The applicability of a hybrid framework for automated phishing detection

peer reviewedPhishing attacks are a critical and escalating cybersecurity threat in the modern digital landscape. As cybercriminals continually adapt their techniques, automated phishing detection systems have become essential for safeguarding Internet users. However, many current systems rely on single-analysis models, making them vulnerable to sophisticated bypass attempts by hackers. This research delves into the potential of hybrid approaches, which combine multiple models to enhance both the robustness and effectiveness of phishing detection. It highlights existing hybrid models' limitations that focus primarily on effectiveness while ignoring broader applicability. To address these gaps, we introduce a novel framework explicitly designed for applicability in the real world, which poses the foundation for practical and robust phishing detection architectures. We develop a proof of concept to evaluate its effectiveness, robustness, and detection speed. Additionally, we introduce an innovative methodology for simulating bypass attacks on single-analysis base models. Our experiments demonstrate that the proposed hybrid framework outperforms individual models, displaying higher effectiveness, robustness against bypassing attempts, and real-time detection capabilities. Our proof of concept achieves an accuracy of 97.44% thereby outperforming the current state-of-the-art approach while requiring less computational time. The results provide insights into the multifaceted factors of hybrid models, extending beyond mere effectiveness, and emphasize the importance of holistic applicability in hybrid approaches to address the critical need for robust defenses against phishing attacks

Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: A multicenter feasibility study

BEAM is a widely used conditioning regimen for relapsed/refractory lymphoma patients undergoing auto-SCT. We conducted a multicenter study with an alternative regimen (fotemustine plus etoposide, cytarabine and melphalan (FEAM)) in which BCNU was substituted by the chloroethylnitrosourea fotemustine (FTM). Eighty-four patients with relapsed/refractory Hodgkin's (n20) and non-Hodgkin's lymphoma (n64) were conditioned with a FEAM regimen (FTM 150 mg/m 2 on days -7, -6, etoposide 200 mg/m 2 and cytarabine 400 mg/m 2 on days -5, -4, -3, -2 and melphalan 140 mg/m 2 on day -1). Patients were evaluated for toxicity and engraftment parameters. Median times to neutrophil (500 × 10 9 /l) and plt (20 000 × 10 9 /l) engraftment were 11 and 13 days, respectively. Grade 3 mucositis occurred in 19 patients (23%), while G3 nausea/vomiting and G3 diarrhea were observed in 13 (15%) and 6 (7%) patients, respectively. No severe hepatic, renal or pulmonary toxicity was detected. Seven patients (7%) experienced G4 mucositis, while no other G4 toxicities or unexpected adverse events of any grade were recorded. Transplant-related mortality was 2.4%. We conclude that a FEAM regimen is feasible and safe. Although toxicity and engraftment times compared favorably with BEAM, longer follow-up is needed to evaluate fully its efficacy and long-term safety. © 2010 Macmillan Publishers Limited All rights reserved

Longitudinal Study of Optic Disk Perfusion and Retinal Structure in Leber's Hereditary Optic Neuropathy

PURPOSE. The purpose of this study was to evaluate optic disk perfusion and neural retinal structure in patients with subacute Leber's hereditary optic neuropathy (LHON) and LHON carriers, as compared with healthy controls. METHODS. This study included 8 patients with LHON in the subacute stage, 10 asymptomatic carriers of a LHON-associated mitochondrial DNA mutation, and 40 controls. All subjects underwent measurement of the retinal nerve fiber layer (RNFL) thickness, the ganglion cell-inner plexiform layer (GCIPL) thickness using optical coherence tomography and optic disk microvascular perfusion (Mean Tissue [MT]) using laser speckle flowgraphy (LSFG). Patients were re-examined after a median interval of 3 months from the baseline visit. RESULTS. LHON carriers had higher values of RNFL thickness, GCIPL thickness, and disk area than controls (P < 0.05), whereas MT was not different between the two groups (P = 0.936). Median MT and RNFL thickness were 32% and 15% higher in the early subacute stage of the disease than in controls (P < 0.001 and P = 0.001). MT declined below the values of controls during the late subacute stage (P = 0.024), whereas RNFL thickness declined later during the dynamic stage (P < 0.001). GCIPL thickness was lower in patients with LHON than in controls independently of the stage of the disease (P < 0.001). CONCLUSIONS. The high blood flow at the optic disk during the early subacute stage may be the consequence of vasodilation due to nitric oxide release as compensation to mitochondrial impairment. Optic disk perfusion as measured by LSFG is a promising biomarker for LHON diagnosis and monitoring as well as an objective outcome measure for assessing response to therapies

A comparative analysis of biosimilar vs. originator filgrastim in combination with plerixafor for stem cell mobilization in lymphoma and multiple myeloma: a propensity-score weighted multicenter approach

