Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.

Buerger's disease or Thromboangiitis Obliterans (TAO) is a nonatherosclerotic segmental vascular disease which affects small and medium arteries and veins in the upper and lower extremities. Based on pathological findings, TAO can be considered as a distinct form of vasculitis that is most prevalent in young male smokers. There is no definitive cure for this disease as therapeutic modalities are limited in number and efficacy. Surgical bypass has limited utility and 24% of patients will ultimately require amputation. Recently, studies have shown that therapeutic angiogenesis and immunomodulatory approaches through the delivery of cells to target tissues are potential options for ischemic lesion treatment. In this review, we summarize the current knowledge of TAO treatment and provide an overview of stem cell-based treatment modalities.

(1) Background: Little research has been done on professionals' perceptions of institutions and governments during epidemics. We aim to create a profile of physicians who feel they can raise public health issues with relevant institutions during a pandemic. (2) Methods: A total of 1285 Romanian physicians completed an online survey as part of a larger study. We used binary logistic regression to profile physicians who felt able to raise public health issues with relevant institutions; (3) Results: Five predictors could differentiate between respondents who tended to agree with the trust statement and those who tended to disagree: feeling safe at work during the pandemic, considering the financial incentive worth the risk, receiving training on the use of protective equipment, having the same values as colleagues, and enjoying work as much as before the pandemic; (4) Conclusions: Physicians who trust the system to raise public health issues with the appropriate institutions feel they share the same values as their colleagues, say they were trained in the use of protective equipment used during the pandemic, felt they were safe at work during the pandemic, enjoyed their work as much as before the pandemic, and felt the financial bonus justified the risk.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

Economic development and population growth lead to increased production of chicken manure (CM), which is a problematic organic waste for its amount, environmental threats, and moisture content. There are different ways of CM, namely anaerobic digestion, composting, combustion, and direct land spreading. Hydrothermal carbonization (HTC) is another emerging way, however. In this study, the HTC of CM was performed to produce energy-rich material called hydrochar (HC). The effects of HTC temperature (180, 240, 300 C) and process time (30, 90, 180 min) were summarized. Proximate and ultimate analysis, as well as heating values (HHV, LHV), have been performed both on raw CM and derived HC. Additionally, the process performance has been examined. The obtained results show that HTC is a feasible method for CM disposal and valorization. Although process time did not influence considerably fuel properties of CM, higher temperature led to significantly higher HHV, reaching 23,880.6734.56 Jg-1 at 300 C and 180 min with an improvement of 8,329 Jg-1 compared with raw CM (15,551.67 Jg-1). The process conducted at 240 C in 30 min has been specified as the most favorable, due to the highest energy gain of HC and relatively low energy consumption.

The increase in the emission of greenhouse gases (GHG) is one of the most important world problems. Decreasing of GHG emission is a big challenge in the future. Transportation sector uses a significant part of petroleum production in the world and it leads to an increase in the emission of GHG. The result of this issue is that population of the world befoul environment of transportation system automatically. Electric Vehicles (EV) have a potentiality to solve a big part of the GHG emission and energy efficiency issues such as stability and reality of energy. The energy actors and their research team determine some targets for 2050; hence, they hope to decrease the world temperature to 6 °C in the best and 2 °C in the normal condition. Fulfillment of these scenarios needs suitable grid infrastructure but in most of the countries, the grid does not have a suitable background to apply those scenarios. In this paper, some problems about energy scenarios, energy storage systems, grid infrastructure and communication systems in supply and demand side of the grid and its solutions have been investigated.

Vehicle to vehicle (V2V) and Vehicle to infrastructure (V2I) or briefly V2X communications are the one of hot topics in automotive industry. Therefore, this situation is providing many advantages of connected vehicles and infrastructures which bring to human life. For instance, vehicles and road infrastructures which shares information with each other, provides a neat flow regulation, more ordered traffic flow and therefore jammed traffic dependent accident’s percentage will be decreased. On the other hand, security is the most important issue for these systems because the operation of V2X networks is completely dependent on uninterrupted and accurate information sharing. In the light of these information, in this paper we review security issues and current solution architectures. We also propose some open problems in this lively field.

Sustaining learners’ motivation to keep learning has been concerned for over 60 years in education and SLA. Most research focusing on Japanese university students has contributed lots of theoretical and practical developments, but research focusing on motivations of non-traditional adult learners and those under 18-year-old to learn Chinese is still little even though previous research findings have proved age is one of the key variables influencing learning besides nationalities and Chinese language levels. In order to find an effective treatment for sustainable Chinese language learning in Japan, this study utilized a survey method to analyze the types of Japanese learners’ motivation to learn Chinese via analysis of a moment structures (AMOS), and to compare the differences of the motivation via one-way ANOVA. This study revealed that Japanese learners’ motivation to learn Chinese consists of eight common types, which are “instrumental motivation”, “personal orientation”, “identified regulation”, “Chinese cultural productions”, “integrating into Chinese community”, “external regulation”, “social responsibility”, and “Chinese for academic purposes”. Also, there are similarities and differences existing in the eight motivation types among the Japanese children, adolescents, (non-) traditional adult learners of Chinese as a foreign language (CFL). The findings contribute the understanding of motivation types and differences among the four aged Japanese learners to teachers of teaching Chinese to speakers of other languages (TCSOL), and to future research further exploring how differently aged Japanese learners can have and use a higher motivation as a main drive to learn Chinese language as a lifelong business.

Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone, dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters, and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to baseline. Downstream effects of these catecholamines and corticosterone appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to baseline by the final measurement. DHEA, used as a ratio with corticosterone, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to understanding crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

A community-level nutrition intervention was implemented among tribal children (3 to 6 years) in Telangana, India. The one-year intervention involved six nutrient-rich formulations of millet-pulse-groundnut based products, suited to local taste preferences. Anthropometric measurements of height, weight and Mid-Upper-Arm -Circumference (MUAC) along with haemoglobin (Hb) levels were monitored at baseline and endline. The treatment group showed considerable gain in height (3.2 cm), weight (1.68 kg) and MUAC (0.33 cm), over the control group. Paired t-test indicated significant differences (p<.01) between pre- and post-intervention anthropometric measurements. Positive shifts were observed in wasting (WHZ; -1.2 ±1.3 to -0.9± 1), stunting (HAZ; -1.8±1.6 to -0.3±1.3) and underweight (WAZ; -1.9±1.2 to -0.7±1) among treatment group. Hb levels in the treatment group also improved significantly from 9.70 ± 0.14 g/dl (moderately-anaemic) to 11.08 ± 0.13 g/dl (non-anaemic). Post-intervention Focus Group Discussions (FGDs) involving mothers and teachers confirmed the positive impact. Thus, nutritional intervention formulated using climate resilient millets, pulses and groundnut, promotes dietary diversity and improves the nutrition & health status of children.

Antibiotic beads were used to treat surgical infections. In this study, polylactide–polyglycolide (PLGA) was mixed with vancomycin, osteogenic enhancer lithium chloride (LiCl), and hot com-pressing to form PLGA-vancomycin-LiCl delivery beads to treat bone infection. An elution method was employed to characterize the in vitro release characteristics of the vancomycin and the Li over a 42-day period. The released profiles lasted for more than 42 days for vancomycin and 28 days for Li. The concentration of vancomycin in each sample was well above the breakpoint sensitivity. Lithium co-treatment enhanced the bactericidal effect of vancomycin. Released Li and vancomycin increased mRNA or protein expressions of osteogenic markers of mesenchymal stem cells (MSCs). In vivo, the PLGA delivery systems were implanted into the rabbit distal femoral cavities and the cavity fluid content was aspirated and analyzed at each time point. The released Li and vancomycin lasted more than 6 weeks, and vancomycin concentrations were much above the breakpoint sensitivity. Four rabbits in each group were killed at 8 weeks for histologic observation. More mature bone tissue was shown in the Li treatment group. This study provides a PLGA drug delivery system to meet the requirements of patients with bone infections.

Purpose of Review Multipotent Mesenchymal stromal cells (MSCs) have recently risen to prominence in regenerative medicine for their powerful intrinsic properties of self-regeneration, immunomodulation, and multi-potency. They exhibited an excellent safety profile in early-phase clinical trials. Nevertheless, MSCs-based therapy suffers reduced efficacy in randomized clinical trials due to a poor understanding of their proper delivery modalities. Here, we intend to explore the current application of MSCs after tissue injuries. We specifically focus on tissue source, delivery routes, metabolic fitness, and cell dose. We further discuss potential approaches to optimize in vivo engraftment. Recent findings MSCs therapeutic effect mediates by paracrine and contact factors, which are cells' intrinsic physiological processes. The cell culture expansion process does not destroy MSCs' intrinsic properties. In vivo persistence of administered MSCs determines their therapeutic potency. Cell viability, fitness, immune match, and delivery route meticulously regulate their in vivo persistency. Different genetic or chemical modification strategies are currently applied to extend their in vivo lifespan and boost their pharmaceutical effect. Summary Improving the in vivo persistence of implanted MSCs could facilitate its clinical translation. This review highlights the pros and cons of different MSCs’ delivery strategies used in clinical or preclinical studies, emphasizing various modification approaches. These can promote prolonged graft cell survival.

Our previous study demonstrated that mesenchymal stem/stromal cells (MSCs) induced the differentiation of myeloid-derived suppressor cells (MDSCs) in the bone marrow (BM) under inflammatory conditions. In the present study, we aimed to explore the signaling pathway in BM cells responsible for MDSC generation. RNA-seq revealed that the mitogen-activated protein kinase (MAPK) pathways, among biochemical pathways, exhibited the highest number of differentially expressed genes in BM cells with MSC coculture relative to those without. Western blot confirmed strong phosphorylation of c-Jun N-terminal kinase (JNK) in BM cells cocultured with MSCs under GM-CSF stimulation, whereas p38 kinase activation remained unaltered by MSCs. Inhibition of JNK by SP600125 significantly abolished the expression of Arg1 and Nos2, the hallmark genes of MDSCs, as well as Hif1α, a molecule mediating monocyte functional re-programming into suppressive phenotype, in MSC-cocultured BM cells, while increasing TNF-α in response to lipopolysaccharides stimulation. Furthermore, JNK inhibition markedly abrogated the effect of MSCs on the production of TGF-β1, TGF-β2 and IL-10 in BM cells. These results suggest that MSCs induce MDSC differentiation in BM during inflammation, at least in part, through the activation of the JNK MAPK signaling pathway.

