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Ahmed Handhle, 1 Adie Viljoen, 2 Anthony S Wierzbicki 3 1Department of Metabolic Medicine/Chemical Pathology, Addenbrookes Hospital, Cambridge, UK; 2Department of Metabolic Medicine/Chemical Pathology, North & East Hertfordshire Hospitals Trust, Lister Hospital, Hertfordshire, UK; 3Department of Metabolic Medicine/Chemical Pathology, Guy’s & St Thomas’, Hospitals, London, SE1 7EH, UKCorrespondence: Anthony S WierzbickiMetabolic Medicine/Chemical Pathology, St Thomas Hospital, Lambeth Palace Road, London, SE1 7EH, UKTel +44 207 188 1256Email Anthony.Wierzbicki@kcl.ac.UkAbstract: Lipoprotein(a) forms a subfraction of the lipid profile and is characterized by the addition of apolipprotein(a) (apo(a)) to apoB100 derived particles. Its levels are mostly genetically determined inversely related to the number of protein domain (kringle) repeats in apo(a). In epidemiological studies, it shows consistent association with cardiovascular disease (CVD) and most recently with extent of aortic stenosis. Issues with standardizing the measurement of Lp(a) are being resolved and consensus statements favor its measurement in patients at high risk of, or with family histories of CVD events. Major lipid-lowering therapies such as statin, fibrates, and ezetimibe have little effect on Lp(a) levels. Therapies such as niacin or cholesterol ester transfer protein (CETP) inhibitors lower Lp(a) as well as reducing other lipid-related risk factors but have failed to clearly reduce CVD events. Proprotein convertase subtilisin kexin-9 (PCSK9) inhibitors reduce cholesterol and Lp(a) as well as reducing CVD events. New antisense therapies specifically targeting apo(a) and hence Lp(a) have greater and more specific effects and will help clarify the extent to which intervention in Lp(a) levels will reduce CVD events.Keywords: lipoprotein (a), cardiovascular disease, aortic stenosis, apheresis, genetics, lipoprotein turnover, statin, PCSK9, antisense therapy

Oluwayemisi Esan, Anthony S Wierzbicki Department of Metabolic Medicine/Chemical Pathology, Guy’s & St Thomas’ Hospitals, London SE1 7EH, UKCorrespondence: Anthony S WierzbickiDepartment of Chemical Pathology, St. Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UKTel +0207 188 1256Fax +0207 188 7325Email anthony.wierzbicki@kcl.ac.ukAbstract: Severe hypertriglyceridaemia is associated with pancreatitis and chronic pancreatitis-induced diabetes. Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder of lipid metabolism characterised by high levels of triglycerides (TGs) due to failure of chylomicron clearance. It causes repeated episodes of severe abdominal pain, fatigue and attacks of acute pancreatitis. There are few current options for its long-term management. The only universal long-term therapy is restriction of total dietary fat intake to < 10-15% of daily calories (15 to 20g per day). Many patients have been treated with fibrates and statins with a variable response, but many remain susceptible to pancreatitis. Other genetic syndromes associated with hypertriglyceridaemia include familial partial lipodystrophy (FPLD). Targeting apolipoprotein C3 (apoC3) offers the ability to increase clearance of chylomicrons and other triglyceride-rich lipoproteins. Volanesorsen is an antisense oligonucleotide (ASO) inhibitor of apoC3, which reduces TG levels by 70– 80% which has been shown also to reduce rates of pancreatitis and improve well-being in FCS and reduce TGs and improve insulin resistance in FPLD. It is now undergoing licensing and payer reviews. Further developments of antisense technology including small interfering RNA therapy to apoC3 as well as other approaches to modulating triglycerides are in development for this rare disorder.Keywords: triglyceride, pancreatitis, familial chylomicronaemia syndrome, lipoprotein lipase, chylomicron, lipodystrophy, familial partial lipodystrophy, volanesorsen

