bluuebunny/crossref_metadata_2025_split huggingface dataset:
Znaczenie rekonstrukcji granic reliktowych na przykładzie granicy pomiędzy monarchią austro-węgierską a Imperium Rosyjskim
Authors: Więckowski Marek 
Published: November 2023

In recent times, a process of the deliberate “re-creation” of relict borders has developed, with a view to serving tourist, heritage-related and remembrance functions. These processes have been observed in many European areas. This article pays attention to the “re-creation” of borders and the way this activity supports tourism- and heritage-related objectives now seen to represent a novel function performed by the former borders. The author illustrates the processes by referring to the border once separating the Austro-Hungarian and Russian Empires as one of those associated with Poland’s erasure from the map of Europe for more than a century. Empirical research on the section of that old border drawn from the Vistula River to the present Polish-Ukrainian border shows at least 15 different places related to it, now playing the role of heritage and tourist attractions. The study of 20 information boards associated with these places is able to point to the significance and content of the information being presented, with the three leading themes being: loss of independence as a result of the Partitions; the regaining of Poland’s independence (in 1918) as well as commemoration of the heroes who contributed to it; and information about local determinants regarding border operations and controls, also in the wider context of its significance for everyday life, and consequently the possibilities of crossing the border.
Przebieg granicy kulturowej między chrześcijaństwem zachodnim (łacińskim) i wschodnim (prawosławnym) w Europie i sposoby jej wyznaczania
Authors: Awramiuk-Godun Alina 
Published: November 2023

The cultural boundary between Western (Latin) and Eastern (Orthodox) Christianity is widely regarded as the main line (zone) of civilizational division in Europe. The aim of the article is to present a theoretical approach to the issue of cultural boundaries in spatial terms and to discuss a research procedure for delineating the boundary between Western and Eastern traditions based on the occurrence rate of sacred sites. The article draws attention to the problems associated with the delineation of cultural boundaries and their graphical representation on maps. It discusses the importance of a religious factor in the formation of cultural areas and presents selected views on the course of cultural boundaries in Europe, providing examples of their visualisation. Furthermore, the article discusses potential applications of cartographic methods and GIS tools in the study of cultural phenomena, using the example of the location of Roman Catholic and Orthodox temples in the border area of Poland, Lithuania and Belarus. Contemporary geo-information technologies provide a broad range of possibilities for conducting comprehensive spatial analyses that consider the distribution intensity of places associated with different traditions, e.g. sacred sites. These tools can support studies aimed at delineating the range of cultures while also facilitating the identification of the zonal nature of cultural boundaries.
THE EFFECT OF DURATION OF INFECTION ON THE SUCCESS RATE OF DEBRIDEMENT, ANTIBIOTICS, AND IMPLANT RETENTION IN PATIENTS WITH A FRACTURE-RELATED INFECTION OF THE LOWER LEG
Authors: Sliepen J. , Buijs M.A.S. , Wouthuyzen-Bakker M. , Depypere M. , Rentenaar R.J. , De Vries J.P.P.M. , Onsea J. , Metsemakers W.J. , Govaert G.A.M. , IJpma F.F.A. 
Published: November 2023

