficial. The refusal rate was higher in the VE program (8.6%) than in the standard treatment (0%). But in general, the VE program was well-accepted by the psychiatric patients and it required minimal involvement of the clinician due to automatic difficulty level adjustment and performance recording. However, the VE program did not prove to be effective in improving cognitive performance in the standardized measures.
Eco-Friendly Coagulant versus Industrially Used Coagulants: Identification of Their Coagulation Performance, Mechanism and Optimization in Water Treatment Process

The evaluation of complex organic and inorganic coagulant’s performances and their relationships could compromise the surface water treatment process time and its efficiency. In this work, process optimization was investigated by comparing an eco-friendly chitosan with the industrially used coagulants namely aluminum sulfate (alum), polyaluminum chloride (PAC), and aluminum chlorohydrate (ACH) in compliance with national drinking water standards. To treat various water samples from different treatment plants with turbidity and pH ranges from 20–826.3 NTU and 5.21–6.80, respectively, 5–20 mg/L coagulant dosages were varied in the presence of aluminum, ferum, and manganese. Among all, 10 mg/L of the respective ACH and chitosan demonstrated 97% and 99% turbidity removal in addition to the removal of the metals that complies with the referred standard. However, chitosan owes fewer sensitive responses (turbidity and residual metal) with the change in its input factors (dosage and pH), especially in acidic conditions. This finding suggested its beneficial role to be used under the non-critical dosage monitoring. Meanwhile, ACH was found to perform better than chitosan only at pH > 7.4 with half dosage required. In summary, chitosan and ACH could perform equally at a different set of optimum conditions. This optimization study offers precise selections of coagulants for a practical water treatment operation.
Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.
Novel Advances to Post-Stroke Aphasia Pharmacology and Rehabilitation

Aphasia is one of the most common clinical features of functional impairment after a stroke. Approximately 21–40% of stroke patients sustain permanent aphasia, which progressively worsens one’s quality of life and rehabilitation outcomes. Post-stroke aphasia treatment strategies include speech language therapies, cognitive neurorehabilitation, telerehabilitation, computer-based management, experimental pharmacotherapy, and physical medicine. This review focuses on current evidence of the effectiveness of impairment-based aphasia therapies and communication-based therapies (as well as the timing and optimal treatment intensities for these interventions). Moreover, we present specific interventions, such as constraint-induced aphasia therapy (CIAT) and melodic intonation therapy (MIT). Accumulated data suggest that using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) is safe and can be used to modulate cortical excitability. Therefore, we review clinical studies that present TMS and tDCS as (possible) promising therapies in speech and language recovery, stimulating neuroplasticity. Several drugs have been used in aphasia pharmacotherapy, but evidence from clinical studies suggest that only nootropic agents, donepezil and memantine, may improve the prognosis of aphasia. This article is an overview on the current state of knowledge related to post-stroke aphasia pharmacology, rehabilitation, and future trends.
Dissociation and Suicidality in Eating Disorders: The Mediating Function of Body Image Disturbances, and the Moderating Role of Depression and Anxiety

In patients with eating disorders (EDs), elevated dissociation may increase the risk of suicide. Bodily related disturbances, depression, and anxiety may intervene in the association between dissociation and suicidality. In this study we aimed to examine the influence of bodily related disturbances, depression, anxiety, severity of ED symptoms, body mass index (BMI), and type and duration of the ED on the relationship between elevated dissociation and elevated suicidality. The study included 172 inpatients: 65 with anorexia nervosa restricting type, 60 with anorexia nervosa binge/purge type, and 37 with bulimia nervosa. Participants were assessed using self-rating questionnaires for dissociation, suicidality, bodily related parameters, and severity of ED symptomatology, depression, and anxiety. We found that dissociation and suicidality were directly associated. In addition, depression and anxiety moderated the mediating role of body image parameters in the association between increased dissociation and increased suicidality. Thus, only in inpatients with high depression and anxiety, i.e., above the median range, body image disturbances were found to mediate the association between dissociation and suicidality. ED-related parameters did not moderate these relationships. Our study demonstrates that in inpatients with EDs, increased dissociation may be significantly associated with increased suicidality, both directly and via the intervening influence of body image, depression, and anxiety.
Moderating Role of Religiosity and the Determinants to Attitude, Willingness to Donate and Willingness to Communicate Posthumous Organ Donation Decisions among University Students in Pakistan

Organ transplantation is considered an alternative treatment to save lives or to improve the quality of life and is a successful method for the treatment of patients with end-stage organ diseases. The main objective of the current study was to explore the determinants of the attitudes and willingness to communicate the posthumous organ donation decisions to the families. Questionnaires were used to test the hypothesized relationships. The results confirmed altruism, knowledge, empathy, and self-identity as the antecedents to attitude. We also found perceived behavioral control, moral norms, and attitude as significant antecedents to the willingness to donate organs after death. The results of the study also indicated that those who were willing to sign the donor card were also willing to communicate their decision to their families. Religiosity moderated the relationship between willingness to donate and signing the donor card, and it strengthened the relationship. The findings of this study would provide insight into the factors which can influence posthumous organ donation among university students in Pakistan.
Ovarian steroid hormone secretion by human granulosa cells after supplementation of sambucus nigra L. extract.

Beneficial effects of Sambucus nigra L. (black elder) as a traditional medicine have been associated with the phytoconstituents including polyphenols, terpenes and lectins. Various antioxidant rich natural products have also been implicated with improvement of reproductive health and fertility, however, the effect of Sambucus nigra on the ovarian cell functions has not been investigated yet. The objectives of the present study were to screen the polyphenols in the elderflower and elderberry extracts, and to examine the secretion activity of steroid hormones 17beta-estradiol and progesterone by human ovarian granulosa cells HGL5 after supplementation of the extracts at a concentration range of 12.5 to 100 microg.ml-1. Qualitative as well as quantitative screening of polyphenols by high-performance liquid chromatography with diode-array detector (HPLC-DAD) analysis revealed rutin to be the most abundant polyphenol in both elderflower and elderberry extracts. In culture, neither elderflower nor elderberry extract caused any significant impact (p>0.05) in cell viability as studied by AlamarBlue assay in comparison to control. However, a dose-dependent stimulation of 17beta-estradiol release was detected by ELISA after supplementation of elderflower (at 50 microg.ml-1; p<0.01) and elderberry (at 100 microg.ml-1; p<0.05) extracts at higher doses used in the study. On the other hand, both elderflower and elderberry extracts stimulated the secretion of progesterone by HGL5 cells at a lower dose (12.5 microg.ml-1; p<0.05), as compared to control. Therefore, elderflower and elderberry extracts may have the potential to regulate steroidogenesis in ovarian cells.