β-Hairpins formed by the β-amyloid peptide Aβ are building blocks of Aβ oligomers. Three different alignments of β-hairpins have been observed in the structures of Aβ oligomers or fibrils. Differences in β-hairpin alignment likely contribute to the heterogeneity of Aβ oligomers and thus impede their study at high-resolution. Here, we designed, synthesized, and studied a series of β-hairpin peptides derived from Aβ12-40 in one of these three alignments and investigated their solution-phase assembly and folding. These assays reveal the formation of tetramers and octamers that are stabilized by intermolecular hydrogen bonding interactions between Aβ residues 12-14 and 38-40 as part of an extended β-hairpin conformation. X-ray crystallographic studies of one peptide from this series reveal the formation of β-barrel-like tetramers and octamers that are stabilized by edge-to-edge hydrogen bonding and hydrophobic packing. Dye-leakage and caspase 3/7 activation assays using tetramer and octamer forming peptides from this series reveal membrane-damaging and apoptotic properties. A molecular dynamics simulation of the β-barrel-like tetramer embedded in a lipid bilayer shows membrane disruption and water permeation. The tetramers and octamers described herein provide additional models of how Aβ may assemble into oligomers and supports the hypothesis that β-hairpin alignment and topology may contribute directly to oligomer heterogeneity.

Abstract Introduction Growth differentiation factor 15 (GDF15) is a cytokine of the TGFβ family. Here, we analyzed GDF15 levels in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who participated in OCOG-ALMERA (NCT02115464), a phase II randomized clinical trial, that investigated metformin in combination with standard of care concurrent chemoradiotherapy (cCRT). OCOG-ALMERA was not able to demonstrate benefit in the metformin arm. Therefore, biomarker studies are needed to better define stratification parameters for future trials. Methods Patients were randomized to treatment with platinum-based chemotherapy and concurrent chest radiotherapy (60–66 Gy), with or without metformin (2000 mg/d). The trial collected tumor volume parameters, survival outcomes, and patient blood plasma at baseline, during (weeks 1 and 6) and 6 months after cCRT. Plasma GDF15 levels were assayed with the ELISA method. Statistical analyses explored associations between GDF15, survival outcomes, and radiotherapy tumor volumes. Results Baseline plasma levels of GDF15 were elevated in study patients, they increased during cCRT (p

Here, a recently commissioned five-analyzer Johann spectrometer at the Inner Shell Spectroscopy beamline (8-ID) at the National Synchrotron Light Source II (NSLS-II) is presented. Designed for hard X-ray photon-in/photon-out spectroscopy, the spectrometer achieves a resolution in the 0.5–2 eV range, depending on the element and/or emission line, providing detailed insights into the local electronic and geometric structure of materials. It serves a diverse user community, including fields such as physical, chemical, biological, environmental and materials sciences. This article details the mechanical design, alignment procedures and data-acquisition scheme of the spectrometer, with a particular focus on the continuous asynchronous data-acquisition approach that significantly enhances experimental efficiency.

Abstract Metal-organic frameworks (MOFs) are highly attractive porous materials with applications spanning the fields of chemistry, physics, biology, and engineering. Their exceptional porosity and structural flexibility have led to widespread use in catalysis, separation, biomedicine, and electrochemistry. Currently, most MOFs are synthesized under equilibrium liquid-phase reaction conditions. Here we show a general and versatile non-equilibrium flame aerosol synthesis of MOFs, in which rapid kinetics of MOF formation yields two distinct classes of MOFs, nano-crystalline MOFs and amorphous MOFs. A key advantage of this far-from-equilibrium synthesis is integration of different metal cations within a single MOF phase, even when this is thermodynamically unfavorable. This can, for example, produce single-atom catalysts and bimetallic MOFs of arbitrary metal pairs. Moreover, we demonstrate that dopant metals (e.g., Pt, Pd) can be exsolved from the MOF framework by reduction, forming nanoclusters anchored on the MOF. A prototypical example of such a material exhibited outstanding performance as a CO oxidation catalyst. This general synthesis route opens new opportunities in MOF design and applications across diverse fields and is inherently scalable for continuous production at industrial scales.

