Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides.

We report the synthesis and characterization of naphthalene and anthracene scaffolds end-capped by cyclic imides. The solid-state structures of the -phenyl derivatives, determined by X-ray crystallography, reveal changes in packing preference based on the number of aromatic rings in the core. The optical and electronic properties of the title compounds compare favorably with other previously described isomers and expand the toolbox of electron-deficient aromatic compounds available to organic materials chemists.

Lestaurtinib's antineoplastic activity converges on JAK/STAT signaling to inhibit advanced forms of therapy resistant ovarian cancer.

Unlabelled: Ovarian cancer is the deadliest gynecological malignancy, owing to its late-stage diagnosis and high rates of recurrence and resistance following standard-of-care treatment, highlighting the need for novel treatment approaches. Through an unbiased drug screen, we identified the kinase inhibitor, lestaurtinib, as a potent antineoplastic agent for chemotherapy- and PARP-inhibitor (PARPi)-sensitive and -resistant ovarian cancer cells and patient derived xenografts (PDXs). RNA-sequencing revealed that lestaurtinib potently suppressed JAK/STAT signaling and lestaurtinib efficacy was shown to be directly related to JAK/STAT pathway activity in cell lines and PDX models.

Electron stimulated desorption from condensed benzene.

The electron induced dissociation of condensed benzene (CH) in thin films deposited on a Pt substrate is investigated by electron stimulated desorption (ESD) of anions and cations. The desorbed yields are recorded as a function of incident electron energy in the range of 10 to 950 eV for a fixed film thickness of 2 monolayers (ML) and for a fixed energy of 950 eV, as well as a function of film thickness from 0.5 to 8 monolayers (ML) for anions, and from 0.

Electron-Induced Damage by UV Photolysis of DNA Attached to Gold Nanoparticles.

Photolysis of DNA attached to gold nanoparticles (AuNPs) with ultraviolet (UV) photons induces DNA damage. The release of nucleobases (Cyt, Gua, Ade, and Thy) from DNA was the major reaction (99%) with an approximately equal release of pyrimidines and purines. This reaction contributes to the formation of abasic sites in DNA.

Improved Syntheses of Halogenated Benzene-1,2,3,4-Tetracarboxylic Diimides.

The preparation of halogenated benzene-1,2,3,4-tetracarboxylic diimide derivatives is challenging because of the possibility of competitive incorrect cyclizations and SAr reactivity. Here, we demonstrate that bypassing traditional cyclic anhydrides and instead directly reacting dihalobenzene-1,2,3,4-tetracarboxylic acids with primary amines in acetic acid solvent successfully provides a range of desirable -diimide products in good yields. Furthermore, we demonstrate that sterically challenging -derivatizations can be readily achieved under microwave reactor conditions.

The sequential natalizumab - alemtuzumab therapy in patients with relapsing forms of multiple sclerosis (SUPPRESS) trial - Part I: Rationale and objectives.

Background: Natalizumab is a recombinant humanized monoclonal antibody (mAb) against α4-integrin that is approved for relapsing forms of multiple sclerosis (MS). Natalizumab is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), and with disease reactivation after cessation of treatment that is likely mediated by an accumulation of pro-inflammatory lymphocytes in the blood during therapy. Alemtuzumab is a mAb against CD52 that reduces the number of peripheral lymphocytes.

Low-Energy Electron Damage to Plasmid DNA in Thin Films: Dependence on Substrates, Surface Density, Charging, Environment, and Uniformity.

The interaction of low-energy electrons (LEEs) with DNA plays a significant role in the mechanisms leading to biological damage induced by ionizing radiation, particularly in radiotherapy, and its sensitization by chemotherapeutic drugs and nanoparticles. Plasmids constitute the form of DNA found in mitochondria and appear as a suitable model of genomic DNA. In a search for the best LEE targets, damage was induced to plasmids, in thin films in vacuum, by 6, 10, and 100 eV electrons under single collision conditions.

Shape Resonances in DNA: Nucleobase Release, Reduction, and Dideoxynucleoside Products Induced by 1.3 to 2.3 eV Electrons.

Understanding the details of DNA damage caused by high-energy particles or photons is complicated by the multitude of reactive species, arising from the ionization and dissociation of HO, DNA, and protein. In this work, oligonucleotides (ODNs) are irradiated with a beam of low-energy electrons of 1.3 to 2.

Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data.

Does preexisting or treatment-emergent autoimmunity increase the risk of subsequent autoimmune disease in individuals with relapsing-remitting multiple sclerosis (MS) after alemtuzumab? In the extended phase 2/3 trials, 34/96 (35.4%) patients with and 395/1120 (35.3%) without preexisting autoimmunity developed non-MS autoimmunity.

Chemical transformation of molecular ices containing NO and CD by low energy electrons: New chemical species of astronomical interest.

