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Introduction. Biliary obstruction is a common manifestation of biliopancreatic malignancies, and its relief is an essential part of the treatment algorithm. Currently, there are three techniques to manage malignant biliary obstruction—endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage (PTBD), and endoscopic ultrasound-guided biliary drainage (EUS-BD). ERCP has been adopted as a first-line treatment modality but EUS-BD is gradually emerging as a viable alternative. The aim of the current article is to assess the clinical outcomes of the three nonsurgical biliary drainage procedures. Materials and methods. A total of 102 consecutive patients with unresectable biliopancreatic malignancy inducing biliary obstruction and subjected to palliative treatment by means of ERCP, EUS-BD, or PTBD were retrospectively included in the study. Results. No difference in clinical and technical success of the procedures was found: ERCP—97.2% technical; 88.9% clinical; PTBD—94.4% technical, 72.2% clinical; EUS-BD—90% technical; 83.3% clinical. Adverse events (AEs) and reinterventions were significantly more common in PTBD (38.9% and 52.8%) and ERCP (27.9% and 25%) compared to EUS-BD (10% and 3.3%). Total duration of hospital stay and number of hospitalizations were lower in the EUS-BD compared to PTBD and ERCP groups. Conclusions. In the presence of adequate expertise, EUS-BD may be superior to PTBD and ERCP in achieving and sustaining biliary drainage in the setting of unresectable malignancy.

The development of the Gleason grading system has proven to be an irreplaceable tool in prostate cancer diagnostics within urology. Despite the advancements and developments in diagnostics, there remains a discrepancy in the grading process among even the most experienced pathologists. AI algorithms have demonstrated potential in detecting cancer and assigning Gleason grades, offering a solution to the issue of significant variability among pathologists’ evaluations. Our paper explores the evolving role of AI in prostate cancer histopathology, with a key focus on outcomes and the reliability of various AI algorithms for Gleason pattern assessment. We conducted a non-systematic review of the published literature to examine the role of artificial intelligence in Gleason pattern diagnostics. The PubMed and Google Scholar databases were searched to gather pertinent information about recent advancements in artificial intelligence and their impact on Gleason patterns. We found that AI algorithms are increasingly being used to identify Gleason patterns in prostate cancer, with recent studies showing promising advancements that surpass traditional diagnostic methods. These findings highlight AI’s potential to be integrated into clinical practice, enhancing pathologists’ workflows and improving patient outcomes. The inter-observer variability in Gleason grading has seen an improvement in efficiency with the implementation of AI. Pathologists using AI have reported successful outcomes, demonstrating its effectiveness as a supplementary tool. While some refinements are still needed before AI can be fully implemented in clinical practice, its positive impact is anticipated soon.

Prostate cancer is the second most common neoplasia and fifth-leading cause of cancer death in men worldwide. Electromagnetic and magnetic fields have been classified as possible human carcinogens, but current understanding of molecular and cellular pathways involved is very limited. Effects due to extremely low magnetic/hypomagnetic fields (LMF) are furthermore poorly understood. Extracellular vesicles (EVs) are crucial mediators of cellular communication with multifaceted roles in cancer progression, including via transport and uptake of various protein and microRNA (miRNA) EV-cargoes. miRNAs regulate gene expression and are implicated in cancer-related processes such as proliferation, metastasis, and chemoresistance. This study investigated the effects of LMF exposure (20 nT) by magnetic shielding on the prostate cancer cell line PC3 compared to the prostate epithelial cell line PNT2 under short-term (4 h) conditions. We examined EV profiles following a 4 h LMF exposure alongside associated functional enrichment KEGG and GO pathways for the EV proteomes. The 4 h LMF exposure significantly reduced cellular EV release and modified PC3 EV cargoes to a more inflammatory and metastatic profile, with 16 Disease Pathways and 95 Human Phenotypes associated specifically with the LMF-treated PC3 EV proteomes. These included cancerous, metabolic, blood, skin, cardiac and skeletal Disease Pathways, as well as pain and developmental disorders. In the normal PNT2 cells, less EV protein cargo was observed following LMF exposure compared with cells not exposed to LMF, and fewer associated functional enrichment pathways were identified. This pointed to some differences in various cellular functions, ageing, defence responses, oxidative stress, and disease phenotypes, including respiratory, digestive, immune, and developmental pathways. Furthermore, we analysed alterations in matrix metalloproteinases (MMPs) and miRNAs linked to metastasis, as this is crucial in cancer aggressiveness. The 4 h LMF exposure caused a significant increase in MMP2 and MMP9, as well as in onco-miRs miR-155, miR-210, miR-21, but a significant reduction in tumour-suppressor miRs (miR-200c and miR-126) in the metastatic PC3 cells, compared with normal PNT2 cells. In addition, 4 h LMF exposure significantly induced cellular invasion of PC3 cells. Overall, our findings suggest that changes in magnetic field exposures modulate EV-mediated and miR-regulatory processes in PCa metastasis, providing a basis for exploring novel therapeutic strategies.

Understanding the mechanisms responsible for the origin, evolution, and failure of pingos with explosive gas emissions and the formation of craters in the Arctic permafrost requires comprehensive studies in the context of fluid dynamic processes. Properly choosing modeling methods for the joint interpretation of geophysical results and analytical data on core samples from suitable sites are prerequisites for predicting pending pingo failure hazards. We suggest an optimal theoretically grounded workflow for such studies, in a site where pingo collapse induced gas blowout and crater formation in the Yamal Peninsula. The site was chosen with reference to the classification of periglacial landforms and their relation to the local deformation pattern, according to deciphered satellite images and reconnaissance geophysical surveys. The deciphered satellite images and combined geophysical data from the site reveal a pattern of periglacial landforms matching the structural framework with uplifted stable permafrost blocks (polygons) bounded by eroded fractured zones (lineaments). Greater percentages of landforms associated with permafrost degradation fall within the lineaments. Resistivity anomalies beneath pingo-like mounds presumably trace deeply rooted fluid conduits. This distribution can be explained in terms of fluid dynamics. N–E and W–E faults, and especially their junctions with N–W structures, are potentially the most widely open conduits for gas and water which migrate into shallow sediments in the modern stress field of N–S (or rather NEN) extension and cause a warming effect on permafrost. The results obtained with a new workflow and joint interpretation of remote sensing, geophysical, and analytical data from the site of explosive gas emission in the Yamal Peninsula confirm the advantages of the suggested approach and its applicability for future integrated fluid dynamics research.

