Two-Key Dependent Permutation for Use in Symmetric Cryptographic System

This paper deals with a two-key based novel approach for generating a permutation table that can be used in a symmetric cryptographic system to cause diffusion. It also discusses how the permutation table generated using the approach can be applied to character based encryption and binary data block produced at intermediate stages by symmetric cipher algorithms. It also describes the effect of our approach on characters of intermediate text as well as on bits of binary data block along with the impact of a single bit change in key information on producing permutation sequences applied to plaintexts to produce ciphertexts. The results are satisfactory and the proposed approach can be employed in any symmetric block cipher algorithm that uses the predefined permutation tables

Fabrication of carbon nano-tubes decorated with ultra fine superparamagnetic nano-particles under continuous flow conditions

Ultra fine (2–3 nm) magnetite (Fe3O4) nano-particles are uniformly deposited on single-walled carbon nano-tubes (SWCNTs) pre-functionalised with carboxylic acid groups using microwave radiation. The deposition process involves chemical precipitation associated with continuous flow spinning disc processing (SDP), as a rapid, environmentally friendly approach which is readily scalable for large scale synthesis. The resulting decorated SWCNTs are superparamagnetic with specific saturated magnetization of 30 emu g−1

The Crystal Structure of Human Placenta Growth Factor-1 (PlGF-1), an Angiogenic Protein, at 2.0 Å Resolution

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Encapsulation and Sustained Release of Curcumin using Superparamagnetic Silica Reservoirs

For controlled release and targeted delivery of curcumin in an aqueous medium a method of encapsulating curcumin and magnetic nanoparticles inside porous silica matrix has been developed. Curcumin and superparamagnetic nanoparticles are loaded inside porous silica in a single process. The graphic shows the TEM image of microtomed sample of Fe3O4 particles surrounded by a silica matrix

Evaluation of a clinical decision support strategy to increase seasonal influenza vaccination among hospitalized children before inpatient discharge

Importance: Hospitalized children are at increased risk of influenza-related complications, yet influenza vaccine coverage remains low among this group. Evidence-based strategies about vaccination of vulnerable children during all health care visits are especially important during the COVID-19 pandemic. Objective: To design and evaluate a clinical decision support (CDS) strategy to increase the proportion of eligible hospitalized children who receive a seasonal influenza vaccine prior to inpatient discharge. Design, Setting, and Participants: This quality improvement study was conducted among children eligible for the seasonal influenza vaccine who were hospitalized in a tertiary pediatric health system providing care to more than half a million patients annually in 3 hospitals. The study used a sequential crossover design from control to intervention and compared hospitalizations in the intervention group (2019-2020 season with the use of an intervention order set) with concurrent controls (2019-2020 season without use of an intervention order set) and historical controls (2018-2019 season with use of an order set that underwent intervention during the 2019-2020 season). Interventions: A CDS intervention was developed through a user-centered design process, including (1) placing a default influenza vaccine order into admission order sets for eligible patients, (2) a script to offer the vaccine using a presumptive strategy, and (3) just-in-time education for clinicians addressing vaccine eligibility in the influenza order group with links to further reference material. The intervention was rolled out in a stepwise fashion during the 2019-2020 influenza season. Main Outcomes and Measures: Proportion of eligible hospitalizations in which 1 or more influenza vaccines were administered prior to discharge. Results: Among 17 740 hospitalizations (9295 boys [52%]), the mean (SD) age was 8.0 (6.0) years, and the patients were predominantly Black (n = 8943 [50%]) or White (n = 7559 [43%]) and mostly had public insurance (n = 11 274 [64%]). There were 10 997 hospitalizations eligible for the influenza vaccine in the 2019-2020 season. Of these, 5449 (50%) were in the intervention group, and 5548 (50%) were concurrent controls. There were 6743 eligible hospitalizations in 2018-2019 that served as historical controls. Vaccine administration rates were 31% (n = 1676) in the intervention group, 19% (n = 1051) in concurrent controls, and 14% (n = 912) in historical controls (P \u3c .001). In adjusted analyses, the odds of receiving the influenza vaccine were 3.25 (95% CI, 2.94-3.59) times higher in the intervention group and 1.28 (95% CI, 1.15-1.42) times higher in concurrent controls than in historical controls. Conclusions and Relevance: This quality improvement study suggests that user-centered CDS may be associated with significantly improved influenza vaccination rates among hospitalized children. Stepwise implementation of CDS interventions was a practical method that was used to increase quality improvement rigor through comparison with historical and concurrent controls