AimsFracture-Related Infection (FRI) is a severe complication caused by microbial infection of bone. It is imperative to gain more insight into the potentials and limitations of Debridement, Antibiotics and Implant Retention (DAIR) to improve future FRI treatment. The aims of this study were to: 1) determine how time to surgery affects the success rate of DAIR procedures of the lower leg performed within 12 weeks after the initial fracture fixation operation and 2) evaluate whether appropriate systemic antimicrobial therapy affects the success rate of a DAIR procedure.MethodsThis multinational retrospective cohort study included patients of at least 18-years of age who developed an FRI of the lower leg within 12 weeks after the initial fracture fixation operation, between January 1st 2015 to July 1st 2020. DAIR success was defined by the absence of recurrence of infection, preservation of the affected limb and retention of implants during the initial treatment. The antimicrobial regimen was considered appropriate if the pathogen(s) was susceptible to the given treatment at the correct dose as per guideline. Logistic regression modelling was used to assess factors that could contribute to the DAIR success rate.ResultsA total of 120 patients were included, of whom 70 DAIR patients and 50 non-DAIR patients. Within a median follow-up of 35.5 months, 21.4% of DAIR patients developed a recurrent FRI compared to 12.0% of non-DAIR patients. The DAIR procedure was successful in 45 patients (64.3%). According to the Willenegger and Roth classification, DAIR success was achieved in 66.7% (n=16/24) of patients with an early infection (<2 weeks), 64.4% (n=29/45) of patients with a delayed infection (2–10 weeks) and 0.0% (0/1) of patients with a late infection (>10 weeks). Univariate analysis showed that the duration of infection was not associated with DAIR success in this cohort (p=0.136; OR: 0.977; 95%CI: [0.947–1.007]). However, an appropriate antimicrobial regimen was associated with success of DAIR (p=0.029; OR: 3.231; 95%CI: [1.138–9.506]).ConclusionsAlthough the results should be interpreted with caution, an increased duration of infection was not associated with a decreased success rate of a DAIR procedure in patients with FRI of the lower leg. The results of this study highlight the multifactorial contribution to the success of a DAIR procedure and emphasize the importance of adequate antimicrobial treatment. Therefore, time to surgery should not be the only key-factor when considering a DAIR procedure to treat FRI.
MANAGEMENT AND OUTCOME FOLLOWING SEVERE OSTEOMYELITIS DUE TO PIN SITE INFECTIONS
Authors: Frank Florian , Pomeroy Eoghan , Hotchen Andrew , Stubbs David , Ferguson Jamie , McNally Martin 
Published: November 2023

AimPin site infection (PSI) is a common complication of external fixators. PSI usually presents as a superficial infection which is treated conservatively. This study investigated those rare cases of PSI requiring surgery due to persistent osteomyelitis (OM), after pin removal.MethodIn this retrospective cohort study we identified patients who required surgery for an OM after PSI (Checketts-Otterburn Classification Grade 6) between 2011 and 2021. We investigated patient demographics, aetiology of the OM, pathogen and histology, treatment strategies and complications. Infection was confirmed using the 2018 FRI Consensus Definition. Successful outcome was defined as an infection-free interval of at least 24 months following surgery, which was defined as minimum follow-up.ResultsTwenty-seven patients were treated due to a pin site infection with an osteomyelitis (22 tibias, 2 humeri, 2 calcanei, 1 radius). 85% identified as male and the median age was 53.9 years. Eighteen infections followed external fixation of fractures, with 4 cases after Ilizarov deformity correction, 2 cases followed ankle fusion and 3 after traction pin insertion. Fifteen patients were classified as BACH Uncomplicated and 12 were BACH Complex. The median follow-up was 3.99 years (2.00–8.05 years).Staphylococci were the most common pathogens (16 MSSA, 2 MRSA, 2 CNS). Polymicrobial infections were present in 5 cases (19%).All surgery was performed in a single stage following the same protocol at one institution. This included deep sampling, debridement, implantation of local antibiotics, culture-specific systemic antibiotics and soft tissue closure. Seven patients required flap coverage (6 local, 1 free flap), which was performed in the same operation.25 (93%) patients had a successful outcome after one surgery. Two had recurrence of infection which was successfully treated by repeat of the protocol. One patient suffered a fracture through the operated site after a fall. This healed without infection recurrence. Wound leakage after local antibiotic treatment was seen in 3/27 (11%) of cases. All resolved without treatment.After a minimum of 2 years follow up, all patients were infection free at the site of the former osteomyelitis.ConclusionsOM after PSI is uncommon but has major implications for the patient as 7 out of 27 patients needed flap coverage. This reinforces the need for careful pin placement and pin site care to prevent deep infection. These infections require appropriate surgery, not just curettage. All patients in our cohort were infection-free after a minimum follow-up of 2 years suggesting that this protocol is effective.
RETHINKING THE INOCULUM USED IN ANIMAL MODELS OF IMPLANT-ASSOCIATED OSTEOMYELITIS: THE FORMATION AND APPLICATION OF BACTERIAL AGGREGATES
Authors: Hartmann Katrine Top , Nielsen Regitze Lund , Mikkelsen Freja , Ingmer Hanne , Kvich Lasse Andersson , Aalbaek Bent , Odgaard Anders , Jensen Henrik Elvang , Lichtenberg Mads , Bjarnsholt Thomas , Jensen Louise Kruse 
Published: November 2023

