Moscow Institute of Modern Business

We show that a completely non-degenerate $B$-group is uniquely determined by its factor: two such groups with conformally equivalent factors are Möbius conjugate. A similar property is inherent to the quasi-Fuchsian groups but not to degenerate $B$-groups. We also study the factor of a $B$-group as a triple: the main factor, the marked characteristic complex, and a homotopy class of maps of the first to the second one.

We propose several constructions of nonbinary constant-weight codes meeting the Johnson bound.

BackgroundBepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins.MethodsWe conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication.ResultsThe intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4).ConclusionsIn this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.)

Introduction: Bulevirtide (BLV) is a first-in-class entry inhibitor for the treatment of chronic hepatitis D virus (cHDV) infection. BLV has shown pronounced virologic and biochemical responses in two Phase 2 trials. We present findings of a predefined 24-week interim analysis of the MYR301 Phase 3 study in HBV/HDV co-infected patients receiving 2 or 10 mg qd BLV monotherapy in comparison to no antiviral treatment. Methods: 150 patients with cHDV infection were randomized 1:1:1 to no antiviral treatment for 48 weeks followed by 10 mg qd BLV for 96 weeks (arm A, n=51) or to 2 mg qd BLV (arm B, n=49) or 10 mg qd BLV (arm C, n=50) for 144 weeks with a 96-week treatment-free follow-up. The primary endpoint, combined response, was defined as undetectable HDV RNA (< LoD) or decrease by ≥2 log10 IU/mL and ALT normalization at week 48; secondary endpoints included undetectable HDV RNA, decline by ≥2 log10 IU/mL, ALT normalization, and HBsAg decline by ≥1 log10 IU/mL. Results: Owing to a communications embargo, Week 48 data were not available for this submission. We will include those data for presentation of this abstract at the ACG conference. Patient characteristics: 57% were male, 83% were white, mean age was 42 years. Baseline HDV RNA levels were 5.05 log10 IU/mL; mean ALT was 110.9 U/L. BLV was well tolerated over the first 24 weeks; 421 treatment-emergent adverse events (TEAE) were reported: 55 TEAEs in 26 patients in arm A, 121 TEAEs in 32 patients in arm B, and 245 TEAEs in 36 patients in arm C. 48 TEAEs in arm B and 100 in arm C were assessed as possibly related to BLV. One serious TEAE was reported in one patient in arm A. At week 24, the proportions of patients achieving combined virologic and biochemical response were 37% in arm B and 28% in arm C (vs 0% in arm A, p< 0.0001). An HDV RNA decrease by ≥2 log10 IU/mL at week 24 from baseline was observed in 55% of patients in arm B and 68% in arm C (vs 4% in arm A, p< 0.0001). At week 24, ALT normalization was reached by 53% of arm B and 38% of arm C (vs 6% of arm A, p< 0.0001). One patient treated with 2 mg BLV achieved an HBsAg reduction ≥1 log10 IU/mL at week 24. Conclusion: This Phase 3 trial confirms that monotherapy with BLV is safe and well tolerated in patients with compensated cHDV infection. 24 weeks of treatment with BLV was associated with significant HDV RNA declines and improvements in biochemical disease activity. These findings further support the conditional approval of BLV.

This article examines the special phenomenon of “Gaokao migration”, points out their specifics and differences from the general educational migration. The reasons and consequences of this phenomenon are analyzed. Based on the laws and regulations adopted in China, possible ideas for solving this problem are proposed. The article points out that, in addition to carefully analyzing the qualifications of candidates to ensure fair admission to universities, the development of large-scale, diversified and high-quality higher education is a more realistic way in the long term. Proposed through the joint creation and use of digital educational resources, as well as strengthening international cooperation to address future migration challenges in education.

It is demonstrated how superconducting iced particles of the protoplanetary cloud of Saturn are coming to magnetic equator plane and create the stable enough rings disk. There are two steps. First, after appearance of the Saturn magnetic field due to Meissner phenomenon, all particles orbits are moving to the magnetic equator plane. Finally they become distributed as rings and gaps like iron particles around magnet on laboratory table. And they are separated from each other by the magnetic field expelled from them. It takes up to few tens of thousands years with ten meters rings disk thickness. Second, because of quantum locking all particles become to be locked within magnetic well at the magnetic equator plane due to Abrikosov vortex for superconductor. Finally each particle is locked within three-dimensional magnetic well. It works even when particles have small fraction of superconductor. During the rings evolution some contribution to the disk also could come from the collision-generated debris of the current moon, coming meteorites and from the geysers like it happened due to magnetic coupling of Saturn and Enceladus. The rings are relict of the early days of the magnetic field of Saturn system.