Background: Epithelial-mesenchymal transition (EMT) is a biological process where epithelial cells lose their adhesive properties and gain invasive, metastatic, and mesenchymal properties. Maintaining the balance between epithelial and mesenchymal stage is essential for tissue homeo-stasis. Many of the genes promoting mesenchymal transformation has been identified; however, our understanding of the genes responsible for maintaining the epithelial phenotype is limited. Our objective was to identify genes responsible for maintaining the epithelial phenotype and in-hibiting EMT. Methods: RNA seq was performed using an vitro model of EMT. CTGF expres-sion was determined by qPCR and Western blot analysis. Knockout of CTGF was done using the CTGF sgRNA CRISPR/CAS9. Tumorigenic potential was determined using NCG mice. Results: Knocked-out of CTGF in epithelial ovarian cancer cells leads to the acquisition of functional characteristics associated with the mesenchymal phenotype such as Anoikis resistance, cytoskel-eton remodeling, increased cell stiffness, and acquisition of invasion and tumorigenic capacity. Conclusions: We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for conserva-tion of epithelial structure and function. These findings provide a new window to understand the early stages on mesenchymal transformation

Background: This review aims to explore the regulatory mechanism of microglial exosomes, particularly focusing on the role of miR-124-3p, in modulating neuroinflammation and promoting neuronal repair following traumatic brain injury (TBI). Methods: Multiple studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. The increased expression of miR-124-3p in microglial exosomes after TBI inhibited neuronal inflammation and promoted neurite outgrowth. This effect was achieved by promoting the anti-inflammatory M2 polarization of microglia, suppressing mTOR signaling through downregulation of PDE4B, and inducing autophagy in BMVECs. These actions collectively contributed to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. Conclusion: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. Targeting miR-124-3p and utilizing microglial exosomes as therapeutic agents hold great potential for future clinical translation in TBI management. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

Prostate cancer is the most occurred malignant disease in the male population in over one-half of the countries and still constitutes the fifth leading cause of death in 2020, worldwide. Metastatic prostate cancer is a lethal malignancy that mostly is terminated within several years through the patient's death. Researchers should focus on the phenomenon which is rigorously appertaining to metastatic cascade and operating as an initiator of metastases to provide the knowledge needed to solve the problem of diagnostics and treatment of advanced prostate cancer patients. The epithelial-mesenchymal transition is one such phenomenon. The current review is based mainly on three papers published in 2021, which describe the most important tissue-specific factors managing epithelial-mesenchymal transition and are discussed with scientific papers published in acknowledged journals. The effect of the current review is the specification of profiles of precise tissue factors predicting the progression of the prostate neoplasm to its metastatic stage in a new edition.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that transcriptionally active p73 (TAp73), a p53 family member, inhibits tumor progression through promoting tumor suppressive canonical TGF-β/Smad signaling, while preventing non-canonical TGF-β signaling through extracellular signal-regulated kinases (ERK)1/2. Here, we have studied whether this mechanism also operates in human PDAC. Using the PDAC-derived tumor cell lines PANC-1 and HPAFII, we show that TAp73 induces the expression of the epithelial marker and invasion suppressor E-cadherin and the common-mediator Smad, SMAD4, while at the same time suppressing expression of the EMT master regulator SNAIL and basal and TGF-β1-induced activation of ERK1 and ERK2. Using dominant-negative and RNA interference-based inhibition of SMAD4 function we went on to show that inhibition of ERK activation by TAp73 is mediated through SMAD4. Intriguingly, both SMAD4 and the α isoform of TAp73 - but not the isoform - interfered with cell migration as shown by xCELLigence technology. Our findings highlight the role of TAp73-SMAD4 signaling in tumor suppression of human PDAC and identify direct inhibition of basal and TGF-β-stimulated pro-invasive ERK activation as an underlying mechanism.

Cell-based therapy in regenerative medicine is a powerful tool that can be used both to restore various cell lost in a wide range of human disorders, and in renewal processes. Stem cells show promise for universal use in clinical medicine, potentially enabling the regeneration of numerous organs and tissues in the human body. This is possible due to their self-renewal capacity, and their ability to differentiate into various cell types. To date, pluripotent stem cells seem to be the most promising regeneration tool. Recently, a novel stem cell niche, called multilineage-differentiating stress-enduring (Muse) cells, is emerging. These cells are of particular interest because they are pluripotent and are found in adult human mesenchymal tissues. One of their most significant features is that they can produce cells representative of all the three germ layers. Furthermore, they can be easily harvested from fat, and isolated from the mesenchymal stem cells. This makes them very promising, allowing autologous treatments and avoiding the problems of rejection, typical of transplants. Muse cells have recently been employed, with encouraging results, in numerous preclinical studies, performed to test their efficacy in the treatment of various pathologies, exploiting their regenerative potential in different tissues. This systematic review aimed to 1) highlight the specific potential of Muse cells, and provide a better understanding of this niche, and 2) originate the first organized review of already tested applications of Muse cells in regenerative medicine. The obtained results could be useful to extend the possible therapeutic applications of Muse cells.

Recessive dystrophic epidermolysis (RDEB) is a rare, inherited and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During 12 weeks of systemic treatment with ABCB5+ MSCs the number of newly occurring wounds declined. When compared to the previously reported healing responses of the wounds present at baseline, the newly occurring wounds healed faster, and a greater portion of healed wounds remained stably closed. These data suggest a previously undescribed skin-stabilizing effect of treatment with ABCB5+ MSCs and support repeated dosing of ABCB5+ MSCs in RDEB to continuously slow the wound development and accelerate the healing of new or recurrent wounds before they become infected or progress to a chronic, difficult-to-heal stage.

Mesenchymal stem cells (MSCs) are involved in the process of extracellular matrix (ECM) remodeling where collagens play a pivotal role. We recently demonstrated that the remodeling of adsorbed collagen type I might be disordered upon oxidation following its fate in the presence of human adipose-derived MSC (ADMSCs). With the present study, we intended to learn more about the effect of polyphenolic antioxidant Epigallocatechin gallate (EGCG) attempting to mimic the conditions of oxidative stress in vivo and its putative prevention by antioxidants. Collagen Type I was isolated from mouse tail tendon (MTC) and labeled with FITC before oxidizing according to Fe2+/H2O2 protocol. FITC-collagen remodeling by ADMSC was assessed morphologically before and after EGCG pretreatment and confirmed via detailed morphometry analysis measuring the anisotropy index (AI) and fluorescence intensity (FI) in selected regions of interest (ROI), namely: outside the cells; over the cells and central (nuclear perinuclear) region, whereas the pericellular proteolytic activity was measured by de-quenching of fluorescent collagen probes (FRET effect). Here we provide morphological evidence that MTC undergoes significant reorganization by the adhering ADMSC along with the substantial activation of pericellular proteolysis, and further confirm that both processes are suppressed upon collagen oxidation. An important observation was that this abrogated remodeling cannot be prevented by the EGCG pretreatment. Conversely, the detailed morphometry analysis showed that oxidized FITC-collagen rather tends to accumulate beneath the cells and around the cell’s nuclei suggesting the activation of alternative routes for its removal, such as internalization and/or transcytosis. Morphometry analysis also revealed that both processes are supported by EGCG pretreatment.

Mesenchymal stem cells (MSCs) showed in vitro mesoderm-lineage differentiation and self-renew capacity. However, no comparative study was reported on the biological characteristics of stem cells derived from skeletal muscle (SM-MSCs), dermal skin (DS-MSCs), and adipose tissues (A-MSCs) from a single donor in camels. The present study aimed to evaluate the influence of MSCs source on stem cell characteristics. We evaluated proliferation capacity and mesoderm-lineage differentiation potential from SM-MSCs, DS-MSCs, and A-MSCs. They showed spindle-like morphology after homogenization. The proliferation ability was no significant difference in all groups. Furthermore, the portion of the cell cycle and expression of pluripotent markers (Oct4, Sox2, and Nanog) were similar in all cell lines at passage 3. The differentiation capacity of A-MSCs into adipocytes was significantly higher than that of SM-MSCs and DS-MSCs. However, the osteoblast differentiation capacity of A-MSCs was significantly lower than that of SM-MSCs and DS-MSCs. Additionally, after osteoblast differentiation, the ALP activity and calcium content was significantly decreased in A-MSCs as compared to SM-MSCs and DS-MSCs. To the best of our knowledge, we primally established MSCs from the single camel and demonstrated their comparative characteristics including expression of pluripotent factors and proliferation, and in vitro differentiation capacity into adipocytes and osteoblasts.

Although oncolytic viruses are currently being evaluated for cancer treatment in clinical trials, systemic administration is hindered by many factors that prevent them from reaching the tumor cells. When administered systemically, mesenchymal stem cells (MSCs) target tumors, and therefore constitute good cell carriers for oncolytic viruses. Methods: MSCs were primed with trichostatin A under hypoxia, which upregulated the expression of CXCR4, a chemokine receptor involved in tumor tropism, and coxsackievirus and adenovirus receptor that plays an important role in adenoviral infection. After priming, MSCs were loaded with conditionally replicative adenovirus that exhibits limited proliferation in cells with a functional p53 pathway and encodes Escherichia coli nitroreductase (NTR) enzymes (CRAdNTR) for targeting tumor cells. Results: Primed MSCs increased tumor tropism and susceptibility to adenoviral infection, and successfully protected CRAdNTR from neutralization by anti-Adenovirus antibodies both in vitro and in vivo, and specifically targeted p53-deficient colorectal tumors when infused intravenously. Analyses of deproteinized tissues by UPLC-MS/QTOF revealed that these MSCs converted the co-administered prodrug CB1954 into cytotoxic metabolites, such as 4-hydroxylamine and 2-amine, inducing oncolysis and tumor growth inhibition without being toxic for the host vital organs. Conclusion: This study shows that the combination of oncolytic viruses delivered by MSCs with the activation of prodrugs is a new cancer treatment strategy that provides a new approach for the development of oncolytic viral therapy for various cancers.

Intermediate filaments constitute the third component of the cellular skeleton. Unlike actin and microtubule cytoskeletons, the intermediate filaments are composed of wide variety of structurally related proteins showing distinct expression patterns in tissues and cell types. Changes in expression patterns of intermediate filaments are often associated with cancer progression, in particular with phenotypes leading to increased cellular migration and invasion. In this review we will describe the role of vimentin intermediate filaments in cancer cell migration, cell adhesion structures, and metastasis formation. The potential for targeting vimentin in cancer treatment and the development of drugs targeting vimentin will be reviewed.

