bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABA guides stomatal proliferation and patterning through the EPF-SPCH signaling pathway in Arabidopsis thaliana
Authors: Mohamed Deka , Vonapartis Eliana , Corcega Dennedy Yrvin , Gazzarrini Sonia 
Published: November 2023

ABSTRACT
Adaptation to dehydration stress requires plants to coordinate environmental and endogenous signals to inhibit stomatal proliferation and modulate their patterning. The stress hormone abscisic acid (ABA) induces stomatal closure and restricts stomatal lineage to promote stress tolerance. Here, we report that mutants with reduced ABA levels, xer-1, xer-2 and aba2-2, developed stomatal clusters. Similarly, the ABA signaling mutant snrk2.2/2.3/2.6, which lacks core ABA signaling kinases, also displayed stomatal clusters. Exposure to ABA or inhibition of ABA catabolism rescued the increased stomatal density and spacing defects observed in xer and aba2-2, suggesting that basal ABA is required for correct stomatal density and spacing. xer-1 and aba2-2 displayed reduced expression of EPF1 and EPF2, and enhanced expression of SPCH and MUTE. Furthermore, ABA suppressed elevated SPCH and MUTE expression in epf2-1 and epf1-1, and partially rescued epf2-1 stomatal index and epf1-1 clustering defects. Genetic analysis demonstrated that XER acts upstream of the EPF2-SPCH pathway to suppress stomatal proliferation, and in parallel with EPF1 to ensure correct stomatal spacing. These results show that basal ABA and functional ABA signaling are required to fine-tune stomatal density and patterning.
FRL and DAAM are required for lateral adhesion of interommatidial cells and patterning of the retinal floor
Authors: Gazsó-Gerhát Gabriella , Gombos Rita , Tóth Krisztina , Kaltenecker Péter , Szikora Szilárd , Bíró Judit , Csapó Enikő , Asztalos Zoltán , Mihály József 
Published: November 2023

ABSTRACT
Optical insulation of the unit eyes (ommatidia) is an important prerequisite of precise sight with compound eyes. Separation of the ommatidia is ensured by pigment cells that organize into a hexagonal lattice in the Drosophila eye, forming thin walls between the facets. Cell adhesion, mediated by apically and latero-basally located junctional complexes, is crucial for stable attachment of these cells to each other and the basal lamina. Whereas former studies have focused on the formation and remodelling of the cellular connections at the apical region, here, we report a specific alteration of the lateral adhesion of the lattice cells, leaving the apical junctions largely unaffected. We found that DAAM and FRL, two formin-type cytoskeleton regulatory proteins, play redundant roles in lateral adhesion of the interommatidial cells and patterning of the retinal floor. We show that formin-dependent cortical actin assembly is crucial for latero-basal sealing of the ommatidial lattice. We expect that the investigation of these previously unreported eye phenotypes will pave the way toward a better understanding of the three-dimensional aspects of compound eye development.
In toto imaging of glial JNK signaling during larval zebrafish spinal cord regeneration
Authors: Becker Clayton J. , Cigliola Valentina , Gillotay Pierre , Rich Ashley , De Simone Alessandro , Han Yanchao , Di Talia Stefano , Poss Kenneth D. 
Published: November 2023

ABSTRACT
Identification of signaling events that contribute to innate spinal cord regeneration in zebrafish can uncover new targets for modulating injury responses of the mammalian central nervous system. Using a chemical screen, we identify JNK signaling as a necessary regulator of glial cell cycling and tissue bridging during spinal cord regeneration in larval zebrafish. With a kinase translocation reporter, we visualize and quantify JNK signaling dynamics at single-cell resolution in glial cell populations in developing larvae and during injury-induced regeneration. Glial JNK signaling is patterned in time and space during development and regeneration, decreasing globally as the tissue matures and increasing in the rostral cord stump upon transection injury. Thus, dynamic and regional regulation of JNK signaling help to direct glial cell behaviors during innate spinal cord regeneration.
Disparities in dosing, drug reduction, and drug discontinuation among US FDA approved tyrosine kinase inhibitors
Authors: Reddy Neha , Coleman Niamh , Andersen Clark , Yuan Ying , Subbiah Vivek 
Published: November 2023