Marta Kutwin,1 Malwina Sosnowska-&Lstrok;awnicka,1 Barbara Nasi&lstrok;owska,2 Agata Lange,1 Mateusz Wierzbicki,1 S&lstrok;awomir Jaworski1 1Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, Poland; 2Institute of Optoelectronics, Military University of Technology, Warsaw, PolandCorrespondence: Marta Kutwin, Email marta_kutwin@sggw.edu.plPurpose: The use of nanotechnology in medicine has gained attention in developing drug delivery systems. GO has the potential to deliver microRNA (miRNA) mimics or antisense structures. MiRNAs regulate gene expression and their dysregulation is implicated in diseases, including cancer. This study aims to observe changes in morphology, viability, mRNA expression of mTOR/PI3K/Akt and PTEN genes in U87, U118, U251, A172 and T98 glioblastoma cells and xenograft models after GO self-assembly with mimic miRNA-7.Methods: Colloidal suspension of graphene oxide (GO) was used for obtaining the GO-mimic miRNA-7 nanosystems by self-assembly method. The ultrastructure, size distribution and ATR-FTIR and UV-Vis spectrum were analyzed. The Zeta potential was measured to verify the stability of obtained nanosystem. The entrapment efficiency, loading capacity and released kinetics of mimic miRNA-7 form GO-mimic miRNA-7 nanosystems were analyzed. The transfection efficiency into the glioblastoma cell lines U87, U118, U251, A172 and T98 of mimic miRNA-7 delivered by GO nanosystems was measure by confocal microscopy and flow cytometry. The changes at mRNA expression level of mTOR, PI3K, AKT1 and PTEN genes was measured by qPCR analysis. The xenograft model of U87 and A172 tumour tissue was performed to analyze the effect at tumor size and volume after GO- mimic miRNA-7 nanosystem administration.Results: The ultrastructure of GO-mimic miRNA-7 nanosystems showed high affinity of mimic miRNA into the GO. The results of transfection efficiency, cell morphology and viability showed that GO -miRNA-7 effectively deliver mimics miRNA-7 into U87, U118, U251, A172 and T98 glioblastoma cells. This approach can reverse miRNA-7 expression’s downstream effects and target the mTOR PI3K/Akt pathway observed at gene expression level, reducing xenograft tumour size and volume.Conclusion: The findings of the study could have significant implications for the development of advanced and precise GO based nanosystems specifically designed for miRNA therapy in cancer treatment.Keywords: GO, micro-RNA, cancer, mTOR/PI3K/Akt

Joanna Cymerys,1,&ast; Michalina Bartak,1,&ast; Anna S&lstrok;o&nacute;ska,1 Agata Lange,2 S&lstrok;awomir Jaworski,2 Marcin Chodkowski,3 Agnieszka Ostrowska,2 Mateusz Wierzbicki,2 Ewa Sawosz,2 Marcin W Ba&nacute;bura1 1Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland; 2Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, Poland; 3Military Institute of Hygiene and Epidemiology, Warsaw, Poland&ast;These authors contributed equally to this workCorrespondence: Joanna Cymerys, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-786, Warsaw, Poland, Email joanna_cymerys@sggw.edu.plBackground: The high infectivity of coronaviruses has led to increased interest in developing new strategies to prevent virus spread. Silver nanoparticles (AgNPs) and graphene oxide (GO) have attracted much attention in the antiviral field. We investigated the potential antiviral activity of GO and AgNPs combined in the nanocomposite GO-Ag against murine betacoronavirus MHV using an in vitro model.Methods: GO, AgNPs, and GO-Ag characterization (size distribution, zeta potential, TEM visualization, FT-IR, and EDX analysis) and XTT assay were performed. The antiviral activity of GO-Ag nanocomposites was evaluated by RT-qPCR and TCID50 assays. The results were compared with free AgNPs and pure GO. Cell growth and morphology of MHV-infected hepatocytes treated with GO-Ag composites were analyzed by JuLI™Br. Immunofluorescence was used to visualize the cell receptor used by MHV. Ultrastructural SEM analysis was performed to examine cell morphology after MHV infection and GO-Ag composite treatment.Results: A significant reduction in virus titer was observed for all nanocomposites tested, ranging from 3.2 to 7.3 log10 TCID50. The highest titer reduction was obtained for GO 5 μg/mL - Ag 25 μg/mL in the post-treatment method. These results were confirmed by RT-qPCR analysis. The results indicate that GO-Ag nanocomposites exhibited better antiviral activity compared to AgNPs and GO. Moreover, the attachment of AgNPs to the GO flake platform reduced their cytotoxicity. In addition, the GO-Ag composite modulates the distribution of the Ceacam1 cell receptor and can modulate cell morphology.Conclusion: Graphene oxide sheets act as a stabilizing agent, inhibiting the accumulation of AgNPs and reducing their cellular toxicity. The GO-Ag composite can physically bind and inhibit murine betacoronavirus from entering cells. Furthermore, the constant presence of GO-Ag can inhibit MHV replication and significantly limit its extracellular release. In conclusion, GO-Ag shows promise as an antiviral coating on solid surfaces to minimize virus transmission and spread. Keywords: graphene oxide, silver nanoparticles, GO-Ag composite, antiviral, coronavirus, MHV