Regeneration is a fundamental process much attributed to functions of adult stem cells. In last decades delivery of suspended adult stem cells is widely adopted in regenerative medicine as a leading mean of cell therapy. However, adult stem cells can not complete the task of human body regeneration effectively by themselves as far as they need a receptive microenvironment (the niche) to engraft and perform properly. Understanding of mechanisms underlying mammalian regeneration lead us to an assumption that improved outcomes of cell therapy requires a specific microenvironment generated in damaged area prior to stem cell delivery. To certain extent it may be achieved by delivery of mesenchymal stromal cells (MSC), not in dispersed form, but rather self-organized in cell sheets (CS) – tissue-like structures comprising of viable cells and microenvironment components: extracellular matrix and soluble factors deposited in the matrix. In this communication we highlight a potential role of mesenchymal stromal cells (MSC) as regeneration organizers and speculate that this function emerges in CS. This concept shifts our understanding of therapeutic mechanism underlying a widely known CS-based delivery method for regenerative medicine.

Mesenchymal Stem Cells derived from bone marrow (hBM-MSCs) are utilized in tendon tissue‐engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSC), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to hGDF-5 we supplemented each at doses of 1, 10, and 100 ng/mL and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated expression of Collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed upregulation of SCX-A (1.7-fold) at day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX (3.8-fold) and TNC (2.3-fold) after 3 days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this we explored expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines upregulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold) but a greater up-regulation of IL-10 (2.5-fold). Collagen type I and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification (fibroblast-like) with a Lenght/Width ratio increase at value higher than 1, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue engineering protocols.

Access to medicines is one of the essential problems in Public Health of low- and middle-income countries (LMICs). The World Health Organization (WHO) defines access to medicines as the possibility of "having continuously accessible and affordable medicines in public or private health facilities that are within a kilometer of the place of residence." Access to medicines, as defined by the WHO, is not fully guaranteed in many LMICs and even in many regions of high-resource countries. The WHO identifies several factors as determinants of limitations in the access to medicines: rational selection, affordable prices, sustainable financing, and reliable health services. The action on these factors makes it possible to improve universal access to medicines with consequent improvement in Public Health. Adequate access to antibiotics and vaccination will avoid a large part of the deaths caused by infectious diseases in the LMICs. However, the emergence of resistance and the difficulties in vaccination campaigns due to socio-political or cultural problems make it challenging to fight many easily treatable infectious diseases. The use and abuse of antibiotics are inevitably associated with the appearance of resistances that make them ineffective. Thus, whereas limited access to antibiotics raises mortality rates from infectious diseases, generalized open access to them ends up eliminating their clinical value. Moreover, the contraction of research in this field for many years has reduced the success in discovering new drugs. Additionally, local market regulations, inadequate selection, inaccessible prices, especially for those of second and third-generation, inefficient health systems, and difficulties of administration and control of prescription compliance, especially in the case of combined therapies, are additional obstacles to universal access to antibiotics. In order to simultaneously improve access to antibiotics and keep resistances under control, it is necessary to develop training and education activities at different social levels (from patients to various Health Care Providers) to complement the national or supranational strategic plans.

Only languages with abundant resources are given the opportunity to build speech recognition systems, whereas low resource languages are disregarded. This project attempts to create a system that can normally convert speech to text in the Myanmar (Burmese) language, a language part of low resource languages. The Burmese language is extremely intricate and is made up of vowels, consonants, tones, and stress. There are 10 numbers, 12 vowels, and 33 letters in the Myanmar alphabet. Deep learning allows for the evolution of numerous algorithms while eradicating ignorance and even low-resource languages may be turned into speech-to-text systems with a small quantity of data. The procedures required to construct a successful speech recognition system that can assist both the corporate sector and society will be covered in this project, including data collecting, preprocessing, modeling, prototyping, assessment, and ultimately deployment.

Poultry farming in Slovakia has a tradition and an irreplaceable position to ensure rational nutrition for the population. In terms of a nutritional value, poultrymeat (Galliformes) contains a high amount of proteins, essential amino acids, essential unsaturated fatty acids, minerals, vitamins and a low fat content. Poultrymeat production has a relatively short reproductive cycle and thus allows regulating the demand and supply. The poultry market also influences the development of domestic consumption. According to the Statistical Office of the Slovak Republic, the consumption of meat has witnessed a persistent increase over the last 10 years. [1] According to the 2023 AVEC (The Voice of European Meat Sector) annual report, the consumption of poultrymeat in Slovakia was 20.0 kg per person per year. The average consumption in the EU-27 (2021) was 23.4 kg, with the countries with the highest consumption being Portugal (37.8 kg), Ireland (36.0 kg), Hungary (33.5 kg) and Spain (29.9 kg). On the other hand, the countries with the lowest consumption of poultrymeat, apart from Slovakia, also include Austria and Greece with a consumption of 21.5, resp. 21.0 kg [2]. The breeding of broiler chickens, as well as the production and placing on the market of poultrymeat must comply with the requirements laid down by legislation, while the compliance is regularly checked by the competent authorities.

Neuropsychiatric manifestations of COVID-19 include delirium, general malaise, headache, and psychiatric symptoms. These manifestations are related to the neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells. Tetracyclines, such as minocycline, have antibacterial and anti-inflammatory properties. Saiko-keishi-to, a traditional Japanese Kampo medicine, also has anti-inflammatory properties. Given the anti-inflammatory properties of minocycline and Saiko-keishi-to, we describe two cases of COVID-19 with prolonged headaches and general malaise successfully treated with these medications.

This study aims to describe the commitment to national heritage, patriotism, nationalism of elementary school students in the border areas between Indonesia and Timor Leste. This research was conducted in three elementary schools, they are SD Inpres Moto Ain, SD Inpres Class Jau Halimuti, SD Kristen Nanaeklot, and SD Negeri Motabenar from June to August 2018. The subjects of this study were elementary students in the Indonesia-Timor Leste border areas precisely around Motaain City, Belu Regency, East Nusa Tenggara. The research questionnaire was adapted from Karazawa and analyzed with descripriptive statistics. The results of this study showed that the commitment to national heritage, patriotism, and nationalism of elementary students on the Indonesian border areas with Timor Leste is in the very high level.

Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p

The study comprehensively evaluated the prognostic roles of PLR, NLR, MLR, BLR, and ELR in patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD). 619 patients with AECOPD and 300 healthy volunteers were retrospectively included into the study. The clinical characteristics containing laboratory findings of the AECOPD patients and the blood cell counts (CBCs) of the healthy volunteers were collected. Compared with the healthy volunteers, PLR, NLR, and MLR were elevated in COPD patients in stable condition, and were further ele-vated during exacerbation. ELR showed the opposite trend. PLR, NLR, and MLR were all posi-tively correlated with hospital LOS as well as CRP. In contrast, ELR was negatively correlated with hospital LOS as well as CRP. Elevated PLR, NLR, and MLR were all associated with more serious airflow limitation in AECOPD. Elevated PLR, NLR, and MLR were all associated with increased in-hospital mortality while Elevated ELR was associated with decreased in-hospital mortality in AECOPD. A nomogram was construct to predict in-hospital mortality in AECOPD. The nomo-gram had a C-index of 0.850 (95% CI: 0.799 – 0.901) with good predictive value and clinical ap-plicability. In summary, PLR, NLR, MLR, and ELR served as predictors for clinical outcomes in patients with AECOPD.

The causal networks are important for understanding the signaling alterations in diseases. To reveal the network pathways affected in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The network pathways in GC were analyzed in Ingenuity Pathway Analysis (IPA). The analysis of the probe sets of which gene expression has significant differences between diffuse- and intestinal-type GC in RNA Sequencing publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of regulation of EMT by growth factors pathway, coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-217, mir-223, mir-25, mir-27, and mir-34. These molecular networks revealed in the study may lead to the identification of drug targets for GC.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Background: Since there is no cure for amyotrophic lateral sclerosis (ALS) currently, it is very important for searching diagnostic biomarkers and novel treatments to reduce the severity of this disease; one of these treatment approaches is stem cell transplantation. This study aims to evaluate the safety and efficacy of repeated transplantation of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS by analyzing molecular data. Methods: In this single-centre, open-label, phase II clinical trial, retrospective study, fifteen confirmed ALS patients entered the study based on defined inclusion and exclusion criteria and underwent repeated stem cell transplantation (3 times BM-MSCs transplantation (1×10^6) , MSC/Kg BW per injection) concurrently intrathecally (IT) and intravenously (IV), with one-month interval). Clinical assessment of molecular investigation by evaluating specific microRNAs expression (Mir206, 133a-3p, 338-3p) in the patient's serum and Cerebra spinal fluid (CSF) samples were done three times during the 3-month follow-up. Statistical analysis includes paired T-test or Wilcoxon signed ranks. Results: No serious adverse effects were reported following stem cell transplantation. Besides, the mentioned microRNA expression slightly increased but still non-significant (P&gt;0.05). Conclusions: Although Our study demonstrated non-signifying results. However, the still increasing of these MircRNAs in serum and CSF overall, can indicate that repeated transplantation of BM-MSCs was a safe procedure in ALS patients, leading to delay in disease progression and improvement in clinical symptoms. Future studies are needed to confirm these results.

Cell sheet (CS) engineering using human MSC is of significant interest for regenerative medicine and this rapidly growing field translates to clinical use in a number of indications. Nevertheless, little is known of factors that define the timing of CS assembly from primary cultures which is important for planning treatments in both – autologous and allogeneic modes of use. We used a comparative in vitro approach with primary donors’ (n=14) adipose-derived MSC and evaluated the impact of healthy subject’s characteristics (age and sex), MSC culture features (population doubling time and lag-phase) and extracellular matrix (ECM) composition along with factors related to connective tissue formations (-SMA and FAP-) on CS assembly duration.

In recent years, bone tissue engineering (BTE) has made significant progress in promoting the direct and functional connection between bone and graft, including osseointegration and osteoconduction, to facilitate the healing of damaged bone tissues. Herein, we introduce a new, environmentally friendly, and cost-effective method for synthesizing reduced graphene oxide (rGO) and hydroxyapatite (HAp). The method uses epigallocatechin-3-O-gallate (EGCG) as a reducing agent to synthesize rGO (E-rGO), and HAp powder is obtained from Atlantic bluefin tuna (Thunnus thynnus). The physicochemical analysis indicated that the E-rGO/HAp composites had exceptional properties for use as BTE scaffolds, as well as high purity. Moreover, we discovered that E-rGO/HAp composites facilitated not only proliferation, but also early and late osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our work suggests that E-rGO/HAp composites may play a significant role in promoting the spontaneous osteogenic differentiation of hMSCs, and we envision that the E-rGO/HAp composites could serve as promising candidates for BTE scaffolds, stem cell differentiation stimulators, and implantable device components due to their biocompatible and bioactive properties. Overall, we suggest a new approach for developing cost-effective and environmentally friendly E-rGO/HAp composite materials for BTE application.

