Patient-level cost analysis of intensive care unit acquired infections: A prospective cohort study.

INTRODUCTION: Hospital-associated infections (HAIs) are associated with increased mortality and prolonged hospital length-of-stay (LOS). Although some studies have shown that HAIs are associated with increased costs, these studies only used cost estimates, were carried out in a small number of centres, or only in high-income countries. METHODS: We carried out a prospective cohort study in ten Brazilian intensive care units (ICUs) selected from a collaborative platform study (IMPACTO MR). We included all patients aged 18 years or older admitted from October 2019 to December 2021 and who had an ICU LOS of at least two days. The costs were adjusted for official inflation until December 2022 and converted into international dollars using the 2021 purchasing power parity (PPP) conversion rate. We used a propensity score matching method to compare patients with HAIs and patients without HAIs, and patients with and without ventilator-associated pneumonia (VAP), central-line bloodstream infection (CLABSI), catheter-associated urinary tract infection (CA-UTI) and multidrug-resistant (MDR) HAIs. RESULTS: We included 7,953 patients in the study, of whom 574 (7.2%) had an HAI during their ICU stay. After propensity-score matching, patients with HAIs had ICU costs that were more than three times higher than those of patients without HAIs [$ 19,642 (IQR; 12,884-35,134) vs. 6,086 (IQR; 3,268-12,550); p <0.001). Patients with VAP, CLABSI, and CA-UTI, but not with MDR-HAIs also had higher total ICU costs. CONCLUSIONS: HAIs acquired in the ICU are associated with higher ICU costs. These findings were consistent across specific types of infection.

Managing Children and Adolescents with Type 1 Diabetes and Coexisting Celiac Disease: Real-World Data from a Global Survey.

INTRODUCTION: Celiac disease (CD) is among the diseases most commonly associated with type 1 diabetes (T1D). This study aimed to evaluate the worldwide practices and attitudes of physicians involved in pediatric diabetes care regarding diagnosing and managing CD in children with T1D. METHODS: The 30-item survey was conducted between July and December 2023 aimed at targeting pediatricians with special interest in T1D and CD. It was shared by the JENIOUS - young investigators group of the International Society of Pediatric and Adolescent Diabetes (ISPAD) - and the YES - early career group of the European Society for Pediatric Endocrinology (ESPE). RESULTS: Overall, 180 physicians (67.8% female) from 25 countries responded. Among respondents, 62.2% expected sustaining optimal glycemic control in children with T1D and CD (T1D + CD) to be more difficult than in children with T1D alone. Majority (81.1%) agreed that more specific guidelines are needed. The follow-up routine for patients with T1D + CD differed, and one-quarter of physicians scheduled more frequent follow-up checkups for these patients. Seventy percent agreed multidisciplinary outpatient clinics for their follow-up is needed. In the multivariate ordinal logistic regression model, a statistically significant predictor of a higher degree of practice according to ISPAD 2022 guidelines was a higher level of country income (OR = 3.34; p < 0.001). CONCLUSIONS: These results showed variations in physicians' practices regarding managing CD in children with T1D, emphasizing the need for more specific guidelines and intensive education of physicians in managing this population, especially in lower-income countries. Our data also suggest the implementation of multidisciplinary outpatient clinics for their follow-up.

Skin Reactions in Children with Type 1 Diabetes Associated with the Use of New Diabetes Technologies-An Observational Study from a Regional Polish Pediatric Diabetes Center.

The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1-3 years, 100% for IP > 3 years; p < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively.

Vascular Complications in Children and Young People with Type 1 Diabetes: A Worldwide Assessment of Diabetologists' Adherence to International Recommendations.