Background: Tyrosine kinase inhibitors (TKIs) have altered the therapeutic landscape of multiple hematological and solid malignancies. FDA approved starting doses of TKIs are based on the recommended phase 2 dose (RP2D) in clinical trials. However, patients are started on lower doses in practice. We assessed the dosing, drug reduction rates, and drug discontinuation rates among FDA approved TKIs and observed the disparity among study populations to understand if there was adequate representation of diversity in race. Methods: We established a database of all FDA approved TKIs from the FDA online label repository. We extracted descriptive data for indications and usage, type of approval, approval dosage, dose reduction recommendation, median age, race, dose reduction rates, drug discontinuation rates, dose modification, warnings, adverse reactions, clinical trial experience, and geriatric use above 65 yrs and 75 yrs. Results: Among all TKIs, median dose was 200 mg and average dose was 307.7 mg; 36 (24%) were approved bid vs 107 (72%) qd. Among approved indications, median rates of dose reduction rate (DRR), drug interruption rate (DIR), drug discontinuations rate (DDR) were 31%, 52%, and 10% respectively. Reasons for DRR, DIR, and DDR were diarrhea, fatigue, nausea, vomiting, hepatotoxicity, rash, and hypertension. Black and Hispanic races are consistently underrepresented among the TKI studies. Conclusions: TKIs have a variable dose reduction and drug discontinuation rate but these studies were done mostly in White individuals. Clinical trials should evaluate multiple dosing regimens and schedules to lessen the toxicity burden and improve QOL in patients while broadening the study population so that the studies will be generalizable to patients in clinical practice. Future studies are warranted to increase representation in the studies to address the disparities.
IMPACT OF POSITIVE CULTURES DURING THE SECOND STAGE OF A TWO-STAGE REPLACEMENT: A SYSTEMATIC REVIEW
Authors: Martos Marta Sabater , Boadas Laia , Trebse Rihard , Marais Leonard , Ruiz Pablo Sanz , Vaznaisiene Danguole , Grenho André , Ferrari Matteo Carlo , Soriano Alex 
Published: November 2023

AimTwo-stage replacement is a frequent procedure in patients with chronic PJI. However, results in the literature after this procedure differ, ranging from 54% to 100% of infection eradication. Positive cultures at reimplantation, when performing the second stage, are perceived as a risk factor for reinfection. This study aims to determine the impact of positive cultures during the second stage on the outcome of patients undergoing a 2-stage septic replacement and the impact of antibiotic holidays between the first and the second stage.MethodWe systematically searched four databases from inception to May 31, 2022. We combined terms related to PJI, joint replacement and culture results. We analysed the risk of failure when positive cultures at second stage and performed a subgroup analysis by antibiotic holiday period.ResultsWe included 24 studies with 2387 patients of which 432 had positive cultures during second stage (18.09%). Global failure rate was 18.01% (430 patients). When dividing failure by culture results during second stage, we found that failure in positive group was 37.01% (161/432 patients) and failure in negative group was 13.7% (269/1953 patients). In the meta-analysis (MA) the odds ratio (OR) was 4.047 (95% CI: 2.954–5.544). When performing the subgroup analysis by antibiotic holidays we found that the rate of positive cultures without and with holidays was 21.3% and 16.05%, respectively. Failure rate without holidays was 15% (90/600 patients) and with holidays was 17.3% (202/1165 patients) (p=0.21). Failure in each group was higher when cultures were positive (without holidays, 25% vs 12.2%, p=0.0003, and with holidays 41.1% vs 12.7%, p<0.0001). In the MA we found that those studies in which antibiotic holiday was reported had higher risk of failure when cultures were positive during second stage (OR 4.798 95%IC 3.142–7.325). When studies reported no antibiotic holidays also had a higher risk of failure when cultures where positive (OR 2.225 95%CI 1.103–4.489), though it was lower.ConclusionsThere exists a higher risk of failure after a two-stage septic replacement when cultures are positive during reimplantation. Patients who followed no antibiotic holidays or antibiotic holidays before reimplantation have similar failure rate when cultures are negative. In both groups they have a higher risk of failure when cultures are positive, having higher risk those positive patients in the antibiotic holidays group. Therefore, importance in detecting these patients before reimplantation is crucial to ensure higher survival rates.
THE INFECTED POLYPROPYLENE MESH: WHICH ANTISEPTIC SOLUTION MOST EFFECTIVELY REMOVES BIOFILM?
Authors: Jo Suenghwan , Chao Christina , Khilnani Tyler , Bostrom Mathias , Carli Alberto 
Published: November 2023

