Search Results (303)

Background: Cancer is a major health concern that significantly impacts the global population. Selective chemotherapeutic delivery is needed to improve the efficacy of cancer therapy while minimizing side effects in healthy cells. This study investigated the potential of gold nanoclusters (AuNCs) functionalized with poly(amidoamine) dendrimers (PAMAM) and folic acid (FA) to selectively deliver doxorubicin (DOX) to cancer cells that express the folate receptor (FR). Methods: AuNC synthesis was confirmed via UV–visible and Fourier transform infrared spectroscopy, nanoparticle tracking analysis, and transmission electron microscopy. Folic acid (FA) was incorporated for cell surface receptor targeting, while the triphenylphosphonium cation (TPP⁺) was added to improve mitochondrial localization. Cytotoxicity (MTT), apoptosis, caspase 3/7, mitopotential, and oxidative stress assays were assessed using human MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), Caco-2 (colon adenocarcinoma), MDA-MB-231 (epithelial breast cancer), and the embryonic kidney (HEK293) cells. Results: Favorable DOX loading (>78%), with more than 90% of the drug released at pH 4.5, was achieved. A dose-dependent increase in cytotoxicity was observed, with IC50 values lower in cancer cells than HEK293 cells, indicating selective toxicity and minimal off-target effects. Targeting nanocomplexes produced the best responses in the mitopotential, caspase, and oxidative stress assays in HeLa and MCF-7 cells. Conclusions: The improved cytotoxicity in cancer cells may be due to folate-receptor-mediated cellular uptake, as well as the mitochondrial uptake of TPP⁺ nanocomplexes. This highlighted the potential of the drug–AuNC nanocomplexes to limit systemic side effects, proposing a potential novel strategy for drug delivery to cancer cells. Full article

Spray drift is one of the most significant challenges in the application of Plant Protection Products (PPPs), as it contributes to water, soil, and food contamination and is highly associated with health risks to agricultural workers, bystanders, and rural residents. Spray drift is defined as the fraction of PPP that is carried away from the target area by air currents during application. Factors such as high wind speeds, low relative humidity, and elevated temperatures increase the risk of drift by promoting droplet evaporation and off-target movement. Technological advancements in spraying equipment, such as low-drift and air induction nozzles, have been shown to significantly reduce drift potential. Air induction nozzles mix air with the spray liquid, creating larger droplets that are less susceptible to drift. The primary objective of this study was to quantify the spray drift reduction achieved using cost-effective and easily applicable drift mitigation techniques that do not require specialized and expensive equipment compared to conventional application methods in vineyards under Southern European conditions. Field measurements followed the ISO 22866:2005 protocol, using a conventional axial fan air-assisted sprayer that is commonly used by vineyard farmers in Greece. This study was conducted on Savatiano vines, the most widely cultivated winemaking variety in the Attica region, characterized by its low height. The spraying techniques evaluated as spray drift mitigation measures were one-sided spraying applications of the outer vineyard row; one-sided spraying applications of the two last rows; spraying with closed air assistance on the outer rows; and finally, spraying with the use of air induction nozzles. Results indicated that each technique produced varying amounts of sedimenting drift over distance. Spraying without air assistance consistently generated the lowest levels of drift at almost all distances. While air induction nozzles initially increased drift deposition within the first 4 m, they significantly reduced drift beyond 5 m. These findings demonstrate that simple operational adjustments to conventional vineyard sprayers, particularly reducing or switching off air assistance in outer rows, can substantially decrease spray drift without requiring additional investment in specialized equipment. Overall, spraying without air support achieved the greatest drift reduction across all distances from the vineyard, followed by air induction nozzles, which were equally effective at further distances (past 5 m) but less so near the application area. The results provide practical guidance for vineyard growers seeking low-cost strategies to minimize agricultural input losses, environmental contamination, and improve the sustainability of pesticide applications. Full article