INTRODUCTION: This global survey evaluated the practices and adherence to international Clinical Practice Consensus Guidelines (CPCG) of physicians involved in pediatric diabetes care regarding screening, prevention and treatment of vascular complications of type 1 diabetes (T1D). METHOD: A web-based survey gathering data about respondents' background, practices related to screening, prevention, and treatment of diabetic nephropathy, retinopathy, neuropathy, and macrovascular diseases and a self-assessment of physicians' knowledge based on the ISPAD CPCG 2018 were shared by ISPAD. RESULTS: We received 175 responses from 62 countries (60% female, median age 42.3 years, 72.0% ISPAD members). Two-thirds of respondents initiated nephropathy and retinopathy screening per CPCG recommendations. Only half of them adhered to recommendations for neuropathy and macrovascular disease risk factors (RFs). Over 85% of respondents used the recommended screening method for nephropathy, retinopathy and macrovascular disease RFs, and only 59% for neuropathy. Lack of access to neuropathy and macrovascular diseases RF screening methods was reported by 22.2% and 11.8% of respondents, respectively. Adherence to recommended screening frequency varied: 92% for nephropathy, around two-thirds for neuropathy and macrovascular disease RFs, and only 17.7% for retinopathy. Most participants aligned their practices for treating T1D complications with CPCG recommendations, except for nephropathy. Significant differences in adherence to CPCG and individuals' financial contributions reflected countries' income levels. Around 50% of the respondents were very familiar with the ISPAD CPCG content. CONCLUSION: Our study highlights global variation in adherence to CPCG for T1D vascular complications, which is influenced by country income and healthcare disparities. It also revealed knowledge gaps among physicians on this critical topic.

Antimalarial Activity of Aqueous Extracts of Nasturtium (Tropaeolum majus L.) and Benzyl Isothiocyanate.

Malaria remains an important and challenging infectious disease, and novel antimalarials are required. Benzyl isothiocyanate (BITC), the main breakdown product of benzyl glucosinolate, is present in all parts of Tropaeolum majus L. (T. majus) and has antibacterial and antiparasitic activities. To our knowledge, there is no information on the effects of BITC against malaria. The present study evaluates the antimalarial activity of aqueous extracts of BITC and T. majus seeds, leaves, and stems. We used flow cytometry to calculate the growth inhibition (GI) percentage of the extracts and BITC against unsynchronized cultures of the chloroquine-susceptible Plasmodium falciparum 3D7 - GFP strain. Extracts and/or compounds with at least 70% GI were validated by IC50 estimation against P. falciparum 3D7 - GFP and Dd2 (chloroquine-resistant strain) unsynchronized cultures by flow cytometry, and the resistance index (RI) was determined. T. majus aqueous extracts showed some antimalarial activity that was higher in seeds than in leaves or stems. BITC's GI was comparable to chloroquine's. BITC's IC50 was similar in both strains; thus, a cross-resistance absence with aminoquinolines was found (RI < 1). BITC presented features that could open new avenues for malaria drug discovery.

High-Pressure Promoted Nazarov-like Electrocyclization Enables Access to trans-4,5-Diamino-cyclopent-2-enones Bearing Electron-Poor Anilines.

Unlike secondary alkyl amines and electron-rich anilines, secondary electron-poor anilines are challenging amine sources to explore the chemical space of Lewis acid-catalyzed condensation-based transformations with furfural. In this work, we report the efficient synthesis of trans-4,5-diamino cyclopentenones (DCP) using a high-pressure promoted Nazarov-like electrocyclization of Stenhouse salts arising from the Sc(III)-catalyzed condensation of furfural with secondary electron-poor anilines. The reaction enables access to otherwise difficult-to-access DCP and compatibility with a large scope of alkyl and aryl secondary amines. A 2- to 18-fold increase in yields for electron-poor anilines was highlighted using this approach in the synthesis of a pharmacologically active compound.

Membranous urethral length is the single independent predictor of urinary continence recovery at 12 months following Retzius-sparing robot-assisted radical prostatectomy.