AimPolypropylene (PPE) synthetic mesh is increasingly used in knee arthroplasty surgery to salvage a disrupted extensor mechanism. Despite its clinical success, it is associated with a high rate of periprosthetic joint infection (PJI), which is hypothesized to be caused by bacterial biofilm. The purpose of the current study is to describe the progression of PPE-based biofilm formation over time and to determine if intraoperative antiseptic solutions could be used to effectively remove biofilm when treating PJI.MethodCommercially available knotted monofilament PPE mesh1 was cut into 10mm circular shape, immersed in tryptic soy broth (TSB) with methicillin-sensitive staphylococcus aureus and cultured individually in 48-well plates for 10 days to elucidate the biofilm grown on mesh over time. At every 24 hours, a triplicate of samples was retrieved and biofilm on the mesh was dislodged by sonicating at 52 kHz for 15 minutes and quantified by counting colony-forming units (CFUs) after overnight growth. The biofilm growth was also verified using scanning electron microscopy.The effect of saline and antiseptic solutions was verified by exposing 1) 0.05% chlorohexidine gluconate2, 2) acetic acid-based mixture3, 3) diluted povidone-iodine (0.35%), 4) undiluted povidone-iodine (10%)4, and 5) 1:1 combination of 10% povidone-iodine & 3% hydrogen peroxide on immature and mature biofilms for 3 minutes, created by culturing with bacteria for 24 hours and 72 hours respectively. All experiments were performed in quintuples and repeated. Antiseptic treatments that produced a three-log reduction in CFU counts compared to controls were considered clinically significant.ResultsPPE-mesh produced reliable CFU counts at 24 hours and reached peak growth at 72 hours. For immature biofilm, all formulations of povidone-iodine produced significant reductions in CFU counts compared to controls. Although not meeting the established threshold, saline irrigation removed 86.5% of CFUs, while formulation based on chlorohexidine and acetic acid removed 99.2% and 99.7% respectively. For mature biofilm, formulations based on povidone-iodine and acetic acid produced significant reductions in CFU counts.ConclusionsOur findings suggest biofilm may form on mesh as early as 24 hours after bacterial exposure. Povidone-iodine formulations were consistently the most effective in removing biofilm on mesh surfaces. We recommend that surgeons consider using an antiseptic solution, preferably povidone-iodine-based, in addition to regular saline lavage when attempting to salvage a PPE mesh in the setting of PJI.1Marlex mesh (CR Bard, Davol Inc, Warwick, RI), 2Irrisept (Irrimax Corp, Gainesville, FL), 3Bactisure (Zimmer-Biomet, Warsaw, IN), 4Aplicare (Inc, Meriden, CT)
NOBLE METAL-BASED ANTIBACTERIAL IMPLANT COATINGS FOR ARTICULATING IMPLANT SURFACES
Authors: van Hoogstraten Sanne , Samijo Steven , Geurts Jan , Arts Chris 
Published: November 2023

