Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Cemiplimab in recurrent cervical cancer: Final analysis of overall survival in the phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks.

Synthesis and exploration of anticancer potential of spirocyclic 1,2,3-triazoline and aziridine derivatives of natural eudesmanolide isoalantolactone.

Eudesmane-type sesquiterpene lactone isoalantolactone 1 is of great interest due to its availability, biological activity and synthetic application. Respective series of original spirocyclic (11S,5') (1,2,3-triazoline-eudesma-4,15-enolides) and (11S)-aziridine-eudesma-4,15-enolides were efficiently synthesized via a chemoselective 1,3-dipolar cycloaddition reaction of organic azides to the exocyclic double bond of the lactone ring of isoalantolactone or 13E-(aryl)isoalantolactones by heating in DMF or toluene. The thermal reactions of isoalantolactone with benzyl azide, 2-azidoethanol, or n-butyl azide in 2-methoxyethanol afforded 13-(alkyamino)isoalantolactones formed as a mixture of (Z) and (E)-isomers.

The influence of the dry ashing procedure on the correctness of Pb determination in lichens and mosses.

Mosses and lichens are often used to assess atmospheric deposition of Pb. The most widely used method for determining this isotope is gamma spectrometric analysis. There is often a need to enhance the sensitivity of the method, which can be achieved by pre-concentrating Pb.

The role of signaling systems of plant in responding to key astrophysical factors: increased ionizing radiation, near-null magnetic field and microgravity.

Plants will form the basis of artificial ecosystems in space exploration and the creation of bases on other planets. Astrophysical factors, such as ionizing radiation (IR), magnetic fields (MF) and gravity, can significantly affect the growth and development of plants beyond Earth. However, to date, the ways in which these factors influence plants remain largely unexplored.

Integrative molecular and physiological insights into the phytotoxic impact of liquid crystal monomer exposure and the protective strategy in plants.

Liquid crystal monomers (LCMs), the integral components in the manufacture of digital displays, have engendered environmental concerns due to extensive utilization and intensive emission. Despite their prevalence and ecotoxicity, the LCM impacts on plant growth and agricultural yield remain inadequately understood. In this study, we investigated the specific response mechanisms of tobacco, a pivotal agricultural crop and model plant, to four representative LCMs (2OdF3B, 5CB, 4PiMeOP, 2BzoCP) through integrative molecular and physiological approaches.

The Evidence-Based Medicine Management of Endometriosis Should Be Updated for the Limitations of Trial Evidence, the Multivariability of Decisions, Collective Experience, Heuristics, and Bayesian Thinking.

: The diagnosis and treatment of endometriosis should be based on the best available evidence. Emphasising the risk of bias, the pyramid of evidence has the double-blind, randomised controlled trial and its meta-analyses on top. After the grading of all evidence by a group of experts, clinical guidelines are formulated using well-defined rules.

Hybrid Materials Based on Carbon Nanotubes and Tetra- and Octa-Halogen-Substituted Zinc Phthalocyanines: Sensor Response Toward Ammonia from the Quantum-Chemical Point of View.

This paper presents the results of quantum-chemical modeling performed by the Density Functional-Based Tight Binding (DFTB) method to investigate the change in the band structure of hybrid materials based on carbon nanotubes and unsubstituted, tetra-, or octa-halogen-substituted zinc phthalocyanines upon the adsorption of ammonia molecules. The study showed that the electrical conductivity of these materials and its changes in the case of interaction with ammonia molecules depend on the position of the impurity band formed by the orbitals of macrocycle atoms relative to the forbidden energy gap of the hybrids. The sensor response of the hybrids containing halogenated phthalocyanines was lower by one or two orders of magnitude, depending on the number of substituents, compared to the hybrid with unsubstituted zinc phthalocyanine.

Low-Coherence Integrated Optical Interferometer for Fibre Optic Sensors.

This paper proposes and implements a novel scheme for recording signals from fibre optic sensors based on tandem low-coherence interferometry with an integrated optical reference interferometer. The circuit allows precision control of the phase shift. Additionally, the paper illustrates the potential for detecting vibration and object deformation using fibre optic Fabry-Perot sensors connected to the registration system.