The influence of anatomical parameters on urinary continence (UC) after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) remains uncharted. Our objective was to evaluate their association with UC at 3, 6 and 12 months post-operatively. Data from patients who underwent RS-RARP were prospectively collected. Continence was defined as no pad use. Anatomic variables were measured on preoperative magnetic resonance imaging (MRI). Regression analyses were performed to identify predictors of UC at each time point. We included 158 patients with a median age of 60 years, most of whom had a localized tumor (≤ cT2). On multivariate analyses, at 3 months post-surgery, urinary incontinence (UI) rises with age, odds ratio (OR) 1.07 [95% confidence interval (CI) 1.004-1.142] and with prostate volume (PV), OR 1.029 (95% CI 1.006-1.052); it reduces with longer membranous urethral length (MUL), OR 0.875 (95% CI 0.780-0.983) and with higher membranous urethral volume (MUV), OR 0.299 (95% CI 0.121-0.737). At 6 months, UI rises with PV, OR 1.033 (95% CI 1.011-1.056) and decreases with MUV, OR 0.1504 (95% CI 0.050-0.444). Significantly, at 12 months post-surgery, the only predictor of UI is MUL, OR 0.830 (95% CI 0.706-0.975), establishing a threshold associated with a risk of UI of 5% (MUL > 15 mm) in opposition to a risk of 25% (MUL < 10 mm). This single institutional study requires external validation. To our knowledge, this is the first prospective cohort study supporting MUL as the single independent predictor of UC at 12 months post-surgery. By establishing MUL thresholds, we enable precise patient counseling.

A Case Study of a Rare Undifferentiated Spindle Cell Sarcoma of the Penis: Establishment and Characterization of Patient-Derived Models.

Rare sarcomas present significant treatment challenges compared to more prevalent soft tissue sarcomas due to limited treatment options and a poor understanding of their biology. This study investigates a unique case of penile sarcoma, providing a comprehensive morphological and molecular analysis. Through the creation of experimental patient-derived models-including patient-derived xenograft (PDX), 3D, and monolayer primary cultures-we successfully replicated crucial molecular traits observed in the patient's tumor, such as smooth muscle actin and CD99 expression, along with specific mutations in genes like TSC2 and FGFR4. These models are helpful in assessing the potential for an in-depth exploration of this tumor's biology. This comprehensive approach holds promise in identifying potential therapeutic avenues for managing this exceedingly rare soft tissue sarcoma.

Topological Kolmogorov complexity and the Berezinskii-Kosterlitz-Thouless mechanism.

Topology plays a fundamental role in our understanding of many-body physics, from vortices and solitons in classical field theory to phases and excitations in quantum matter. Topological phenomena are intimately connected to the distribution of information content that, differently from ordinary matter, is now governed by nonlocal degrees of freedom. However, a precise characterization of how topological effects govern the complexity of a many-body state, i.e., its partition function, is presently unclear. In this paper, we show how topology and complexity are directly intertwined concepts in the context of classical statistical mechanics. We concretely present a theory that shows how the Kolmogorov complexity of a classical partition function sampling carries unique, distinctive features depending on the presence of topological excitations in the system. We confront two-dimensional Ising, Heisenberg, and XY models on several topologies and study the corresponding samplings as high-dimensional manifolds in configuration space, quantifying their complexity via the intrinsic dimension. While for the Ising and Heisenberg models the intrinsic dimension is independent of the real-space topology, for the XY model it depends crucially on temperature: across the Berezkinskii-Kosterlitz-Thouless (BKT) transition, complexity becomes topology dependent. In the BKT phase, it displays a characteristic dependence on the homology of the real-space manifold, and, for g-torii, it follows a scaling that is solely genus dependent. We argue that this behavior is intimately connected to the emergence of an order parameter in data space, the conditional connectivity, which displays scaling behavior. Our approach paves the way for an understanding of topological phenomena emergent from many-body interactions from the perspective of Kolmogorov complexity.

Developmental changes in school burnout: The importance of sleep and problematic Internet use.

INTRODUCTION: School burnout remains a prevalent problem among adolescents; it is associated with low academic achievement and school dropout risk, in turn linked to a whole host of deleterious developmental outcomes. The current longitudinal study sought to better understand the developmental course of school burnout by testing whether poor sleep and problematic internet use each uniquely and additively explained the variance in school burnout over time. METHOD: Data were collected four times over 18 months, 6 months apart from N = 405 adolescents, grades 9 to 11. RESULTS: Sleep quality, but not quantity, was significantly associated with the school burnout intercept (ß = -0.29); no effects were found for the slope. Problematic internet use was also significantly associated with the intercept (ß = .44), but not the slope. In a combined model, both sleep quality and problematic internet use significantly predicted the school burnout intercept. The slope was only predicted by age (ß = -0.21). CONCLUSIONS: The study found partial support for the hypotheses that both poor sleep quality and problematic internet use predicted school burnout, intercept only, not the rate of change. The evidence suggests that school burnout increased across high school; however, the rate of increase slowed with age. In contrast to some previous work, study findings highlight the importance of separately considering both poor sleep and problematic internet use in understanding the development of school burnout during adolescence. N = 229.