Metabolic surgery can promote integrated physiologic improvement to ameliorate metabolic illness, particularly type 2 diabetes. Nevertheless, the therapeutic scope has been limited by unexpectedly inconsistent surgical outcomes. Therefore, the purpose of this study is to overcome the obstacles by determining the core mechanism of conflicting results. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified types of duodenal-jejunal bypass procedures, were compared to comprehend specific surgical patterns from distinctive perspectives. Patients in exclusively nonobese groups are subjected to avoid compounding by weight fluctuations. During intestinal anastomosis, the epithelial identity of the succeeding intestine is replaced by that of the proximal epithelium through altered crosstalk between the epithelium and opposing mesenchymal cells. The rapid turnover rate and compensatory proliferation of the succeeding intestine accelerate the propagation of the replaced epithelium. Propagation of replaced epithelium could provoke inconsistent outcomes of metabolic surgery. The major determinants of the conflicting results of metabolic surgery are inadequate duodenal exclusion and inappropriate length of the biliopancreatic limbs. The replaced enteroendocrine cells during regeneration provoke inconsistent outcomes of metabolic surgery. The critical factors are the type and density of enteroendocrine cells distributed at the terminal end of the preceding proximal intestine.

Characterization of cancer cells and neural stem cells indicates that tumorigenicity and pluripotency are coupled cell properties determined by neural stemness, and tumorigenesis represents a process of progressive loss of original cell identity and gain of neural stemness. This reminds of a most fundamental process required for the development of the nervous system and body axis during embryogenesis, i.e., embryonic neural induction. Neural induction is that, in response to extracellular signals that are secreted by the Spemann-Mangold organizer in amphibians or the node in mammals and inhibit epidermal fate in ectoderm, the ectodermal cells lose their epidermal fate and assume the neural default fate and consequently, turn into neuroectodermal cells. They further differentiate into the nervous system and also some non-neural cells via interaction with adjacent tissues. Failure in neural induction leads to failure of embryogenesis, and ectopic neural induction due to ectopic organizer or node activity or activation of embryonic neural genes causes a formation of secondary body axis or a conjoined twin. During tumorigenesis, cells progressively lose their original cell identity and gain of neural stemness, and consequently, gain of tumorigenicity and pluripotency, due to various intra-/extracellular insults in cells of a postnatal animal. Tumorigenic cells can be induced to differentiation into normal cells and integrate into normal embryonic development within an embryo. However, they form tumors and cannot integrate into animal tissues/organs in a postnatal animal because of lack of embryonic inducing signals. Combination of studies of developmental and cancer biology indicates that neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal. Tumorigenicity is the manifestation of aberrant occurrence of pluripotent state in a postnatal animal. Pluripotency and tumorigenicity are both but different manifestations of neural stemness in pre- and postnatal stage, respectively, of animal life. The unique property of neural stemness is derived from the evolutionary advantage of neural genes and the neural-biased state of the last common unicellular ancestors of metazoan. Based on these findings, I discuss about some confusion in cancer research, propose to distinguish the causality and associations and discriminate causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.

Regeneration is a fundamental perpetual tissue process much attributed to functions of adult stem cell. In last decades delivery of adult stem cells to restore tissue structure is widely adopted in regenerative medicine. However, delivery of stem cells can not complete the task of human body regeneration effectively as far as cells need a basis to form a tissue. Certain improvement can be achieved when cells are organized to cells sheets (CS) – primitive tissue-engineered structures comprising of viable cells and ECM proteins. This led us to an assumption that after damage an intermediate feeder is structure formed as a ground for future tissue resulting in gradients of stimuli required to attract other cells (vascular, neural, epithelial, parenchyma etc.) in an organized manner. This feeder acquires increasing heterogeneity and becomes a guiding feeder that provides basic level of organization to increase complexity of structure up to normal tissue. We also highlight potential role of adult mesenchymal stromal cells (MSC) as the main source of guiding feeder and support it by our recent knowledge of their biological function. Finally, we assume that CS known to be a feasible delivery tool in therapeutics resemble guiding feeder and show our own data indicating properties of MSC-based CS. Furthermore, this concept shifts our understanding of therapeutic mechanism underlying a widely known delivery method for regenerative medicine.

This study explores the properties and behavior of bi-close-to-convex functions, introducing new subclasses defined by their relationship with fractional differential operator and bi-univalent functions. Using the Faber polynomial technique, we derive upper bounds for the n^{th} coefficient of functions in these classes. We also investigate the erratic behavior of initial coefficients in bi-close-to-convex functions, as characterized by the (λ,q)-fractional differintegral operator. Furthermore, we address Fekete-Szegö problems and present notable findings from our investigation, contributing to the continued growth and refinement of geometric function theory, yielding new insights and practical uses.

Background. IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as platelet (PLT) count, platelet-to-albumin ratio (PAR) and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. Methods. 150 IgAN patients were devided into two groups based on the cut-off value of PAR. All-cause mortality, major CV events and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results. The patient’s mean age was 43.7 ± 13.5 years, and the follow-up time was 124 ± 67 months. The K-M curve showed that PLR, PAR and PLT were strongly associated with primary combined (p = 0.002, p = 0.004, p = 0.001) and renal outcomes (p < 0.001, p < 0.001, p < 0.001), but not with CV outcomes in IgAN. However, when combined with left ventricular hypertrophy (LVH) or metabolic syndrome (MetS) PAR was found to be a significant predictor of both primary (p < 0.001, p < 0.001) and secondary outcomes (p = 0.001 and p = 0.038; p = 0.001 and p = 0.015). Additionally, PLR correlated with microalbuminuria (r = -0.165, p = 0.033) and LVH (r = -0.178, p = 0.025), while PLT correlated with eGFR (r = 0.158, p = 0.040). Conclusion. Elevated PAR and PLR may predict progression to end-stage kidney disease, but in combination with LVH and MetS, they showed CV events also in IgAN. The determination of PAR and PLR can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in CKD.

Background: The aim of this study has been to investigate if inflammatory biomarkers such as the systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have any correlation with the recurrence of pleomorphic adenomas (PA) in patients afflicted by this disease. Methods: A retrospective multicentre study involving two Italian centres, the Maxillofacial Sur-gery at the Policlinico Federico II in Naples and the ENT and Maxillofacial Surgery at the IRCCS G. Pascale National Cancer Institute in Naples, has been performed. The study, involving 608 pa-tients who had received a diagnosis of PA, was conducted between January 2000 and January 2020. A Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cut-off values for the SII, PLR and NLR. A linear regression model (LRM) and a non-linear logistic re-gression model (NLRM) were realized with respect to the NLR, PLR and SII. Results: The highest performance was achieved by the NLR (cut-off 2.960) with the AUC = 0.91, with an accuracy of 96.1%, sensitivity of 78.4% and specificity of 97.2%, PPV = 64.4% and NPV = 98.6%. The LRM and NLRM including all the haematological parameters did not increase the per-formance in terms of recurrence detection. Conclusion: The NLR is an excellent support tool in predicting the recurrence of PA with a cut-off of 2.960. It can be a good reference point for surgical decision-making and follow-up in clinical practice.

Background: Tuberculosis (TB) continues to be a serious public health threat that affects the most vulnerable population. Patients who are LTFU after TB diagnosis still represent one of the biggest challenges to TB control. Method: In this prospective observational study, we aimed to identify and analyse the risk factors associated with LTFU among TB patients who started first-line TB treatment in the Sanatorium Hospital in Luanda. Result: A total of 113 patients with TB were included between August 2018 and September 2019. Seventy-six (67.3%) patients were cured, 27 (23.9%) were LTFU, 5 (4.4%) died, 4 (3.5%) were transferred and 1 (0.9%) presented a treatment failure. After excluding those dead, transferred or who failed to treatment, we observed that severe TB at the time of diagnosis (OR 9.24, 95% CI 2.18-39.04) and food insecurity were significantly associated with LTFU (OR 5.96, 95% CI 1.66-21.41). Conclusion: The findings of our study are of enormous value to understand the reasons for the LTFU of patients with TB and can guide polices and facilitate designing measures to allow better adherence, and therefore, greater treatment success

Breast cancer (BC) affects millions of women; it is the leading cause of death by neoplasia in wom-en worldwide, with at least 500 thousand deaths each year, 70% of which occur in developing countries. Elastography evaluates tissue stiffness, making this a promising non-invasive real-time technique. BI-RADS is recognized as a standard and helpful technique for establishing BC risk. This study aimed to determine, by strain elastography (SE), the fat-to-lesion index (F/L index), sen-sitivity, specificity, and optimal cut-off to diagnose BC. This prospective study included 216 wom-en who underwent SE, ultrasound, mammography, and breast biopsy; according to mammogra-phy, we recruited BI-RADS category 2 (n= 5), category 3 (n=29), category 4 (n= 94), category 5 (n= 71) and category 6 (n=17); after biopsy, 108 women were classified as negative, and 108 were pos-itive for BC. Three expert BC radiologists performed all imaging interpretations and biopsies. Our results show mean values of the F/L index for negative biopsies of 3.70±2.57 and positive biopsies of 18.10±17.01; we developed two models for the prediction of BC, a logistic regression model with an AUC of 0.893 and a neural network with an AUC of 0.902. The Youden index yielded a F/L index cut-off >5.76, with a sensitivity and specificity of 84.26%. Positive Spearman's Rho cor-relation coefficient was observed between the F/L index and BI-RADS, r=.073 (p< 0.001). ANOVA test showed a difference between F/L index vs. molecular subtypes (p=0.002). SE is helpful as a di-agnostic complement to mammography, or in cases where the latter is contraindicated, elas-tography has an adequate predictive capacity and is a fast and minimally invasive procedure.

