bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute expression of human APOBEC3B in mice results in RNA editing and lethality
Authors: Alonso de la Vega Alicia , Temiz Nuri Alpay , Tasakis Rafail , Somogyi Kalman , Salgueiro Lorena , Zimmer Eleni , Ramos Maria , Diaz-Jimenez Alberto , Chocarro Sara , Fernández-Vaquero Mirian , Stefanovska Bojana , Reuveni Eli , Ben-David Uri , Stenzinger Albrecht , Poth Tanja , Heikenwälder Mathias , Papavasiliou Nina , Harris Reuben S. , Sotillo Rocio 
Published: November 2023

Abstract
Background
RNA editing has been described as promoting genetic heterogeneity, leading to the development of multiple disorders, including cancer. The cytosine deaminase APOBEC3B is implicated in tumor evolution through DNA mutation, but whether it also functions as an RNA editing enzyme has not been studied.

Results
Here, we engineer a novel doxycycline-inducible mouse model of human APOBEC3B-overexpression to understand the impact of this enzyme in tissue homeostasis and address a potential role in C-to-U RNA editing. Elevated and sustained levels of APOBEC3B lead to rapid alteration of cellular fitness, major organ dysfunction, and ultimately lethality in mice. Importantly, RNA-sequencing of mouse tissues expressing high levels of APOBEC3B identifies frequent UCC-to-UUC RNA editing events that are not evident in the corresponding genomic DNA.

Conclusions
This work identifies, for the first time, a new deaminase-dependent function for APOBEC3B in RNA editing and presents a preclinical tool to help understand the emerging role of APOBEC3B as a driver of carcinogenesis.
The epidemiology of Helicobacter pylori resistance in a university affiliated hospital: a comparison between two time periods—a cross-sectional design
Authors: Shmuely Haim , Shvartsman Yekaterina , Berdinstein Rita , Yahav Jacob , Melzer Ehud 
Published: November 2023

Abstract
Purpose
During the last few decades, the increased use of various types of antibiotics in the general population caused a significant change in regional Helicobacter pylori (H. pylori) antibiotic resistance. Our aim is to study the changes in H. pylori resistance in patients who had undergone an esophagogastroduodenoscopy (EGD) and susceptibility testing and found positive for H. pylori. The study was conducted in a university affiliated hospital between 2013–2020.

Methods
A cross-sectional study was performed on all consecutive patients who had undergone an EGD and tested positive for H. pylori at the Kaplan Medical Center, Israel. The study period was divided into two sub-periods: 2013–2016 and 2017–2020. Data on age, sex, comorbidities, previous treatments, and antimicrobial susceptibility testing for six antimicrobial agents were compared.

Results
The resistance rates of H. pylori to clarithromycin and dual resistance to clarithromycin and metronidazole were found significantly higher during the late period. Multivariable analysis showed that the later period, older age, and diabetes mellitus were independent predictors for antimicrobial resistance.

Conclusions
Our study has shown that there is an increasing resistance of H. pylori to clarithromycin and metronidazole while its susceptibility is unaffected with time to other antibiotics. More recent cross-sectional studies with larger samples are warranted in order to evaluate the changes in the resistance patterns of H. pylori to various antibiotics with time.
A common mechanism of detoxification for lambda-cyhalothrin and abamectin in Cydia pomonella
Authors: Ju Di , Hu Chao , Li Peirong , Gao Ping , Li Yuting , Yang Xueqing 
Published: November 2023

Abstract
Background
The primary method utilized by orchard owners to combat Cydia pomonella is the application of various chemical insecticides. However, this has resulted in the development of resistance. The resistance mechanisms to insecticides from different chemical classes are diverse but interconnected. Therefore, it is crucial to comprehend the commonalities in these mechanisms to effectively develop strategies for managing resistance.

