Search Results (51)

Privacy-preserving data mining (PPDM) seeks to extract useful patterns from shared data without revealing sensitive information. Within PPDM, knowledge hiding—encompassing both association rule hiding (ARH) and frequent itemset hiding (FIH)—forms a coherent family of techniques that sanitize transactional databases before release. This focused survey synthesizes the main algorithmic paradigms for knowledge hiding (1999–2026), covering heuristic sanitization, border-based and exact optimization via integer linear programming, constraint-based and graph-based formulations, emerging learning-guided support mechanisms, and extensions to utility mining and non-relational structures. We use a PRISMA-style search and selection protocol to make the evidence base transparent and to mitigate selection bias. We trace the evolution from early disclosure-limitation heuristics to graph-guided and knowledge-graph approaches, and we treat deep-learning, GNN, and federated graph-learning work as adjacent tools that may support candidate selection, representation learning, or distributed deployment rather than as replacements for classical hiding validation. We identify persistent challenges around scalability, infeasibility in LP formulations, and evaluation standardization, and outline directions for future research. Unlike broader PPDM overviews, this review centers exclusively on transactional knowledge hiding. Beyond cataloging algorithms, it compares method families through their intervention mechanisms, side-effect profiles, scalability assumptions, and benchmark regimes, and it distills reporting recommendations for more reproducible empirical evaluation. Full article

Family firms are central to global economic stability and employment. Generational transitions, however, involve not only the transfer of leadership but also changes in organizational structures and culture. As digitalization becomes increasingly important for competitiveness, successors are introducing digital marketing practices that may influence organizational culture during leadership transitions. While previous research has examined digital transformation in family businesses, limited attention has been given to the role of digital marketing as a mechanism of cultural change during generational succession. This article addresses the question: How do second-generation successors use digital marketing practices to shape organizational culture during generational transitions in family firms? Drawing on practice theory and Schein’s model of organizational culture, the study explores how cultural change unfolds through everyday practices within organizations. The research employs a qualitative multiple-case study approach based on semi-structured interviews with representatives from 35 family firms in Latvia. The findings identify key digital marketing practices implemented by second-generation successors and illustrate how these practices influence organizational culture during the transition process. The results suggest that digital marketing can both reinforce existing organizational values and selectively reshape organizational identity and legitimacy. The study highlights digital marketing as a culturally legitimate tool through which successors can influence decision-making processes, coordination mechanisms, and authority structures during generational succession. Full article

Background/Objectives: Arteriovenous grafts (AVGs) are critical for hemodialysis access in patients with inadequate native vasculature. The Xeltis aXess graft, a novel bioresorbable vascular access conduit, promotes endogenous tissue restoration. While early outcomes have been promising, longer-term data remain limited. This report presents the longest reported, four-year follow-up on two of the first implanted aXess devices. Case Summaries: Case 1: A 64-year-old woman underwent aXess graft placement on 10 June 2021, between the right brachial artery and vein. She experienced graft thrombosis after 12 months and 18 months, both of which were successfully resolved with thrombectomy, in one instance in combination with drug-coated balloon (DCB) angioplasty. The graft remains functional. Case 2: A 76-year-old man received an aXess graft on 11 June 2021, in the left arm. After 6 months, he underwent balloon and DCB angioplasty for graft–vein (G–V) anastomosis stenosis. After 28 months, to resolve multiple pseudoaneurysms, followed by aneurysm resection and AVG reconstruction at month 29, a tunneled catheter was placed to perform dialysis sessions in the meantime. At month 44, graft-venous (G–V) angioplasty with DCB was performed to resolve G–V and axillary vein stenoses diagnosed at month 43. The graft remains in use. Results: Both patients retained functional dialysis access after four years, despite requiring multiple interventions for thrombosis, stenosis, and pseudoaneurysms. Conclusions: These cases demonstrate that the aXess graft can maintain functionality over four years with appropriate management, although close surveillance and reinterventions may be required. Full article