AimTo make an inoculum for induction of Implant-Associated Osteomyelitis (IAO) in pigs based on bacterial aggregates resembling those found on the human skin, i.e. aggregates of 5–15 µm with low metabolic activity. The aggregates were evaluated and compared to a standard planktonic bacterial inoculum.MethodThe porcine Staphylococcus aureus strain S54F9 was cultured in Tryptone Soya Broth for seven days. Subsequently, the culture was filtered through cell strainers with pore sizes of 15 µm and 5 µm, respectively. The fraction of 5–15 µm aggregates in the top of the 5 µm filter was collected as the aggregate-inoculum. The separation of aggregates into different size fractions was evaluated by light microscopy. The metabolism of the aggregate-inoculum and a standard overnight planktonic inoculum was evaluated with isothermal microcalorimetry. In total, six female minipigs were allocated into three groups (n=2), receiving different inoculums. Group A: overnight planktonic inoculum; 104 CFU S. aureus (S54F9), Group B: seven days old 5–15 µm aggregate-inoculum; 104 CFU S. aureus (S54F9), Group C: saline. All inoculums were placed in a pre-drilled implant cavity in the right tibia of the pig and a sterile stainless-steel implant was inserted. The pigs were euthanized seven days after surgery. Postmortem macroscopic pathology, microbiology, computed tomography and histopathology were performed.ResultsThe separation of aggregates into different size fractions was done successfully by the filtering method. Isothermal microcalorimetry showed, a delayed Time-to-peak metabolic activity of the aggregate-inoculum compared to the planktonic inoculum. S. aureus was isolated from subcutis, bone and implants from all animals in groups A and B. Both group A animals showed osteomyelitis at gross inspection with suppuration and sequestration, while groups B and C animals had no macroscopic lesions. From CT scans, both group A animals also showed positive signs of osteomyelitis, i.e., osteolysis, while only one animal in group B did, and none in group C. Histopathological examination of the bones showed more extensive inflammation in group A animals compared to those in group B, which showed more osteoid formation.ConclusionsFormation and separation of low metabolism bacterial aggregates into different size fractions was possible. The aggregates can be used as inoculum in the porcine IAO model, with microbiological re-isolation from both implants and tissue. Furthermore, the aggregates caused a less aggressive IAO, than the planktonic counterparts. Using aggregated bacteria as inoculum appears to be more relevant to the clinical situation of infecting bacteria.
EMERGING ROLES OF THE LONG PENTRAXIN PTX3 IN STAPHYLOCOCCUS AUREUS-DEPENDENT OSTEOMYELITIS
Authors: Parente Raffaella , Possetti Valentina , Granata Valentina , Schiavone Maria Lucia , Strina Dario , Davi Francesca , Menale Ciro , Palagano Eleonora , Filipović Maša , Grčević Danka , Bottazzi Barbara , Mantovani Alberto , Sobacchi Cristina , Inforzato Antonio 
Published: November 2023

AimOsteomyelitis (OM) is a debilitating infection of the bone that originates from hematogenous spreading of microbes or contamination after surgery/fracture. OM is mainly caused by the opportunistic bacterium Staphylococcus aureus (SA), which can evade the host immune response, acquire antibiotic resistance and chronically colonize the musculoskeletal tissue 1,2, yet the underlying molecular and cellular processes are largely unclear. This study aimed to characterize the pathogenetic mechanisms of SA-OM with a focus on the long pentraxin 3 (PTX3), a soluble pattern recognition molecule and bone tissue component that is emerging as a new player in osteoimmunology 3 and a diagnostic marker of periprosthetic joint infections, a common form of OM4.MethodA murine model of OM based on intra-bone injection of SA was developed that closely mimicked surgery/trauma-related OM in humans and allowed addressing the role of PTX3 in gene-modified (Ptx3-/-) animals. Local and systemic infection and inflammation were assessed via microbiology, flow cytometry, histochemistry and microCT techniques.ResultsSA-injected mice developed chronic infection with measurable levels of viable bone-resident bacteria up until 30 days from microbial challenge. The infection was confined to the treated limbs only and accompanied by extensive tissue remodelling. The bacterial load was higher in WT than Ptx3-/- animals at 6 and 14 days from SA injection. Accordingly, WT mice had enhanced systemic inflammation with expanded innate immune compartment in the spleen and increased serum levels of inflammatory cytokines and chemokines. PTX3 levels were higher in SA- than vehicle (PBS)-injected WT animals both in the serum and bone tissue. Furthermore, administration of a PTX3-targeting antibody reduced the bacterial burden in the bones of SA-injected WT mice.ConclusionsIn a mouse model of SA-OM, genetic deficiency of PTX3 protected from infection and inflammation, pointing to this pentraxin as a crucial player in OM pathogenesis and a novel therapeutic target in bone infections.The study was approved by the Italian Ministry of Health (approval n. 520/2019-PR issued on 19/07/2019) and supported by Fondazione Beppe and Nuccy Angiolini.
SYNERGISTIC ACTION OF BACTERIOPHAGE AND VANCOMYCIN IN A CO-DELIVERY HYDROGEL FOR LOCALIZED TREATMENT OF FRACTURE-RELATED INFECTION CAUSED BY METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS
Authors: Chen Baixing , Chittò Marco , Benavente Luis Ponce , Post Virginia , Moreno Mercedes González , Zeiter Stephan , Trampuz Andrej , Wagemans Jeroen , Lavigne Rob , Onsea Jolien , Metsemakers Willem-Jan , Moriarty Fintan 
Published: November 2023