Abstract Background Convenient therapeutic protocols for hepatocellular carcinoma (HCC) are often ineffective due to late diagnosis and high tumor heterogeneity, leading to poor long-term outcomes. However, recently performed studies suggest that using nanostructures in liver cancer treatment may improve therapeutic effects. Inorganic nanoparticles represent a unique material that tend to accumulate in the liver when introduced in-vivo. Typically, this is a major drawback that prevents the therapeutic use of nanoparticles in medicine. However, in HCC tumours, this may be advantageous because nanoparticles may accumulate in the target organ, where the leaky vasculature of HCC causes their accumulation in tumour cells via the EPR effect. On the other hand, recent studies have shown that combining low- and high-LET radiation emitted from the same radionuclide, such as 161Tb, can increase the effectiveness of radionuclide therapy. Therefore, to improve the efficacy of radionuclide therapy for hepatocellular carcinoma, we suggest utilizing radioactive palladium nanoparticles in the form of 109Pd/109mAg in-vivo generator that simultaneously emits β− particles and Auger electrons. Results Palladium nanoparticles with a size of 5 nm were synthesized using 109Pd produced through neutron irradiation of natural palladium or enriched 108Pd. Unlike the 109Pd-cyclam complex, where the daughter radionuclide diffuses away from the molecules, 109mAg remains within the nanoparticles after the decay of 109Pd. In vitro cell studies using radioactive 109Pd nanoparticles revealed that the nanoparticles accumulated inside cells, reaching around 50% total uptake. The 109Pd-PEG nanoparticles exhibited high cytotoxicity, even at low levels of radioactivity (6.25 MBq/mL), resulting in almost complete cell death at 25 MBq/mL. This cytotoxic effect was significantly greater than that of PdNPs labeled with β− (131I) and Auger electron emitters (125I). The metabolic viability of HCC cells was found to be correlated with cell DNA DSBs. Also, successful radioconjugate anticancer activity was observed in three-dimensional tumor spheroids, resulting in a significant treatment response. Conclusion The results indicate that nanoparticles labeled with 109Pd can be effectively used for combined β− - Auger electron-targeted radionuclide therapy of HCC. Due to the decay of both components (β− and Auger electrons), the 109Pd/109mAg in-vivo generator presents a unique potential in this field.

Abstract Background Reduction of inflammation and early detection of complications after surgical procedures are important objectives for proper veterinary practice. This study aimed to evaluate the differences between shelter and pet female cats in selected acute-phase parameters scheduled to ovariohysterectomy. Postoperative monitoring after ovariohysterectomy with the same laboratory parameters was performed in shelter cats, in which two different types of surgical sutures were used for the entire procedure. The experimental group comprised 40 female cats from animal shelters (‘shelter cats,’ n = 40). These cats were divided into two subgroups: group A (n = 20) operated on with absorbable sutures and group NA (n = 20) operated on with non-absorbable sutures. In addition, the same parameters were evaluated in pet female cats (n = 19). Blood was collected from shelter cats immediately before surgery (term 0), at 24 and 72 h (terms 1 and 3, respectively), and at 7 and 14 days (terms 7 and 14, respectively) after ovariohysterectomy. Blood samples from the pet cat group were collected only once. Result The mean haptoglobin concentration before ovariohysterectomy in pet cats was significantly lower than that in shelter cats. Fibrinogen concentration was significantly lower in pet cats than in cats from group A. Serum albumin, beta-1, beta-2, and gamma-globulin concentrations were significantly higher in the shelter cats than in the pet cats. Subcutaneous tissue thickening at the site of the postoperative wound was observed in five patients cats (25%) in group A, and two (10%) cats in the NA group. Conclusion These results indicate that ovariohysterectomy leads to local and general inflammatory responses. The majority of cats from animal shelters suffered from subclinical inflammation.