The rapid digital transformation of the financial sector has driven supervisory authorities to develop new tools for engaging with fintech innovation. Among these, Innovation Hubs have become essential mechanisms for improving regulatory dialogue, interpretive clarity, and institutional learning. This article examines the Romanian Fintech Innovation Hub (FIH), launched by the National Bank of Romania (NBR) as a consultative platform to support fintech and payment service providers operating within complex legal environments. Using a qualitative, single-case methodology (2019–2023), the study draws on internal NBR documentation, anonymized supervisory materials, and interviews with fintech founders, oversight officers, and policy specialists. The analysis evaluates the Hub’s performance across five key dimensions: stakeholder engagement, regulatory learning, policy calibration, innovation barriers, and institutional reflexivity. Findings reveal that while the Hub strengthened supervisory understanding and enhanced trust-based interaction, its influence on rulemaking and market access was limited by structural and procedural constraints, including resource gaps and the absence of a regulatory sandbox function. Nonetheless, the Romanian experience demonstrates how institutional learning can emerge even in bank-dominated markets, generating internal adaptation and improving fintech compliance readiness. Comparative insights from Hungary and Italy highlight the advantages of modular, risk-proportionate engagement models that integrate advisory and testing functions. The study contributes to the theory of adaptive regulation by proposing that innovation hubs function as feedback loop mechanisms linking market experimentation with supervisory evolution, offering a replicable model for small and emerging financial systems seeking to balance innovation facilitation with prudential soundness and legal certainty. As such, it provides generalizable insights for central banks and government policymakers on developing FinTech hubs that balance innovation facilitation with prudential soundness and legal certainty. Full article

The Co(II) complex [CoCl₂(AImd)₂] (AImd = 1-allylimidazole) was reinvestigated using a combination of experimental and theoretical methods. The previously reported crystal structure was redetermined and Hirshfeld surface analysis and enrichment ratios were added showing that intermolecular H⋯Cl and π⋯π interactions are the primary forces in the crystal structure, while H⋯H interactions dominate the surface of the molecule, making it rather hydrophobic in keeping with a low solubility in water. A Quantum Theory of Atoms in Molecules (QTAIM)/Non-Covalent Interactions (NCI)-Reduced Density Gradient (RDG) analysis on a dimeric model showed that the energies V(r) of the classical H⋯Cl hydrogen bonds range from −3.64 kcal/mol to −0.75 kcal/mol and were augmented by hydrophobic H⋯C interactions of >1 kcal/mol. T-dependent magnetization measurements reveal paramagnetic behavior with an effective magnetic moment of µ_eff = 4.66(2) µ_B. UV-vis absorption spectra in solution showed intense absorptions peaking at 240 nm, corresponding to intraligand π→π* transitions within the 1-allylimidazole moiety and a structured absorption around 600 nm, which is attributed to the spin-allowed d→d transitions of the high-spin Co(II) d⁷ ion in a distorted tetrahedral geometry. Both assignments were confirmed through TD-DFT calculations on the electronic transitions and agree with the DFT-calculated compositions of the frontier molecular orbitals. Molecular docking to hypoxia-inducible factor-1 alpha (HIF-1α) gave a docking score of −5.48 kcal/mol and showed hydrophobic⋯hydrophobic π-stacking interactions with the Ile233, Leu243, Val338, and Leu262 residues. A higher docking score of −6.11 kcal/mol and predominant hydrophobic⋯hydrophobic interactions with Trp296, His279, and Ile281 were found for HIF-1 inhibiting factor (FIH-1). Full article

Financial fragility among non-financial corporations (NFCs) has become a critical concern in developing economies, where both firm-specific and macroeconomic conditions shape corporate financial stability. Understanding these dynamics is essential to enhancing corporate resilience and informing effective regulatory interventions. This study is motivated by Minsky’s Financial Instability Hypothesis (FIH), to empirically investigate the determinants of financial fragility in Jordanian non-financial firms (NFCs) using panel data from 71 companies listed on the Amman Stock Exchange (ASE) between 2015 and 2021. By employing a panel logistic regression analysis, results reveal that Return on Assets (ROA) significantly supports financial stability, while inflation negatively impacts it, underlining the detrimental impact of increasing inflation rates on corporate financial health. The beneficial effects of GDP growth and institutional quality also emphasize how important governance and economic conditions are in promoting financial stability. The study offers an original insight on the dynamics of financial fragility in a developing market, with important ramifications for regulators, business managers, and policymakers looking to boost institutional quality, control inflation, and increase corporate profitability. The findings extend Minsky’s hypothesis to a developing-market context and provide implications for policymakers seeking to strengthen institutional frameworks, contain inflationary pressures, and promote corporate financial stability. Full article