Materials and methods
To determine whether target-site insensitivity to LCT and AM plays a role in resistance, the sequences of voltage-gated sodium channel (VGSC) and glutamate-gated chloride channel (GluCl) containing the mutation domains were detected. To validate whether similar mechanisms were involved in the detoxification process of lambda-cyhalothrin (LCT) and abamectin (AM) at sublethal doses (specifically LD10 and LD30), cytochrome P450 monooxygenases (P450), glutathione S-transferases (GST), and carboxylesterases (CarE) activities were evaluated after insecticides exposure; synergistic experiments were conducted using piperonyl butoxide (PBO), diethyl maleate (DEM), and triphenyl phosphate (TPP) as inhibitors of P450, GST, and CarE respectively. RNA-sequencing (RNA-Seq) was performed to compare the expression levels of detoxification-related genes between susceptible (SS) and resistant strains.

Results
The best known target-site mutations caused by LCT and AM, including L1014F in VGSC and V263I, A309V, I321T, and G326E in GluCl were not occurred. We observed that PBO had a strong synergistic effect on LCT and AM, while DEM on LCT. The activities of detoxification enzymes increased after insecticide exposures, indicating that the detoxification of LCT was primarily carried out by P450 and CarE enzymes, while P450 and GST enzymes played a major role in the detoxification of AM. A total of 72 P450 genes and 75 CarE genes were identified in the C. pomonella transcriptome, with 43 of these genes (including 11 P450, 3 GST, 10 CarE, 11 ABC transporters, and 8 UDP-glycosyl transferases) being over-expressed in response to both insecticides Interestingly, ABC transporters were predominantly induced by AM treatment, while GST showed higher induction levels with LCT treatment. Furthermore, LCT-resistant strains of C. pomonella exhibited higher levels of induction of detoxification-related genes compared to susceptible strains.

Conclusion
The up-regulation of these detoxification genes is a common metabolic mechanism employed by C. pomonella to counteract the effects of insecticides, although the extent of gene expression change varies depending on the specific insecticide.
REVISION DUE TO PJI INCREASES RISK OF PERIOPERATIVE MYOCARDIAL INJURY AND DEATH IN COMPARISON TO PRIMARY AND NON-PJI REVISION ARTHROPLASTY
Authors: Stuetzle Adrian , Puelacher Christian , Morgenstern Mario , Sendi Parham , Mueller Christian , Clauss Martin 
Published: November 2023

AimPerioperative myocardial infarction/injury (PMI) is a common complication in noncardiac surgery, contributing to postoperative morbidity and mortality. We aimed to identify the risk for PMI in periprosthetic joint infection (PJI) in comparison to primary hip (THA) and knee arthroplasty (TKA) and to non-PJI revision surgery.MethodsPatients undergoing primary/revision THA/TKA at a University Hospital who were eligible for the institutional PMI screening and response program were prospectively included. Revision arthroplasties were divided into 2 groups (PJI revision and non-PJI revision). PJI was defined according to the EBJIS criteria, and included DAIR, one-stage and two-stage revisions. Non-PJI revisions included partial and/or complete exchange of components. The primary endpoint was PMI, secondary endpoints were major adverse cardiovascular events (MACE) and all-cause mortality within 120 days.ResultsThe study population included 673 patients (443 primary THA/TKA, 119 PJI revision, 111 Non-PJI revision) enrolled from 05/2014 to 06/2018. The median age in all groups was 75 years. In primary, non-PJI and PJI revision surgery, 39%, 41% and 50%, respectively were male.PMI occurred in 12% of patients with primary arthroplasty compared to 20% and 35% in non-PJI and PJI revision, respectively (p<0.001 overall), with PJI having a significantly elevated risk over non-PJI revisions (p=0.014). Conversely, in MACE (4% primary vs 9% non-PJI vs 12% PJI, p=0.002) an all-cause mortality (2% primary vs 4% non-PJI vs 9% PJI, p<0.001) no significant difference between PJI and non-PJI revisions was observed. We found no difference for the risk of PMI comparing DAIR vs one-/two-stage PJI revision (p=0.88).In multivariable analysis (primary arthroplasty as reference), significant odds ratios for PMI included PJI (3, 1.7–5.3), coronary artery disease (2.9, 1.9–4.4), chronic heart faiure (1.3, 1.1–1.7) and age (1.1, 1.0–1.1 per each year age). Urgency of surgery, duration of surgery, to the presence of Staphylococcus aureus were not significant. impact on PMI.ConclusionIn PJI, PMI and MACE were 3-times, and death 4.5 times, respectively, more frequently observed than in primary arthroplasty. Also, PJI had the highest odds for PMI (3.0). Orthopaedic surgeons should be aware of the high PMI risk when performing revision surgery. This work confirms the importance of a peri-/postpoperative PMI screening and response program in the field of septic surgery.
CLOSED-INCISIONAL NEGATIVE PRESSURE WOUND THERAPY IN POST-SURGICAL MANAGEMENT OF BONE AND JOINT INFECTIONS
Authors: De Meo Daniele , Martini Paolo , Pennarola Mariafrancesca , Candela Vittorio , Torto Federico Lo , Ceccarelli Giancarlo , Gumina Stefano , Villani Ciro 
Published: November 2023