Abstract Familial chylomicronemia syndrome (FCS) is a rare inherited disorder characterized by severe hypertriglyceridemia, posing a heightened risk of acute pancreatitis. Recently, Volanesorsen, an APOC3 antisense oligonucleotide, gained approval for FCS treatment in the UK. Caution is advised during pregnancy due to limited safety data, although animal studies show no toxicity/teratogenicity. Two case scenarios are presented: In the first case, a patient with FCS continued Volanesorsen injections without having thrombocytopenia during an unplanned pregnancy until third trimester, maintaining triglyceride control. Upon discovering the pregnancy at 38 weeks, Volanesorsen was ceased, and a low‐fat diet reinstated. Despite a heightened risk of pancreatitis, no episodes of pancreatitis occurred during the pregnancy. In the second case, stopping Volanesorsen before conception led to elevated triglycerides, and an episode of acute pancreatitis at 22 weeks, despite strict very low‐fat diet and fibrate therapy from 14 weeks. At 23 weeks, Volanesorsen was reintroduced concurrently with regular therapeutic plasma exchange. No further episodes of pancreatitis occurred. In both case, fetal health was maintained throughout pregnancy, fetal scans revealed no anomalies, and planned C‐sections delivered healthy babies without congenital issues. Both babies are well and developing normally at 24 and 19 months.

Expanding on ideas presented by Danijela Kulezic-Wilson in a chapter of her 2020 book Sound Design Is the New Score, this article explores the nature of “reticent” films both old and new, and it suggests that often it is because their soundtracks have so little to “say” that these films communicate so very, very much.

SBAS systems are applied in precise positioning of UAV. The paper presents the results of studies on the improvement of UAV positioning with the use of the EGNOS+SDCM solutions. In particular, the article focuses on the application of the model of totaling the SBAS positioning accuracy to improve the accuracy of determining the coordinates of UAVs during the realisation of a test flight. The developed algorithm takes into account the position errors determined from the EGNOS and SDCM solutions. as well as the linear coefficients that are used in the linear combination model. The research was based on data from GPS observations and SBAS corrections from the AsteRx-m2 UAS receiver installed on a Tailsitter platform. The tests were conducted in September 2020 in northern Poland. The application of the proposed algorithm that sums up the positioning accuracy of EGNOS and SDCM allowed for the improvement of the accuracy of determining the position of the UAV by 82-87% in comparison to the application of either only EGNOS or SDCM. Apart from that, another important result of the application of the proposed algorithm was the reduction of outlier positioning errors that reduced the accuracy of the positioning of UAV when a single SBAS solution (EGNOS or SDCM) was used. The study also presents the effectiveness of the proposed algorithm in terms of calculating the accuracy of EGNOS+SDCM positioning for the weighted average model. The developed algorithm may be used in research conducted on other SBAS supporting systems.

The modern development of urban areas is related to, among others, the location of industrial facilities on the outskirts of cities. More and more often, commercial buildings are founded on areas that have not been used for construction so far. Such areas include, among others: reclaimed lignite mine banks in the Konin region. The man-made soil is a chaotic mixture of fragments of glacial tills and Pliocene clays, often exceeding 20 m in thickness, which is naturally consolidated over time. Due to the method of formation of the embankment, despite the fact that banks are made of natural soil, their strength and deformation characteristics clearly differ from those characteristic of lithologically similar soils deposited as a result of geological processes. In this case, the use of a standard test approach may overestimate the strength and stiffness of the soil. Due to the complex structure of the bank in-situ tests were used for geotechnical exploration: CPTU and FVT, as well as laboratory tests in a triaxial apparatus and an oedometer. The results were compared with the results of studies conducted in similar naturally deposited soils. The obtained results provide valuable geotechnical characteristics of the embankment soil, which in its large fragments is built of natural soil clasts. The obtained results indicate a relatively small change in the geotechnical properties of the soils incorporated into the embankment within individual clasts of the natural soil (on a local scale) and a clear deterioration in the scale of the entire embankment, treated as the impact zone of building structures.

Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.

Abstract Dietary supplementation of ruminants with fish oil is a strategy for favorably modifying the fatty acid composition of milk fat. This study investigated the effect of supplementing cows’ diet with fish oil after low-temperature crystallisation (LTC-FO) compared to its raw form (FO) on milk yield, milk components (fat, protein, and lactose), and milk fatty acid profile. Twenty-four mid-lactating multiparous Polish Holstein–Friesian cows fed a total-mix ration were randomly assigned to two homogeneous groups (n = 12 cows each) and supplemented with LTC-FO or FO at 1% of dry matter. Milk samples were collected on days 14 and 30 of the 30-day experiment. No significant differences between the groups in terms of milk yield, milk protein, and lactose content were found, however, the fat yield and content decreased in the LTC-FO group. Milk fat from cows in the LTC-FO group contained significantly higher levels of C18:1 trans-11, C18:2 cis-9, trans-11, C18:3n − 3, C20:5, and C22:6, and lower levels of saturated fatty acids compared to the FO group (p

In this study, the authors present a theoretical analysis and experimentally verified methods to improve the Energy Efficiency Design Index (EEDI) of ships. The improvements were studied via the application of an innovative solution of a thruster supplied by a hybrid power system on board a passenger-car ferry. The authors performed sea trials of a ship’s electrical power system supplied by battery packs with diesel generating set power units. The experimental study focused on energy balance and management, which were considered together with related power quality issues. The authors found that the application of an energy storage system to the ferry, such as batteries, with the simultaneous adaption of the operation modes of the electrical power system for current exploitation, significantly improved energy efficiency. Fuel consumption and CO2 emission were reduced, while adequate parameters of electrical power quality were maintained to meet classification standards.

Mateusz Wierzbicki,1 Magdalena Kot,2 Agata Lange,1 Aleksandra Kali&nacute;ska,2 Marcin Go&lstrok;&eogon;biewski,2 S&lstrok;awomir Jaworski1 1Department of Nanobiotechnology, Warsaw University of Life Sciences, Warsaw, 02-786, Poland; 2Animal Breeding Department, Warsaw University of Life Sciences, Warsaw, 02-786, PolandCorrespondence: S&lstrok;awomir Jaworski, Department of Nanobiotechnology, Warsaw University of Life Sciences, Ciszewskiego 8 street, Warsaw, 02-786, Poland, Email slawomir_jaworski@sggw.edu.plPurpose: Mastitis in dairy cows is a worldwide problem faced by dairy producers. Treatment mainly involves antibiotic therapy, however, due to widespread antibiotic resistance among bacteria, such treatments are no longer effective. For this reason, scientists are searching for new solutions to combat mastitis, which is caused by bacteria, fungi, and algae. One of the most promising solutions, nanotechnology, is attracting research due to its biocidal properties. The purpose of this research was to determine the biocidal properties of nanocomposites as a potential alternative to antibiotics in the control of mastitis, as well as to determine whether the use of nanoparticles and what concentration is safe for the breeder and the animal.Patients and Methods: In this study, the effects of Ag, Au, Cu, Fe, and Pt nanoparticles and their complexes were evaluated in relation to the survival of bacteria and fungi isolated from cattle diagnosed with mastitis, their physicochemical properties, and their toxicity to bovine and human mammary epithelial cells BME-UV1 and HMEC (human microvascular endothelial cells). Moreover, E. coli, S. aureus, C. albicans, and Prototheca sp. invasion was assessed using the alginate bead (bioprinted) model. The NPs were tested at concentrations of 25, 12.5, 6.25, 3.125, 1.56 mg/l for Au, Ag, Cu and Fe NPs, and 10, 5, 2.5, 1.25, 0.625 mg/l for Pt.Results: With the exception of Fe and Pt, all exhibited biocidal properties against isolates, while the AgCu complex had the best effect. In addition, nanoparticles showed synergistic effects, while the low concentrations had no toxic effect on BME-UV1 and HMEC cells.Conclusion: Synergistic effects of nanoparticles and no toxicity to bovine and human cells might, in the future, be an effective alternative in the fight against microorganisms responsible for mastitis, and the implementation of research results in practice would reduce the percentage of dairy cows suffering from mastitis. The problem of increasing antibiotic resistance is posing a global threat to human’s and animal’s health, and requires comprehensive research to evaluate the potential use of nanoparticles – especially their complexes – as well as to determine whether nanoparticles are safe for the breeders and the animals. The conducted series of studies allows further consideration of the use of the obtained results in practice, creating a potentially new alternative to antibiotics in the treatment and prevention of mastitis in dairy cattle.Keywords: cattle, mastitis, bacteria, fungi, nanocomposites