Background/Objectives: The Wavelia Microwave Breast Imaging (MWBI) technology aims to increase sensitivity in dense breasts, where X-ray mammography is of limited value. Its potential contribution to the reduction in the false positives in breast cancer diagnosis, by developing MWBI image descriptors supporting malignant-to-benign lesion discrimination, is also being investigated. After a First-In-Human (FiH) study with interesting findings on a small dataset of 24 symptomatic breast lesions, an upgraded 2nd prototype of Wavelia was manufactured and tested on a larger and more diverse dataset, including 62 patients and a balanced distribution of malignant and benign symptomatic breast lesions. Methods: A set of technological and methodological evolutions, outlined in this article, was implemented in Wavelia#2 to handle the diversity in larger patient datasets. Multi-modal MWBI imaging is employed to parameterize the interaction mechanisms between the microwaves and the imaged breast at varying geometrical and tissue consistency conditions. MWBI Region-Of-Interest (ROI) extraction and characterization based on multidimensional radiomic feature vectors is implemented to expand the malignant-to-benign lesion diagnostics potential of MWBI compared to the limited scope of the FiH study with Wavelia#1, which employed three specific preselected features. Results: This study demonstrates significant diagnostic accuracy of multiple texture-based and intensity-based features to discriminate between malignant and benign breast lesions with Wavelia#2 MWBI. A phenomenological qualitative assessment of the false positive rate on healthy breasts is also presented for the MWBI technology for the first time. Conclusions: The analysis contributes to the rationalization of the MWBI imaging and image analysis outputs towards standardization, objective interpretability, and ultimate clinical acceptance. Full article

Background/objectives: MDG1011 is a Preferentially Expressed Antigen in Melanoma (PRAME)-specific autologous T cell receptor (TCR) T cell therapy for HLA-A*02:01-positive patients. Data from the first-in-human (FIH) clinical trial, CD-TCR-001, are reported here regarding treatment feasibility, safety, tolerability, and clinical activity of MDG1011 in patients with relapsed/refractory (r/r) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). Methods: Nine of thirteen enrolled patients received MDG1011 at dose levels ranging from 0.1 to 5 × 10⁶ TCR-T cells per kg body weight. In addition to clinical assessments, immune monitoring of cytokines associated with cytokine release syndrome (CRS), presence and persistence of MDG1011, and changes in levels of PRAME mRNA were used to assess safety and potential biological activity at defined time points. Results: The treatment was well tolerated. No dose-limiting toxicities (DLTs) were observed, and the most common serious adverse events were associated with lymphodepleting chemotherapy and/or disease progression. Various parameters, such as measurable clinical responses in two patients, the occurrence of CRS in two additional patients, and reductions in PRAME mRNA levels in bone marrow (BM) or peripheral blood (PB) in seven patients, served as signs of the clinical and biological activity of MDG1011 TCR-T therapy. Conclusions: Patients enrolled in the phase 1 part of CD-TCR-001 displayed signs of potential clinical and biological activity of MDG1011 among the small number of patients studied. Advanced disease stage and rapid progression in the r/r AML patients limited clinical impact. The acceptable safety profile of MDG1011 merits further investigation of this TCR-T therapy, potentially in patients at an earlier stage of their disease and with lower tumor burden. Full article

Immigrant households frequently face liquidity constraints upon arrival, which potentially hinders their long-term economic integration. The Family Investment Hypothesis (FIH) suggests that couples may respond to these constraints by coordinating their labor supply: one spouse works to finance the other’s investment in local human capital. Previous studies have tested the FIH by comparing married immigrants to married natives, attributing differences in outcomes to financial constraints. However, this approach may conflate such constraints with other inherent differences between immigrants and natives. This paper introduces a novel identification strategy that compares the differences in labor market outcomes of married and single immigrants to those of their native-born counterparts, allowing for better isolation of the effects of liquidity. Applying this strategy to repeated cross-sectional data on immigrants from the Former Soviet Union who arrived in Israel during the 1990s, the analysis finds no supporting evidence for the FIH. One possible explanation for this finding is the substantial government support extended to these immigrants, which may have mitigated their financial constraints. Alternatively, the results may indicate that immigrant households do not systematically adjust their labor supply in accordance with the FIH framework. These findings highlight the importance of the institutional context in shaping household labor supply decisions. Full article