AimThere are no studies in literature that analyze the effectiveness of closed-incisional negative pressure wound therapy (ciNPWT) in the treatment of bone and joint infections (BJI). The aim of the study was to evaluate the efficacy and the safety of the application of ciNPWT in the postsurgical wound management of patients with osteoarticular infections.MethodWe conducted a perspective single-center study on patients with BJI treated between 01/2022 and 10/2022 with ciNPWT dressing application at the end of the surgical procedure. All patients were treated by a multidisciplinary team (MDT) approach and operated by the same surgical equipe. Inclusion criteria were: presence of periprosthetic joint infection (PJI), fracture-related infection (FRI), osteomyelitis (OM), septic arthritis (SA) surgically treated, after which ciNPTW was applied over the closed surgical wound. 30 patients (19M, 11F) have been analyzed with mean age of 56,10±17,11 years old; BJIs were all localized in the lower limb (16 PJI, 12 FRI, 1 SA, 1 OM).ResultsWe considered the following clinical local pre-operative parameters: presence of fistula (10 patients, 33,33%), presence of erythema (18 patients, 60%), presence of previous flap in the incisional site (7 patients, 23,33%). In 11 cases (36,67%) more than 3 previous surgical procedures were performed in the surgical site. The following surgical procedures were performed: 8 debridement and implants removal, 7 DAIR, 3 one-stage exchange, 6 two-stage exchange, 3 spacer exchange, 3 resection arthroplasty. Nineteen patients (63,34%) showed no occurrence of any local post-operative complication (erythema, hematoma, wound breakdown, wound blister, necrosis). Seven (23,33%) patients showed the presence of one or more postoperative complications that didn't require additional surgery. We observed four (13,33%) failures, defined as the need for further surgical procedures following the onset of a local complication: two patients had a wound breakdown before wound closure and two had a recurrence of infection after an uneventfully wound closure. All failures were within the group of joint infection (PJI+SA) and were affected by a multi drug resistant pathogen.ConclusionsIn our series four patients required further surgery, but only two cases were related to incisional wound problems, that is consistent with aseptic joint revision surgeries data that are available in literature (3.4%-6.9%)[1-2]. Patients affected by BJI are a group with significant high risk of failure and therefore the use of ciNPWT should be considered. However, randomized clinical trials are needed to establish the superiority of the ciNPWT dressing over the standard one.
THE ROLE OF MACROPHAGES AND INTRACELLULAR SURVIVAL OF STAPHYLOCOCCUS AUREUS: NEW INSIGHTS FROM DIRECT EVALUATION OF HUMAN TISSUE SAMPLES
Authors: Morin Benedict , Tripathi Vishwachi , Iizuka Aya , Clauss Martin , Morgenstern Mario , Baumhoer Daniel , Jantarug Krittapas , Fuentes Pablo Rivera , Kuehl Richard , Bumann Dirk , Khanna Nina 
Published: November 2023