It has been proposed that upregulation of the noradrenergic (NA) system through exposure to novelty might be one of the key components for building cognitive reserve and resilience to neurodegeneration. A personality trait that promotes greater interest in novel experiences is Openness to Experience (OE). Individuals who are high in OE exhibit strong curiosity towards novelty and are more likely to be exposed to novel stimuli throughout the lifespan.Performing voxel-based morphometry analyses, we examined whether OE in 135 healthy young adults was associated with Locus Coeruleus (LC) - the main core of the noradrenergic system. We also investigated whether LC mediates the relationship between OE and a key measure of reserve, I.Q. In comparison with other neuromodulators’ seeds (Dorsal and Median Raphe [DR-MR] -5-HT, Ventral Tegmental Area [VTA] -DA- and Nucleus Basalis of Meynert [NBM] -Ach-), results show that greater LC integrity was related to greater OE and IQ. Additionally, mediation analyses revealed that only LC mediated the relationship between OE and IQ. Furthermore, a Bayesian multiple regression was conducted to model the contribution of both isolated and combined neuromodulator seeds to OE trait express. This approach found that the LC + VTA could account for more variance in OE expression compared to the LC alone. Other weaker but significant associations were observed between DR and OE, between LC + NBM and Conscientiousness and between DR + NBM and Extraversion. These results are together suggestive that OE is primarily underpinned by monoaminergic functioning, and that the LC-NA system plays a central role mediating the interdependence between OE expression and cognition (IQ level). While offering further understanding of the neurobiology of human personality, these findings indicate a pivotal role of LC-NA system integrity in novelty seeking in daily life. This provides a psychobiological account for how OE expression may be beneficial for maintaining the noradrenergic system to facilitate cognitive reserve and resilience to neurodegenerative conditions.

This paper compares the performance of three text-to-speech (TTS) models released from June 2021 to January 2022 in order to establish a baseline for Brazilian Portuguese. Those models were trained using dataset for Brazilian Portuguese. The experimental setup considers tts-portuguese dataset to fine-tune the following TTS models: VITS end-to-end model; glowtts and gradtts acoustic models both using hifi-gan vocoder. Performance metrics are arranged into objective and subjective metrics. As subjective metrics, the naturalness and intelligibility are measured based on the mean opinion score (MOS). Results shows that gradtts+hifigan model achieved naturalness of 4.07 MOS, close to performance of current commercial models.

Background: Vaccinating children against COVID-19 is an essential public health strategy in order to reach herd immunity and prevent illness among children and adults. Parents are facing tremendous stress in relation to the COVID-19 pandemic and the effectiveness of the COVID-19 vaccination program for children. In this study, we aimed to investigate parents’ willingness to vaccinate their children against COVID-19 in North Kivu province (DRC). Methods: A cross-sectional survey between December 01, 2021 to January 20, 2022 in 6 health zones (Goma, Karisimbi, Butembo, Beni, Kamango and Katwa) was conducted in the province of North Kivu. In each health zone, we selected 5 clusters (Health area) using the method of probabilistic selection proportional to population size. In total, 522 parents participated in our study. Results: Overall, 32.8% of parents intended to vaccinate their children. In the multivariate analysis, younger age of parents (aOR : 2.40, CI : [1.50-3.83]), higher level of fear that “a member of my family” could contract COVID-19 (aOR : 2.35, CI : [1.38-4.02]), higher level of perceived vulnerability to COVID-19 within the family (aOR : 1.70, CI : [1.005-2.2881]), higher level of perceived susceptibility to COVID-19 within the family (aOR : 3.07, CI : [1.80-5.23]), and history of vaccination against COVID-19 among parents (aOR : 16.47, CI : [8.39-32.33]), were significantly associated with the intention to have their children or adolescents vaccinated. Conclusion: Willingness of parents to vaccinate their children against the COVID-19 vaccination was low in North Kivu. There is undeniably in this region a need to reinsure the populations about vaccine safety for both children and adults. Public health authorities should also address widespread misinformation about vaccines in a timely manner.

With the COVID-19 pandemic continuing and the resulting economic burden increasingly apparent, the Indonesian government began to prepare a "new normal" phase and make peace with COVID-19. From this new decision arises the question of the readiness of businesses and the industrial sector to resume operations amid COVID-19. This article aims to provide concise and precise information about the preparations that can be made by businesses to operate safely amid COVID-19 based on existing scientific studies and literatures. From the literature visits it can be concluded that transmission and danger of a COVID-19 pandemic can be prevented through: creation of infectious disease prevention and response plan, implementing basic infection prevention measures, policies and procedures for proper identification and isolation of sick people, applying flexibilities in policies, and protections in the workplace.

Here we review and describe a set of research priorities to meet present and future challenges posed to farmed animal production that build on progress, successes and resources from the Functional Annotation of ANimal Genomes (FAANG) project.

South America has become the new epicenter of the coronavirus, especially in Brazil where the disease continues to spread exponentially across the country. This text aims to analyze the psychosocial factors of Covid-19 on back to school strategies in Brazil from a bioecological perspective. At the microsystem level, the population is experiencing different levels of stress and fear; at the mesosystem level, changes in routines, separation from family and friends, and closure of schools; and at the macrosystem level, national guidelines to control the pandemic, institutional standards on a national and international scale. Therefore, the main focus for the success of school return must be in the prevention of contagion and with physical and psychological health, and should not only consider the demands of curricula, financial or administrative management. For this reason, it is paramount that greater female representativeness is increased in decision-making levels of the meso and macrosystem, regarding the resumption of school and academic activities in the pandemic period, since the number of female leaders in decision-making, is still insufficient.

The COVID-19 pandemic has presented the world with increased challenges. The response to this pandemic has led to a sudden disruption of routine medical and elective surgical care. Most hospitals across the globe have had to change the way outpatient clinics are carried out and postpone non-urgent elective surgical procedures. NHS England ceased all elective general surgeries to train and re-deploy their staff to support the increased pressures from COVID-19 in an intensive care setting. However, with a decline of reported cases and deaths, the return to undertaking non-urgent elective services is imminent. In May 2020, Radha and Afzal published the first evidence-based guidelines for the resumption of elective orthopaedic services titled “Evidence based suggestions for the return to elective orthopaedic surgery following the COVID-19 Pandemic”. The pathway presented is adapted from the “Evidence based suggestions for the return to elective orthopaedic surgery following the COVID-19 Pandemic” and could potentially be used as a model for other surgical specialities. We present a three-phased return back to urological services. Safe resumption of elective care is possible but needs to be carefully planned.

Most large fibers in central nervous system of vertebrates are decussated. The cause or the evolutionary force of this phenomenon is not convincingly described. Here we show a pattern for this nervous system property that simultaneously is found to a more basic rule in evolution.The idea here is the "function to anatomy" theorem. We claim that functions of physical, biochemical, enzymatic, etc., in lower scale of living organisms "emerge" to anatomy in larger scales. And reversely, the anatomy we see in multicelular organisms are/were functions in microscopic scales.We propose descriptions, predictions, and a probable road map to what this can implicate in biological and medical issues.

In 2014, the outbreak of adenoviral pneumonia occurred in Korean military training center. However, there is limited data on characteristics of fever and its response to antipyretics therapy in immunocompetent adults with adenoviral positive community-acquired pneumonia (CAP). Medical records of patients who were admitted to Armed Forces Chuncheon Hospital for treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. We evaluated demographics, clinico-laboratory findings and radiologic findings at admission were compared between adenovirus positive (Adv) group and adenovirus negative (non-Adv) group. Out of 251 military personnel with CAP during the study periods, 67 were classified into Adv group while 184 were Non-Adv group. Patients with Adv group had a longer duration of fever after admission and symptom onset. Adv group patients had a higher mean temperature at admission and more observed over 40 and 39 to 40℃. Adv group patients had more commonly observed no response to antipyretic treatment and adverse events after antipyretics use. Length of hospital stay had no significant difference between two groups and no patient died in both groups. In our study, Adv positive CAP in patients with immunocompetent military personnel had distinct characteristics of fever and response to antipyretic treatment.

An understanding of the cultural conditions that determine the factors affecting nurses’ intention to leave is important for countries suffering from nurse shortage. Aim: to examine factors influencing intention to leave among female hospital nurses in a large Japanese sample, classified into four generations by age considering economic conditions. Methods: a cross-sectional survey with convenience sampling was conducted. Anonymous self-administered questionnaires were distributed to all nurses in 30 hospitals. To assess intention to leave, basic attributes, life conditions, work characteristics, and factors of psychosocial work environment were addressed. After classifying data into four generations based on age cohorts, we conducted multivariate logistic regression analysis using the completed data (N = 5,074, mean age = 36.24). Results: regardless of generational characteristics influenced by economic conditions, effort and monetary reward were generation-common factors. Over-commitment, social support, and the presence of a role model were generation-common factors in three generations. While having children increased intention to leave in the generation born 1965–1979, having family members in need of caregiving other than children decreased the risk in the generation born in the 1980s. Conclusion: generational countermeasures considering factors of psychosocial work environment and life conditions are needed to avert female nurse turnover.

Microaggressions are subtle verbal and non-verbal slights based on group membership, and they are ubiquitous in the lives of racial minorities, women, and LGBTQ individuals (Sue, 2010). The goal of the current paper is to introduce a role-playing based exercise on effective responses to microaggressions. The workshop draws on the prejudice responding workshops of Plous (2000) and Lawson, et al. (2010) but integrates research-based strategies. The activity was tested in two groups of undergraduate students, and the findings suggested that both groups felt more prepared to deal with microaggressions after participating.

Monochromatic documents claim for much less computer bandwidth for network transmission and storage space than their color or even grayscale equivalent. The binarization of historical documents is far more complex than recent ones as paper aging, color, texture, translucidity, stains, back-to-front interference, kind and color of ink used in handwritting, printing process, digitalization process, etc. are some of the factors that affect binarization. This article presents a new binarization algorithm for historical documents. The new global filter proposed is performed in four steps: filtering the image using a bilateral filter, splitting image into the RGB components, decision-making for each RGB channel based on an adaptive binarization method inspired by Otsu's method with a choice of the threshold level, and classification of the binarized images to decide which of the RGB components best preserved the document information in the foreground. The quantitative and qualitative assessment made with 21 binarization algorithms in three sets of “real world” documents showed very good results.

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_x/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.

Neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR 6.97, 95% CI 1.65-10.55, p= 0.002) and OS (HR 7.79, 95% CI 1.25-15.07, p= 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67≥ 14% were also associated with worse DFS (p= 0.016, p= 0.002, and p= 0.001, respectively). In multivariate analysis, luminal B subtype, post-treatment Ki67≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

Uterine Tumor Resembling Ovarian Sex Cord Stromal Tumor (UTROSCT) is a rare uterine mesenchymal neoplasm, which resembles ovarian sex cord tumors of the ovary. Although, in general, UTROSCT exhibits benign behavior with a favorable prognosis, this neoplasm is nonetheless classified as being of an uncertain ma-lignant potential, given its low rate of recurrence and the fact that it rarely pro-duces metastases (lymph nodes, epiploic appendix, omentum, small bowel, subcutaneous, lungs). Its histogenesis too is uncertain. Typically, UTROSCT oc-curs in peri-menopausal or menopausal women but can sometimes be observed in young women. Usually, this neoplasm can be found in the uterine corpus as a nodular intramural lesion, less frequently submucosal, subserosal or poly-poid/intracavitary. UTROSCT can cause abnormal bleeding, pelvic pain, enlarged uterus, mass sensation, but sometimes it is found purely by chance. This neo-plasm can be considered polyphenotypic on morphological, immunohistochem-ical, and genetic analyses. Generally, on microscopic examination, UTROSCT shows a predominant pattern of the cords, nests, and trabeculae typical of sex cord tumors of the ovary while, immunohistochemically, it is characterized by a co-expression of epithelial, smooth muscle, and sex cord markers. The aim of this review is to report clinical and pathological data and genetic alterations to estab-lish its impact on the prognosis and management of patients affected by this rare entity.

Tri-dimensional (3D) cell aggregates or spheroids are considered to be closer to physiological conditions than traditional 2D cell culture. Mesenchymal stem cells (MSCs) assembling in spheroids have increased the survival of transplanted cells. The regulation of the biological processes that maintain crucial physiological reactions of MSCs is closely related to the functioning of ion channels. The pattern of expression, role and regulatory mechanisms of ion channels could be significantly different in 3D compared to 2D culture, and, thus, needed to be properly analyzed on the level of ionic currents. We developed a specific approach that allowed us to register, for the first time, endogenous ion channels in endometrial MSCs (eMSCs) assembled in spheroids. Particularly, using the single-channel patch-clamp technique, we have recorded the activity of ion channels and observed their functional interplay in mechanosensitive clusters. Our experimental protocol could be applied for identification and studying of ion channels in 3D cell cultures.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions that can lead to the loss of structure and/or function impairment. These changes can cause a partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, what in turn can affect the quality of life. For those reasons, PNI is a major public health concern. This review aims to revisit the concepts associated with the PNI. First, the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to explain the urge for new approaches and to understand the methods to evaluate nerve regeneration in a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

This work aims to characterize a new method to recover low-manipulated human adipose tissue, enriched of adipose tissue-derived mesenchymal stem cells (ATD-MSCs) for autologous use in regenerative medicine applications. Lipoaspirated fat collected from patients was processed through Lipocell, a II-a medical device for dialysis of adipose tissue, by varying filter sizes and washing solutions. ATD-MSCs yield was measured with flow cytometry after SVF isolation in fresh and cultured samples. Purification from oil and blood was measured after centrifugation with spectrophotometer analysis. Extracellular matrix preservation was assessed through H&E staining and biochemical assay for total collagen, type-2 collagen, and GAGs quantification. Flow cytometry showed a 2-fold increase of ATD-MSCs yield in treated samples in comparison with untreated lipoaspirate; no differences where reported when varying filter size. The association of dialysis and washing thoroughly removed blood and oil from samples. Tissue architecture and extracellular matrix integrity were unaltered after Lipocell processing. Dialysis procedure associated with Ringer’s lactate preserves the proliferation ability of ATD-MSCs in cell culture. The characterization of the product shows that Lipocell is an efficient method to purify the tissue from undesired byproducts, preserving ATD-MSCs vitality and ECM integrity, resulting in a promising tool for regenerative medicine applications.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p&lt;0,001; 217 versus 136, p&lt; 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

The migration from MATLAB to Python (M-to-PY) has gained significant traction in recent computational research. While MATLAB has long served as a linchpin in myriad scientific endeavors, there's an emerging trend to rejuvenate these projects using Python's extensive AI tools and libraries. This study presents a semi-automated process for M-to-PY conversion, using a detailed case study of an image skeletonization project comprising fifteen MATLAB files and a 1404-image dataset. Skeletonization is foundational for ongoing 3D motion detection research using AI transformers, predominantly developed in Python. The utilization of ChatGPT-4, acting as an AI co-programmer, is pivotal in this conversion. By leveraging the public OpenAI API, we developed an M-to-PY converter prototype, evaluated its efficacy using test cases from the Bard bot, and subsequently employed the converted code in an AI application. The dual contributions encompass a well-tested M-to-PY converter and a Skeleton App capable of sketching and skeletonizing any given image, enriching the AI toolset. This study accentuates how AI resources, like ChatGPT-4, can simplify code transitions, opening doors for innovative AI implementations using primarily MATLAB-coded scientific research.

Waterbomb structures are origami-inspired deformable structural components used in new types of robots. They have a unique radially deployable ability that enables robots to better adapt to their environment. In this paper, we propose a series of new waterbomb structures with square, rectangle, and parallelogram base units. Through quasi-static axial and radial compression experiments and numerical simulations, we prove that the parallelogram waterbomb structure has a twist displacement mode along the axial direction. Compared with the square waterbomb structure, the proposed optimal design of the parallelogram waterbomb structure reduces the critical axial buckling load-to-weight ratio by 55.4% and increases the radial stiffness-to-weight ratio by 67.6%. The significant increase in the radial stiffness-to-weight ratio of the waterbomb structure and decrease in the critical axial buckling load-to-weight ratio make the proposed origami pattern attractive for practical robotics applications.

The world has been highly impacted by the COVID-19 as the virus has spread to all continents – about 200 countries in total. The latest update claims about 4,000,000 confirmed cases and about 300,000 confirmed deaths owing to the COVID-19 pandemic. This probably makes the COVID-19 as the most dangerous contagious disease in the era 2000s. Apart from massive publications on this topic, there is no available qualitative analysis that describes the dynamic spreads of the COVID-19 and its impacts on healthcare and the economy. Through the system archetypes analysis, this paper explains that the dynamic spread of the COVID-19 consists of the limits to growth and the success to successful structures. The limits to growth elucidates that more symptomatic and asymptomatic patients owing to infected droplets may be bounded by self-healing and isolated treatments. The success to successful structure explains that once the COVID-19 affects the economy through the lockdown, there will be a limited fund to support the government aids and the aggregate demand. In overall, this paper gives readers simplified holistic insights into understanding the dynamic spread of the COVID-19.

Background Telomere shortening is related to aging and unfavourable health outcomes. Obesity and metabolic diseases are important factors for accelerating aging. This study aimed to find out the association between obesity, metabolic disease, and telomere length in metabolically healthy adults. Methods 237 adults were enrolled with written consents at a health promotion centre of a tertiary hospital from February 2014 to March 2015. After excluding 99 subjects who met the exclusion criterion, a total of 130 metabolically healthy subjects were selected for final analysis. The subjects were divided into quartile groups according to the telomere lengths of their oral mucosal cells. Results The subjects consisted of 66 (50.8%) males with a mean age of 58.59 years. The body mass index (BMI, kg/m2) increased significantly along with the quartile groups (Q1, 23.00; Q2, 23.96; Q3, 23.70; Q4, 25.20; P-for trend=0.008). Waist circumference (WC, P-for trend=0.022), waist-to-hip ratio (WHR, P-for trend=0.005), and waist-to-height ratio (WHtR, P=0.001) also increased along with the quartile groups. Obesity prevalence (BMI ≥25 kg/m2), abdominal obesity (WC ≥90 cm for men, ≥85 cm for women), WHR 〉1.0 for men or 〉0.85 for women, and WHtR ≥0.5 increased significantly as the telomere length increased (P-for trend <0.05). After adjusting for covariates, the ORs for each obesity markers increased as the telomere length increased (P-for trend <0.05); and the ORs of WHtR were especially meaningful (Q1, 1.00; Q2, 2.53; Q3, 2.97; Q4, 7.81; P-for trend = 0.001). There were no significant trends for metabolic syndrome and its components along with the prevalence of fatty liver disease. Conclusion Obesity markers and telomere length had significant positive correlation despite the established theory. The obesity paradox may exist in metabolically healthy adults with regard to telomere length, However, further studies with larger sample sizes for the association between obesity and telomere length are needed.

The injury causes resistance in human gastric cancer (GC). This Adverse Outcome Pathway (AOP) entitled “Increases in cellular reactive oxygen species (ROS) and chronic ROS leading to human treatment-resistant gastric cancer (GC)” consists of molecular initiating event (MIE) as “Increases in cellular ROS” and “Chronic ROS”, followed by series of key events (KEs); “porcupine-induced Wnt secretion and Wnt signaling activation”, “beta-catenin activation”, “epithelial-mesenchymal transition (EMT), and adverse outcome (AO) as “human treatment-resistant GC” in the sequence. ROS has multiple roles in disease such as development and progression of cancer, or apoptotic induction causing anti-tumor effects. In this AOP, we focus on the role of sustained levels of chronic ROS to induce the therapy-resistance in human GC. EMT, which is cellular phenotypic change from epithelial to mesenchymal-like features, demonstrates cancer stem cell (CSC)-like characteristics in human GC. EMT is induced by Wnt/beta-catenin signaling, providing the rationale to have Wnt secretion and beta-catenin activation as KEs in the AOP.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease due to early metastatic spread, late diagnosis and the lack of efficient therapies. A major driver of cancer progression and hurdle to successful treatment is the desmoplastic reaction of the tumor stroma, the formation of which is orchestrated by transforming growth factor (TGF)-β. Recent data from pancreatic cancer mouse models have shown that the TGF-β pathway is controlled by transcriptionally active p73 (TAp73) through secretion of biglycan (Bgn) via intermittent expression of the TGF-β signaling intermediates, Smad3 and Smad4. Genetic knockout of TP73, and, as a consequence, deficient induction of Smad3/Dpc4 and secretion of Bgn led to activation of TGF-β signaling through a (Smad-independent) ERK pathway, favoring epithelial-mesenchymal transition (EMT) and cell motility. Except for BGN, these functions of TAp73 have recently been shown to also operate in human PDAC cells and are reminiscent of what we previously observed for the small GTPase, RAC1b. This prompted us to hypothesize that TAp73 and RAC1b are part of the same tumor-suppressive pathway in human PDAC cells. The two objectives of this study, therefore, were to reveal i) if the regulatory interactions between TAp73 and Bgn previously discovered in murine PDAC-derived cells also operate in their human counterparts, and ii) if RAC1b collaborates with TAp73 in these tumor-suppressive activities in human PDAC cells. Using a variety of experimental approaches, including mutual rescue experiments, we were able to show that the previously proposed tumor-suppressive TAp73-Smad4-Bgn signaling also operates in human cells and that RAC1b is as an upstream activator of this pathway. Our findings highlight the complex role of TGF-β in pancreatic tumorigenesis and might have implications for therapeutic approaches targeting this growth factor for inhibition.