Background/Objectives: P2X3 receptor antagonists have been suggested as a potential treatment for urogenital, respiratory and pain conditions. This first-in-human (FiH) study evaluated filapixant, a new P2X3 receptor antagonist with high receptor selectivity. It was anticipated that filapixant would cause fewer taste-related side effects compared to the unselective P2X3/P2X2/3 antagonist gefapixant and the less selective P2X3 antagonist eliapixant. This study assessed the tolerability, safety and PK of filapixant, the effect of food on PK and relative BA of a tablet vs. solution. Methods: This study (NCT03212586) followed a randomized, double-blind single-ascending-dose design. A total of 72 healthy male subjects received a solution (6–60 mg) or immediate-release tablets (120–1250 mg) of filapixant or corresponding placebo in fasted state. The subjects at 60 mg were re-dosed with 60 mg tablets in both fasted and fed states. The endpoints included PK parameters, dose proportionality, adverse events, and taste assessments (taste strips; dysgeusia questionnaire). Results: Filapixant showed dose-proportional PK with a half-life (about 10–15 h), supporting once-daily dosing. Food minimally affected PK and BA was comparable between tablet and solution. Filapixant was well tolerated; however, the number of taste side effects was unexpectedly high. Comparing the results observed across clinical filapixant studies, the threshold for such side effects seems to be well below the in vitro IC₅₀ for P2X2/3. Conclusions: Treatment with filapixant was safe and well tolerated. Filapixant showed dose-proportional PK, bioavailability similar to that of a solution and a tablet, and a minor effect of food on PK. The number of taste side effects was unexpectedly high considering the high in vitro P2X3 receptor selectivity. Factors other than selectivity are needed to explain taste profile differences between P2X3 antagonists. Full article

Introduction: Recently, alpha-emitting radionuclides like astatine-211 have offered promising results in clinical development. Non-muscle-invasive bladder cancer (NMIBC) presents a need for novel therapies. One promising approach is radioimmunotherapy targeting Carbonic Anhydrase IX (CA-IX), which is supported by preclinical and clinical evidence. The aim of our preclinical and clinical studies was to evaluate the [²¹¹At]At-anti-CA-IX antibody (ATO-101™) for future use in NMIBC patient care. Methods: The anti-CA-IX antibody, girentuximab (TLX250), was labeled with lutetium-177 and astatine-211 for in vitro studies. Affinity constant measurements of [²¹¹At]At-girentuximab in RT-112 cells were taken, and toxicity evaluations were conducted in vitro and in healthy mice. Additionally, a clinical proof-of-concept study, PERTINENCE, that used [⁸⁹Zr]Zr-girentuximab for PET/CT imaging in bladder cancer patients was conducted. Results: The measurement of the affinity constant of [²¹¹At]At-girentuximab in RT112 cells revealed high binding affinity and significant cytotoxicity compared to [177Lu]Lu-girentuximab. Biodistribution studies in healthy mice indicated low systemic radioactivity uptake, and a bladder post-instillation examination showed no abnormalities in bladder mucosa, suggesting safety. In the PERTINENCE study, which involved patients with NMIBC tumors expressing CA-IX, [⁸⁹Zr]Zr-girentuximab PET/CT showed no extravesical leakage. Wall bladder uptake spots correlated with recurrence or inflammatory reaction. A dosimetric study suggested the potential efficacy and favorable safety profile of intravesical alpha therapy with the [²¹¹At]At-anti-CA-IX antibody (ATO-101™) in NMIBC treatment. Conclusions: Preclinical and clinical data demonstrate the promising therapeutic role of ²¹¹At-targeted alpha agents in NMIBC, and the [²¹¹At]At-anti-CA-IX antibody (ATO-101™) could fulfill this role. A phase I FIH clinical trial is in preparation, and results are expected within the next years. Full article

Background: HOSU-53 (JBZ-001), an orally bioavailable new chemical entity, represents a highly potent dihydroorotate dehydrogenase (DHODH) inhibitor in late preclinical development for application in cancer therapy. Methods: Multiple Good Laboratory Practice (GLP) and non-GLP preclinical studies were conducted in mice, rats, and dogs. Plasma samples of HOSU-53 and dihydroorotate (DHO), the substrate of DHODH, were collected for pharmacokinetic (PK) and pharmacodynamic (PD) assessment and modeling. Two modeling approaches were utilized to understand the PK/PD properties of HOSU-53 and to recommend a first-in-human (FIH) dose. Results: A population PK/PD model was developed using a stochastic approximation of the expectation-maximization method and evaluated using graphical and numerical methods. The PK of HOSU-53 was well described by a two-compartment model with a first-order absorption and linear elimination, and the PD was described by a turnover model. No covariates were considered significant on PK/PD parameters. This model was subsequently used to predict DHO exposures in humans across a range of doses. Additionally, predicted human hepatocellular HOSU-53 concentrations were obtained from a physiologically based PK model constructed in PK-Sim. Conclusions: A first-in-human starting dose of 5 mg once daily was established from the model approaches and will be utilized in the upcoming FIH clinical study. Full article