Conventional axial sprayers are poorly suited to orchards located in sensitive contexts (near water bodies, frequented by bystanders) or to large-volume trees. The result is often poor distribution within the canopy leading to more or less effective disease or insect control, off-target drift leading to environmental pollution and economic inefficiency. Trunk microinjection of plant protection products (PPPs) as a target-precise delivery system could greatly reduce the drift and improve the PPPs application. This study investigated the efficacy of five PPPs (flonicamid, spirotetramat, azadirachtin, lambda-cyhalothrin and deltamethrin) microinjected into the trunk of apple trees in 2022, 2023 and 2024 for managing Apple Rosy Aphid (Dysaphis plantaginea). Observations focused on aphid colonization and residue dynamics in buds, leaves and fruits. Under the conditions of the experiments, azadirachtin microinjection significantly reduced autumn infestation from 87 to 100% and spring infestation from 88 to 97%. The results obtained with flonicamid showed greater variability: from 50 to 80% fall infestation reduction and from 26 to 89% spring infestation reduction depending on the strategy and year. Spirotetramat and the two pyrethroids tested did not provide satisfactory control of populations. Residue levels varied by injected compound and the analyzed tissues. This study demonstrated that trunk microinjection could be an effective delivery method for existing PPPs, depending on the active ingredient, for controlling rosy apple aphids in orchards. Full article

Background: Neuropathic pain remains a major unmet clinical challenge. Growing evidence identifies sigma receptors (σRs) as pivotal intracellular modulators of maladaptive stress signaling, positioning them as promising non-opioid targets for chronic pain management. Notably, despite the pleiotropic nature of σRs in regulating diverse cellular pathways—which might theoretically suggest a high risk of off-target effects—current selective antagonists have demonstrated remarkable safety and tolerability profiles. Sigma-1 and sigma-2 receptors (σ1R and σ2R) are molecularly and functionally distinct proteins that regulate neuronal excitability, proteostasis, and neuroimmune communication, all mechanisms that characterize neuronal excitability and cellular stress adaptation. σ1R acts as a ligand-operated molecular chaperone at the mitochondria-associated endoplasmic reticulum membrane. Extensive preclinical data demonstrate that σ1R antagonism attenuates peripheral and central sensitization, suppresses neuroinflammation, and restores opioid analgesic efficacy. These findings are supported by the advanced clinical candidate E-52862, which has shown efficacy and a favorable safety profile in neuropathic pain conditions. σ2R, identified as transmembrane protein 97 (σ2R/TMEM97), functions as a regulator of cholesterol trafficking, lysosomal integrity, and integrated stress response (ISR). σ2R modulation alleviates neuropathic pain by restoring proteostatic balance and reducing ISR-driven neuronal vulnerability rather than directly suppressing excitability. Emerging σ2R ligands such as FEM-1689, UKH-1114, and CM-398 provide compelling proof-of-concept for durable, disease-modifying analgesia. Methods: A structured literature search was conducted using PubMed, Scopus, and Web of Science to identify studies published within the last decade describing σ1R and σ2R/TMEM97 biology, ligand development, and their preclinical or clinical evaluation in neuropathic pain. Reference lists were manually screened to ensure comprehensive coverage. Conclusions: This review synthesizes pharmacology, ligand development, and translational evidence supporting σRs as next-generation targets for neuropathic pain therapy, highlighting convergent roles of σ1R and σ2R in pain chronification and outlining future directions for structure-guided therapeutic strategies. Full article

Lactic acid bacteria (LAB) are pivotal microorganisms in the food industry. Current approaches for functional gene validation and trait improvement in LAB primarily rely on traditional gene editing and homologous recombination techniques. These methods are often cumbersome, inefficient, and time-consuming, hindering the rapid and precise customization of strains. This limitation has, to some extent, constrained the rapid selection and industrial application of functional LAB strains. The engineering of LAB through gene editing technologies has significantly advanced both fundamental and applied research. Among these, CRISPR/Cas gene editing has successfully achieved precise modification of multiple genes in various LAB species. Compared to conventional methods, it offers superior editing efficiency and lower operational costs, opening new avenues for functional gene identification and genetic improvement in LAB. However, the application of exogenous CRISPR/Cas systems in LAB faces technical challenges such as high off-target rates, chromosomal abnormalities, and cytotoxicity. The development of endogenous CRISPR/Cas-based editing tools for LAB provides novel pathways for precise regulation, rational design, and flexible application. This paper first outlines the structural components and mechanistic principles of CRISPR/Cas gene editing tools. It then explores the research progress and applications of both endogenous and exogenous CRISPR/Cas systems in LAB. Finally, it provides an outlook on the future application of CRISPR/Cas gene editing technology in LAB, offering a reference for its implementation in this field. The advent of gene editing technologies has significantly propelled functional gene validation and trait improvement in lactic acid bacteria (LAB), thereby advancing both fundamental research and industrial applications. Notably, the CRISPR/Cas system has emerged as a transformative tool enabling precise genetic modification in diverse LAB species, offering marked improvements in editing efficiency and cost reduction relative to conventional approaches. CRISPR/Cas-based editing strategies in LAB are broadly classified into exogenous and endogenous systems. Exogenous systems operate independently of the host’s native immune repertoire, conferring the advantages of broad strain applicability and high editing efficiency. These systems have been successfully deployed for functional gene characterization, metabolic pathway engineering, such as augmenting antimicrobial production, and probiotic safety enhancement via virulence gene deletion. Conversely, endogenous systems leverage the intrinsic CRISPR/Cas machinery of LAB, offering superior biocompatibility and minimized off-target risks. Notable applications include precise gene knockout and integration using the native Type I-E system in Lacticaseibacillus paracasei. This review provides a concise overview of CRISPR/Cas system architecture and mechanisms, followed by a systematic synthesis of research progress and applications for both exogenous and endogenous systems in LAB. Finally, future directions are outlined to guide the continued development and application of CRISPR/Cas technologies in this field. Full article