Introduction. Mirizzi syndrome (MS) represents a rare clinical entity caused by impaction of one or multiple stones in the infundibulum of the gall bladder or the cystic duct resulting in partial or complete obstruction of the common hepatic or common bile duct (CBD). Though described more than a century ago, MS is still one of the most challenging diseases in the spectrum of biliary pathology. In recent years, endoscopic treatment has become an increasingly popular treatment modality. Patients and methods. Three consecutive patients subjected to cholangioscopy-assisted laser lithotripsy (CA-LL) for postocholecystectomy MS (pMS) were retrospectively evaluated. Case reports. Successful clearance of the cystic duct was achieved in all patients in one or two sessions. One complication in the form of mild cholangitis was observed. Clinical success was 100%. Discussion. According to current research, CA-LL achieves a high rate of ductal clearance and acceptable complication rate in patients with pMS. A 250 µm laser fiber seems to be the optimal choice for CA-LL. Our results suggest that procedure duration is closely associated to the stone size and possibly to the operator experience. In our opinion, upon obtainment of successful ductal clearance and drainage, prophylactic stenting does not improve clinical outcome. Conclusions. Our results demonstrate that CA-LL is a safe and effective treatment for pMS.

Introduction: Descending necrotizing mediastinitis is one of the most lethal forms of acute mediastinitis. It originates from an odontogenic or deep neck infection, which descends to the mediastinum through the fascial planes. It is a rare condition, but mortality rates remain high, especially in the presence of comorbidities or predisposing factors. Delay in diagnosis has been shown to be one of the most important factors for the disease outcome. Therefore, early diagnosis and treatment by a multidisciplinary team are of utmost importance. Case series: Four healthy young males with descending necrotizing mediastinitis were treated at our institution. None of them had any comorbidities, but all of them waited between 3 and 4 days before seeking medical help. Upon their arrival at the hospital, in addition to the presence of a severe neck infection, the presence of mediastinitis was also found. Despite the timely surgical treatment of both the source of the infection and the mediastinitis, three of the four cases had a fatal outcome. Conclusion: We believe that the time factor is of greater importance for the outcome of acute descending mediastinitis than the factors of age and presence of accompanying diseases. Proper and rapid treatment by a multidisciplinary team is essential, even for young and healthy people.

Background and objectives: This review aims to delve into the role of artificial intelligence in medicine. Ulcerative colitis (UC) is a chronic, inflammatory bowel disease (IBD) characterized by superficial mucosal inflammation, rectal bleeding, diarrhoea and abdominal pain. By identifying the challenges inherent in UC diagnosis, we seek to highlight the potential impact of artificial intelligence on enhancing both diagnosis and treatment methodologies for this condition. Method: A targeted, non-systematic review of literature relating to ulcerative colitis was undertaken. The PubMed and Scopus databases were searched to categorize a well-rounded understanding of the field of artificial intelligence and its developing role in the diagnosis and treatment of ulcerative colitis. Articles that were thought to be relevant were included. This paper only included articles published in English. Results: Artificial intelligence (AI) refers to computer algorithms capable of learning, problem solving and decision-making. Throughout our review, we highlighted the role and importance of artificial intelligence in modern medicine, emphasizing its role in diagnosis through AI-assisted endoscopies and histology analysis and its enhancements in the treatment of ulcerative colitis. Despite these advances, AI is still hindered due to its current lack of adaptability to real-world scenarios and its difficulty in widespread data availability, which hinders the growth of AI-led data analysis. Conclusions: When considering the potential of artificial intelligence, its ability to enhance patient care from a diagnostic and therapeutic perspective shows signs of promise. For the true utilization of artificial intelligence, some roadblocks must be addressed. The datasets available to AI may not truly reflect the real-world, which would prevent its impact in all clinical scenarios when dealing with a spectrum of patients with different backgrounds and presenting factors. Considering this, the shift in medical diagnostics and therapeutics is coinciding with evolving technology. With a continuous advancement in artificial intelligence programming and a perpetual surge in patient datasets, these networks can be further enhanced and supplemented with a greater cohort, enabling better outcomes and prediction models for the future of modern medicine.

The naturally occurring compounds ecdysterone and turkesterone, which are present in plants, including Rhaponticum carthamoides Willd. (Iljin), Spinacia oleracea L., Chenopodium quinoa Willd., and Ajuga turkestanica (Regel) Briq, are widely recognized due to their possible advantages for both general health and athletic performance. The current review investigates the beneficial biological effects of ecdysterone and turkesterone in nutrition, highlighting their roles not only in enhancing athletic performance but also in the management of various health problems. Plant-based diets, associated with various health benefits and environmental sustainability, often include sources rich in phytoecdysteroids. However, the therapeutic potential of phytoecdysteroid-rich extracts extends beyond sports nutrition, with promising applications in treating chronic fatigue, cardiovascular diseases, and neurodegenerative disorders.

