SAFETY AND THERAPEUTIC EFFECTS OF ORALLY ADMINISTERED AKST4290 IN NEWLY DIAGNOSED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

Purpose: To evaluate the safety and therapeutic effects of orally administered AKST4290 (formerly BI 144807 and ALK4290) in treatment-naive patients with neovascular age-related macular degeneration.

Methods: In this prospective, multicenter, open-label Phase 2a pilot clinical study, 30 patients with newly diagnosed neovascular age-related macular degeneration self-administered AKST4290 (400 mg) orally twice daily for 6 weeks. Patients were examined weekly for safety, to measure best-corrected visual acuity (BCVA), and to perform exploratory morphologic assessments.

Safety and tolerability of GRF6019 in mild-to-moderate Alzheimer's disease dementia.

Introduction: This phase 2 trial evaluated the safety, tolerability, and feasibility of repeated infusions of the plasma fraction GRF6019 in mild-to-moderate Alzheimer's disease.

Methods: In this randomized, double-blind, dose-comparison trial, 47 patients were randomized 1:1 to receive daily infusions of 100 mL (n = 24) or 250 mL (n = 23) of GRF6019 for 5 consecutive days over two dosing periods separated by a treatment-free interval of 3 months.

Results: The mean (standard deviation [SD]) age of the enrolled patients was 74.

A Phase 2a, Double-Blind, Placebo-controlled Randomized Trial of Inhaled TLR9 Agonist AZD1419 in Asthma.

To examine the potential of TLR9 (Toll-like receptor 9) activation to modulate the type 2 immune response in asthma. To evaluate efficacy and safety of AZD1419, an inhaled TLR9 agonist, in a phase 2a, randomized, double-blind trial. Adult patients with asthma with a history of elevated eosinophils (>250 cells/μl) were randomized 1:1 to receive 13 once-weekly doses of inhaled AZD1419 (1, 4, or 8 mg;  = 40) or placebo ( = 41).

Machine learning and big scientific data.

This paper reviews some of the challenges posed by the huge growth of experimental data generated by the new generation of large-scale experiments at UK national facilities at the Rutherford Appleton Laboratory (RAL) site at Harwell near Oxford. Such 'Big Scientific Data' comes from the Diamond Light Source and Electron Microscopy Facilities, the ISIS Neutron and Muon Facility and the UK's Central Laser Facility. Increasingly, scientists are now required to use advanced machine learning and other AI technologies both to automate parts of the data pipeline and to help find new scientific discoveries in the analysis of their data.

Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial.

Importance: Young mouse plasma restores memory in aged mice, but, to our knowledge, the effects are unknown in patients with Alzheimer disease (AD).

Objective: To assess the safety, tolerability, and feasibility of infusions of young fresh frozen plasma (yFFP) from donors age 18 to 30 years in patients with AD.

Design, Setting, And Participants: The Plasma for Alzheimer Symptom Amelioration (PLASMA) study randomized 9 patients under a double-blind crossover protocol to receive 4 once-weekly infusions of either 1 unit (approximately 250 mL) of yFFP from male donors or 250 mL of saline, followed by a 6-week washout and crossover to 4 once-weekly infusions of an alternate treatment.

Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults.

Background: Hepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV-B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine.

State anxiety and information processing: A 7.5% carbon dioxide challenge study.

We used the 7.5% carbon dioxide model of anxiety induction to investigate the effects of state anxiety on simple information processing. In both high- and low-anxious states, participants (n = 36) completed an auditory-visual matching task and a visual binary categorization task.

Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults.

Background: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke.

Methods: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age.

First-in-Human Study With the Inhaled TLR9 Oligonucleotide Agonist AZD1419 Results in Interferon Responses in the Lung, and Is Safe and Well-Tolerated.

Current asthma treatments address symptoms rather than the underlying disease pathophysiology, a better understanding of which has led to the identification of the Th2 high endotype. The activation of Toll-like receptors to induce Type I interferons directly in the lungs represents a novel therapeutic approach to reset this underlying Th2 pathophysiology with the potential to provide long-term disease modification. We present the nonclinical data and phase I clinical profile of an inhaled TLR9 agonist, AZD1419, a C-type CpG designed to induce interferon in the lung.

Significant Improvement of Optoelectronic and Photovoltaic Properties by Incorporating Thiophene in a Solution-Processable D-A-D Modular Chromophore.

Through the incorporation of a thiophene functionality, a novel solution-processable small organic chromophore was designed, synthesized and characterized for application in bulk-heterojunction solar cells. The new chromophore, (2Z,2'Z)-2,2'-(1,4-phenylene)bis(3-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)acrylonitrile) (coded as AS2), was based on a donor-acceptor-donor (D-A-D) module where a simple triphenylamine unit served as an electron donor, 1,4-phenylenediacetonitrile as an electron acceptor, and a thiophene ring as the π-bridge embedded between the donor and acceptor functionalities. AS2 was isolated as brick-red, needle-shaped crystals, and was fully characterized by ¹H- and (13)C-NMR, IR, mass spectrometry and single crystal X-ray diffraction.

Immunogenicity of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in subpopulations of healthy adults 18-70 years of age.

Background: Immunologic response to a complete vaccine regimen of currently licensed alum-adjuvanted hepatitis B vaccines is reduced in several subpopulations, including older adults, men, obese persons, and smokers. Two phase 3 trials in healthy adults demonstrated that 2 doses over 1 month of an investigational hepatitis B vaccine (HBsAg-1018) induced superior seroprotection rates (SPRs) to 3 doses over 6 months of the licensed vaccine Engerix-B (HBsAg-Eng).

Methods: An exploratory analysis of immunogenicity was conducted in subpopulations from pooled data for the 2 phase 3 trials.

Tetraphenylethene-based star shaped porphyrins: synthesis, self-assembly, and optical and photophysical study.

Supramolecular self-assembly and self-organization are simple and convenient ways to design and create controlled assemblies with organic molecules, and they have provoked great interest due to their potential applications in various fields, such as electronics, photonics, and light-energy conversion. Herein, we describe the synthesis of two π-conjugated porphyrin molecules bearing tetraphenylethene moieties with high fluorescence quantum yield. Photophysical and electrochemical studies were conducted to understand the physical and redox properties of these new materials, respectively.

Progression in multiple sclerosis is associated with low endogenous NCAM.

Multiple sclerosis (MS) is a CNS disorder characterized by demyelination and neurodegeneration. Although hallmarks of recovery (remyelination and repair) have been documented in early MS, the regenerative capacity of the adult CNS per se remains uncertain with the wide held belief that it is either limited or non-existent. The neural cell adhesion molecule (NCAM) is a cell adhesion molecule that has been widely implicated in axonal outgrowth, guidance and fasciculation.

Neurofilament a biomarker of neurodegeneration in autoimmune encephalomyelitis.

Monitoring neuroaxonal loss in multiple sclerosis is an important objective to study the pathogenesis and response to treatment of the disease. The release of neurofilaments is a potential surrogate biomarker of neurodegeneration. One route to explore this aspect further is through the use of animal models that have well-defined, and predictable, disease courses.