AimProsthetic joint infections pose a major clinical challenge. Developing novel material surface technologies for orthopedic implants that prevent bacterial adhesion and biofilm formation is essential. Antimicrobial coatings applicable to articulating implant surfaces are limited, due to the articulation mechanics inducing wear, coating degradation, and toxic particle release. Noble metals are known for their antimicrobial activity and high mechanical strength and could be a viable coating alternative for orthopaedic implants [1]. In this study, the potential of thin platinum-based metal alloy coatings was developed, characterized, and tested on cytotoxicity and antibacterial properties.MethodThree platinum-based metal alloy coatings were sputter-coated on medical-grade polished titanium discs. The coatings were characterized using optical topography and scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). Ion release was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Cytotoxicity was tested according to ISO10993-5 using mouse fibroblasts (cell lines L929 and 3T3). Antibacterial surface activity, bacterial adhesion, bacterial proliferation, and biofilm formation were tested with gram-positive Staphylococcus aureus ATCC 25923 and gram-negative Escherichia coli ATCC 25922. Colony forming unit (CFU) counts, live-dead fluorescence staining, and SEM-EDS images were used to assess antibacterial activity.ResultsThree different platinum-based metal alloys consisting of platinum-iridium, platinum-copper, and platinum-zirconium. The coatings were found 80 nm thick, smooth (roughness average < 60 nm), and non-toxic. The platinum-copper coating showed a CFU reduction larger than one logarithm in adherent bacteria compared to uncoated titanium. The other coatings showed a smaller reduction. This data was confirmed by SEM and live-dead fluorescence images, and accordingly, ICP-OES measurements showed low levels of metal ion release from the coatings.ConclusionsThe platinum-copper coating showed low anti-adhesion properties, even with extremely low metal ions released. These platinum-based metal alloy coatings cannot be classified as antimicrobial yet. Further optimization of the coating composition to induce a higher ion release based on the galvanic principle is required and copper looks most promising as the antimicrobial compound of choice.AcknowledgmentsThis publication is supported by the DARTBAC project (with project number NWA.1292.19.354) of the research program NWA-ORC which is (partly) financed by the Dutch Research Council (NWO); and the AMBITION project (with project number NSP20–1-302), co-funded by the PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health to ReumaNederland.
RISK ANALYSIS OF PERIPROSTHETIC KNEE JOINT INFECTION (PJI) IN TOTAL KNEE ARTHROPLASTY AFTER PREOPERATIVE CORTICOSTEROID INJECTION: A SYSTEMATIC REVIEW
Authors: Pérez-Prieto Daniel , Baums Mike , Aquilina Julian , Sleiman Obeida , Geropoulos Georgious , Totlis Trifon 
Published: November 2023

PurposeIntra-articular corticosteroid injection is widely used for symptomatic relief of knee osteoarthritis. However, if pain is not improved which consequences a total knee arthroplasty (TKA), there is a potential risk of post-operative periprosthetic joint infection (PJI). The aim of this study is to investigate whether the use of preoperative intra-articular corticosteroid injection increases the risk of PJI and to investigate a time frame in which the risk of subsequent infection is significantly increased.MethodsA systematic search was performed in PubMed (Medline), Scopus, and the Cochrane Library. Inclusion criteria were original studies investigating the rate of PJI in patients receiving pre-operative intra-articular corticosteroid injection compared to controls.ResultsA total of 380 unique articles were screened. Six studies met the inclusion criteria with 255,627 patients in total. Overall, no statistical significance was observed in the intra-articular infection rate in corticosteroid compared to controls groups. However, intra-articular corticosteroid injections within 3 months prior to TKA were associated with a significantly increased risk of infection (OR: 1.52, 95% CI 1.37–1.67, p < 0.01); this was not observed in the 6-month period (OR: 1.05, 95% CI 0.80–1.39, p = 0.72).ConclusionsPerforming an intra-articular corticosteroid injection within 3 months prior to TKA is associated with a significantly increased risk of PJI. The current evidence supports the safe use of intra-articular corticosteroid injection more than 6 months before TKA. However, additional studies are needed to clarify the risk of PJI after TKA implantation between 3 and 6 months after the last corticoid injection.
IS DÉLAFLOXACINE A THERAPEUTIC OPTION FOR BONE AND JOINT INFECTIONS? A CRIOGO MULTICENTRE RETROSPECTIVE STUDY
Authors: Tessier Eve , d'Epenoux Louise Ruffier , Lartigue Marie-Frédérique , Guerin François , Plouzeau-Jayle Chloé , Tandé Didier , Chenouard Rachel , Bemer Pascale , Corvec Stephane 
Published: November 2023