Tanacetum parthenium L. (Asteraceae) is a perennial herbaceous plant with a long-standing historical use in traditional medicine. Recently Tanacetum parthenium L. essential oil has been associated with a promising potential for future applications in the pharmaceutical industry, in the cosmetics industry, and in agriculture. Investigations on the essential oil (EO) have indicated antimicrobial, antioxidant, and repellent activity. The present study aimed to evaluate the chemical composition of Bulgarian T. parthenium essential oil from two different regions, to compare the results to those reported previously in the literature, and to point out some of its future applications. The essential oils of the air-dried flowering aerial parts were obtained by hydrodistillation using a Clevenger-type apparatus. The chemical composition was evaluated using gas chromatography with mass spectrometry (GC-MS). It was established that the oxygenated monoterpenes were the predominant terpene class, followed by the monoterpene hydrocarbons. Significant qualitative and quantitative differences between both samples were revealed. Camphor (50.90%), camphene (16.12%), and bornyl acetate (6.05%) were the major constituents in the feverfew EO from the western Rhodope Mountains, while in the EO from the central Balkan mountains camphor (45.54%), trans-chrysanthenyl acetate (13.87%), and camphene (13.03%) were the most abundant components.

Background: The aim of this review is to explore the role of artificial intelligence in the diagnosis of colorectal cancer, how it impacts CRC morbidity and mortality, and why its role in clinical medicine is limited. Methods: A targeted, non-systematic review of the published literature relating to colorectal cancer diagnosis was performed with PubMed databases that were scouted to help provide a more defined understanding of the recent advances regarding artificial intelligence and their impact on colorectal-related morbidity and mortality. Articles were included if deemed relevant and including information associated with the keywords. Results: The advancements in artificial intelligence have been significant in facilitating an earlier diagnosis of CRC. In this review, we focused on evaluating genomic biomarkers, the integration of instruments with artificial intelligence, MR and hyperspectral imaging, and the architecture of neural networks. We found that these neural networks seem practical and yield positive results in initial testing. Furthermore, we explored the use of deep-learning-based majority voting methods, such as bag of words and PAHLI, in improving diagnostic accuracy in colorectal cancer detection. Alongside this, the autonomous and expansive learning ability of artificial intelligence, coupled with its ability to extract increasingly complex features from images or videos without human reliance, highlight its impact in the diagnostic sector. Despite this, as most of the research involves a small sample of patients, a diversification of patient data is needed to enhance cohort stratification for a more sensitive and specific neural model. We also examined the successful application of artificial intelligence in predicting microsatellite instability, showcasing its potential in stratifying patients for targeted therapies. Conclusions: Since its commencement in colorectal cancer, artificial intelligence has revealed a multitude of functionalities and augmentations in the diagnostic sector of CRC. Given its early implementation, its clinical application remains a fair way away, but with steady research dedicated to improving neural architecture and expanding its applicational range, there is hope that these advanced neural software could directly impact the early diagnosis of CRC. The true promise of artificial intelligence, extending beyond the medical sector, lies in its potential to significantly influence the future landscape of CRC’s morbidity and mortality.

This comprehensive review delves into the complex realm of antinuclear antibodies (ANAs), expanding beyond their traditional involvement in autoimmune rheumatic disorders. By digging into historical changes, diagnostic complexity, and clinical significance, the debate reveals the shifting relationships between ANAs, particularly with cancer. Specialized studies provide practical insights on ANA testing processes, standardization, and upcoming challenges. Examining prevalence trends in the United States provides a time dimension to ANA dynamics, linking autoimmune and oncological considerations. The debate delves into the complexity of lupus erythematosus, emphasizing ANAs’ diverse presentations and their potential as flexible diagnostic and prognostic indicators. The complex relationship between ANAs and cancer is highlighted, demonstrating their potential as early markers or indicators of malignancies. Looking ahead, this synthesis anticipates advances in personalized medicine and collaborative research, putting ANAs at the forefront of advanced diagnostics and treatments for autoimmune disorders and cancer. This synthesis envisions a future for ANA research in which these antibodies play a critical role in promoting personalized treatment, enhancing diagnostics, and fostering collaborative initiatives that cross traditional boundaries. As ANAs grow more prominent at the junction of autoimmune illnesses and cancer, this synthesis lays the path for further research and novel advances in understanding, diagnosing, and treating complicated medical conditions.

Background and Objectives: The aim of this review is to explore the recent surgical innovations in tracheal reconstruction by evaluating the uses of synthetic material fabrication when dealing with tracheomalacia or stenotic pathologies, then discussing the challenges holding back these innovations. Materials and Methods: A targeted non-systematic review of published literature relating to tracheal reconstruction was performed within the PubMed database to help identify how synthetic materials are utilised to innovate tracheal reconstruction. Results: The advancements in 3D printing to aid synthetic material fabrication have unveiled promising alternatives to conventional approaches. Achieving successful tracheal reconstruction through this technology demands that the 3D models exhibit biocompatibility with neighbouring tracheal elements by encompassing vasculature, chondral foundation, and immunocompatibility. Tracheal reconstruction has employed grafts and scaffolds, showing a promising beginning in vivo. Concurrently, the integration of resorbable models and stem cell therapy serves to underscore their viability and application in the context of tracheal pathologies. Despite this, certain barriers hinder its advancement in surgery. The intricate tracheal structure has posed a challenge for researchers seeking novel approaches to support its growth and regeneration. Conclusions: The potential of synthetic material fabrication has shown promising outcomes in initial studies involving smaller animals. Yet, to fully realise the applicability of these innovative developments, research must progress toward clinical trials. These trials would ascertain the anatomical and physiological effects on the human body, enabling a thorough evaluation of post-operative outcomes and any potential complications linked to the materials or cells implanted in the trachea.

