Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

Intermittent enteral nutrition shortens the time to achieve nutritional goals in critically ill patients.

Nutritional support is associated with improved clinical outcomes in critically ill patients; however, loss of muscle mass during critical illness leads to weakness, delayed return to work, and increased healthcare consumption. Animal data have suggested that intermittent feeding decreases protein catabolism. This study was aimed at determining whether the mode of enteral nutrition administration might lead to differences in meeting nutritional goals, tolerance, and complications.

Negative prognostic significance of primary cilia and cytoplasmic β-catenin expression in non-small cell lung cancer.

The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts with adenocarcinoma and 93 pts with squamous cell carcinoma. In the whole group of 218 pts with NSCLC, overall survival (OS) was significantly inferior among pts with present PC than without PC (p=0.024) and with higher cytoplasmic β-catenin expression (25-75%) than with lower cytoplasmic β-catenin expression (<25%) (p=0.

[Clinical and tomographic comparisons in patients with aphasia in the acute period of ischemic stroke].

Objective: To investigate the structural damage in patients with aphasia in the acute phase of ischemic stroke using X-ray computed tomography (CT) scans of the brain.

Material And Methods: We examined 65 right-handed individuals in the acute stage of ischemic stroke in the left middle cerebral artery, including 39 men and 26 women aged 41 to 87 years. The patients were divided into two groups: those with aphasia (group 1, 48) and those without aphasia (group 2, 17).

Targeting CD45 by gene-edited CAR T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning.

Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells.

Punctuated versus gradual shifts in the multivariate evolutionary process: a test with paired radiations of scincid lizards.

As lineages become separated in time, they are expected to accumulate mutational (or developmental-genetic) differences that influence the macroevolutionary trajectories of those lineages even under similar environmental conditions. Here, we compare the dynamics of phenotypic evolution in radiations of scincid lizards from Australia and Madagascar that are separated by more than 100 million years of independent evolution and show rampant phenotypic parallelism. We collected linear measurements of the skull, limbs, and limb girdles from micro-CT scans of 94 Australian and 29 Malagasy species.

Environmental impact of the launch vehicle "Soyuz-FG" emergency falling in Kazakhstan.

On October 11, 2018, in the Ulytau region of the Republic of Kazakhstan, the Soyuz-FG launch vehicle carrying a crewed MS-10 spacecraft failed. It resulted in the release into the fragile arid ecosystems of rocket propellants, i.e.

Neuraminidase Antibody Response to Homologous and Drifted Influenza A Viruses After Immunization with Seasonal Influenza Vaccines.

Background/objectives: Humoral immunity directed against neuraminidase (NA) of the influenza virus may soften the severity of infection caused by new antigenic variants of the influenza viruses. Evaluation of NA-inhibiting (NI) antibodies in combination with antibodies to hemagglutinin (HA) may enhance research on the antibody response to influenza vaccines.

Methods: The study examined 64 pairs of serum samples from patients vaccinated with seasonal inactivated trivalent influenza vaccines (IIVs) in 2018 according to the formula recommended by the World Health Organization (WHO) for the 2018-2019 flu season.

Safety, Immunogenicity and Protective Activity of a Modified Trivalent Live Attenuated Influenza Vaccine for Combined Protection Against Seasonal Influenza and COVID-19 in Golden Syrian Hamsters.

Background/objectives: Influenza viruses and SARS-CoV-2 are currently cocirculating with similar seasonality, and both pathogens are characterized by a high mutational rate which results in reduced vaccine effectiveness and thus requires regular updating of vaccine compositions. Vaccine formulations combining seasonal influenza and SARS-CoV-2 strains can be considered promising and cost-effective tools for protection against both infections.

Methods: We used a licensed seasonal trivalent live attenuated influenza vaccine (3×LAIV) as a basis for the development of a modified 3×LAIV/CoV-2 vaccine, where H1N1 and H3N2 LAIV strains encoded an immunogenic cassette enriched with conserved T-cell epitopes of SARS-CoV-2, whereas a B/Victoria lineage LAIV strain was unmodified.

Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS).

Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here that this impairment in the crosstalk between mitochondria and the ER impedes the use of glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids to sustain energy production.

Association between serum total indoxyl sulfate, intraperitoneal inflammation, and peritoneal dialysis technique failure: a 3-year prospective cohort study.

Background: The impact of protein-bound uremic toxins, specifically indoxyl sulfate (IS) on peritoneal dialysis (PD) complications remains controversial. This study aimed to explore the link between serum total IS (tIS) levels, proinflammatory cytokines in serum and peritoneal dialysis effluent (PDE), and PD technique survival.

Methods: In this prospective cohort study, 84 patients were followed up for three years and analyzed.

Effect of 2-Aminoethoxydiphenyl Borate on the State of Skeletal Muscles in Dystrophin-Deficient Mice.

Objective: Ca overload of muscle fibers is one of the factors that secondarily aggravate the development of Duchenne muscular dystrophy (DMD). The purpose of this study is to evaluate the effects of the Ca channel modulator 2-aminoethoxydiphenyl borate (APB) on skeletal muscle pathology in dystrophin-deficient mice.

Methods: Mice were randomly divided into six groups: wild type (WT), WT+3 mg/kg APB, WT+10 mg/kg APB, , +3 mg/kg APB, +10 mg/kg APB.

