In-situ photo-crosslinkable elastomer based on polyalphaolefin/halloysite nanohybrid.

In this research, new injectable and in situ photocurable elastomeric nanohybrids have been fabricated from polyalphaolefin (PAO) resins and halloysite nanofiller. In this regard, the co-oligomerization of long α-olefin monomers (C6, C8 and C10) with alkenol counterparts was carried out via a simple cationic route to provide OH-functionalized PAOs. The newly formed PAO type copolymer resins as well as halloysite nanoclay were then equipped with photocurable CC bonds containing an acrylate moiety.

C-F bond activation enables synthesis of aryl difluoromethyl bicyclopentanes as benzophenone-type bioisosteres.

Bioisosteric design has become an essential approach in the development of drug molecules. Recent advancements in synthetic methodologies have enabled the rapid adoption of this strategy into drug discovery programs. Consequently, conceptionally innovative practices would be appreciated by the medicinal chemistry community.

Achieving High Piezoelectric Performance across a Wide Composition Range in Tetragonal (Bi,Na)TiO-BaTiO Films for Micro-electromechanical Systems.

Tetragonal (1-)(Bi,Na)TiO-BaTiO films exhibit enhanced piezoelectric properties due to domain switching over a wide composition range. These properties were observed over a significantly wider composition range than the morphotropic phase boundary (MPB), which typically has a limited composition range of 1-2%. The polarization axis was found to be along the in-plane direction for the tetragonal composition range = 0.

GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles.

Homologous recombination deficiency (HRD) is a predictive biomarker for poly(ADP-ribose) polymerase 1 inhibitor (PARPi) sensitivity. Routine HRD testing relies on identifying BRCA mutations, but additional HRD-positive patients can be identified by measuring genomic instability (GI), a consequence of HRD. However, the cost and complexity of available solutions hamper GI testing.

% index and steric maps: from predictive catalysis to machine learning.

Steric indices are parameters used in chemistry to describe the spatial arrangement of atoms or groups of atoms in molecules. They are important in determining the reactivity, stability, and physical properties of chemical compounds. One commonly used steric index is the steric hindrance, which refers to the obstruction or hindrance of movement in a molecule caused by bulky substituents or functional groups.

Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance Study.

Introduction: Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years.

Methods: Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo).

Heteroresistance to cefiderocol in carbapenem-resistant in the CREDIBLE-CR study was not linked to clinical outcomes: a analysis.

The population analysis profiling (PAP) test is considered the "gold standard" method to detect heteroresistance. It exposes bacteria to increasing concentrations of antibiotics at high cell densities to detect any minority resistant subpopulations that might be missed by the low inoculums used for reference susceptibility tests. However, its clinical relevance has not been well established.

Cost-effectiveness analysis comparing repetitive transcranial magnetic stimulation therapy with antidepressant treatment in patients with treatment-resistant depression in Japan.

Repetitive transcranial magnetic stimulation (rTMS) for patients with treatment-resistant depression (TRD) became covered by the National Health Insurance (NHI) in Japan since 2019. Although the evidence of rTMS for TRD is well established, the cost-effectiveness of rTMS versus antidepressants has not been thoroughly analyzed in Japan. Thus, we aimed to evaluate the cost-effectiveness of rTMS for TRD under the NHI system using a microsimulation model to compare the direct costs and quality-adjusted life years (QALYs).

Clinical and molecular characterization of long-term survivors with extensive-stage small cell lung cancer treated with first-line atezolizumab plus carboplatin and etoposide.

Objectives: In the Phase I/III IMpower133 study, first-line atezolizumab plus carboplatin and etoposide (CP/ET) treatment for extensive-stage small cell lung cancer (ES-SCLC) significantly improved overall survival (OS) and progression-free survival versus placebo plus CP/ET. We explored patient and disease characteristics associated with long-term survival in IMpower133, and associations of differential gene expression and SCLC-A (ASCL1-driven), SCLC-N (NEUROD1-driven), SCLC-P (POU2F3-driven), and SCLC-inflamed (SCLC-I) transcriptional subtypes with long-term survival.

Materials And Methods: Patients with previously untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo.

Probing RNA-Small Molecule Interactions Using Biophysical and Computational Approaches.

Interest in small molecules that target RNA is flourishing, and the expectation set on them to treat diseases with unmet medical needs is high. However, several challenges remain, including difficulties in selecting suitable tools and establishing workflows for their discovery. In this context, we optimized experimental and computational approaches that were previously employed for the protein targets.