The combination of biosimilar filgrastim and plerixafor appears to be at least equally and might be more effective as compared to originator filgrastim and plerixafor for stem cell mobilization in patients at high risk of mobilization failure. This data strongly support standard inclusion of biosimilar filgrastim in mobilizing protocols even in the challenging setting of patients who mobilize poorly, as significant cost saving seems to be accompanied by strong efficacy

Longitudinal Study of Optic Disk Perfusion and Retinal Structure in Leber's Hereditary Optic Neuropathy

Purpose: The purpose of this study was to evaluate optic disk perfusion and neural retinal structure in patients with subacute Leber's hereditary optic neuropathy (LHON) and LHON carriers, as compared with healthy controls. Methods: This study included 8 patients with LHON in the subacute stage, 10 asymptomatic carriers of a LHON-associated mitochondrial DNA mutation, and 40 controls. All subjects underwent measurement of the retinal nerve fiber layer (RNFL) thickness, the ganglion cell-inner plexiform layer (GCIPL) thickness using optical coherence tomography and optic disk microvascular perfusion (Mean Tissue [MT]) using laser speckle flowgraphy (LSFG). Patients were re-examined after a median interval of 3 months from the baseline visit. Results: LHON carriers had higher values of RNFL thickness, GCIPL thickness, and disk area than controls (P < 0.05), whereas MT was not different between the two groups (P = 0.936). Median MT and RNFL thickness were 32% and 15% higher in the early subacute stage of the disease than in controls (P < 0.001 and P = 0.001). MT declined below the values of controls during the late subacute stage (P = 0.024), whereas RNFL thickness declined later during the dynamic stage (P < 0.001). GCIPL thickness was lower in patients with LHON than in controls independently of the stage of the disease (P < 0.001). Conclusions: The high blood flow at the optic disk during the early subacute stage may be the consequence of vasodilation due to nitric oxide release as compensation to mitochondrial impairment. Optic disk perfusion as measured by LSFG is a promising biomarker for LHON diagnosis and monitoring as well as an objective outcome measure for assessing response to therapies

Capturing the Pattern of Transition From Carrier to Affected in Leber Hereditary Optic Neuropathy

center dot PURPOSE: To capture the key features patterning the transition from unaffected mutation carriers to clinically affected Leber hereditary optic neuropathy (LHON), as investigated by optical coherence tomography. center dot DESIGN: Observational case series. center dot METHODS: Four unaffected eyes of 4 patients with LHON with the first eye affected were followed across conversion to affected, from 60 days before to 170 days after conversion. The primary outcome measures were multiple timepoints measurements of peripapillary retinal nerve fiber layer (RNFL) thickness for temporal emiside of the optic nerve (6 sectors from 6-11, clockwise for the right eye and counterclockwise for the left eye) in all patients and nasal emi-macular RNFL and ganglion cell layer (GCL) thickness in 2 patients. center dot RESULTS: While the presymptomatic stage was characterized by a dynamic thickening of sector 8, the beginning of the conversion coincided with an increase in the thickness of the sectors bordering the papillo-acular bundle (6 and 7 for the inferior sectors, 10 and 11 for the superior sectors) synchronous with the thinning of sectors 8 and then 9. Conversely, the GCL did not undergo significant changes until the onset of visual loss when a significant reduction of thickness became evident. center dot CONCLUSION: In this study we demonstrated that the thinning of sector 8 can be considered the structural hallmark of the conversion from the presymptomatic to the affected state in LHON. It is preceded by its own progressive thickening extending from th

A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Objective: We evaluated ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who had received 1-3 prior therapies. Methods: This was a phase 2, single-arm, open-label, multicentre study (NCT02902965). The primary endpoint was progression-free survival (PFS). Results: Seventy-six patients were enrolled; 74 received ≥1 dose of study treatment. After median follow-up of 19.6 months, median PFS was 8.5 months (95% CI: 6.2-10.8); median overall survival was not reached. Overall response rate was 57% (95% CI: 45-68), and median duration of response was 9.5 months (95% CI: 6.9-10.6). Grade 3/4 AEs occurred in 73% of patients and fatal AEs occurred in 15% of patients. Incidence of major haemorrhage was 5%; one patient died from cerebral haemorrhage. After an observed increased incidence of serious (42%) and fatal (11%) infections, enrolment was suspended to implement risk-minimisation measures. The safety profile was otherwise consistent with known safety profiles of the individual drugs. Conclusion: Ibrutinib combined with bortezomib and dexamethasone elicited clinical responses. However, efficacy assessments conducted at potential restart of enrolment indicated that the targeted PFS could not be reached with additional patient enrolment, and the study was terminated