Planetary Laser Interferometric Seismoacoustic Observatory.

The paper describes a planetary laser interferometric seismoacoustic observatory consisting of six stationary unequal arm laser strainmeters. Based on the triangulation method, the fundamentals of direction finding of various infrasound disturbances at any planetary distance have been developed. The authors show that in addition to determining locations of the occurrence of the recorded disturbance, using data from spatially separated laser strainmeters, it is possible to determine the nature of these signals' divergence and, also, the loss of their energy in the propagation medium.

Algorithmic Generation of Parameterized Geometric Models of the Aortic Valve and Left Ventricle.

Simulating the cardiac valves is one of the most complex tasks in cardiovascular modeling. As fluid-structure interaction simulations are highly computationally demanding, machine-learning techniques can be considered a good alternative. Nevertheless, it is necessary to design many aortic valve geometries to generate a training set.

Association of Proteasome Activity and Pool Heterogeneity with Markers Determining the Molecular Subtypes of Breast Cancer.

Background: Proteasomes degrade intracellular proteins. Different proteasome forms were identified. Proteasome inhibitors are used in cancer therapy, and novel drugs directed to specific proteasome forms are developed.

Current Status of Neoadjuvant Treatment Before Surgery in High-Risk Localized Prostate Cancer.

Localized high-risk (HR) prostate cancer (PCa) is a heterogeneous disease whose likelihood of a biochemical recurrence, metastatic progression and cancer-related mortality after initial treatment is higher when compared with patients with low (LR) or intermediate-risk (IR) disease. In the past, neoadjuvant therapy has shown an improvement in postoperative oncological variables but failed to demonstrate any survival advantages. With the promising results from novel treatments in metastatic and non-metastatic castration resistant PCa settings, new evidence has appeared in the literature in the neoadjuvant setting.

Optimization of the Meat Flavoring Production Process for Plant-Based Products Using the Taguchi Method.

The development of plant-based meat substitutes is imperative for reducing animal fat intake and promoting dietary diversification. However, the flavor profiles of these products frequently fall short of consumer expectations. This study sought to optimize the production process of meat flavorings for plant-based products using the Taguchi method.

Towards a Quantitative Description of Proteolysis: Contribution of Demasking and Hydrolysis Steps to Proteolysis Kinetics of Milk Proteins.

The hydrolysis of proteins by proteases (proteolysis) plays a significant role in biology and food science. Despite the importance of proteolysis, a universal quantitative model of this phenomenon has not yet been created. This review considers approaches to modeling proteolysis in a batch reactor that take into account differences in the hydrolysis of the individual peptide bonds, as well as the limited accessibility (masking) for the enzymes of some hydrolysis sites in the protein substrate.

Development of a Wine Yeast Strain Capable of Malolactic Fermentation and Reducing the Ethyl Carbamate Content in Wine.

In winemaking, malolactic fermentation (MLF), which converts L-malic acid to L-lactic acid, is often applied after the alcoholic fermentation stage to improve the sensory properties of the wine and its microbiological stability. MLF is usually performed by lactic acid bacteria, which, however, are sensitive to the conditions of alcoholic fermentation. Therefore, the development of wine yeast strains capable of both alcoholic fermentation and MLF is an important task.

Highly Sensitive Lateral Flow Immunodetection of the Insecticide Imidacloprid in Fruits and Berries Reached by Indirect Antibody-Label Coupling.

A highly sensitive lateral flow immunoassay (LFIA) for imidacloprid, a widely used neonicotinoid insecticide, has been developed. The LFIA realizes the indirect coupling of anti-imidacloprid antibodies and gold nanoparticle (GNP) labels directly in the course of the assay. For this purpose, the common GNPs conjugate with anti-imidacloprid antibodies and are changed into a combination of non-modified, anti-imidacloprid antibodies, and the GNPs conjugate with anti-species antibodies.

