Accuracy of Reaction Coordinate Based Rate Theories for Modelling Chemical Reactions: Insights From the Thermal Isomerization in Retinal.

Modern potential energy surfaces have shifted attention to molecular simulations of chemical reactions. While various methods can estimate rate constants for conformational transitions in molecular dynamics simulations, their applicability to studying chemical reactions remains uncertain due to the high and sharp energy barriers and complex reaction coordinates involved. This study focuses on the thermal cis-trans isomerization in retinal, employing molecular simulations and comparing rate constant estimates based on one-dimensional rate theories with those based on sampling transitions and grid-based models for low-dimensional collective variable spaces.

Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial.

Purpose: The CDK4/6 inhibitor palbociclib inhibits cyclin A, which is overexpressed in endometrial cancer. Combining palbociclib with endocrine therapy improves efficacy in hormone receptor-positive breast cancer. We investigated palbociclib combined with endocrine therapy for estrogen receptor-positive advanced/recurrent endometrial cancer.

Biomechanically induced regulation of Damage-Regulated Autophagy Modulator 1 in periodontal cells and tissues.

Purpose: Autophagy is an important adaptive process for mechanotransduction, in which Damage-Regulated Autophagy Modulator 1 (DRAM1) has a key function in cell fate determination. This study aimed to analyze the influence of biomechanical loading on DRAM1 expression in periodontal cells and tissues.

Methods: Human periodontal ligament (PDL) fibroblasts were stimulated with different pressure protocols, physiological load and overload, in the presence and absence of autophagy inhibitor 3-methyladenine (3-MA) and compared with untreated cells.

Prognostic Value of Coronary CT Angiography-Derived Quantitative Flow Ratio in Suspected Coronary Artery Disease.

Background The prognostic value of coronary CT angiography (CTA)-derived quantitative flow ratio (CT-QFR) remains unknown. Purpose To determine the prognostic value of CT-QFR in predicting the long-term outcomes of patients with suspected coronary artery disease (CAD) in comparison with invasive coronary angiography (ICA)/SPECT and to determine the influence of prior percutaneous coronary intervention (PCI) on the prognostic value of CT-QFR. Materials and Methods In this secondary analysis of the prospective international CORE320 study, 379 participants who underwent coronary CTA and SPECT within 60 days before ICA between November 2009 and July 2011 were included for follow-up.

Type 2 responses determine skin rash during recombinant interleukin-2 therapy.

The skin is the organ most often affected by adverse drug reactions. Although these cutaneous adverse drug reactions (CADRs) often are mild, they represent a major burden for patients. One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy.

Changes in Functional Connectivity Relate to Modulation of Cognitive Control by Subthalamic Stimulation.

Subthalamic (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients not only improves kinematic parameters of movement but also modulates cognitive control in the motor and non-motor domain, especially in situations of high conflict. The objective of this study was to investigate the relationship between DBS-induced changes in functional connectivity at rest and modulation of response- and movement inhibition by STN-DBS in a visuomotor task involving high conflict. During DBS ON and OFF conditions, we conducted a visuomotor task in 14 PD patients who previously underwent resting-state functional MRI (rs-fMRI) acquisitions DBS ON and OFF as part of a different study.

Guanidine Derivative ADS1017, a Potent Histamine H Receptor Antagonist with Promising Analgesic Activity and Satisfactory Safety Profile.

In this study, we selected 12 guanidine derivatives from the previously described ligand library and determined their affinity at histamine H and H receptors (HR and HR, respectively). Moreover, we also checked their intrinsic activity toward HR and muscarinic M, M, and M receptors (MR, MR, and MR, respectively). Since ADS1017 has been proved to be the most selective and highly potent H antagonist in our series, we chose it as the lead structure for further biological evaluation.

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Intraspecific genetic diversity with unrestricted gene flow in the domoic acid-producing diatom Nitzschia navis-varingica (Bacillariophyceae) from the Western Pacific.

The benthic pennate diatom Nitzschia navis-varingica, known for producing domoic acid (DA) and its isomers, is widely distributed in the Western Pacific (WP) region. To investigate the genetic differentiation and gene flow patterns among the populations in the WP, the genetic diversity of 354 strains of N. navis-varingica was analysed using two nuclear-encoded rDNA loci: the large subunit rDNA (LSU rDNA) and the internal transcribed spacer 2 (ITS2).

Biological, as opposed to classic antipsoriatic drug or apremilast, treatment mitigates the risk of death and cardiovascular disease in psoriasis.

Background: Cardiovascular comorbidity increases morbidity and mortality in psoriasis. Systemic treatments, particularly biologics, are effective in alleviating skin and joint inflammation. Conversely, the impact of systemic therapy on cardiovascular disease risk and mortality in psoriasis remains uncertain.

Microplastic analysis in soils: A comparative assessment.

Microplastic (MiP) contamination poses environmental risks, but harmonizing data from different quantification methods and sample matrices remains challenging. We compared analytical protocols for MiP quantification in soil, consisting of Digital, Fluorescence, Fourier-transform infrared (FTIR), and Raman Microscopy as well as quantitative Pyrolysis-Gas Chromatography-Mass Spectroscopy (Py-GC-MS) and 1-proton nuclear magnetic resonance (H NMR) spectroscopy as detection techniques. Each technique was coupled with a specific extraction procedure and evaluated for three soils with different textures and organic carbon contents, amended with eight types of large MiPs (0.

To consolidate or not to consolidate: the role of autologous stem cell transplantation in MCL.

An Ara-C-containing intensified induction therapy followed by autologous stem cell transplantation (ASCT) is considered a highly effective treatment strategy in younger mantle cell lymphoma (MCL) patients, inducing long-lasting remissions. However, ASCT is also hampered by acute and delayed toxicity. Thus, alternative first-line treatment strategies without ASCT but including novel agents are under investigation.

PSMA - Targeted Clinical Molecular Imaging of Atherosclerosis: Correlation with Cardiovascular Risk Factors.

Aim: The early diagnosis of atherosclerotic changes to prevent ischemic events represents a clinical challenge.Prostate-specific membrane antigen (PSMA) as an established diagnostic in the field of prostate cancer also appears to detect neovascularization and inflammation in other diseases. We hypothesized that it might be also suited for detection of inflammation in atherosclerosis.

A conserved cell-pole determinant organizes proper polar flagellum formation.

The coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear.

Multicenter Clinical Performance Evaluation of the NeuMoDx™ CT/NG Assay 2.0.

Background: Given the continued increases in rates of both Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, additional diagnostic assays may be useful in increasing access to testing for these sexually transmitted infections. We evaluated the performance of the NeuMoDx™ CT/NG Assay 2.0 on the NeuMoDx-96 and NeuMoDx-288 Molecular Systems.

Autoimmune-Like Mechanism in Heart Failure Enables Preventive Vaccine Therapy.

Background: Heart failure (HF) is strongly associated with inflammation. In pressure overload (PO)-induced HF, cardiac stress triggers adaptive immunity, ablation or inhibition of which blocks disease progression. We hypothesized that PO-HF might fulfill the often-used criteria of autoimmunity: if so, the associated adaptive immune response would be not only necessary but also sufficient to induce HF; it should also be possible to identify self-antigens driving the autoimmune response.