DARA-VD VERSUS DARA-RD AS SALVAGE THERAPY FOR PATIENTS WITH MYELOMA. INITIAL FOLLOW-UP OF AN ITALIAN MULTICENTER RETROSPECTIVE CLINICAL EXPERIENCE BY RETE EMATOLOGICA PUGLIESE

Background: Daratumumab is a CD38 monoclonal antibody approved in monotherapy or in combination with bortezomib and dexamethasone (Dara-Vd) or lenalidomide and dexamethasone (Dara-Rd) for the treatment of relapsed or refractory myeloma (rrMM). Aims: We report here an initial multicenter retrospective analysis of 126 consecutive patients with rrMM treated with daratumumab in combination with bortezomib or lenalidomide as salvage therapy at 9 haematological centers in Puglia, conducted to evaluate the outcomes, as well as the toxicity profile of these combination in a daily practice setting outside clinical trials. Methods: Of 126 patients, 122 were evaluable for response and toxicity. Forty-two patients (33%) (15 F and 27 M) received Dara-Vd and 84 patients (67%) (41 F and 43 M) with Dara-Rd; 74% of them had relapsed MM and 26% MM refractory to one or more previous treatment lines. The median age at diagnosis was 62 years (range 36-77) in the Vd-group, 66 years (range 32-83) in the Rd-group. The median time to initiation of daratumumab from diagnosis was 5 years (range 3-9) in the Vd-group, 3 years (range 1-10) in the Rd-group. Patients had received a median 2 prior lines of therapy (range 1-6) in the Vd-group, a median 1 prior course of therapy (range 1-4) in the Rd-group. Twenty patients (48%) in the Vd-group and 30 patients (37%) in the Rd-group had previously undergone single or tandem ASCT. In the Vd-group all patients were previously exposed to at least one proteasome inhibitor (91% of patients to bortezomib, 37% of patients to carfilzomib), in the Rd-group only 18% of patients was exposed to lenalidomide. Results: The median number of administered cycles was 9 (range 1-23) in the VD-group and 8.5 (range 1-23) in the Rd-group. The ORR was 68.2% in the Vd-group (CR 4.8%, VGPR 12.2%, PR 51.2%) and 81.5% in the Rd-group (CR 21%, VGPR 35.8%, pr 24.7%). Median TTR was 2 months (range 1-6) in the Vd-group and 1.5 months (range 1-5) in the Rd-group. Median PFS was 10 months (range 8-16; 95% > CI) in the Vd-group; median PFS was not reached in the Rd-group (fig.1). Grade 3/4 neutropenia (37%) was the most common adverse event in the Rd-group, grade 3/4 thrombocytopenia (24%) was the most common adverse event in the Vd-group. Seventeen (41%) patients in the Vd-group discontinued treatment due to relapse, 16 patients (19%) in the Rd-group because of haematological toxicity (4.5%), relapse (7.5%), death (6%) and the development of urological cancer (1%). Summary/Conclusion: A higher rate of ORR (81.5% vs 68.2%) and very good partial response or better (responses > VGPR 56.8% vs 17%) was observed in the Dara-Rd group compared to Dara-Vd group. This difference could be due to the fact that: 1) in the Dara- Rd group the patients had received a lower number of prior antimyeloma therapies compared to Dara-Vd group; 2) the patients in the Dara-Rd group had a more indolent myeloma (median ISS 1) compared to the patients in the Dara-Vd group, who had a more advanced disease (median ISS 3); 3) in the Rd-group only 18% of patients was exposed to lenalidomide, in the Vd-group all patients were previously exposed to at least one proteasome inhibitor. Unfortunately, the interference of daratumumab with immunofixation and serum protein electrophoresis assays may lead to underestimation of CR

Validation and reference values of the EORTC QLQ-CML24 questionnaire to assess health-related quality of life in patients with chronic myeloid leukemia

Health-related quality of life (HRQOL) assessment is important to facilitate decisions in the current treatment landscape of chronic myeloid leukemia (CML). Therefore, the availability of a validated HRQOL questionnaire, specifically developed for CML patients treated with tyrosine kinase inhibitors (TKIs), may enhance quality of research in this area. We performed an international study including 782 CML patients to assess the validity of the EORTC QLQ-CML 24 questionnaire, and to generate HRQOL reference values to facilitate interpretation of results in future studies. Internal consistency, assessed with Cronbach’s alpha coefficients, ranged from 0.66 to 0.83. In the confirmatory factor analysis, all standardized factor loadings exceeded the threshold of 0.40 (range 0.49–0.97), confirming the hypothesized scale structure. Reference values stratified by age and sex were also generated. Our findings support the use of the EORTC QLQ-CML 24, in conjunction with the EORTC QLQ-C30, as a valuable measure to assess HRQOL in CML patients