Phase I study of MLN8237—investigational Aurora A kinase inhibitor—in relapsed/refractory multiple myeloma, Non-Hodgkin lymphoma and chronic lymphocytic leukemia

Purpose Amplification or over-expression of the mitotic Aurora A kinase (AAK) has been reported in several heme-lymphatic malignancies. MLN8237 (alisertib) is a novel inhibitor of AAK that is being developed for the treatment of advanced malignancies. The objectives of this phase I study were to establish the safety, tolerability, and pharmacokinetic profiles of escalating doses of MLN8237 in patients with relapsed or refractory heme-lymphatic malignancies. Methods Sequential cohorts of patients received MLN8237 orally as either a powder-in-capsule (PIC) or enteric-coated tablet (ECT) formulation. Patients received MLN8237 PIC 25–90 mg for 14 or 21 consecutive days plus 14 or 7 days’ rest, respectively, or MLN8237 ECT, at a starting dose of 40 mg/day once-daily (QD) for 14 days plus 14 days’ rest, all in 28-day cycles. Subsequent cohorts received MLN8237 ECT 30–50 mg twice-daily (BID) for 7 days plus 14 days’ rest in 21-day cycles. Results Fifty-eight patients were enrolled (PIC n = 28, ECT n = 30). The most frequent grade ≥3 drug-related toxicities were neutropenia (45 %), thrombocytopenia (28 %), anemia (19 %), and leukopenia (19 %). The maximum tolerated dose on the ECT 7-day schedule was 50 mg BID. The terminal half-life of MLN8237 was approximately 19 h. Six (13 %) patients achieved partial responses and 13 (28 %) stable disease. Conclusion The recommended phase II dose of MLN8237 ECT is 50 mg BID for 7 days in 21-day cycles, which is currently being evaluated as a single agent in phase II/III trials in patients with peripheral T-cell lymphoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10637-013-0050-9) contains supplementary material, which is available to authorized users

Topical Application of an Irreversible Small Molecule Inhibitor of Lysyl Oxidases Ameliorates Skin Scarring and Fibrosis

Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma

PURPOSE: Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT). METHODS AND MATERIALS: We performed a single institutional retrospective review of 44 patients who received BVRT. RESULTS: Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; CONCLUSIONS: Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control

High resolution crystal structure of a KRAS promoter G-quadruplex reveals a dimer with extensive poly-A pi-stacking interactions for small-molecule recognition

Aberrant KRAS signaling is a driver of many cancers and yet remains an elusive target for drug therapy. The nuclease hypersensitive element of the KRAS promoter has been reported to form secondary DNA structures called G-quadruplexes (G4s) which may play important roles in regulating KRAS expression, and has spurred interest in structural elucidation studies of the KRAS G-quadruplexes. Here, we report the first high-resolution crystal structure (1.6 A) of a KRAS G-quadruplex as a 5'-head-to-head dimer with extensive poly-A π-stacking interactions observed across the dimer. Molecular dynamics simulations confirmed that the poly-A π-stacking interactions are also maintained in the G4 monomers. Docking and molecular dynamics simulations with two G4 ligands that display high stabilization of the KRAS G4 indicated the poly-A loop was a binding site for these ligands in addition to the 5'-G-tetrad. Given sequence and structural variability in the loop regions provide the opportunity for small-molecule targeting of specific G4s, we envisage this high-resolution crystal structure for the KRAS G-quadruplex will aid in the rational design of ligands to selectively target KRAS.National Health and Medical Research Council; Australian Research Council; National Breast Cancer Foundation; A.O. would like to thank the Australian Government and UWA for scholarships and financial support. Funding for open access charge: University of Western Australia

Clinical Relevance of Myc/BCL2 Expression and Cell of Origin in Patients With Diffuse Large B-Cell Lymphoma Treated With Autologous Transplant

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall survival. On multivariable analysis, DEL/DHL, age \u3e60 years, and \u3e2 prior therapies, but not COO, were important prognostic factors for overall survival. When we explored the interaction of COO and BCL2 expression, patients with germinal center B-cell (GCB)/BCL2 (+) had inferior progression-free survival (PFS) compared to GCB/BCL2 (-) patients (HR, 4.97; P = 0.027). We conclude that the DEL/non-DHL and non-DEL/non-DHL subtypes of DLBCL have similar survival after ASCT. The negative impact of GCB/BCL2 (+) on PFS warrants future trials targeting BCL2 after ASCT. The inferior outcomes in DEL/DHL need to be verified in a larger number of patients