In vitro culture of mechanically isolated murine primary follicles in the presence of human platelet lysate PLTMax.

OBJECTIVE: To develop a system for the culture of murine preantral ovarian follicles using Human Serum Albumin (HSA) and Human Platelet Lysate (PLTMax). METHODS: Mechanically isolated preantral follicles (N=146) were obtained from Swiss mice and cultured in DMEM:F12 medium for ten days in a 96-well plate with conical bottom. The medium was supplemented with penicillin, streptomycin, and equine chorionic gonadotropin. Additional proteins were tested in 4 test groups: G1: human serum albumin (HSA), G2: human platelet lysate (PLTM), and G3 and G4: HSA + PLTMax at lower and higher concentrations, respectively. Cellular vitality and oocyte morphology were evaluated on day 11 of culture. RESULTS: The highest follicular growth (3.4 fold) was achieved in HSA (G1), while a significantly lower (1.8 fold) growth was achieved in the presence of PLTM (G2, G4) and even further reduced (1.2 fold) when HSA and PLTM were combined (G3). Cellular vitality was close to 70-80% among the four groups, and the highest number of intact oocytes were found in G1. CONCLUSIONS: PLTM did not improve follicular development and oocyte maturation compared to HSA but preserved cell vitality.

Enhanced Antimalarial Activity of Extracts of Artemisia annua L. Achieved with Aqueous Solutions of Salicylate Salts and Ionic Liquids.

Artemisinin, a drug used to treat malaria, can be chemically synthesized or extracted from Artemisia annua L. However, the extraction method for artemisinin from biomass needs to be more sustainable while maintaining or enhancing its bioactivity. This work investigates the use of aqueous solutions of salts and ionic liquids with hydrotropic properties as alternative solvents for artemisinin extraction from Artemisia annua L. Among the investigated solvents, aqueous solutions of cholinium salicylate and sodium salicylate were found to be the most promising. To optimize the extraction process, a response surface method was further applied, in which the extraction time, hydrotrope concentration, and temperature were optimized. The optimized conditions resulted in extraction yields of up to 6.50 and 6.44 mg·g-1, obtained with aqueous solutions of sodium salicylate and cholinium salicylate, respectively. The extracts obtained were tested for their antimalarial activity, showing a higher efficacy against the Plasmodium falciparum strain compared with pure (synthetic) artemisinin or extracts obtained with conventional organic solvents. Characterization of the extracts revealed the presence of artemisinin together with other compounds, such as artemitin, chrysosplenol D, arteannuin B, and arteannuin J. These compounds act synergistically with artemisinin and enhance the antimalarial activity of the obtained extracts. Given the growing concern about artemisinin resistance, the results here obtained pave the way for the development of sustainable and biobased antimalarial drugs.

Assessing the adductor musculature and jaw mechanics of Proterochampsa nodosa (Archosauriformes: Proterochampsidae) through finite element analysis.

Proterochampsids are a group of South American nonarchosaurian archosauromorphs whose general morphology has been historically likened to that of the extant Crocodylia, which purportedly exhibited similar habits by convergence. Taxa from the genus Proterochampsa, for example, show platyrostral skulls with dorsally faced orbits and external nares and elongated snouts that might indicate a feeding habit similar to that of crocodilians. Nonetheless, some aspects of their craniomandibular anatomy are distinct. Proterochampsa has comparatively larger skull temporal fenestrae, and a unique morphology of the mandibular adductor chamber, with a remarkably large surangular shelf and a fainter retroarticular region in the mandible. In light of this, we conducted biomechanical tests on a 3-dimensional model of Proterochampsa nodosa including the first Finite Element Analysis for proterochampsians and compared it with models of the extant crocodylians Tomistoma schlegelii and Alligator mississippiensis. Our analyses suggested that, despite the differences in adductor chamber, Proterochampsa was able to perform bite forces comparable to those modeled for Alligator and significantly higher than Tomistoma. However, the morphology of the surangular shelf and the adductor chamber of Proterochampsa renders it more prone to accumulate stresses resulting from muscle contraction, when compared with both analogs. The elongated lower jaw of Proterochampsa, like that of Tomistoma, is more susceptible to bending, when compared with Alligator. As a result, we suggest that Proterochampsa might employ anteriorly directed bites only when handling small and soft-bodied prey. In addition, Proterochampsa exemplifies the diversity of arrangements that the adductor musculature adopted in different diverging archosauromorph groups.