Probiotic interventions in peritoneal dialysis: A review of underlying mechanisms and therapeutic potentials.

Peritoneal dialysis (PD) is a commonly used modality for kidney replacement therapy for patients with end-stage kidney disease (ESKD). PD offers many benefits, including home-based care, greater flexibility, and preservation of residual kidney function compared to in-center hemodialysis. Nonetheless, patients undergoing PD often face significant challenges, including systemic inflammation, PD-related peritonitis, metabolic disorders, and cardiovascular issues that can negatively affect their quality of life and treatment outcomes.

Ammonium and nitrate in ice accretions and snow at two Central European montane locations: δN and δ [Formula: see text] isotope ratios, fluxes and sources.

In many countries worldwide, NO emissions currently decrease as a result of pollution control, while NH emissions stagnate or continue to increase. Little is known about horizontal deposition of NO and NH, the oxidation/neutralization products of these primary pollutants. To close the knowledge gap, we studied atmospheric inputs of NO and NH at two mountain-top sites near the Czech-German-Polish borders during winter.

[Recommendations for the rehabilitation of patients with chronic kidney disease requiring hemodialysis (literature review)].

Unlabelled: Chronic kidney disease (CKD) is a global health problem, CKD is widespread in the world, on average it is detected in 10-13% of the adult population. Sedentary patients with CKD on dialysis have a higher risk of mortality. Despite the significant association of physical function with mortality in patients with CKD, physical function is not routinely assessed and exercise is not a component of the routine management of patients with CKD on dialysis.

Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial.

Background: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs.

Pivotal Role of the Intracellular Microenvironment in the High Photodynamic Activity of Cationic Phthalocyanines.

To investigate the influence of phthalocyanine aggregation on their photodynamic activity, a series of six cationic water-soluble zinc(II) phthalocyanines bearing from four to sixteen 4-((diethylmethylammonium)methyl)phenoxy substituents was synthesized. Depending on their structure, the phthalocyanines have different aggregation behaviors in phosphate buffer solutions ranging from fully assembled to monomeric states. Remarkably, independent of aggregation in buffer, very high photodynamic efficiencies against the tumor cell lines MCF-7 and MDA-MB-231 in the nanomolar range were found for all investigated phthalocyanine, and the IC(light) varied from 27 to 358 nM (3.

Renal Epithelial Complement C3 Expression Affects Kidney Fibrosis Progression.

Kidney fibrosis is a hallmark of chronic kidney diseases. Evidence shows that genetic variability and complement component 3 (C3) might influence tubulointerstitial fibrosis. Still, the role of renal C3 production in the epithelial-to-mesenchymal transition (EMT) and genetically determined fibrosis progression remains undiscovered.

Novel Mixed-Matrix Pervaporation Membrane Based on Polyether Block Amide Modified with Ho-Based Metal-Organic Framework.

Segmented polymers, such as polyether block amide (PEBA), exhibit unique properties due to the combination of different segments. PEBA consists of soft polyester and rigid polyamide blocks, enabling its use in various industrial applications, including membrane technologies. In this study, PEBA membranes modified with a holmium-based metal-organic framework (Ho-1,3,5-Hbtc) were developed for enhanced pervaporation separation of water/isopropanol and water/phenol mixtures.

Type 2 diabetes and the minor allele of PNPLA3 consistently identify high-risk metabolic dysfunction associated steatotic liver disease.

Background: Association of genetic factors with non-invasive tests (NITs) for MASLD has not been well established.

Methods: Clinical and laboratory data, liver biopsy and/or liver stiffness measurement (LSM) by transient elastography were collected from MASLD patients seen in tertiary care hepatology practices. Minor allele frequency for genomic loci rs641738 (MBOAT7), rs58542926 (TM6SF2), rs738409 (PNPLA3), rs62305723 (HSD1713B) were evaluated for association with high ELF (≥11.

Application of a modified lactate dehydrogenase assay to evaluate the viability of cells cultured on 3D scaffolds when commonly used assays fail.

The development of new compounds or materials for medicine suggests a study of their cytotoxicity. The effect of a material on cell viability can be evaluated by several methods based on DNA content, DNA synthesis, plasma membrane integrity, cellular enzyme activity, cellular reducing potential, and ATP level. Sometimes it is impossible to apply widely used commercially available reagents, e.

Targeted DNA ADP-ribosylation triggers templated repair in bacteria and base mutagenesis in eukaryotes.

Base editors create precise genomic edits by directing nucleobase deamination or removal without inducing double-stranded DNA breaks. However, a vast chemical space of other DNA modifications remains to be explored for genome editing. Here, we harness the bacterial anti-phage toxin DarT2 to append ADP-ribosyl moieties to DNA, unlocking distinct editing outcomes in bacteria versus eukaryotes.

Chimeric Virus-like Particles of Physalis Mottle Virus as Carriers of M2e Peptides of Influenza a Virus.

Plant viruses and virus-like particles (VLPs) are safe for mammals and can be used as a carrier/platform for the presentation of foreign antigens in vaccine development. The aim of this study was to use the coat protein (CP) of Physalis mottle virus (PhMV) as a carrier to display the extracellular domain of the transmembrane protein M2 of influenza A virus (M2e). M2e is a highly conserved antigen, but to induce an effective immune response it must be linked to an adjuvant or carrier VLP.