A tri-functional self-supported electrocatalyst featuring mostly NiTeO perovskite for H production methanol-water co-electrolysis.

A self-supported NiTeO perovskite is made by deploying an extended hydrothermal tellurization strategy with a restricted Te content, which was found to be exceptionally active towards the oxidation of water and methanol and the reduction of water in 1.0 M KOH where it delivered -10 mA cm at just -1.54 V for a full cell featuring MOR‖HER.

The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study.

The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.

Hyperautofluorescent Ring Pattern in Retinitis Pigmentosa: Clinical Implications and Modifications Over Time.

Purpose: The purpose of this study was to investigate the relation among hyperautofluorescent ring patterns, visual acuity (VA), and optical coherence tomography (OCT) features in patients with retinitis pigmentosa (RP), and to describe its modifications over time.

Methods: This was a retrospective, longitudinal, and observational study. Clinical and imaging data from the first and last available visits of patients with a clinical diagnosis of RP were reviewed.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

Background: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.

Methods: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium.

The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results.

Background: The pathfinder6 (NCT02137850) international phase 3 trial examined immunogenicity, safety, and efficacy of the extended half-life factor VIII (FVIII) replacement product N8-GP (turoctocog alfa pegol; Esperoct) in previously untreated patients (PUPs) with hemophilia A.

Objectives: We present end-of trial results for extended PUP N8-GP treatment for up to a median (range) 2.5 (0.

Clinical Classification of Variants in the Valosin-Containing Protein Gene Associated With Multisystem Proteinopathy.

Background And Objectives: Pathogenic variants in the valosin-containing protein () gene cause a phenotypically heterogeneous disorder that includes myopathy, motor neuron disease, Paget disease of the bone, frontotemporal dementia, and parkinsonism termed multisystem proteinopathy. This hallmark pleiotropy makes the classification of novel variants challenging. This retrospective study describes and assesses the effect of 19 novel or nonpreviously clinically characterized variants identified in 28 patients (26 unrelated families) in the retrospective VCP International Multicenter Study.

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results.

Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing.

Pilot Testing of a Lightweight, Pulmonary Assist System in an Ambulatory Sheep Model of Destination Therapy Respiratory Support.

A new, lightweight (2.3 kg), ambulatory pulmonary assist system (PAS) underwent preliminary evaluation in ambulatory sheep. The PAS was purposefully designed for long-term extracorporeal respiratory support for chronic lung disease and utilizes a novel, small (0.

Tetraphenylethene Derivatives Bearing Alkylammonium Substituents: Synthesis, Chemical Properties, and Application as BSA, Telomere DNA, and Hydroxyl Radical Sensors.

Tetraphenylethene derivatives (TPEs) are used as luminescence probes for the detection of metal ions and biomolecules. These sensors function by monitoring the increase in the photoluminescence (PL) intensity of the TPEs resulting from aggregation-induced emission (AIE) upon interaction with the analytes. The AIE behavior of the sensors was investigated by measuring their PL.

Long-Term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety.

Introduction: The results from 2 phase 3 studies, through 2 years, in chronic hepatitis B infection showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. We report updated results through 5 years.

Methods: Patients with HBeAg-negative or HBeAg-positive chronic hepatitis B infection with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years.

Lifelong Heterogeneous Contribution of Cardiovascular Risk Factors to Slow and Fast Progression of Arterial Stiffness.

Background: Although some cardiovascular risk factors (CVRFs) are known to be associated with increased arterial stiffness, increased arterial stiffness does not mediate the cardiovascular risk associated with all CVRFs. Here, based on long-term repeated-measurement data, we examined the association of the lifelong status of each CVRF with the rate of progression of arterial stiffness.

Methods: We utilized the data from annual health checkups with the brachial-ankle pulse wave velocity measurements over a 16-year period in middle-aged Japanese occupational cohort.

Analysis of Volatile Esters and Alkanoic Acids by an Atmospheric Pressure Corona Discharge Ionization Collision-Induced Dissociation Mass Spectrometry in Positive-Ion Mode: Ionization, Fragmentation Patterns, and Discrimination between Isomeric Compounds.

The ionization and fragmentation patterns of 24 compounds with elemental composition of CHO, including isomeric esters and alkanoic acids, were investigated by atmospheric pressure corona discharge ionization collision-induced dissociation (CID) mass spectrometry in the positive-ion mode. All compounds were ionized as protonated molecules and NH adducts. In addition, fragment ions were observed in mass spectra of esters other than methyl esters, which are owing to the dissociation of the alkyl group in the alcohol side from the protonated molecules.