Janus kinase (JAK) inhibitors have heralded a paradigm shift in the management of immune-mediated diseases. While their efficacy is well-established, the safety concerns associated with these agents, particularly regarding thromboembolic events (TE), remain a focus of extensive research and clinical scrutiny. This comprehensive literature review embarks on an exploration of the multifaceted landscape of JAK inhibitors, providing insights into their safety profiles across diverse immune-mediated diseases. The introduction highlights the transformative influence of JAK inhibitors in the treatment of immune-mediated diseases. Historically, the therapeutic arsenal for these conditions included corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics. The advent of JAK inhibitors has revolutionized this landscape, although concerns about their safety persist. This review strives to comprehensively evaluate their safety, amalgamating knowledge from multiple studies and trials. The subsequent sections delve into the safety of specific JAK inhibitors in the context of rheumatoid arthritis, inflammatory bowel diseases, and dermatologic conditions and their associations with venous thromboembolism. The evolving understanding of TE risk, particularly the intricate relationship between these agents and immune-mediated diseases, is meticulously unravelled. The concluding remarks underscore the dynamic nature of TE risk assessment with regard to immune-mediated diseases involving JAK inhibitors. It underscores that risk assessment is multifactorial, influenced not only by the choice of JAK inhibitor but also by the nuances of the underlying immune-mediated disease and the unique patient characteristics. This review offers a holistic perspective on TE risks associated with JAK inhibitors and contributes to the ongoing dialogue regarding their safety in the realm of immune-mediated diseases.

Febuxostat, initially developed as a xanthine oxidase inhibitor to address hyperuricemia in gout patients, has evolved into a versatile therapeutic agent with multifaceted applications. This review provides a comprehensive overview of febuxostat’s mechanism of action, its effectiveness in gout management, its cardiovascular safety profile, renal and hepatic effects, musculoskeletal applications, safety considerations, and emerging research prospects. Febuxostat’s primary mechanism involves selective inhibition of xanthine oxidase, resulting in reduced uric acid production. Its pharmacokinetics require personalized dosing strategies based on individual characteristics. In gout management, febuxostat offers a compelling alternative, effectively lowering uric acid levels, relieving symptoms, and supporting long-term control, especially for patients intolerant to allopurinol. Recent studies have demonstrated its cardiovascular safety, and it exhibits minimal hepatotoxicity, making it suitable for those with liver comorbidities. Febuxostat’s potential nephroprotective effects and kidney stone prevention properties are noteworthy, particularly for gout patients with renal concerns. Beyond gout, its anti-inflammatory properties hint at applications in musculoskeletal conditions and a broader spectrum of clinical contexts, including metabolic syndrome. Emerging research explores febuxostat’s roles in cardiovascular health, neurological disorders, rheumatoid arthritis, and cancer therapy, driven by its anti-inflammatory and antioxidative properties. Future directions include personalized medicine, combination therapies, mechanistic insights, and ongoing long-term safety monitoring, collectively illuminating the promising landscape of febuxostat’s multifaceted therapeutic potential.

This retrospective case-control study examined the relationship between the serum and synovial levels of cathepsin G (CatG) and cathepsin K (CatK) in patients with psoriatic arthritis (PsA) and their association with disease activity. Methods: This case-control study involved 156 PsA patients, 50 patients with gonarthrosis (GoA), and 30 healthy controls. The target parameters were measured using enzyme-linked immunosorbent assay (ELISA) kits. The serum levels of CatG and CatK were found to be significantly higher in PsA patients compared to both control groups (p < 0.001). Moreover, they could distinguish PsA patients from healthy controls with 100% accuracy. Synovial fluid CatG and CatK were positively associated with the following indicators of disease activity: the VAS (rs = 0.362, rs = 0.391); the DAPSA (rs = 0.191, rs = 0.182); and the mCPDAI (rs = 0.378, rs = 0.313). Our results suggest that serum and synovial fluid CatG and CatK levels could serve as biomarkers for PsA. In PsA patients with synovial fluid crystals, elevated synovial CatG levels demonstrated a sensitivity of 89.54% and a specificity of 86.00% in distinguishing them from PsA patients without crystals. Similarly, elevated synovial CatK levels had a sensitivity of 93.67% and a specificity of 94.34% for distinguishing PsA patients with synovial fluid crystals from those without. Furthermore, the synovial fluid levels of both CatG and CatK showed positive associations with key indicators of disease activity, including the visual analog scale (VAS) (rs = 0.362, rs = 0.391), the disease activity in psoriatic arthritis (DAPSA) (rs = 0.191, rs = 0.182), and the modified composite psoriatic disease activity index (mCPDAI) (rs = 0.378, rs = 0.313). In conclusion, our findings suggest that the serum and synovial fluid levels of CatG and CatK hold promise as potential biomarkers for assessing disease activity in psoriatic arthritis.

This review explores the link between immune interactions and chronic pain, offering new perspectives on treatment. It focuses on Janus kinase (JAK) inhibitors’ potential in pain management. Immune cells’ communication with neurons shapes neuroinflammatory responses, and JAK inhibitors’ effects on pain pathways are discussed, including cytokine suppression and microglial modulation. This review integrates studies from rheumatoid arthritis (RA) pain and central sensitization to highlight connections between immune interactions and pain. Studies on RA joint pain reveal the shift from cytokines to sensitization. Neurobiological investigations into central sensitization uncover shared pathways in chronic pain. Clinical evidence supports JAK inhibitors’ efficacy on pain-related outcomes and their effects on neurons and immune cells. Challenges and future directions are outlined, including interdisciplinary collaboration and dosing optimization. Overall, this review highlights JAK inhibitors’ potential to target immune-mediated pain pathways, underscoring the need for more research on immune–pain connections.

Introduction: Gallstone disease (GSD) is among the most common disorders worldwide. Gallstones are established in up to 15% of the general population. Laparoscopic cholecystectomy (LC) has become the “gold standard” for treatment of GSD but is associated with a higher rate of certain complications, namely, bile duct injury (BDI). Biliary fistulas (BF) are a common presentation of BDI (44.1% of all patients); however, they are mainly external. Post-cholecystectomy internal BF are exceedingly rare. Case report: a 33-year Caucasian female was admitted with suspected BDI after LC. Strasberg type E4 BDI was established on endoscopic retrograde cholangiopancreatography (ERCP). Urgent laparotomy established biliary peritonitis. Delayed surgical reconstruction was planned and temporary external biliary drains were positioned in the right and left hepatic ducts. During follow-up, displacement of the drains occurred with subsequent evacuation of bile through the external fistula, which resolved spontaneously, without clinical and biochemical evidence of biliary obstruction or cholangitis. ERCP established bilio-duodenal fistula between the left hepatic duct (LHD) and duodenum, with a stricture at the level of the LHD. Endoscopic management was chosen with staged dilation and stenting of the fistulous tract over 18 months until fistula maturation and stricture resolution. One year after stent extraction, the patient remains symptom free. Discussion: Management of post-cholecystectomy BDI is challenging. The optimal approach is determined by the level and extent of ductal lesion defined according to different classifications (Strasberg, Bismuth, Hannover). Type E BDI are managed mainly surgically with a delayed surgical approach generally deemed preferable. Only three cases of choledocho-duodenal fistulas following LC BDI currently exist in the literature. Management is controversial, with expectant approach, surgical treatment (biliary reconstruction), or liver transplantation being described. Endoscopic treatment has not been described; however, in the current paper, it proved to be successful. More reports or larger case series are needed to confirm its applicability and effectiveness, especially in the long term.