AimStaphylococcus aureus (SA) can cause various infections and is associated with high morbidity and mortality rates of up to 40%. Antibiotic treatment often fails to eradicate SA infections even if the causative strain has been tested susceptible in vitro. The mechanisms leading to this persistence is still largely unknown. In our work, we to reveal SA interactions with host cells that allow SA to persist at the site of infection.MethodWe established a sampling workflow to receive tissue samples from patients requiring surgical debridement due to SA bone-and joint or soft-tissue infections. We developed a multiplex immunofluorescent staining protocol which allowed us to stain for SA, leukocytes, neutrophils, macrophages, B-cells, T-cells, DAPI and cytoplasmatic marker on the same sample slide. Further, distance of SA to cell nuclei was measured. Interaction of immune cells and SA on a single cell level was investigated with high-resolution 3D microscopy. We then validated our findings applying fluorescence-activated cell sorting (FACS) on digested patient samples. Finally, we aimed to reproduce our ex vivo patient results in an in vitro co-culture model of primary macrophages and clinical SA strains, where we used live cell microscopy and high-resolution microscopy to visualize SA-immune cell interactions and a gentamicin protection assay to assess viability of SA.ResultsHere, we revealed that CD68+ macrophages were the immune cells closest to SA with a mean distance of 56μm (SD=36.4μm). Counting the amount of SA, we found in total >7000 single SA in nine patients. Two-thirds of SA were located intracellularly. Two-thirds of the affected immune cells with intracellular SA were macrophages. The distribution of intra- to extracellular SA was independent of ongoing antibiotic therapy and underlying infection type. FACS confirmed these findings. In our co-culture model, intracellular SA remained alive for the whole observation period of eight hours and resided in RAB5+ early phagosomes.ConclusionsOur study suggests an essential role of intracellular survival in macrophages in SA infections. These findings may have major implication for future treatment strategies.
ANTIBIOTIC PROPHYLAXIS FOR ENDOPROSTHETIC REPLACEMENTS IMPLANTED FOR MUSCULOSKELETAL TUMOURS: AN INTERNATIONAL SURVEY OF PRACTICE
Authors: Azamgarhi Tariq , Warren Simon , Ghert Michelle , Gerrand Craig 
Published: November 2023

AimDeep infection following endoprosthetic replacement (EPR) of long bones is a devastating complication occurring in 15% of musculoskeletal tumour patients. The recently published PARITY Trial demonstrated that extending antibiotic prophylaxis from 24 hours to 5 days does not reduce infection rates. However, questions remain about the optimal antibiotic choice and dose.MethodA 23-question multiple-choice questionnaire was designed and piloted through an iterative feedback process until the final version was agreed by all authors. Open and closed-ended questions were used to gather information on practice and Likert-type scale responses were used to grade responses to ascertain surgeon perceptions and preferences. The online survey was sent to all surgeon delegates of the 34th Annual Meeting of the European Musculo-Skeletal Oncology Society in London in October 2022.ResultsAmongst 61 respondents, 43 were based in Europe and 18 outside of Europe. The majority (48/61) had been in clinical practice over 11 years.Antibiotic choice1st or 2nd generation cephalosporins were the first line choice practiced among 49 (80.3%) of respondents. Of these, 39 responded had a 2nd line protocol for beta-lactam allergy which was most commonly clindamycin (18), vancomycin (11) or a combination of a glycopeptide or clindamycin plus gentamicin (4). Respondents changed their first line regimen for radiotherapy in 6/61, chemotherapy in 8/61 and tumour site in 20/61.Re-dosingIntraoperative re-dosing intervals of 1st and 2nd generation cephalosporins ranged from 2 to 8 hourly. Re-dosing for blood loss ranged from never to when 2 litres was lost. Of the 47 respondents, 24 said intraoperative re-dosing is always reliably administered.DurationSix (10%) of 61 respondent routinely cover the intraoperative period only, whereas 30 (49%) give 24 hours, 16 (give 48 hours or longer and 8 continue until surgical drains are removed. 31 of 61 change duration depending on clinical situation. The most common reasons for changing were patient risk factors, soft tissue status and previous radiotherapy. 57/61 surgeons were aware of the PARITY Trial. When these respondents were asked whether they had changed practice based on PARITY, 12 said yes, 24 said no and 21 said they always give 24 hours anyway.ConclusionsAmongst an international cohort of orthopaedic oncology surgeons there was a wide variation in practice. Further research should focus on the optimum choice and re-dosing strategy, which have not been defined.
BACTERIAL RESERVOIR IN DEEPER SKIN IS A POTENTIAL SOURCE FOR SURGICAL SITE AND BIOMATERIAL-ASSOCIATED INFECTIONS
Authors: Pérez Clara Mar Guarch , Riool Martijn , de Boer Leonie , Kloen Peter , Zaat Sebastian 
Published: November 2023