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment yet, and AD's pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second the Carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in pre-symptoms stages. Finally, we analyzed the differential expressed proteins (DEPs) for biological and functional enrichment. These proteins showed an impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways resembling previous AD reports. Our study is the first proteomic analysis in MSCs from FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/ noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.

Extracellular vesicles (EV) such as exosomes, are newly recognized fundamental, natural and physiologic particles of life that seemingly are involved all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and the potential therapeutic uses of these nano-vesicles requires innovative experimental approaches, in virtually every field. Of the EV group, exosome nano-vesicles and larger companion extracellular micro vesicles (MV) can mediate completely new phenomena dependent on intercellular transfer of proteins and selected RNAs; particularly miRNAs, between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern day exosomes to withstand unusually harsh conditions; perhaps due to unusual membrane lipid compositions. This is exemplified by maternal milk exosome survival of the neonatal acid/enzyme rich stomach. It is postulated that this also applies to their durable presence in phagolysosomes; suggesting unique intracellular release of contents. A major issue discussed is the generally poorly realized superiority of these naturally evolved nano vesicles to therapies compared human engineered artificial nanoparticles; say for treatment of cancers.

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. For several cancers, breast and prostate in particular, bone is the primary site of metastasis. Efforts to treat bone metastases have been stymied by a lack of models to study the progression and cellular players and signaling pathways driving bone metastasis. In this review, we examine the newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic and in silico computational models bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cell enter and escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.

This study explores the evolution of price-to-book (P/B) ratios among European banks from 2005 to 2020, period where the majority of banks in different countries had a P/B ratio below 1. By dissecting banks' accounting equity into investor contributions and earnings-derived components, the research aims to evaluate how each component of equity affects these ratios and investigates whether their dynamics shifted during the period. We address a gap in prior research that has not extensively examined how individual equity components affect the overall P/B ratio. This aspect is crucial, especially in scenarios where the increase of specific components compensates for declines in others, thereby stabilizing total equity values. Our methodology involves regression analyses using a panel data model with random effects. The findings reveal that earnings-related equity components significantly influence P/B ratios. In contrast, investor contributions; which strengthen the solvency of the entity, appear to have a minimal impact. Additionally, our analysis highlights a significant quadratic relationship between the P/B ratios and both the profit or loss reported on Income Statements and distributed dividends.

Recent advancements in cognitive neuroscience, particularly in Electroencephalogram (EEG) signal processing, image generation, and brain-computer interfaces (BCI), have opened up new avenues for research. This study introduces a novel framework, Bridging Artificial Intelligence and Neurological Signals (BRAINS), which leverages the power of AI to extract meaningful information from EEG signals and generate images. The BRAINS framework addresses the limitations of traditional EEG analysis techniques, which struggle with nonstationary signals, spectral estimation, and noise sensitivity. Instead, BRAINS employs Long Short-Term Memory (LSTM) networks and contrastive learning, which effectively handle time-series EEG data and recognize intrinsic connections and patterns. The study utilizes the MNIST dataset of handwritten digits as stimuli in EEG experiments, allowing for diverse yet controlled stimuli. The data collected is then processed through an LSTM-based network employing contrastive learning and extracting complex features from EEG data. These features are fed into an image generator model, producing images as close to the original stimuli as possible. This study demonstrates the potential of integrating AI and EEG technology, offering promising implications for the future of brain-computer interfaces.

Background: The risk to physicians who worked with patients without confirmed COVID-19 testing during the pandemic has been little studied. However, they were at high risk. Methods: A total of 1285 Romanian physicians completed an online survey. We performed Mann-Whitney comparisons between physicians who reported that they knowingly had direct contact with COVID patients and those who didn't regarding their willingness to work. Results: Compared with their colleagues, physicians who reported not knowingly having direct contact with COVID patients reported less access to protective equipment, less overall willingness to respond when asked to work with infected patients, more likely to work out of fear of losing their jobs, and fear of legal repercussions. They received less training in the use of protective equipment. Conclusions: Physicians who worked with patients not yet diagnosed with COVID-19 were significantly less willing to work. The perception of invisible risk may explain the observed differences.

The challenge of accessing finance by entrepreneurs from traditional financial sources is pervasive. The COVID-19 pandemic further exacerbated the problem of limited access to finance from banks. Against this backdrop, the objective of the study was to determine the factors driving crowdfunding success during the COVID-19 pandemic in Africa. The ordinary least squares (OLS) and probit regression models were estimated to analyse 216 crowdfunding projects in Africa. The results of the study documented that targeted amount (TA), and COVID-19 pandemic were negative and significant drivers of crowdfunding success. Furthermore, comments (CMM) and duration (DRN) were negative and significantly affected crowdfunding success. Conversely, images (IM), videos (VD), backers (BCK), and updates (UPD) were positive and significantly affected crowdfunding success. The study contributes to the body knowledge by investigating the drivers of crowdfunding success during the COVID-19 pandemic period which hitherto had not been researched on extenisvely.

We aimed to explore symptoms severity and adherence to therapy for patients with myelofibrosis treated with ruxolitinib in Bulgaria. It is a prospective, non-interventional study performed at the Specialized hospital for active treatment of hematological diseases in Sofia during 2022 - 2023. Date of diagnosis, demographic characteristics, clinical indicators, ruxolitinib dose, and other data points were collected. Clinical indicators were assessed at baseline, in the middle and at the end of observation. Severity of symptoms was measured with MPN-SAF TSS and adherence to therapy with the Morisky 4 questionnaire 6 times during the observation. The mean age of diagnosis was 58.5 years, with the average duration of disease of 3 years. Pa-tients’ laboratory results were within physiological ranges, with spleen size experiencing a con-stant decrease. The average value for the severity of the symptoms per MPN-SAF TSS results decreased significantly, indicating better disease control. The average adherence to therapy did not change and remained high at around 9 points, except for one patient. In conclusion the treatment of myelofibrosis patients with ruxolitinib decreased symptoms se-verity and spleen size. Patients were adherent to the therapy over the observed period but as treatment duration increases the risk of adherence decreasing.

Recent advances in deep learning technology have led to increased interest in text-to-image technology, which enables computers to create images from text by simulating the human process of forming mental images. The GAN-based text-to-image technology involves the extraction of features from input text, which are combined with noise and then used as input to a GAN that generates images that are similar to the original images through competition between the generator and discriminator. Although generating images from English text is a mature area of research, text-to-image technology based on multilingualism, such as Korean, is still in its early stages of development. Webtoon is a digital comic format that allows comics to be viewed online. The creation process for webtoons is divided into story planning, content/sketching, coloring, and background drawing. Since each stage of webtoon production requires human intervention, it is both time-consuming and expensive. As a result, deep learning technologies such as automatic coloring and automatic line drawing are being used to reduce human involvement. However, there is a shortage of technology that can assist authors with story creation in webtoon production. Therefore, this study proposes a multilingual text-to-image model capable of generating webtoon images when presented with multilingual input text. The proposed model employs Multilingual BERT to extract feature vectors for multiple languages, and trains a DCGAN in conjunction with the images. The experimental results demonstrate that the model can generate images that are similar to the original images when presented with multilingual input text after training.

Small and medium-sized enterprises (SMEs) help and support the country in financial and business aspects and employs in the country, overcomes unemployment, and creates job opportunities in different sectors of the country. The study aims to know the entrepreneurial-specific factors like age, gender, education, experience, and skills used as predictors for access to financing of small firms in Khyber Pakhtunkhwa. The questionnaire is used for data collection, and about 204 questionnaires were distributed, of which 192 returned and analyzed through binary logistic regression. The study results reveal that age and level of education have been found significant while gender, experience and skills have insignificant with the access to finance in Khyber Pakhtunkhwa, Pakistan.

Circular Economy involves structural changes in traditional business models and consumers’ behaviour toward recycled products. The recycling of PET products has been increasing but there is still a gap between consumption and demand for PET packaging in Brazil. In this research, the waste reduction was examined under a projective scenario to the current ecological purposes in Brazil for reducing environmental pollution. In that manner, this paper aimed to comprehend the intention to purchase recycled PET products of Brazilian consumers. With a non-probabilistic and convenience sample, the study counts 422 participants. The method employed was based on Structural Equation Modelling and Partial Least Squares, used to test the hypotheses of causality among the variables. Results showed the perception of low quality about recycled products reduced consumers’ intention to purchase. Also, the sustainability of recycled products positively influenced the intention to purchase. In addition, recycled products presented a negative impact on the perceived safety, which could influence the purchase of recycled products in Brazil. We conclude that the image that Brazilian consumers have about recycled products positively affects the intention to purchase.

Microbial symbioses exhibit astounding adaptations, yet all symbionts face the problem of how to reliably associate with host offspring every generation. A common strategy is vertical transmission, in which symbionts are directly transmitted from the female to her offspring. The diversity of symbionts and vertical transmission mechanisms is as expansive as the diversity of eukaryotic host taxa that house them. However, there are several common themes among these mechanisms based on the degree to which symbionts associate with the host germline during transmission. In this review, we detail three distinct vertical transmission strategies, starting with associations that are transmitted from host somatic cells to offspring somatic cells, either due to lacking a germline or avoiding it. A second strategy involves somatically-localized symbionts that migrate into the germline during host development. The third strategy we discuss is one in which the symbiont maintains continuous association with the germline throughout development. Unexpectedly, the vast majority of documented vertically inherited symbionts rely on the second strategy: soma-to-germline migration. Given that not all eukaryotes contain a sequestered germline and instead produce offspring from somatic stem cell lineages, this soma-to-germline migration is discussed in the context of multicellular evolution. Lastly, as recent genomics data have revealed an abundance of horizontal gene transfer events from symbiotic and non-symbiotic bacteria to host genomes, we discuss their impact on eukaryotic host evolution.