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment.

Development of energy-efficient and high-performance bioreactors requires progress in methods for assessing the key parameters of the biosynthesis process. With a wide variety of approaches and methods for determining the phase contact area in gas–liquid flows, the question of obtaining its accurate quantitative estimation remains open. Particularly challenging are the issues of getting information about the mass transfer coefficients instantly, as well as the development of predictive capabilities for the implementation of effective flow control in continuous fermentation both on the laboratory and industrial scales. Motivated by the opportunity to explore the possibility of applying classical and non-classical computer vision methods to the results of high-precision video records of bubble flows obtained during the experiment in the bioreactor vessel, we obtained a number of results presented in the paper. Characteristics of the bioreactor’s bubble flow were estimated first by classical computer vision (CCV) methods including an elliptic regression approach for single bubble boundaries selection and clustering, image transformation through a set of filters and developing an algorithm for separation of the overlapping bubbles. The application of the developed method for the entire video filming makes it possible to obtain parameter distributions and set dropout thresholds in order to obtain better estimates due to averaging. The developed CCV methodology was also tested and verified on a collected and labeled manual dataset. An onwards deep neural network (NN) approach was also applied, for instance the segmentation task, and has demonstrated certain advantages in terms of high segmentation resolution, while the classical one tends to be more speedy. Thus, in the current manuscript both advantages and disadvantages of the classical computer vision method (CCV) and neural network approach (NN) are discussed based on evaluation of bubbles’ number and their area defined. An approach to mass transfer coefficient estimation methodology in virtue of obtained results is also represented.

This study proposes a method for detecting small-length fluctuations for fiber-optic sensors (FOS). The method is based on a tracking tandem low-coherence interferometer and enables the ability to compensate for temperature and deformation drifts in FOS. As a result, the constant high sensitivity of FOS over a wide frequency range is guaranteed. Sensitivity to the level of 2 nm in the frequency range of 200 kHz has been demonstrated. The operation of the circuit is demonstrated on the example of the 2D location of acoustic signals using a correlation algorithm for signal processing, known as the time reversal method. It is shown that this system enables us to determine the place of the impact on the sample under the test with an accuracy of about 2 cm using a single sensor.

Photoactive, optically transparent heterostructures from silver nanowires and titanium dioxide were obtained by the sol-gel method on the surface of a polyethylene terephthalate film. The characteristics of optical transmission on the wavelength and those of dielectric permittivity, conductivity and dissipation on frequency in the range of 25–1,000,000 Hz were investigated.

Pancreatic ductal adenocarcinoma remains an aggressive cancer with a low 5-year survival rate. Although gemcitabine has been a standard treatment for advanced pancreatic cancer, patients often develop resistance to this therapeutic. We have previously shown that treating pancreatic cancer cells in vitro with a combination of gemcitabine and the cytokine TRAIL significantly reduced both cell viability and survival. The data presented here demonstrate that this response to treatment is inhibited when cells are incubated with a conditioned medium derived from untreated cells. We show that this inhibition is specifically mediated by extracellular vesicles present in the conditioned medium, as seen by a significant decrease in apoptosis. Additionally, we further demonstrate that this effect can be reversed in the presence of GW4869, an inhibitor of exosome biogenesis and release. These results show that pancreatic cancer cell-derived extracellular vesicles can confer resistance to treatment with gemcitabine and TRAIL. The implications of these findings suggest that removal of EVs during treatment can improve the response of cells to gemcitabine and TRAIL treatment in vitro.

Recently, designers of electronic equipment have paid special attention to the issue of electromagnetic compatibility (EMC) of devices with their own components and assemblies. This is due to the high sensitivity of semiconductor microcircuits to electromagnetic interference. This interference can be caused either by natural phenomena, such as lightning strikes, or by technical processes, such as transients in circuits during fast periodic or random switching. Either way, interference implies a sudden change in voltage or current in a circuit, which is undesirable, whether it propagates along a cable or is transmitted as an electromagnetic wave. The purpose of this article is to review the works devoted to the development, creation, and investigation of modern polymeric nanocomposite materials used for shielding electromagnetic radiation and their effective application for solving problems of electromagnetic compatibility. Additionally, the approach to design EMI shielding complex media with predetermined parameters based on investigation of various properties of possible components is shown. In the review, all polymer composites are classified according to the type of filler. The issues of the interaction of a polymer with conductive fillers, the influence of the concentration of fillers and their location inside the matrix, and the structure of the nanocomposite on the mechanisms of electromagnetic interaction are considered. Particular attention is paid to a new generation of nanocomposite materials with widely adjustable electrical and magnetic properties. A wide class of modern filled polymeric materials with dielectric and magneto-dielectric losses is considered. These materials make it possible to create effective absorbers of electromagnetic waves that provide a low level of reflection coefficient in the microwave range. The model mechanisms for shielding electromagnetic radiation are considered in the paper. A detailed review of the electro-physical properties of polymer nanocomposites is provided. Multilayer electrodynamic media containing combinations of layers of filled polymer composite materials with nanoparticles of different compositions and manufactured using a single technology will make it possible to create electrodynamic media and coatings with the required electro-physical characteristics of absorption, transmission, and reflection. Within the framework of the two-layer coating model, the difference in the effects of the interaction of electromagnetic radiation with conductive layers located on a dielectric and metal substrate is demonstrated. It is shown that in order to achieve optimal (maximum) values of reflection and absorption of electromagnetic radiation in the appropriate frequency range, it is necessary to fit the appropriate layer thicknesses, specific conductivity, and permittivity. Such approach allows designers to create new shielding materials that can effectively vary the shielding, absorbing, and matching characteristics of coatings over a wide frequency band. In general, it can be said that the development of innovative polymer composite materials for shielding electronic devices from electromagnetic interference and excessive electromagnetic background is still an important task. Its solution will ensure the safe and uninterrupted operation of modern digital electronics and can be used for other applications.