Abstract BackgroundThe treatment of bone and joint infections (BJI) involving multi-drug resistant bacteria remains a challenge. MDR Staphylococcus epidermidis (MDRSE) clones, resistant to methicillin, clindamycin, levofloxacin, rifampicin and even linezolid, have been reported worldwide. The interest of delafloxacin (DFX), theoretically active on MRSA, remains to be evaluated with respect to MDRSE.PurposeOur objective was to evaluate during a retrospective multicenter study the DFX minimal inhibitory concentrations (MICs) and compare its efficacy between ofloxacin-susceptible and ofloxacin-resistant S. epidermidis clinical strains involved in BJI.MethodsIn this multicenter retrospective study (Reference centers from the West part of France, CRIOGO), 529 strains were collected mostly from BJI. DFX MICs were determined by using a 0.5 Mc Farland bacterial inoculum on Mueller-Hinton agar plates with gradient strips incubated for 24h at 35°C. For S. aureus, breakpoints differentiate skin and soft tissue infections from other infections. Breakpoints followed 2022 EUCAST criteria, with S. aureus values adopted for S. epidermidis.ResultsOf the 529 strains collected, 355 were from prosthetic infections, 159 from synthetic infections and 15 from non-device infections. 152 strains were susceptible to ofloxacin (110 males vs 42 females) and 377 resistant (210 vs 167). As presented in Figure 1, all the ofloxacin-susceptible strains presented a DFX MIC ≤0.006mg/L. Resistant strains presented a double population distribution, with 3.7% categorized susceptible according to skin and soft tissues infections breakpoint, against 88.9% according to other breakpoint infections (0.016 or 0.25mg/L respectively).ConclusionDFX shows excellent activity against ofloxacine-susceptible strains. Concerning the ofloxacin-resistant strains, more than 80% strains or less than 10% can be considered as DFX-susceptible depending on the breakpoints used. Further clinical studies are needed to validate the real breakpoints that must be used in MDRSE BJI, allowing a microbiological cure and a favourable clinical outcome.For any tables or figures, please contact the authors directly.
IMPACT OF ANTIMICROBIAL SUPPRESSION ON LONG-TERM OUTCOME OF STREPTOCOCCAL PERIPROSTHETIC JOINT INFECTIONS
Authors: Dos Santos Maria Virginia , Meller Sebastian , Perka Carsten , Trampuz Andrej , Renz Nora 
Published: November 2023

AimAntimicrobial suppression has shown to significantly improve treatment success of streptococcal periprosthetic joint infection (PJI) compared to 12-week standard antimicrobial therapy, however, only short-term follow-up was investigated. In this study we assessed the impact of suppression on the long-term outcome of streptococcal PJI.MethodConsecutive patients with streptococcal PJI (defined by EBJIS criteria) treated 2009–2021 were prospectively included and allocated into standard and suppression (> 6 months) treatment group. Infection-free survival was assessed with Kaplan-Meier-method and compared between the groups with log rank test. Rates of infection-free, streptococcal infection-free and relapse-free status as well as tolerability of suppression were assessed.ResultsSixty-three PJI episodes (36 knee, 26 hip and one shoulder prosthesis) of patients with a median age of 70 (35–87) years were included. Twenty-seven (43%) were females. Predominant pathogens were S. agalactiae (n=20), S. dysgalactiae (n=18) and S. mitis/oralis (n=13). The main surgical procedures used were two-stage exchange (n=35) and prosthesis retention (n=21). Standard 12-week treatment was administered in 33 patients and suppression in 30 patients, of whom 10 had ongoing suppression and 20 had discontinued antibiotics at time of follow-up. Used oral antibiotics for suppression were amoxicillin (n=29), doxycycline (n=5) and clindamycin (n=2); 6 patients changed antibiotic substance due to side effects. The median follow-up time was 3.9 (0.3–13.3) years. Infection-free survival after 7.5 years was 38% with standard treatment and 62% with suppression (p=0.038). Of all failures, 52% (14/27) were due to streptococci. Suppression was effective in preventing streptococcal infection for the duration of antimicrobial treatment, however, after discontinuation relapses or new infections due to streptococci occurred in 5/20 (25%) patients and infection with any Streptococcus spp. was observed in 9/19 (47%) failures with standard treatment, 5/6 (83%) failures after discontinuing suppression and none during suppression. All failures in patients with ongoing suppression were caused by gram-negative rods.ConclusionAt long-term follow-up, the success rate was superior with suppression compared to standard treatment. Most failures after stopping suppression were caused by streptococci, whereas failures under suppression were caused by aerobic gram-negative rods.