AimBacteriophages are remerging as alternative and adjunctive therapy for fracture-related infection (FRI). However, current administration protocols involve prolonged retention of a percutaneous draining tube with potential risk of developing superinfection. In this study, we applied a cocktail of in vitro evolved biofilm-targeting phages for Methicillin-resistant Staphylococcus aureus (MRSA) in a hydrogel platform co-delivering vancomycin. In vitro synergy and antibiofilm activity was assessed and a subsequent in vivo study was performed in a mouse FRI model with MRSA.MethodTwo evolved bacteriophages (MRSA-R14 and COL-R23) with improved antibiofilm activity against a clinical isolate (MRSA3) were tested in combination with vancomycin and a carboxymethylcellulose (CMC) hydrogel in vitro and in vivo. MRSA3 bacterial biofilms were formed on sterile 4 mm sintered porous glass beads at 37 °C for 24 h. Biofilms were exposed to i-phage cocktail (107 PFU/ml), ii-vancomycin at concentrations of 0.5, 1, 10 and 100 times the MIC, or iii-combination of phage cocktail and vancomycin. Recovered biofilm cells, were quantified by colony counting. The stability and release profiles of phage cocktail and vancomycin in co-delivery hydrogel were assessed in vitro for 8 days and 72 hrs, respectively, and subsequently tested in the treatment of 5-day-old MRSA3 infection of a femoral plate osteotomy in mice.ResultsIn vitro: The cocktail of evolved phages (107 PFU/ml, 1:1) combined with 0.5 MIC vancomycin achieved 99.72% reduction in MRSA3 biofilm in vitro compared to the growth control. This combination was stable in the co-delivery hydrogel over 8 days. The release profile showed that 57% of phages and 80% of vancomycin were released after 72hrs, which was identical to the performance for gels loaded with phage or antibiotic alone. In the in vivo study, the bacterial load from animals that received co-delivery hydrogel and systemic vancomycin was significantly reduced compared to controls, animals that received systemic vancomycin and animals that received co-delivery hydrogel alone (p<0.05).ConclusionsOur study demonstrates the potential of using evolved phages in combination with vancomycin and hydrogel delivery systems for the treatment of MRSA-related infections. Further research in this area may lead to the development of specific therapies for biofilm-related infection.
ANTIBACTERIAL ACTIVITY OF NEW DEVELOPED MULTIELEMENT NANOGRANULAR COATINGS
Authors: De Vecchi Elena , Balzano Vincenzo , Bottagisio Marta , Gavioli Luca 
Published: November 2023