AimThe origin of surgical site and biomaterial-associated infection is still elusive. Microorganisms contaminating the wound may come from the air, the surgical team, or from the skin of the patient. Prior to surgery the skin of patients is disinfected, but bacteria deeper in the skin (e.g. in sweat glands or sebaceous glands), may not be reached. This study aims to assess a potential role of this intracutaneous bacterial reservoir in biomaterial-associated infection.MethodTo study if cutaneous microbiota colonize the wound when released from the skin upon cutting, we isolated, quantified and identified aerobic and anaerobic bacteria from the skin of 99 patients undergoing trauma surgery, before and after skin disinfection, from the knife blades and from the wound directly after the first cut.ResultsNinety-nine percent of the patients were culture-positive before disinfection with chlorhexidine. Of these, 40% were still culture-positive after disinfection. Of these, 54% had a positive culture of the wound after the skin cut. Twenty percent of the patients with a negative culture after disinfection, nevertheless had a positive wound culture after cutting the skin. Staphylococcus epidermidis and Cutibacterium acnes were the most often cultured bacterial species. In 9%, more than 100 bacterial colonies were cultured from the wound, a dose that may cause biomaterial-associated infections.ConclusionsBacteria residing in the skin and not eradicated by disinfection may enter the surgical wound upon cutting, resulting in contamination which may cause a biomaterial-associated infection. Use of two knifes likely reduces the risk of wound contamination.
RISK FACTORS AND OUTCOME OF POLYMICROBIAL PROSTHETIC JOINT INFECTIONS COMPARED TO MONO MICROBIAL: A SINGLE-INSTITUTION REVISION OF 536 PATIENTS
Authors: Martín Ignacio Ortiz , Ortiz Salvador Peñarrubia , Sádaba Estibaliz Torrecilla , García Antonio Blanco , Moreno Jaime Esteban , Rubio Alvaro Auñon 
Published: November 2023