Understanding the corpus luteum (CL) and its role in cattle reproduction is crucial, particularly as it is a progesterone source for the establishment and maintenance of pregnancy. Reduced oxygen levels significantly impact these processes. This study investigated the effects of the luteal stage on the spatio-temporal gene expression patterns of HIF1α and oxygen-sensing factors, as well as the impact of lipopolysaccharide (LPS)-induced inflammation on these factors. Endothelial inflammatory responses were also addressed. The samples included CL collected at the early, mid, and late stages, as well as biopsies from mid-luteal stage cows treated either with saline (controls) or LPS. Samples collected in subsequent cycles assessed potential carryover effects. RT-PCR revealed upregulation of HIF1α, PHD1, PHD3, FIH, and VHL encoding genes in the mid-luteal stage. In situ hybridization revealed the compartmentalization of HIF1α and its regulators within the luteal and endothelial cells, suggesting their cell-specific roles. LPS treatment affected PHD1 and PHD3 expression, while increasing endothelial pro-inflammatory factors ICAM1 and NFκB, suggesting vascular inflammation and modulated oxygen sensing. These findings reveal new insights into the spatio-temporal expression of HIF1α-regulating factors in the CL, highlighting their potential role in controlling luteal function, detailing their cellular compartmentalization, and the effects of LPS-mediated inflammatory responses. Full article

Background/Objectives: MDG1011 is an autologous TCR-T therapy developed as a treatment option for patients with myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). It is specific for the target antigen PReferentially expressed Antigen in MElanoma (PRAME). The recombinant TCR used in MDG1011 recognizes PRAME_100–108 VLD-peptide presented by HLA-A*02:01-encoded surface molecules. Methods: Two preclinical batches of MDG1011, produced from enriched CD8+ T cells of healthy donors, underwent rigorous evaluation of on-target and off-target recognition of tumor cells and test cells representing healthy tissues. MDG1011 investigational medicinal products (IMPs) were produced for 13 patients. VLD-TCR surface expression was assessed using dual-marker flow cytometry using TCR V-beta-specific antibody and VLD/HLA-A2-specific multimer. Functionality was assessed by interferon-gamma (IFN-γ) secretion and cell-mediated cytotoxicity of target cells. Results: Preclinical MDG1011 batches displayed strong VLD-TCR expression, cytokine secretion, and cytotoxicity after antigen-specific activation, while showing no signals of on-target/off-tumor or off-target recognition. All IMPs had good VLD-TCR expression as well as functionality after activation by multiple target cells. Conclusions: Preclinical studies demonstrated that MDG1011 displayed key 3S attributes of high specificity, sensitivity, and safety required for regulatory approval of a first-in-human (FIH) clinical study of patients with myeloid malignancies (CD-TCR-001: ClinicalTrials.gov Identifier: NCT03503968). MDG1011 IMP manufacturing was successful at 92%, even including heavily pretreated elderly patients with very advanced disease. The IMPs applied in nine patients all displayed antigen-specific functionality. Elsewhere, clinical study results for MDG1011 showed no dose-limiting toxicity and signs of biological and/or clinical activity in several patients. Full article

Bacterial diseases of the gastrointestinal (GI) tract continue to be a major worldwide cause of human morbidity and mortality. Among various enteric pathogens, Shigella spp. are some of the most common and deadly bacterial pathogens. They are responsible for ~125 million worldwide cases of shigellosis, and ~14,000 deaths annually, the majority in children under the age of 5 and occurring in developing countries. Preventing and treating shigellosis with conventional drugs (e.g., vaccines and antibiotics) has proven to be very difficult. Here, we assessed the safety and tolerability of ShigActive™, a lytic bacteriophage preparation targeting Shigella spp., in a randomized, placebo-controlled, double-blind Phase 1 clinical trial. Ten participants randomized 4:1 received ShigActive™ or placebo co-administered with sodium bicarbonate orally three times daily for 7 days. Solicited and unsolicited adverse events (AEs) were observed for 29 days. Fifty percent of the subjects receiving ShigActive™ reported mild GI-related symptoms, while one participant experienced moderate fatigue. No serious or medically attended AEs occurred through day 90. Additionally, no significant differences in GI-associated inflammatory mediators or fecal microbiome changes were observed between placebo- and ShigActive™-treated subjects, or from a participants’ baseline value. The results of this first-in-human (FIH) randomized, controlled Phase 1 trial of ShigActive™ demonstrate that it is safe and well tolerated when orally administered with no significant differences compared to placebo controls. Full article