Barbara Wójcik, Katarzyna Zawadzka, Ewa Sawosz, Malwina Sosnowska, Agnieszka Ostrowska, Mateusz Wierzbicki Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, 02-786, PolandCorrespondence: Mateusz Wierzbicki, Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Ciszewskiego 8, Warsaw, 02-786, Poland, Tel +48 22 5936676, Email mateusz_wierzbicki@sggw.edu.plIntroduction: Disorganisation of the extracellular matrix (ECM) is strongly connected to tumor progression. Even small-scale changes can significantly influence the adhesion and proliferation of cancer cells. Therefore, the use of biocompatible nanomaterials capable of supporting and partially replenishing degraded ECM might be essential to recover the niche after tumor resection. The objective of this study was to evaluate the influence of graphene, graphene oxide, fullerene, and diamond nanofilms on breast cancer and glioblastoma grade IV cell lines.Methods: Nanomaterials were characterized using SEM and TEM techniques; zeta potential analysis was also performed. Nanofilms of graphene, fullerene, and diamond nanoparticles were also characterized using AFM. The toxicity was tested on breast cancer MDA.MB.231 and glioblastoma grade IV U-87 MG cell lines, using LDH assay and by counting stained dead cells in bioprinted 3D models. The following parameters were analyzed: proliferation, adhesion to the nanofilm, and adhesion to particular ECM components covered with diamond nanoparticles.Results and Discussion: Our studies demonstrated that nanofilms of graphene and diamond nanoparticles are characterized by cell-specific toxicity. Those nanomaterials were non-toxic to MDA.MB.231 cells. After applying bioprinted 3D models, diamond nanoparticles were not toxic for both cell lines. Nanofilms made of diamond nanoparticles and graphene inhibit the proliferation of MDA.MB.231 cells after 48 and 72 hours. Increased adhesion on nanofilm made of diamond nanoparticles was only observed for MDA.MB.231 cells after 30 and 60 minutes from seeding the cells. However, analysis of adhesion to certain ECM components coated with diamond nanoparticles revealed enhanced adhesion to tenascin and vitronectin for both tested cell lines.Conclusion: Our studies show that nanofilm made of diamond nanoparticles is a non-toxic and pro-adhesive nanomaterial that might stabilize and partially replenish the niche after breast tumor resection as it enhances the adhesion of breast cancer cells and inhibits their proliferation.Keywords: 3D models, breast cancer, carbon-based nanomaterials, cytotoxicity, glioblastoma

This article reviews the current state of standardization in specific areas of the medical sector in Poland, focusing on terminology and the unique context of the Polish language. The primary objective was to analyze the existing resources and examine possibilities, challenges, and opportunities associated with integrating Artificial Intelligence, particularly natural language processing methods, into the healthcare system. The additional goal of this review was to place Poland in the international context by comparing the current state of the Polish standardization of healthcare with those of selected countries with more and less developed systems. The exploration highlights the main challenges that impact integration, including the specificity of the language and challenges in transferring knowledge from other languages, lack of communication between parties, and lack of stakeholder involvement in the standardization processes. This review also presents potential solutions to the mentioned challenges and provides insights into future directions, possibilities, proposals, and recommendations for all stakeholders. The practical application of this research extends beyond Poland. Many countries with underrepresented languages face similar challenges in clinical data processing, and the advances in CER for Polish could serve as a model for implementing AI-driven solutions in these regions. By refining CER models and adapting them to diverse linguistic and healthcare contexts, this research can foster improvements in patient care, medical research, and healthcare administration on a global scale.