Sea Anemone Kunitz Peptide HCIQ2c1 Reduces Histamine-, Lipopolysaccharide-, and Carrageenan-Induced Inflammation via the Suppression of Pro-Inflammatory Mediators.

Inflammation is a physiological response of the immune system to infectious agents or tissue injury, which involves a cascade of vascular and cellular events and the activation of biochemical pathways depending on the type of harmful agent and the stimulus generated. The Kunitz peptide HCIQ2c1 of sea anemone is a strong protease inhibitor and exhibits neuroprotective and analgesic activities. In this study, we investigated the anti-inflammatory potential of HCIQ2c1 in histamine- and lipopolysaccharide (LPS)-activated RAW 264.

Role of PI3 Kinases in Cell Signaling and Soleus Muscle Atrophy During Three Days of Unloading.

During skeletal muscle unloading, phosphoinositide 3-kinase (PI3K), and especially PI3K gamma (PI3Kγ), can be activated by changes in membrane potential. Activated IP3 can increase the ability of Ca to enter the nucleus through IP3 receptors. This may contribute to the activation of transcription factors that initiate muscle atrophy processes.

Cellular Partners of Tobamoviral Movement Proteins.

The size of viral genomes is limited, thus the majority of encoded proteins possess multiple functions. The main function of tobamoviral movement protein (MP) is to perform plasmodesmata gating and mediate intercellular transport of the viral RNA. MP is a remarkable example of a protein that, in addition to the initially discovered and most obvious function, carries out numerous activities that are important both for the manifestation of its key function and for successful and productive infection in general.

Asymmetry of Motif Conservation Within Their Homotypic Pairs Distinguishes DNA-Binding Domains of Target Transcription Factors in ChIP-Seq Data.

Transcription factors (TFs) are the main regulators of eukaryotic gene expression. The cooperative binding of at least two TFs to genomic DNA is a major mechanism of transcription regulation. Massive analysis of the co-occurrence of overrepresented pairs of motifs for different target TFs studied in ChIP-seq experiments can clarify the mechanisms of TF cooperation.

Anticancer Plant Secondary Metabolites Evicting Linker Histone H1.2 from Chromatin Activate Type I Interferon Signaling.

Previously we discovered that among 15 DNA-binding plant secondary metabolites (PSMs) possessing anticancer activity, 11 compounds cause depletion of the chromatin-bound linker histones H1.2 and/or H1.4.

4-Alkyl-4-thieno[2',3':4,5]pyrrolo[2,3-]quinoxaline Derivatives as New Heterocyclic Analogues of Indolo[2,3-]quinoxalines: Synthesis and Antitubercular Activity.

The synthetic approach based on a sequence of Buchwald-Hartwig cross-coupling and annulation through intramolecular oxidative cyclodehydrogenation has been used for the construction of novel 4-alkyl-4-thieno[2',3':4,5]pyrrolo[2,3-]quinoxaline derivatives. For the first time, these polycyclic compounds were evaluated for antimycobacterial activity, including extensively drug-resistant strains. A reasonable bacteriostatic effect against HRv was demonstrated.

Quantitative Analysis of Pseudogene-Associated Errors During Germline Variant Calling.

A pseudogene is a non-functional copy of a protein-coding gene. Processed pseudogenes, which are created by the reverse transcription of mRNA and subsequent integration of the resulting cDNA into the genome, being a major pseudogene class, represent a significant challenge in genome analysis due to their high sequence similarity to the parent genes and their frequent absence in the reference genome. This homology can lead to errors in variant identification, as sequences derived from processed pseudogenes can be incorrectly assigned to parental genes, complicating correct variant calling.

Nosocomial , , , and : Sensitivity to Chlorhexidine-Based Biocides and Prevalence of Efflux Pump Genes.

The widespread use of disinfectants and antiseptics has led to the emergence of nosocomial pathogens that are less sensitive to these agents, which in combination with multidrug resistance (MDR) can pose a significant epidemiologic risk. We investigated the susceptibility of nosocomial , , , and to a 0.05% chlorhexidine (CHX) solution and a biocidal S7 composite solution based on CHX (0.