Nano-encapsulated Cu(II) complex as a promising insecticidal for Aedes aegypti (Diptera: Culicidae).

Nanoparticle (NP) research is an area of scientific interest with high potential for application in biomedical, optical, and electronic fields. Due to their relatively large surface area compared to their mass, NPs can be more chemically reactive and change their reactive strength or other properties. NP-based drug delivery systems provide transport and an effective and controlled way to release the drugs. This work aimed to study the solubility and biological activity of nano-encapsulated copper metal complexes for the induction of toxicity and mortality in larvae of Aedes aegypti mosquitoes. After the nano-encapsulated metal complexes were prepared, the efficiency of this incorporation was determined by electron paramagnetic resonance, and toxicity bioassays were performed. The polymeric-based PLGA NPs encapsulating metal complexes exhibited high toxicity and specificity for target organisms (insect vectors, i.e., A. aegypti), with relatively less environmental impact and long-term control of their breeding.

Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors.

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3'UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors-highly deadly diseases in urgent need of effective advanced therapies.

A Randomized, Open-Label, Non-inferiority Clinical Trial Assessing 7 Versus 14 Days of Antimicrobial Therapy for Severe Multidrug-Resistant Gram-Negative Bacterial Infections: The OPTIMISE Trial Protocol.

INTRODUCTION: Shorter courses of antimicrobials have been shown to be non-inferior to longer, "traditional" duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. METHODS: This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. PLANNED OUTCOMES: The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. CONCLUSION: The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).

Whipple’s disease-A typical endoscopic finding of a rare disease

A 49-year-old female presented with a 5-month course of diarrhoea, nocturn abdominal pain, asthenia, and weight loss of 30% of her body mass in three months. The patient had also a four-year medical history of bilateral mechanic gonalgy and arthralgias of the metacarpophalangeal and interphalangeal joints, despite treatment with prednisolone. On examination the patient had hyperpigmentation of the face and thorax, low-grade fever, and a BMI of 15,8 Kg/m2. Diarrhoea was documented with watery stools seven times per day despite loperamide, brownish, with no visible blood or mucous. Since the upper GI endoscopy and colonoscopy had no macroscopic abnormalities, the patient underwent a capsule endoscopy, which revealed continuous mucosal lesion with lymphangiectasia, oedema, villous atrophy and areas of denudation with hematinic punctate from the duodenum to the ileum. Diagnosis of Whipple’s Disease was made with typical histology findings in duodenum material and a positive PCR for Tropheryma whipplei. (AU)

Establishment and Comprehensive Molecular Characterization of an Immortalized Glioblastoma Cell Line from a Brazilian Patient.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, with few effective treatment strategies. The research on the development of new treatments is often constrained by the limitations of preclinical models, which fail to accurately replicate the disease's essential characteristics. Herein, we describe the obtention, molecular, and functional characterization of the GBM33 cell line. This cell line belongs to the GBM class according to the World Health Organization 2021 Classification of Central Nervous System Tumors, identified by methylation profiling. GBM33 expresses the astrocytic marker GFAP, as well as markers of neuronal origin commonly expressed in GBM cells, such as ßIII-tubulin and neurofilament. Functional assays demonstrated an increased growth rate when compared to the U87 commercial cell line and a similar sensitivity to temozolamide. GBM33 cells retained response to serum starvation, with reduced growth and diminished activation of the Akt signaling pathway. Unlike LN-18 and LN-229 commercial cell lines, GBM33 is able to produce primary cilia upon serum starvation. In summary, the successful establishment and comprehensive characterization of this GBM cell line provide researchers with invaluable tools for studying GBM biology, identifying novel therapeutic targets, and evaluating the efficacy of potential treatments.

A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex.

Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies. Methods: We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility. Results: ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-ß and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs. Conclusions: Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.