The integration of advanced image analysis using artificial intelligence (AI) is pivotal for the evolution of autonomous vehicles (AVs). This article provides a thorough review of the most significant datasets and latest state-of-the-art AI solutions employed in image analysis for AVs. Datasets such as Cityscapes, NuScenes, CARLA, and Talk2Car form the benchmarks for training and evaluating different AI models, with unique characteristics catering to various aspects of autonomous driving. Key AI methodologies, including Convolutional Neural Networks (CNNs), Transformer models, Generative Adversarial Networks (GANs), and Vision Language Models (VLMs), are discussed. The article also presents a comparative analysis of various AI techniques in real-world scenarios, focusing on semantic image segmentation, 3D object detection, vehicle control in virtual environments, and vehicle interaction using natural language. Simultaneously, the roles of multisensor datasets and simulation platforms like AirSim, TORCS, and SUMMIT in enriching the training data and testing environments for AVs are highlighted. By synthesizing information on datasets, AI solutions, and comparative performance evaluations, this article serves as a crucial resource for researchers, developers, and industry stakeholders, offering a clear view of the current landscape and future directions in autonomous vehicle image analysis technologies.

Undergraduate and graduate teaching assistants (TAs) are tasked with instructing undergraduate courses with little to no professional development (PD). To better develop PD opportunities, it is important to understand the benefits of improving TAs' self-efficacy and the stressors associated with their roles. This study investigated how stress related to the COVID-19 disruption of the spring 2020 semester affected TAs' self-efficacy. Pre-, mid-, and postsemester surveys of self-efficacy and perceived stress were analyzed along with a structured postsemester interview addressing TAs' stress related to the disruption. Although no relationships were found between self-efficacy and stress, qualitative results indicated that stressors related to changes in and uncertainty around their responsibilities influenced TAs' confidence in their teaching. The results of this study are discussed in relation to PD programs providing experiences with multiple teaching modalities, strategies for time management, and mental health resources.

BackgroundAlthough researchers extensively study the rapid generation and spread of misinformation about the novel coronavirus during the pandemic, numerous other health-related topics are contaminating the internet with misinformation that have not received as much attention. ObjectiveThis study aims to gauge the reach of the most popular medical content on the World Wide Web, extending beyond the confines of the pandemic. We conducted evaluations of subject matter and credibility for the years 2021 and 2022, following the principles of evidence-based medicine with assessments performed by experienced clinicians. MethodsWe used 274 keywords to conduct web page searches through the BuzzSumo Enterprise Application. These keywords were chosen based on medical topics derived from surveys administered to medical practitioners. The search parameters were confined to 2 distinct date ranges: (1) January 1, 2021, to December 31, 2021; (2) January 1, 2022, to December 31, 2022. Our searches were specifically limited to web pages in the Polish language and filtered by the specified date ranges. The analysis encompassed 161 web pages retrieved in 2021 and 105 retrieved in 2022. Each web page underwent scrutiny by a seasoned doctor to assess its credibility, aligning with evidence-based medicine standards. Furthermore, we gathered data on social media engagements associated with the web pages, considering platforms such as Facebook, Pinterest, Reddit, and Twitter. ResultsIn 2022, the prevalence of unreliable information related to COVID-19 saw a noteworthy decline compared to 2021. Specifically, the percentage of noncredible web pages discussing COVID-19 and general vaccinations decreased from 57% (43/76) to 24% (6/25) and 42% (10/25) to 30% (3/10), respectively. However, during the same period, there was a considerable uptick in the dissemination of untrustworthy content on social media pertaining to other medical topics. The percentage of noncredible web pages covering cholesterol, statins, and cardiology rose from 11% (3/28) to 26% (9/35) and from 18% (5/28) to 26% (6/23), respectively. ConclusionsEfforts undertaken during the COVID-19 pandemic to curb the dissemination of misinformation seem to have yielded positive results. Nevertheless, our analysis suggests that these interventions need to be consistently implemented across both established and emerging medical subjects. It appears that as interest in the pandemic waned, other topics gained prominence, essentially “filling the vacuum” and necessitating ongoing measures to address misinformation across a broader spectrum of health-related subjects.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.