Population Pharmacokinetics of Ledipasvir/Sofosbuvir in Pediatric Patients: Impact of Acute Lymphoblastic Leukemia.

Purpose: The pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF), might be altered in patients with acute lymphoblastic leukemia (ALL), affecting the optimum dose needed for hepatitis C virus treatment. Limited data are available evaluating the population PK of LDV/SOF and SOF metabolite GS-331007. We aimed to study whether ALL could affect population PK parameters of LDV, SOF, and the SOF major metabolite GS-331007 in hepatitis C virus-infected children, develop and validate a predictive PK model of LDV/SOF disposition in this special population, and identify their explained and unexplained sources of variability.

Potential Therapeutic Benefit of the Selective Inhibitors of Casitas B Cell Lymphoma-b (CBL-B) in Cancer Immunotherapy.

The invention in this patent application relates to 1,6-dihydro-7-pyrrolo[2,3-]pyridin-7-one derivatives represented generally by formula 1. These compounds are inhibitors of the E3 ubiquitin ligase, casitas B-lineage lymphoma proto-oncogene-b (CBL-B), and may be useful for the treatment of immunosuppression-associated diseases and disorders such as cancer and chronic viral infections.

Inhibition of the Binding of Interleukin 17A with Interleukin 17A Receptor as a Treatment for Immune System and Inflammation Disorders, Cancer, and Neurodegenerative Diseases.

The invention in this patent application relates to -(2-amino-2-oxoethyl)heteroarylcarboxamide derivatives, represented herein generally by formula 1. These compounds are inhibitors of the binding of interleukin 17A (IL-17A) with its receptor IL-17RA and may potentially be used for the treatment of diseases or disorders associated with IL-17A activity, which include psoriasis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis, cancer, and neurodegenerative disorders.

Linear optical properties of organic microcavity polaritons with non-Markovian quantum state diffusion.

Hybridisation of the cavity modes and the excitons to polariton states together with the coupling to the vibrational modes determine the linear optical properties of organic semiconductors in microcavities. In this article we compute the refractive index for such system using the Holstein-Tavis-Cummings model and determine then the linear optical properties using the transfer matrix method. We first extract the parameters for the exciton in our model from fitting to experimentally measured absorption of a 2,7-bis[9,9-di(4-methylphenyl)-fluoren-2-yl]-9,9-di(4-methylphenyl) fluorene (TDAF) molecular thin film.

Inhibitors of the Cyclic GMP-AMP Synthase (cGAS) as Potential Treatment for Autoimmune and Inflammatory Diseases.

The invention in this patent application relates to macrocyclic benzimidazole derivatives represented herein generally by Formula 1. The compounds of Formula 1 are cGAS inhibitors and may potentially provide treatments of autoimmune diseases such as systemic lupus erythematosus, systemic sclerosis (SSc), interferonopathies, and others.

Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) as Treatment for Inflammatory Diseases.

The invention in this patent application relates to 9,10,11,12-tetrahydro-8-[1,4]diazepino[5',6':4,5]thieno[3,2-]quinolin-8-one derivatives represented herein generally by Formula . These compounds are inhibitors of MK2 kinases and may provide useful treatments for MK2-mediated diseases or disorders such as autoimmune disorders, chronic or acute inflammatory disorders, autoinflammatory disorders, fibrotic disorders, metabolic disorders, neoplasia, or cardiovascular or cerebrovascular disorders.

Effects of Particle Size on Mechanical Properties and Forming Accuracy of Powder/Polyethersulfone Composites Produced via Selective Laser Sintering.

Wood-plastic composites are becoming increasingly recognized for their sustainability and their potential for use in various production processes. Nevertheless, enhancing their mechanical strength continues to be a difficult challenge. The objective of this research was to improve the mechanical strength of wood-plastic composite components manufactured through selective laser sintering (SLS).

The Inhibitors of Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT-1) Protease as Potential Treatment of ABC-DLBCL and Similar Diseases.

The invention in this patent application relates to thiazolo[5,4-]pyridine derivatives represented generally by formula . These compounds are inhibitors of the activity of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT-1) protease and may potentially be useful in the treatment of some forms of cancer, particularly ABC-DLBCL.

Somatostatin Receptor Subtype 4 Agonists for Potential Treatment of Alzheimer's Disease and Other Central Nervous System Disorders.

The invention in this patent application relates to -(pyrrolidine-3-yl or piperidin-4-yl)acetamide derivatives represented generally by formula 1. These compounds possess activities as somatostatin receptor 4 (SSTR4) agonists and may potentially be beneficial in the treatment of diseases or disorders, associated with SSTR4 such as Alzheimer's disease (AD) and other CNS disorders such as epilepsy and depression.

Identifying the origin of delayed electroluminescence in a polariton organic light-emitting diode.

Modifying the energy landscape of existing molecular emitters is an attractive challenge with favourable outcomes in chemistry and organic optoelectronic research. It has recently been explored through strong light-matter coupling studies where the organic emitters were placed in an optical cavity. Nonetheless, a debate revolves around whether the observed change in the material properties represents novel coupled system dynamics or the unmasking of pre-existing material properties induced by light-matter interactions.

Inhibitors of Son of Sevenless Isoform 1 (SOS1) as a Potential Treatment for RAS Mutant Cancers.

The invention in this patent application relates to 1-aminophthalazine derivatives represented generally by formula 1. These compounds are inhibitors of the interaction of the catalytic site of SOS1 with RAS-family proteins which are involved in controlling cell proliferation. They may potentially be used as a treatment for RAS mutant cancers such as pancreatic, lung, and colorectal cancers, cholangiocarcinoma, multiple myeloma, melanoma, and thyroid cancer.