Bidirectional gene promoters affect the transcription of two genes, leading to the hypothesis that they should exhibit protection against genetic or epigenetic changes in cancer. Therefore, they provide an excellent opportunity to learn about promoter susceptibility to somatic alteration in tumors. We tested this hypothesis using data from genome-scale DNA methylation (14 cancer types), simple somatic mutation (10 cancer types), and copy number variation profiling (14 cancer types). For DNA methylation, the difference in rank differential methylation between tumor and tumor-adjacent normal matched samples based on promoter type was tested by Wilcoxon rank sum test. Logistic regression was used to compare differences in simple somatic mutations. For copy number alteration, a mixed effects logistic regression model was used. The change in methylation between non-diseased tissues and their tumor counterparts was significantly greater in single compared to bidirectional promoters across all 14 cancer types examined. Similarly, the extent of copy number alteration was greater in single gene compared to bidirectional promoters for all 14 cancer types. Furthermore, among 10 cancer types with available simple somatic mutation data, bidirectional promoters were slightly more susceptible. These results suggest that selective pressures related with specific functional impacts during carcinogenesis drive the susceptibility of promoter regions to somatic alteration.

The traditional herbal medicine, Hochu-ekki-to, has been shown to have preventive effects on viral infection and stress. This study aimed to evaluate the clinical effects of Hochu-ekki-to on two stress-related rat models of polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into control and treatment groups, the latter of which were subjected to stress induced by exposure to adrenocorticotropic hormone (ACTH) or cold temperatures. After these stress inductions, rats were orally treated with dissolved Hochu-ekki-to once per day for 7 days. Rats subjected to the two different stressors exhibited upregulation of steroid hormone receptors (in ovaries) and reproductive hormones (in blood), and consequent stimulation of abnormal follicle development accompanied by elevation of Hsp 90 expression (in ovaries). Treatment with Hochu-ekki-to for 7 days after stress induction increased immune functions, reduced the stress-induced activation of Hsp 90, and normalized the levels of the tested steroid hormone receptors and reproductive hormones. Our findings suggest that stress stimulations may promote the activation of Hsp 90 via the dysregulation of steroid hormone receptors and reproductive hormones, but that post-stress treatment with Hochu-ekki-to improves reproductive and immune functions in the ovaries of stressed rats.

Objective: Meningococcal meningitis (MM) is an acute, severe respiratory infectious disease caused by Neisseria meningitidis and remains an important cause of morbidity/mortality in children. Immunization with meningococcal vaccine (MV) is the most effective measure to control and prevent the transmission of MM. In this study, in order to support the appropriate use of various MVs in the prevention of MM, the effects of MVs, especially single-dose and inter-booster administered, on inflammatory parameters in

CT scans are currently the most common imaging modality used for suspected stroke patients due to their short acquisition time and wide availability. However, MRI offers superior tissue contrast and image quality. In this study, eight deep learning models are developed, trained, and tested using a dataset of 181 CT/MR pairs from stroke patients. The resultant synthetic MRIs generated by these models are compared through a variety of qualitative and quantitative methods. The synthetic MRIs generated by a 3D UNet model consistently demonstrated superior performance across all methods of evaluation. Overall, the generation of synthetic MRIs from CT scans using the methods described in this paper produces realistic MRIs that can guide the registration of CT scans to MRI atlases. The synthetic MRIs enable the segmentation of white matter, gray matter, and cerebrospinal fluid using algorithms designed for MRIs, exhibiting a high degree of similarity to true MRIs.

The number of people owning vehicles has been steadily growing, resulting in increased numbers of vehicles on the roads, making roads more congested, and increasing the risk of accidents. In addition, heavy rain, snow, and fog have increased due to abnormal weather caused by global warming. These bad weather conditions can also affect the safety of vehicles and drivers. The need to disseminate safety messages on the social internet of vehicles due to these problems has been steadily increasing. In this paper, we propose an efficient safety message dissemination scheme that focuses on urban environments with high vehicle density and mobility to address these problems. The proposed scheme reduces packet loss by considering frequent cluster departures and subscriptions through an efficient cluster management technique. In a vehicle-to-vehicle environment, the dissemination of safety messages is divided into an intra-cluster and an inter-cluster emergency as well as general safety message dissemination technique. In a vehicle to infrastructure environment, the proposed scheme reduces the number of processing requests and duplicate messages made to roadside units (RSUs) through a request operation process for each vehicle and an RSU scheduling technique. We conducted several performance evaluations of message packet loss and the number of RSU processing requests to demonstrate the superiority of the proposed scheme.

Peat is the main type of peloid used in Polish cosmetic/healing spa facilities. Depending on treatment and origin, peat waste can be contaminated microbiologically, and as result, it has to be incinerated in medical waste incineration plants without energy recovery (local law). Such a situation leads to peat waste management costs increase. Therefore in this work, we checked the possibility of peat waste upcycling to carbonized solid fuel (CSF) using torrefaction. Torrefaction is a thermal treatment process that removes microbiological contamination and improves the fuel properties of peat waste. In work torrefaction conditions (temperature and time) on CSF quality were tested. Parallelly, peat decomposition kinetics using TGA, and torrefaction kinetics with lifetime prediction using macro-TGA were determined. Furthermore, torrefaction theoretical mass and energy balance were determined. The results of the tested peat were compared with reference material (wood), and as result, obtained data can be used to adjust currently used wood torrefaction technologies for peat torrefaction. The results show that torrefaction can improve the high heating value of peat waste from 19.0 MJ x kg-1 to 21.3 MJ x kg-1, peat main decomposition takes place at 200-550 °C following second reaction order (n=2), with an activation energy of 33.34 kJ x mol-1 and pre-exponential factor of 4.40 x 10-1 s-1. Moreover, DSC analysis revealed that peat torrefaction required slightly more energy than wood torrefaction, and macro TGA showed that peat torrefaction has lower torrefaction constant reaction rates (k) than wood 1.05 x 10-5 - 3.15 x 10-5 vs 1.43 x 10-5 - 7.25 x 10-5 s-1.

Several studies have shown that physical activity (PA) is related to physical and mental health. Yet, there are few studies on the frequency of PA as it relates to health and a healthy lifestyle. The purpose of this study was to investigate the relationship between the frequency of practicing different types of physical activities (dependent variables), living a healthy lifestyle (BMI, smoking and alcohol consumption), physical health (sum of all doctor visits except psychiatrists) and mental health (a sum of visits to psychiatrists) at different ages (independent variables). We fo-cused on three types of PA: (1) medium to high-intensity aerobic exercises; (2) low to medium intensity relaxing and stretching exercises, (3) outdoor leisure PA. 9,617 participants (ages: 19 -81) were included in the study (with health registries over a period of 10 years prior to a cross-sectional survey). Descriptive statistics and multinomial logistic regression on frequencies of three types of PA and factors related to health and healthy lifestyles, as well as age and sex, were performed in this study. The results indicate that a higher frequency of practicing PA had a higher probability of association with the following factors: lower BMI, less or non-smoking behavior (types 1 & 3); higher education (types 1 & 2); higher age (types 2 & 3) and better physical health (type 1). Occasional (practicing sometimes) PA, type 2, was positively associated with poorer mental health (higher number of psychiatrist visits). Women were more likely to practice PA type 2, and men – PA types 3 & 1. Conclusion: In general, a higher frequency of PA is related with better health and healthy life styles; with the exception of PA type 2 that is related to poorer mental health.

Adipose tissue-derived stem cells (ADSCs) represent a subset of mesenchymal stem cells in every adipose compartment throughout the body. ADSCs can differentiate into various cell types, including chondrocytes, osteocytes, myocytes, and adipocytes. Moreover, they exhibit a notable potential to differentiate in vitro into cells from other germinal lineages, including endothelial cells and neurons. ADSCs have a wide range of clinical applications, from breast surgery to chronic wounds. Furthermore, they are a promising cell population for future tissue-engineering uses. Accumulating evidence indicates decreased proliferation and differentiation potential of ADSCs with increasing age, body mass index, diabetes mellitus, metabolic syndrome, or exposure to radiotherapy. Therefore, recent literature thoroughly investigates this cell population's senescence mechanisms and how they can hinder their possible therapeutic applications. This review will discuss the biological mechanisms and the physio-pathological causes behind ADSC senescence and how they can impact cellular functionality. Moreover, we will examine the possible strategies to invert these processes, re-establishing the full regenerative potential of this progenitor population.

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC-phenotypes exist along the EMT-axis and how these impact malignancy-associated properties, we aimed to characterize CSC-populations of epithelial and mesenchymal PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. Panc1 Holoclone cells showed a mesenchymal phenotype dominated by high expression of the stemness marker Nestin, while Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. Panc89 Holoclone cells showed enhanced cell growth and self-renewal capacity but slow cluster-like invasion. Contrarily, Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, Panc1 and Panc89 cell variants significantly differed regarding number and size of metastases as well as organ manifestation leading to different survival outcomes. Overall, these data support the existence of different CSC-phenotypes along the EMT-axis in PDAC manifesting in different metastatic propensities.

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burns healing, in the absence of regenerating epidermis, is infections which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating recruitment of macrophages into burns may contribute to faster regeneration of the epidermis and thus, decreasing the risk of infections. This review describes a unique method for rapid recruitment of macrophages into burns and activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on application of bio-degradable “alpha-gal” nanoparticles to burns. These nanoparticles present multiple alpha-gal epitopes (Gal alpha1-3Gal beta1-4GlcNAc-R) which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/alpha-gal nanoparticles interaction activates the complement system, resulting in localized production of the complement cleavage-peptides C5a and C3a that are highly effective chemotactic factors for monocytes derived macrophages. The macrophages recruited into the alpha-gal nanoparticles treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophages cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on healing of thermal injuries in the skin of anti-Gal producing mice, demonstrated a much faster recruitment of macrophages into burns treated with alpha-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns takes ~12 days. alpha-Gal nanoparticles are non-toxic, and do not cause chronic granulomas or keloids. These findings suggest that alpha-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans.

Background: Obtaining adipose-derived stem cells is limited by its capacity to differentiate. Stimulation by platelet-rich fibrin appears to have the beneficial effects to accelerate differentiation. Objective: To obtain immunohistochemistry evidence of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells. Methods: We used post-test only controlled-group design. Adipose-derived stem cells were isolated and cultured until 4 passages in α-MEM culture medium. Results: GATA-4 expression increased in platelet-rich fibrin group compared with control group (68.20±6.82 vs 58.15±1.23 counts; p<0.05; 68.20±6.82 vs 52.96±2.02 counts; p<0.05). Troponin expression also increased in platelet-rich fibrin group (50.66±7.2 vs 10.73±2.39 counts; p<0.05; 50.66±7.2 vs 26.00±0.4 counts; p<0.05). Conclusion: There is an immunohistochemistry benefit of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells into cardiomyocyte-like cells.