We have employed electron stimulated desorption (ESD) and x-ray photoelectron spectroscopy (XPS) to study the chemical species generated from multilayer films of NO, CD, and mixtures thereof (i.e., NO/CD) by the impact of low energy electrons with energies between 30 and 70 eV.

Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial.

Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline.

Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2.

CLICK-MS and MASTER-2 Phase IV trial design: cladribine tablets in suboptimally controlled relapsing multiple sclerosis.

Cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) are approved for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting MS and active secondary progressive MS. However, real-world data on cladribine tablets are limited.

Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years.

Background: Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]).

Methods: Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years).

Effect of Multiple Sclerosis on Daily Activities, Emotional Well-being, and Relationships: The Global vsMS Survey.

Background: The vsMS survey was conducted to better understand the negative effects of fatigue, cognitive impairment, emotional burden, and decreased physical functioning on the personal, professional, and social lives of individuals with multiple sclerosis (MS).

Methods: The vsMS survey was an online survey conducted in Australia, Canada, France, Italy, Spain, the United Kingdom, and the United States that assessed the impact of MS on individuals' daily activities, emotional well-being, relationships, and employment.

Results: The survey included 1075 participants with relapsing-remitting MS.

Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study.

Background: Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously.

Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223.

Background: In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing-remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656).

Methods: In CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course.

Low energy (6-18 eV) electron scattering from condensed thymidine (dT) III: absolute electronic excitation cross sections.

Absolute cross sections (CSs) for electronic excitation by low-energy electron (LEE) scattering, from condensed thymidine (dT) in the 6-18 eV incident energy range, were measured by high-resolution electron energy loss spectroscopy (HREELS). Various electron energy loss (EEL) spectra were acquired using 1 ML of dT condensed on a multilayer film of Ar held at about 20 K under ultra-high vacuum (∼1 × 10-11 Torr). dT is one of the most complex DNA constituents to be studied by HREELS and these spectra provide the first LEE energy-loss data for electronic excitation of a nucleoside.

Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies.

Background: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses.

Objective: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) studies and their extensions.

Increased cognitive load during acquisition of a continuous task eliminates the learning effects of self-controlled knowledge of results.

Previous research has demonstrated that providing learners with self-control over some aspect of practice enhances motor learning (for a review see Wulf, 2007). One explanation for the self-control effect is that learners engage in deeper information processing when they are allowed to make choices during practice. Recent research has supported this line of thinking by showing that the self-control effect was eliminated for learners who engaged in a cognitive load task during the interval following completion of discrete task trials (Carter & Ste-Marie, 2017).

Low energy (1-19 eV) electron scattering from condensed thymidine (dT) II: comparison of vibrational excitation cross sections with those of tetrahydrofuran and the recalibrated values of thymine.

Recent measurements of absolute vibrational cross sections (CSs) for low-energy electron (LEE) scattering from condensed thymidine (dT) allows comparison with CSs of its constituents; thymine and tetrahydrofuran (THF). To facilitate this comparison, the vibrational CSs of condensed thymine were remeasured at six electron incident energies and a correction was applied to the earlier thymine CS values measured by Lévesque et al. [Nucl.

Low energy (1-19 eV) electron scattering from condensed thymidine (dT) I: absolute vibrational excitation cross sections.

Absolute cross sections (CSs) for vibrational excitation by electrons of energy between 1-19 eV scattering from condensed thymidine (dT) were measured by means of high-resolution electron energy loss spectroscopy (HREELS). The CSs were extracted from electron energy loss spectra of dT condensed on multilayers film of Ar held at about 20 K under ultra-high vacuum (∼1 × 10-11 Torr). dT is one of the most complex molecules to be studied in condensed phase by HREELS.

Best Practices for Long-Term Monitoring and Follow-Up of Alemtuzumab-Treated MS Patients in Real-World Clinical Settings.

Multiple sclerosis (MS) is a chronic autoimmune neurological disease that typically affects young adults, causing irreversible physical disability and cognitive impairment. Alemtuzumab, administered intravenously as 2 initial courses of 12 mg/day (5 consecutive days at baseline, and 3 consecutive days 12 months later), resulted in significantly greater improvements in clinical and MRI outcomes vs. subcutaneous interferon beta-1a over 2 years in patients with active relapsing-remitting MS (RRMS) who were either treatment-naive (CARE-MS I; NCT00530348) or had an inadequate response to prior therapy (CARE-MS II; NCT00548405).

Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.

Background: Alemtuzumab is a highly effective therapy for relapsing-remitting multiple sclerosis (RRMS), and immune thrombocytopenia (ITP) has been identified as a risk.

Objective: To examine ITP incidence, treatment, and outcomes during the clinical development of alemtuzumab for RRMS and discuss postmarketing experience outside clinical trials.

Methods: CAMMS223 and Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and II investigated two annual courses of alemtuzumab 12 mg (or 24 mg in CAMMS223/CARE-MS II) versus subcutaneous interferon beta-1a three times per week.