Most methane (CH4) and carbon dioxide (CO2) emissions originate from the biodegradation of organic matter of soils and of degrading permafrost in the Arctic. However, there is limited evidence of the activity of geological sources, and little understanding of the pathways of migration of gaseous fluids through the porous mineral matrix filled with ice. We estimated the effect of geological factors on the winter storage of the greenhouse gases in frozen soils by statistical analysis of the geodatabase, which combined a field gas survey of frozen soils, subsurface sounding, and remote sensing data. Frozen soils stored on average 0.016 g CH4 m−3 and 11.5 g CO2 m−3. Microseeps, recognized by isolated anomalies of helium, had 30% higher CH4 concentrations. Lineaments marking margins of tectonic blocks were estimated to have 300% higher CH4 concentrations. High concentrations of propane and ethane indicated the contribution of diffuse fluid flow from hydrocarbon-bearing beds on 95% of the 130 km2 study area. In addition to the fluid contribution, we estimated an overwintering pool of greenhouse gases in frozen soil for the first time. Being at least 0.01–0.1% of the soil organic matter mass, these gaseous forms of carbon can be critical for the early-summer Arctic ecosystem functioning.

Peptidylarginine deiminases (PADs) and extracellular vesicles (EVs) may be indicative biomarkers of physiological and pathological status and adaptive responses, including to diseases and disorders of the central nervous system (CNS) and related to hypoxia. While these markers have been studied in hypoxia-intolerant mammals, in vivo investigations in hypoxia-tolerant species are lacking. Naked mole-rats (NMR) are among the most hypoxia-tolerant mammals and are thus a good model organism for understanding natural and beneficial adaptations to hypoxia. Thus, we aimed to reveal CNS related roles for PADs in hypoxia tolerance and identify whether circulating EV signatures may reveal a fingerprint for adaptive whole-body hypoxia responses in this species. We found that following in vivo acute hypoxia, NMR: (1) plasma-EVs were remodelled, (2) whole proteome EV cargo contained more protein hits (including citrullinated proteins) and a higher number of associated KEGG pathways relating to the total proteome of plasma-EVs Also, (3) brains had a trend for elevation in PAD1, PAD3 and PAD6 protein expression, while PAD2 and PAD4 were reduced, while (4) the brain citrullinome had a considerable increase in deiminated protein hits with hypoxia (1222 vs. 852 hits in normoxia). Our findings indicate that circulating EV signatures are modified and proteomic content is reduced in hypoxic conditions in naked mole-rats, including the circulating EV citrullinome, while the brain citrullinome is elevated and modulated in response to hypoxia. This was further reflected in elevation of some PADs in the brain tissue following acute hypoxia treatment. These findings indicate a possible selective role for PAD-isozymes in hypoxia response and tolerance.

Most of the developing oil and gas fields in Russia are located in Arctic regions and constructed on permafrost, where recent environmental changes cause multiple hazards for their infrastructure. The blowing-up of pingos, resulting in the formation of gas emission craters, is one of the disastrous processes associated both with these external changes and, likely, with deep sources of hydrocarbons. We traced the channels of fluid migration which link a gas features reservoirs with periglacial phenomena associated with such craters with the set of geophysical methods, including common depth point and shallow transient electromagnetic methods, on an area of a prospected gas field. We found correlated vertical anomalies of acoustic coherence and electrical resistivity associated with gas chimneys in the upper 500–600 m of the section. The thickness of the ice-bonded permafrost acting as a seal for fluids decreased in the chimney zone, forming 25–50 m deep pockets in the permafrost base. Three pingos out of six were located above chimneys in the study area of 200 km2. Two lakes with parapets typical for craters were found. We conclude that the combination of applied methods is efficacious in terms of identifying this type of hazard and locating potentially hazardous objects in the given territory.

Various research issues related to soil organic matter in permafrost soils are still poorly investigated. At the same time, numerous investigations have shown the importance of permafrost soils, as they serve as a huge reservoir of organic matter. This work is aimed at the investigation of permafrost-affected soils in the southern part of the Yamal region, namely at the assessment of composition (fractional, elemental and molecular) of soil organic matter in topsoils formed under different biogeoclimatogenic conditions in tundra and forest tundra. Special attention was given to assessment of potential vulnerability of soil organic matter in the context of Arctic warming. Results showed the predominance of fulvic acids in the humus of the studied soils, which indicates mineralization risks in the humic substances system of Arctic soils under conditions of further warming. The 13C-NMR analysis of humic acids revealed that all the studied soils are characterized by higher portions of aliphatic groups of carbon and decreased portions of aromatic groups and revealed early stages of the humification process in studied soils. These results contribute to scarcely distributed research of soil organic matter in permafrost soils of the Arctic. Moreover, our research provided new data on the vulnerability of soil organic matter and its possible mineralization risks under pronounced climate change in the Arctic using the modern instrumental technique.