Background: Accurate evaluation of the Near Point of Convergence (NPC) is essential for diagnosing and managing convergence insufficiency (CI). Conventional assessment relies on the patient’s verbal feedback and the examiner’s visual observation, making it subjective and examiner-dependent. The AI-based MobileS platform, previously validated for both diagnosis and home-based therapy of CI, enables smartphone-based measurement and visualisation of NPC through eye tracking, without the need for verbal responses or additional equipment. This study, the third stage of our research programme, examined how ophthalmologists interpret NPC data when presented as videos versus AI-derived graphs. Methods: Twenty-two ophthalmologists completed an online questionnaire with 20 NPC test cases from the validated MobileS database, presented as both silent videos and AI-derived graphs. Accuracy was analysed using mixed-effects logistic regression, and continuous error was assessed using clustered bootstrap. Results: Graph-based interpretation showed higher odds of accurate NPC identification than video-based interpretation at the primary ±5 mm threshold (OR = 19.7, 95% CI: 13.50–28.74; p < 0.0001). Absolute error was lower for graphs than videos (Graphs − Videos: −22.73 mm; 95% CI: −26.88 to −18.59; p < 0.0001). “Uncertain” responses occurred in 28.2% of video-based assessments and 0% of graph-based assessments. Off-target errors decreased from 50.2% (videos) to 3.6% (graphs). Conclusions: AI-derived graphs of eye-movement data were associated with improved NPC estimation, suggesting a potential role in supporting clinical and tele-ophthalmology workflows. Full article

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, a genome-editing technology pioneered in 2012, enables the precise correction of deleterious mutations or disruption of disease-causing genes through targeted double-strand breaks (DSBs), offering potential for treating genetic diseases. However, CRISPR/Cas9 can cause off-target cleavage at non-specific DNA sites, leading to unintended insertions or deletions (indels), which limit its safety and applicability despite ongoing improvements in specificity. Recently, prime editing (PE), an advanced CRISPR-derived technology, has been employed with a Cas9 nickase (Cas9n) fused with a reverse transcriptase and a prime editing guide RNA (pegRNA) to enable precise insertions, deletions, and transversions without inducing DSBs, thus reducing risks of indels and chromosomal aberrations. Furthermore, ongoing optimizations, such as improved pegRNA design and enhanced editing efficiency, have expanded the applications of PE in medical therapeutics, agriculture, and fundamental research. This review summarizes recent advancements in the PE system, including optimized pegRNA designs and enzyme engineering for enhanced efficiency and specificity, alongside novel delivery methods. It also evaluates cutting-edge delivery strategies, such as adeno-associated virus (AAV) vectors, lipid nanoparticles (LNPs) and novel extracellular vesicle (EV)-based systems, and explores PE applications in vitro and in vivo, including disease modeling and therapeutic gene correction. Full article