AimTo describe the risk factors, microbiology and treatment outcome polymicrobial prosthetic joint infections (PJI) compared to monomicrobial PJI.MethodsBetween January 2011 and December 2021, a total of 536 patients were diagnosed with PJI at our institution. Clinical records were revised, and 91(16.9%) had an isolation of two or more pathogens. Age, sex, previous conditions, Charlson comorbidity score, previous surgery, PJI diagnosis and surgical and antibiotic treatment, from the index surgery onwards were reviewed and compared between groups.ResultsPolymicrobial PJI success rate was 57.1%, compared to 85.3% of the monomicrobial PJI(p=0.0036). There were no statistically significative differences between acute and chronic infections. In terms of related risk factors, revision surgery(p=0.0002), fracture(p=0.002), tobacco(p=0.0031) and Body Mass Index (BMI) between 20–25(p=0.0021) were associated to monomicrobial PJI, whereas overweight(p=0.005) and obesity(p=0.02) were linked to polymicrobial PJI. Regarding pathogens, the most common microorganism isolated in monomicrobial was S.aureus (33.5%), followed by S. epidermidis(20%) and gram negative bacilli (12.2%); while S. epidermidis(56%), gram negative bacilli (41.8%) and E.colli (30.8%) were the most frequent in the polymicrobial PJI. Enterococci(p=0.0008), S. epidermidis(p=0.007), E.colli (p=0.0008), gram negative bacilli (p=0.00003) and atypical bacteria (p=0.00001) statistically significative linked to polymicrobial PJI; while S.aureus (p=0.018) was related to monomicrobial PJIConclusionPolymicrobial PJI showed worse outcome compared to monomicrobial PJI in our cohort. In terms of risk factors, overweight, obesity and some pathogens like gram negative bacilli, atypical bacteria, enterococci, S. epidermidis and E.colli were associated with Polymicrobial PJI
STRUGGLING WITH A CEFAZOLIN IMPREGNATION PROTOCOL OF BONE CHIPS: THE EFFECT OF THE TIMING OF THE IMPREGNATION AND GAMMA IRRADIATION ON THE CEFAZOLIN RELEASE
Authors: Dendoncker Karen , Putzeys Guy , Cornu Olivier , Nieuwenhuizen Tara , Bertrand Manon , Valster Henriëtte , Croes Kathleen 
Published: November 2023

AimLocal antibiotics released through a carrier is a commonly used technique to prevent infection in orthopaedic procedures. An interesting carrier in aseptic bone reconstructive surgery are bone chips impregnated with AB solution. Systemically administered Cefazolin (CFZ) is used for surgical site infection prophylaxis however in vitro study showed that fresh frozen and processed bone chips impregnated with CFZ solution completely release the CFZ within a few hours. On the other hand irradiated freeze-dried bone chips, treated with supercritical CO2 (scCO2) have been shown to be an efficient carrier for the antibiotics vancomycine or tobramycine.With this pilot study we wanted to investigate if CFZ solution impregnation of bone chips treated with scCO2 shows a more favorable release pattern of CFZ.MethodThe bone chips were prepared using the standard scCO2 protocol and were impregnated with 100 mg/ml cefazolin at different timepoints during the process: before freeze drying (BC type A), after freeze drying (BC type B) and after gamma-irradiation. 0.5g of the impregnated bone grafts were incubated with 5ml of fetal calf serum (FCS) at 37°C. At 2, 4, 6, 8 and 24h of incubation 200µl of eluate was taken for analysis. After 24h the remaining FCS was removed, bone grafts were washed and new FCS (5ml) was added. Consecutive eluate samples were taken at 48, 72 and 96h of incubation.The concentration of CFZ in the eluates was measured with the validated UPLC-DAD method. Analysis was performed in triplicate.ResultsThe mean concentration of CFZ in the eluate obtained from BC type A incubated for 2h was higher compared to BC type B, respectively 581 mg/l and 297 mg/l. However, the elution profile is the same for both types: the CFZ concentration in the eluates drops within the first 24h from 581 mg/l to 365 mg/l (37%) for BC type A and from 297 mg/l to 132 mg/l (56%) for BC type B. After 24h no further significant CFZ release is seen.Impregnation of the bone chips before or after gamma irradiation did not affect this elution profile.ConclusionsBone chips treated with scCO2 show a comparable elution pattern compared to non-scCO2 treated bone chips. AB release depends on the properties of the AB, making it impossible to copy the same impregnation protocol for different antibiotics. The stability of CFZ in solution at 37°C and its release are a major concern when establishing an impregnation protocol with CFZ.