Climate warming in the Russian Arctic over the past 40 years shows a variety of patterns at different locations and time periods. In the second half of the 20th century, the maximum rates of warming were characteristic of the subarctic permafrost regions of Russia. But in the 21st century, the locations of the greatest rates of climate warming moved to the Arctic zone of Russia. It was one of the reasons for a sharp increase in permafrost temperatures, an increase in the depth of seasonal thaw, and the formation of closed taliks. It was found that as a result of climate change, the differences in permafrost temperatures between different cryogenic landscapes in the area of continuous and discontinuous permafrost distribution have decreased, and in the area of sporadic permafrost distribution are now practically absent. The thermal regime of the ground shows dramatic changes everywhere with a pronounced reduction in the depth of zero annual amplitude.

The role of IFN-α-induced chemokines CCL2, CXCL10 and CCL19 in different forms of SLE has not been studied in Bulgaria, with worldwide sources attributing varying degrees of importance. The aim of this study was to investigate the correlation between IFN-induced chemokines CCL2, CXCL10 and CCL19 and disease activity in patients with SLE over 24 months. Materials and methods: This study used data from 70 patients with SLE (age range 24–62 years) and a control group of 30 healthy volunteers matched for age and gender. Levels of chemokines CCL2, CXCL10 and CCL19 in lupus patients’ serum were measured by ELISA. The study examined clinical and clinical laboratory indicators, as well as measures of disease activity developed for lupus patients (SLEDAI and SLICC). Statistical program SPSS, Version 26 were used for statistical data processing with p < 0.05. At 24 months of follow-up, 12 patients were with deterioration, and they had an IFN-a of 363.76 ± 9.23 versus 116.1 ± 22.1 pg/mL of those who did not worsen, CCL2 278.3 ± 5.12 versus 89.4 ± 12.8, CXCL10 234.2 ± 6.13 versus 115.23 ± 5.9 p CCL19 776.25 ± 5.1 vs. 651.34 ± 9.0 during the first visit. Results: The mean values of CCL2, CXCL10 and CCL19 were higher in patients with SLE compared to healthy controls (p = 0.01). A strong significant association (p = 0.01) was found between the concentration of CCL2, CXCL10 and CCL19 and with patients’ age, disease duration, SLEDAI and SLICC. Conclusion: CCL2, CXCL10 and CCL19 serum levels were found to correlate with patients’ age and disease duration. The level of IFN-induced chemokines CCL2, CXCL10 and CCL19 has a prognostic value in terms of SLE disease activity and degree of organ damage.

The paper proposes a technology based on UV-LIGA process for microoptoelectromechanical systems (MOEMS) manufacturing. We used the original combination of materials and technological steps, in which any of the materials does not enter chemical reactions with each other, while all of them are weakly sensitive to the effects of oxygen plasma. This made it suitable for long-term etching in the oxygen plasma at low discharge power with the complete preservation of the original geometry, including small parts. The micromembranes were formed by thermal evaporation of Al. This simplified the technique compared to the classic UV-LIGA and guaranteed high quality and uniformity of the resulting structure. To demonstrate the complete process, a test MOEMS with electrostatic control was manufactured. On one chip, a set of micromembranes was created with different stiffness from 10 nm/V to 100 nm/V and various working ranges from 100 to 300 nm. All membranes have a flat frequency response without resonant peaks in the frequency range 0–200 kHz. The proposed technology potentially enables the manufacture of wide low-height membranes of complex geometry to create microoptic fiber sensors.

The purple sea urchin (Strongylocentrotus purpuratus) is a marine invertebrate of the class Echinoidea that serves as an important research model for developmental biology, cell biology, and immunology, as well as for understanding regenerative responses and ageing. Peptidylarginine deiminases (PADs) are calcium-dependent enzymes that mediate post-translational protein deimination/citrullination. These alterations affect protein function and may also play roles in protein moonlighting. Extracellular vesicles (EVs) are membrane-bound vesicles that are released from cells as a means of cellular communication. Their cargo includes a range of protein and RNA molecules. EVs can be isolated from many body fluids and are therefore used as biomarkers in physiological and pathological responses. This study assessed EVs present in the coelomic fluid of the purple sea urchin (Strongylocentrotus purpuratus), and identified both total protein cargo as well as the deiminated protein cargo. Deiminated proteins in coelomic fluid EVs were compared with the total deiminated proteins identified in coelomic fluid to assess putative differences in deiminated protein targets. Functional protein network analysis for deiminated proteins revealed pathways for immune, metabolic, and gene regulatory functions within both total coelomic fluid and EVs. Key KEGG and GO pathways for total EV protein cargo furthermore showed some overlap with deimination-enriched pathways. The findings presented in this study add to current understanding of how post-translational deimination may shape immunity across the phylogeny tree, including possibly via PAD activity from microbiota symbionts. Furthermore, this study provides a platform for research on EVs as biomarkers in sea urchin models.

The reindeer (caribou) Rangifer tarandus is a Cervidae in the order Artiodactyla. Reindeer are sedentary and migratory populations with circumpolar distribution in the Arctic, Northern Europe, Siberia and North America. Reindeer are an important wild and domesticated species, and have developed various adaptive strategies to extreme environments. Importantly, deer have also been identified to be putative zoonotic carriers, including for parasites, prions and coronavirus. Therefore, novel insights into immune-related markers are of considerable interest. Peptidylarginine deiminases (PADs) are a phylogenetically conserved enzyme family which causes post-translational protein deimination by converting arginine into citrulline in target proteins. This affects protein function in health and disease. Extracellular vesicles (EVs) participate in cellular communication, in physiological and pathological processes, via transfer of cargo material, and their release is partly regulated by PADs. This study assessed deiminated protein and EV profile signatures in plasma from sixteen healthy wild female reindeer, collected in Iceland during screening for parasites and chronic wasting disease. Reindeer plasma EV profiles showed a poly-dispersed distribution from 30 to 400 nm and were positive for phylogenetically conserved EV-specific markers. Deiminated proteins were isolated from whole plasma and plasma EVs, identified by proteomic analysis and protein interaction networks assessed by KEGG and GO analysis. This revealed a large number of deimination-enriched pathways for immunity and metabolism, with some differences between whole plasma and EVs. While shared KEGG pathways for whole plasma and plasma EVs included complement and coagulation pathways, KEGG pathways specific for EVs were for protein digestion and absorption, platelet activation, amoebiasis, the AGE–RAGE signaling pathway in diabetic complications, ECM receptor interaction, the relaxin signaling pathway and the estrogen signaling pathway. KEGG pathways specific for whole plasma were pertussis, ferroptosis, SLE, thyroid hormone synthesis, phagosome, Staphylococcus aureus infection, vitamin digestion and absorption, and prion disease. Further differences were also found between molecular function and biological processes GO pathways when comparing functional STRING networks for deiminated proteins in EVs, compared with deiminated proteins in whole plasma. This study highlights deiminated proteins and EVs as candidate biomarkers for reindeer health and may provide information on regulation of immune pathways in physiological and pathological processes, including neurodegenerative (prion) disease and zoonosis.