Positive Allosteric Modulators of alpha7 Nicotinic Acetylcholine Receptor for the Treatment of Several Central Nervous System Diseases.

The invention in this patent application relates to spirocyclopropane-2-carboxamide derivatives represented generally by formula 1. These compounds are positive allosteric modulators of α7 nAChR and may be useful in preventing, treating, or ameliorating central nervous system diseases and disorders such as cognitive impairments in Alzheimer's disease, Parkinson's disease, schizophrenia, and L-DOPA-induced dyskinesia as well as inflammation and cough.

Ledipasvir/Sofosbuvir in Hepatitis C Virus-Infected Children With Hematological Malignancies: A Pharmacokinetic Study.

Purpose: Children with hematological malignancies and chronic hepatitis C virus (HCV) infection are at a higher risk for rapid progression of liver disease and malignancy relapse due to multiple hepatitis flares and chemotherapy interruption. They are therefore potential candidates for microelimination of HCV infection. This study aimed to assess the effect of acute lymphoblastic leukemia (ALL) on the pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF) and the SOF major metabolite GS-331007.

Targeting the Inhibition of B-Cell Lymphoma 2 Protein for the Treatment of Cancer.

The invention in this patent application relates to 1,3,4,7-tetrahydro-2-pyrrolo[3',2':5,6]pyrido[2,3-][1,4]oxazepine derivatives represented generally by Formula 1. These compounds are Bcl-2 inhibitors and may be useful for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, and/or acute lymphocytic lymphoma.

The Potential of NOD-like Receptor Protein 3 Inflammasome Inhibitors in the Treatments of Diseases.

The invention in this patent application relates to 4-aminopyridazin-6-one derivatives represented generally by formula 1. These compounds are inhibitors of the NOD-like receptor protein 3 (NLRP3) inflammasome pathway and may potentially provide a useful treatment for one or more of the diseases and disorders mediated by NLRP3, including but not limited to immune diseases, inflammatory diseases, autoimmune diseases, autoinflammatory fever syndromes, cryopyrin-associated periodic syndrome, chronic liver disease, kidney-related disease, hyperoxaluria, lupus nephritis, Type I and Type II diabetes, nephropathy, neurodegenerative diseases, Alzheimer's disease, cardiovascular diseases, metabolic diseases and many more.

Influence of Particle Size on the Mechanical Performance and Sintering Quality of Peanut Husk Powder/PES Composites Fabricated through Selective Laser Sintering.

This study intends to enhance the mechanical strength of wood-plastic composite selective laser sintering (SLS) parts by using a sustainable composite, peanut husk powder (PHP)/poly ether sulfone (PES) (PHPC). The study aims to address agricultural waste pollution by encouraging the eco-friendly utilization of such waste in SLS technology. To ensure the sintering quality and mechanical properties and prevent deformation and warping during sintering, the thermo-physical properties of PHP and PES powders were analyzed to determine a suitable preheating temperature for PHPC.

Developing Solution-Processed Distributed Bragg Reflectors for Microcavity Polariton Applications.

Improving the performance of organic optoelectronics has been under vigorous research for decades. Recently, polaritonics has been introduced as a technology that has the potential to improve the optical, electrical, and chemical properties of materials and devices. However, polaritons have been mainly studied in optical microcavities that are made by vacuum deposition processes, which are costly, unavailable to many, and incompatible with printed optoelectronics methods.

Inhibitors of Interleukin 4 Induced Protein 1 (IL4I1) as Potential Treatment for Cancer.

The invention in this patent application relates to piperazine-2,3-dione derivatives represented generally by formula 1. These compounds show activities as selective interleukin 4 induced protein 1 (IL4I1) inhibitors and may potentially be useful in preventing and treating IL4Il-related diseases, such as endometrial, ovarian, and triple negative breast cancers.

Plasma Kallikrein Inhibitors as Potential Treatment for Diabetic Macular Edema, Retinal Vein Occlusion, Hereditary Angioedema and Other Related Diseases.

The invention in this patent application relates to ()-spiro[benzo[][1,3]oxazine-4,3'-pyrrolidin]-2(1)-one derivatives, represented generally by formula 1. These compounds are selective plasma kallikrein inhibitors and may potentially be beneficial in the treatment of several diseases and disorders, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy, and retinal vein occlusion.

Common coronary artery occlusions in patients with myocardial infarction.

Introduction: coronary artery disease (CAD) is a significant cardiovascular disease (CVD) that affects people worldwide. This study aimed to determine the main occluded coronary arteries in patients with myocardial infarction in Najran, Kingdom of Saudi Arabia (KSA).

Methods: a retrospective cross-sectional study conducted between March 2020 and March 2021 and involving 661 myocardial infarction patients recruited from two hospitals (King Khalid Hospital and Prince Sultan Centre for Healthcare in Najran) used sampling for enrolled patients.

Glyphosate-induced liver and kidney dysfunction, oxidative stress, immunosuppression in Nile tilapia, but ginger showed a protection role.

The water-borne herbicides are involved in the toxicity of aquatic animals resulting in impaired health status and low productivity. Dietary medicinal herbs present a practical solution to relieve the impacts of herbicides toxicity on the performances of aquatic animals. Herein, we investigated the toxicity of commercial glyphosate-induced oxidative stress, immunosuppression, liver and kidney dysfunction, and the protective role of ginger or ginger nanoparticles in Nile tilapia.