AimAntibacterial activity of coatings based on metal and metal oxide nanoparticles (NPs) often depends on materials and biotic targets resulting in a material-specific killing activity of selected Gram-positive and Gram-negative bacteria, including drug-resistant strains. In this perspective, the NPs loading amount, the relative elemental concentration inside the nanogranular building blocks and the deposition method are of paramount importance when the goal is to widen the antimicrobial spectrum, but at the same time to avoid high levels of metal content to limit undesired toxic effects. Aim of the present study was evaluation of the antimicrobial properties of two multielement nanogranular coatings composed of Titanium-Silver and Copper and of Magnesium-Silver and Copper.MethodTi-Ag-Cu and Mg-Ag-Cu NPs were deposited on circular cover glasses (VWR) by Supersonic Cluster Beam Deposition. Biofilm-producer strains of Staphylococcus aureus (methicillin susceptible and resistant), Staphylococcus epidermidis (methicillin susceptible and resistant), Escherichia coli (fully susceptible and producer of extended spectrum beta lactamases), and Pseudomonas aeruginosa (susceptible and multidrug-resistant) were selected. The abilities of the selected strains to adhere, colonize and produce biofilm on the discs coated with Ti-Ag-Cu or Mg-Ag-Cu NPs were compared to uncoated circular cover glasses which were used as growth control. Cytotoxicity was also evaluated in order to assess the biocompatibility of the newly synthesized NPs.ResultsIn comparison to uncoated controls, both coatings showed significant anti-adhesive properties against S. aureus, S. epidermidis, and E. coli. Reduction in adhesion to Mg-Ag-Cu coated discs was observed also for P. aeruginosa isolates, although differences vs uncoated controls did not reach statistical significance. Biofilm formation was reduced on discs coated with Mg-Ag-Cu compared to Ti-Ag-Cu and, again, coatings had a milder effect on P. aeruginosa, probably due to its exceptional capability of attachment and matrix production. These results were confirmed by the evaluation of bacterial colonization on nanoparticles-coated discs by means of confocal laser scanning microscopy. A viability of 95.8% and 89.4% of cells cultured in the presence of Ti-Ag-Cu and Mg-Ag-Cu discs, respectively, when compared to negative controls was observed, thus excluding cytotoxic effects on eukaryotic cells.ConclusionsThe newly synthesized Ti-Ag-Cu and Mg-Ag-Cu coatings are able to limit bacterial adhesion colonization and biofilm production, thus highlighting the safe use of multi-element families of NPs as new strategies against bacterial attachment to the surface of biomedical implants. However, further studies addressing activity against P. aeruginosa and including a wide number of isolates are warranted.
SHORT-TERM CELECOXIB PROMOTES BONE FORMATION WITHOUT COMPROMISING ANTIBIOTIC EFFICACY IN EARLY ORTHOPAEDIC DEVICE-RELATED INFECTION: EVIDENCE FROM A RAT MODEL
Authors: Mdingi Vuyisa , Gens Lena , Mys Karen , Zeiter Stephan , Marais Leonard , Richards Geoff , Moriarty Fintan , Chitto Marco 
Published: November 2023

AimIn this study we investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a rat model. Specifically, we aimed to measure the impact of NSAID therapy on bone changes, bacterial load, and cytokine levels after treatment with antibiotics. In addition, we compared the effects of long vs short-term celecoxib (a COX-2 inhibitor) treatment on the same outcomes.MethodSkeletally mature female Wistar rats were implanted with Staphylococcus epidermidis-contaminated polyetheretherketone (PEEK) screws (1.5 × 106 CFU per screw) in the proximal right tibia and monitored for 7 days. All animals received subcutaneous antibiotics (rifampicin plus cefazolin) for two weeks from day 7 to 21. In phase I of the study, rats were randomly assigned to receive 28 days of oral treatment with acetylsalicylic acid, ibuprofen, celecoxib, or vehicle control. In phase II, an additional group received seven days of celecoxib treatment from day 0 to 7. After implantation, bone changes were monitored using in vivo micro-CT and histology. Quantitative bacteriology was performed at euthanasia. Plasma samples were collected to measure cytokine levels at four time points (day 0, 6, 20, and 28).ResultsThe combination of antibiotic therapy resulted in treatment success in 85.71% of cases, while the addition of long-term celecoxib treatment reduced it to 45.45%. Long-term celecoxib treatment significantly reduced bone loss (33.85% mean difference [95% CI 14.12–53.58], p=0.0004 on day 6 bone fraction) and periosteal reaction (0.2760 μm mean difference [95% CI 0.2073–0.3448], p<0.0001 on day 14 periosteal thickness) during the early post-infection period compared to the control group. Short-term celecoxib treatment showed similar radiological results, however, there was no significant reduction in treatment success in the celecoxib group (88.9%). No differences in the selected inflammatory markers were observed.ConclusionOur findings highlight the potential benefits of short-term use of celecoxib in improving bone fraction during the early post-infection period without impairing the efficacy of antibiotic therapy. This study suggests that celecoxib may be a useful addition to the multimodal approach to pain management in orthopaedic device-related infections.