Because of the effort to preserve petroleum resources and promote the development of eco-friendly materials, bio-based polymers produced from sustainable resources have attracted great attention. Among them, polylactide (PLA) and natural rubber (NR) present prominent polymers with unique barrier and mechanical features. A series of samples with improved phase compatibility were obtained by blending PLA and NR using a double-rotor mixer. A plasticizing and enhancing effect on the polymers’ compatibility was achieved by using epoxidized soybean oil (ESO) as a natural plasticizer and compatibilizer. ESO compounding in the PLA-NR blends increased the mobility of the biopolymer’s molecular chains and improved the thermal stability of the novel material. The size of the NR domains embedded in the continuous PLA matrix decreased with the ESO content increment. The combination of thermal analysis and scanning electron microscopy enabled the authors to determine the features of potential packaging material and the optimal content of PLA-NR-ESO for the best mechanical properties.

Extracellular vesicles (EVs) are lipid bilayer vesicles which are released from cells and play multifaceted roles in cellular communication in health and disease. EVs can be isolated from various body fluids, including serum and plasma, and are usable biomarkers as they can inform health status. Studies on EVs are an emerging research field in teleost fish, with accumulating evidence for important functions in immunity and homeostasis, but remain to be characterised in most fish species, including halibut. Protein deimination is a post-translational modification caused by a conserved family of enzymes, named peptidylarginine deiminases (PADs), and results in changes in protein folding and function via conversion of arginine to citrulline in target proteins. Protein deimination has been recently described in halibut ontogeny and halibut serum. Neither EV profiles, nor total protein or deiminated protein EV cargos have yet been assessed in halibut and are reported in the current study. Halibut serum EVs showed a poly-dispersed population in the size range of 50–600 nm, with modal size of EVs falling at 138 nm, and morphology was further confirmed by transmission electron microscopy. The assessment of EV total protein cargo revealed 124 protein hits and 37 deiminated protein hits, whereof 15 hits were particularly identified in deiminated form only. Protein interaction network analysis showed that deimination hits are involved in a range of gene regulatory, immune, metabolic and developmental processes. The same was found for total EV protein cargo, although a far wider range of pathways was found than for deimination hits only. The expression of complement component C3 and C4, as well as pentraxin-like protein, which were identified by proteomic analysis, was further verified in EVs by western blotting. This showed that C3 is exported in EVs at higher levels than C4 and deiminated C3 was furthermore confirmed to be at high levels in the deimination-enriched EV fractions, while, in comparison, C4 showed very low detection in deimination-enriched EV fractions. Pentraxin was exported in EVs, but not detected in the deimination-enriched fractions. Our findings provide novel insights into EV-mediated communication in halibut serum, via transport of protein cargo, including post-translationally deiminated proteins.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with limited survival rate. Roles for peptidylarginine deiminases (PADs) have been studied in relation to a range of cancers with roles in epigenetic regulation (including histone modification and microRNA regulation), cancer invasion, and extracellular vesicle (EV) release. Hitherto though, knowledge on PADs in PDAC is limited. In the current study, two PDAC cell lines (Panc-1 and MiaPaCa-2) were treated with pan-PAD inhibitor Cl-amidine as well as PAD2, PAD3, and PAD4 isozyme-specific inhibitors. Effects were assessed on changes in EV signatures, including EV microRNA cargo (miR-21, miR-126, and miR-221), on changes in cellular protein expression relevant for pancreatic cancer progression and invasion (moesin), for mitochondrial housekeeping (prohibitin, PHB), and gene regulation (deiminated histone H3, citH3). The two pancreatic cancer cell lines were found to predominantly express PAD2 and PAD3, which were furthermore expressed at higher levels in Panc-1, compared with MiaPaCa-2 cells. PAD2 isozyme-specific inhibitor had the strongest effects on reducing Panc-1 cell invasion capability, which was accompanied by an increase in moesin expression, which in pancreatic cancer is found to be reduced and associated with pancreatic cancer aggressiveness. Some reduction, but not significant, was also found on PHB levels while effects on histone H3 deimination were variable. EV signatures were modulated in response to PAD inhibitor treatment, with the strongest effects observed for PAD2 inhibitor, followed by PAD3 inhibitor, showing significant reduction in pro-oncogenic EV microRNA cargo (miR-21, miR-221) and increase in anti-oncogenic microRNA cargo (miR-126). While PAD2 inhibitor, followed by PAD3 inhibitor, had most effects on reducing cancer cell invasion, elevating moesin expression, and modulating EV signatures, PAD4 inhibitor had negligible effects and pan-PAD inhibitor Cl-amidine was also less effective. Compared with MiaPaCa-2 cells, stronger modulatory effects for the PAD inhibitors were observed in Panc-1 cells, which importantly also showed strong response to PAD3 inhibitor, correlating with previous observations that Panc-1 cells display neuronal/stem-like properties. Our findings report novel PAD isozyme regulatory roles in PDAC, highlighting roles for PAD isozyme-specific treatment, depending on cancer type and cancer subtypes, including in PDAC.