Background: Local delivery after resection of high-grade glioma, particularly glioblastoma (GBM), aims to increase intratumoral drug exposure while limiting systemic toxicity. The only U.S. Food and Drug Administration (FDA)-approved implantable intracranial chemotherapy is the carmustine (1,3-bis[2-chloroethyl]-1-nitrosourea; BCNU)-impregnated polyanhydride wafer (Gliadel wafer), indicated for newly diagnosed high-grade glioma and recurrent GBM. More than two decades of clinical use and randomized data show that intracavitary chemotherapy is feasible and confers a modest survival benefit in carefully selected patients. Nevertheless, Gliadel wafer has not altered the overall poor prognosis of GBM because of biological resistance to nitrosoureas, constrained brain-parenchymal pharmacokinetics, and device-related adverse effects. Objective: The aim is to synthesize clinical and preclinical evidence defining the current limitations of Gliadel wafer and to outline strategies for next-generation local delivery systems, with emphasis on GBM within the broader high-grade glioma setting. Methods: A narrative review of randomized and observational clinical studies, pharmacokinetic studies, and preclinical investigations evaluating Gliadel wafer and potential next-generation local delivery systems in GBM and other high-grade gliomas was performed. Results: The literature delineates key limitations of Gliadel wafer: short diffusion distances and burst-weighted carmustine release, high tumor cell resistance to carmustine due to heterogeneity, and device-related side effects. Emerging approaches to address these limitations include (i) multidrug systems with synergistic effects against GBM cells; (ii) advanced biomaterials that enable controlled and sustained release; and (iii) targeted agents with minimal off-target effects. Testing newer generations of local drug-delivery systems in more predictive translational models, such as patient-derived organoids and spontaneous large-animal glioma models, is essential to maximize the translatability of preclinical studies to human studies. However, broader adoption of spontaneous large-animal glioma models is constrained by ethical oversight, animal-welfare considerations, cost, and limited availability compared with rodent platforms. Conclusions: Next-generation local drug-delivery systems should include multiple synergistic tumor-selective drugs that can be released in a controlled, sustained manner deep into the residual tumor. Preclinical testing of these systems should be conducted in clinically relevant animal models that are more translatable than those used in early Gliadel wafer studies. Full article

Prime editing (PE) is a precise genome-editing technology that avoids double-strand breaks, holding great promise for clinical and agricultural applications. However, its genome-wide off-target effects are not fully understood, raising safety concerns. Here, we systematically compared the safety profiles of four prime editor variants (PE2max, PE3max, PE4max, and PE5max) using PEM-seq and RNA-seq. We further applied an ultra-sensitive method, Genome-wide Off-target analysis by Two-cell embryo Injection (GOTI), to assess PE5max. Our results show that PE5max did not produce detectable sgRNA-dependent off-target single-nucleotide variants (SNVs) in the GOTI assay and induced only limited large deletions and chromosomal translocations. Collectively, this side-by-side benchmarking under matched conditions demonstrates that PE5max achieves an improved specificity profile, with no detectable increase in genome-wide off-target SNVs, advancing its potential for safer therapeutic use. Full article

Background/Objectives: CEU-938, an innovative antimicrotubule prodrug bioactivated by cytochrome P450 1A1 (CYP1A1), represents a promising targeted alternative for cancer cells overexpressing this enzyme. To optimize its clinical utility and minimize off-target effects in breast cancer (BC) patients, this study aims to identify predictive biomarkers of CEU-938 efficacy. Methods: The antiproliferative activity of CEU-938 was assessed across a panel of 39 human breast cancer and non-tumorigenic cell lines. Differential expression analyses were subsequently performed to distinguish CEU-938-responsive from non-responsive cell lines using a threshold of 1000 nM. Candidate biomarkers identified through this approach were then validated by RT-qPCR and Western blot analyses. Results: CEU-938 demonstrated marked and selective antiproliferative activity across molecular subtypes of human breast cancer, with efficacy observed in approximately 40% of triple-negative breast cancer (TNBC), 70% of estrogen receptor-positive (ER⁺), and 80% of human epidermal growth factor receptor 2-positive (HER2⁺) breast cancer cell lines, while sparing non-tumorigenic human breast cells (MCF 10A, MCF-12A, 184B5). Differential expression analysis identified five candidate biomarkers associated with CEU-938 responsiveness, namely, FOXA1 (log2-fold change (LFC) = 3.1), RAB25 (LFC = 3.8), RHOV (LFC = 2.9), PRKCH (LFC = 1.6), and HDAC9 (LFC = −1.7). Among these, FOXA1 and RAB25 robustly validated by RT-qPCR and Western blot analyses, showing strong inverse correlations with CEU-938 sensitivity (Spearman correlation coefficients of −0.82 and −0.61, respectively, at the protein level). The predictive value of FOXA1 and RAB25 was further confirmed by Western blot analyses in two independent breast cell line models, the non-responsive MCF-12A and the responsive MDA-kb2. Conclusions: Collectively, these findings identify FOXA1 and RAB25 as robust predictive biomarkers of response to CEU-938. Notably, FOXA1 and RAB25 are strongly implicated in breast cancer biology, and FOXA1 has been directly linked to the aryl hydrocarbon receptor (AHR), the main regulator of CYP1A1. These results position CEU-938 as a strong precision-therapy candidate that combines target selectivity, a favorable toxicity profile, and biomarker-enabled patient stratification, with potential clinical benefit in ER⁺ and HER2⁺ enriched tumors, as well as a subset of TNBC. Full article

Background: Tubulin plays a pivotal role in cell division and other essential cellular processes, making it a key pharmacological target for cancer therapy, antiparasitic treatments, and neurodegenerative diseases. Numerous compounds have been developed to regulate microtubule polymerization through tubulin binding; however, most have shown significant limitations, including adverse side effects, poor bioavailability and limited specificity. In recent years, peptide-based therapies have gained considerable attention, particularly for their ability to modulate protein–protein interaction while offering improved selectivity and safety profiles. Methods: In this study, we employed an integrated computational–experimental approach combining molecular docking, molecular dynamics simulations, and MM-GBSA free energy calculations to design and evaluate 14 peptides derived from the αβ-tubulin dimer interface. Results: The peptide NH₂-P14-COOH emerged as the most promising candidate, displaying the stronger inhibition of tubulin polymerization activity (IC₅₀ = 11.24 ± 3.82 μM), selective cytotoxicity against NCI-H1299 lung carcinoma cells (IC₅₀ = 45.64 ± 3.20 μM), and no significant toxicity toward non-cancerous EA.hy926 endothelial cells (IC₅₀ > 100 μM). Flow cytometry analysis confirmed that NH₂-P14-COOH induces apoptosis, supporting a mechanism of action based on microtubule disruption. Conclusions: These findings highlight NH₂-P14-COOH as a selective antimitotic peptide with a favorable therapeutic index and demonstrate the potential of structure-guided peptide design for the development of novel microtubule-targeting agents with reduced off-target toxicity. Full article

Background/Objectives: Antigen presenting cells (APCs) and immune cells have unique properties to drive or suppress immune responses. They are therefore key targets for the expression of vaccine antigens or transgene proteins. To better determine the utility of different molecular therapies to modify these cells, mRNA and DNA-based molecular therapy vectors were compared for their ability to genetically modify immune cells after intradermal injections in mice. DNA-based vectors included naked plasmid DNA, plasmid packaged in lipid nanoparticles (LNPs), and replication-defective adenovirus (Ad) vectors. mRNA delivery was mediated by packaging into LNPs like those used in COVID-19 vaccines. Methods: Each vector was used to deliver Cre recombinase into Cre reporter mice whose cells were activated to express green fluorescent protein (GFP) and firefly luciferase after Cre recombination. The mice were injected intradermally (ID) near the base of their tail at a site that drains into the inguinal lymph node. Luciferase activity was imaged in the living mice 1 or 4 days after vector injection. The animals were then euthanized, and luciferase activity was imaged in the draining inguinal lymph node. Cells were prepared from the intradermal injection site and from the draining lymph node to determine which immune cells were genetically modified by phenotyping CD45, CD3, and CD11b GFP-positive cells by flow cytometry. Given that the skin uniquely contains Langerhans dendritic cells, these CD207⁺ cells were also phenotyped in skin samples and in the draining lymph node. Results: In both the skin and in the draining lymph node, the rank order of luciferase and GFP activation by the vectors were: (1) Ad; (2) mRNA-LNP; (3) DNA-LNP; and (4) naked DNA. Only mRNA-LNP and Ad vectors mediated obvious luciferase activity in the living animals and in the draining lymph nodes by imaging. Notably, both vectors appeared to leak from the ID injection site and not only modify the draining lymph node but also strongly modify the livers of the mice. Naked DNA and DNA-LNP mediated detectable GFP activation in the skin and draining lymph node in some mice, but this activity was low and did not reach statistical significance when compared to PBS-treated animals. mRNA-LNPs and Ad both mediated significant Cre delivery in CD45⁺, CD3⁺, CD11b⁺, and CD207⁺ immune cells in the skin and in the lymph node, with adenovirus mediating consistently higher levels of expression in all of the tested cells. Conclusions: These data indicate that mRNA-LNP and Ad vectors mediate stronger modification of skin and lymph node immune cells after intradermal injections. Naked DNA and DNA-LNPs were markedly less potent at this activity than the other vectors. These data are consistent with the higher vaccine potency of mRNA-LNP and Ad vectors and suggest that approaches that increase targeting of immune cell subsets may have utility to increase efficacy while also reducing off-target modification of tissues like the liver. Full article

Background: Artesunate (ART), a natural product derivative of artemisinin, exhibits striking antitumor activity. However, the clinical translation of ART is limited by rapid clearance, poor tumor selectivity, and severe off-target toxicity. To address these limitations, we developed an unsaturated aliphatic chain-driven nanoassembly strategy to optimize the therapeutic performance of ART. Methods: We designed and synthesized two ART derivatives by conjugating saturated aliphatic chains (ART-SAs) or unsaturated aliphatic chains (ART-LAs) to ART, which subsequently self-assembled into carrier-free nanoassemblies (NAs). These NAs were characterized for their self-assembly capacity and colloidal stability. Biological evaluations included studies on cellular uptake efficiency, in vivo pharmacokinetics, and antitumor efficacy in a tumor-bearing mouse model. Results: The saturated aliphatic chain is found to drive nanoassembly of ART-SA but significantly shields the antitumor activity of ART. Interestingly, the conjugate of an unsaturated aliphatic chain to ART (ART-LA) not only shows outstanding self-assembly capacities but also retains the native antitumor activity of ART. The P-AL NAs with improved pharmacokinetics and tumor-specific biodistribution exert potent antitumor activity and favorable safety. Conclusions: We successfully applied ART for highly effective antitumor therapy by employing an unsaturated aliphatic chain-driven strategy. This study is conducive to promoting the clinical application of ART. Full article

Introduction: Ball velocity is a critical determinant of shot effectiveness in football, yet its influence on advanced post-shot metrics, such as expected shot impact timing (xSIT) and expected goals on target (xGOT), remains poorly understood, particularly in the context of sex-specific differences. This study examined the relationship between ball velocity and these metrics in men’s and women’s elite European tournaments. Methods: A total of 2174 shots were analyzed from all matches of the 2024 UEFA Men’s EURO (n = 1305) and 2025 UEFA Women’s EURO (n = 869), classified as goal shots on target, non-goal shots on target, and shots off target. Ball velocity was measured for each shot, and its associations with xSIT, our own xGOT model and the StatsBomb xGOT model were quantified using correlation coefficients. Results: Ball velocity differed significantly between sexes (p < 0.001), with higher values in men, and goal shots on target exhibited lower velocities than non-goal or off-target shots, indicating a speed–accuracy trade-off. Only xSIT and our own xGOT model were sensitive to ball velocity, reflecting sex-specific differences (p < 0.001). When comparing shot types across advanced metrics, a consistent trend was observed in both tournaments: xSIT showed no significant differences between goal and non-goal shots, whereas both xGOT models were higher for goal shots on target. Correlations indicated a moderate positive relationship between xSIT and ball velocity, and moderate negative correlations for both xGOT models, slightly stronger in men. Conclusions: Ball velocity is a critical factor influencing shot performance and advanced post-shot metrics, with notable sex-specific differences. Full article

Background/Objectives: Treatment of HIV-associated lymphoma (HIV-Ly) with autologous stem cell transplantation (ASCT) has shown a surprisingly low relapse rate in several series. The aim of this study was to compare the clinical outcomes of HIV-Ly and lymphomas in the general population receiving ASCT. Methods: We compared two series of consecutive HIV-positive and HIV-negative patients, based on a 1:1 propensity score analysis, matching for age, sex, histology, disease status and prior therapies. Results: After propensity matching we identified a final population of 88 patients (44 HIV-positive vs. 44 HIV-negative). All HIV-positive patients received combination antiretroviral therapy (cART). With a median follow-up of 51 months, PFS was significantly higher in HIV-positive patients (4-year PFS 81% and 51%, in HIV-positive and HIV-negative patients, respectively, p = 0.027). Four-year OS was 81% for HIV-positive and 67% in HIV-negative patients (p = 0.15). The relapse rate was significantly higher in HIV-negative patients (36% vs. 23%) (p = 0.04). Conclusions: Our results clearly show that ASCT is an effective curative option for HIV-Ly, with better PFS and a lower relapse rate compared to patients without HIV. A favorable effect of ASCT on HIV infection and immune system recovery, potential off-target effects of cART or other yet unknown factors may account for this observation. Full article