Extrapolation of the Efficacy and Pharmacokinetics of Belimumab to Support its Use in Children with Lupus Nephritis.

Background And Objective: Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, has greater severity in children versus adults. Belimumab is approved for systemic lupus erythematosus treatment in patients aged ≥ 5 years, and for active LN in adults in the European Union, China, Japan and Latin America, and patients aged ≥ 5 years in the USA. Low prevalence of paediatric active LN makes conducting a clinical study within a reasonable period unfeasible.

HAF prevents hepatocyte apoptosis and progression to MASH and HCC through transcriptional regulation of the NF-κB pathway.

Background And Aims: HCC incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways driving MASH-HCC are poorly understood. We have previously reported that male mice with haploinsufficiency of hypoxia-associated factor (HAF) ( SART1+/ - ) spontaneously develop MASH-HCC.

Convergent evolution of plant prickles by repeated gene co-option over deep time.

An enduring question in evolutionary biology concerns the degree to which episodes of convergent trait evolution depend on the same genetic programs, particularly over long timescales. In this work, we genetically dissected repeated origins and losses of prickles-sharp epidermal projections-that convergently evolved in numerous plant lineages. Mutations in a cytokinin hormone biosynthetic gene caused at least 16 independent losses of prickles in eggplants and wild relatives in the genus .

Recommendations from Black and Latinx sexual minority males to include pharmacists to increase greater accessibility and OnlyFans stars to promote uptake of injectable PrEP.

Background: Pre-exposure prophylaxis (PrEP) medication is the keystone of preventative measures to curtail the spread of human immunodeficiency virus (HIV). However, oral PrEP, the tablet intended to prevent HIV, has been slow to proliferate among men who have sex with men (MSM). This is of major concern given that MSM account for the largest number of new HIV diagnoses in the United States.

HAF Prevents Hepatocyte Apoptosis and Hepatocellular Carcinoma through Transcriptional Regulation of the NF-κB pathway.

Background: Hepatocellular carcinoma (HCC) incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways that lead to MASH-HCC are poorly understood. We have previously reported that male mice with global haploinsufficiency of hypoxia-associated factor, HAF ( ) spontaneously develop MASH/HCC.

Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial.

Background: Data on belimumab efficacy in patients with lupus nephritis (LN) according to diagnosis duration or induction therapy are limited. Post hoc analyses of the phase 3, randomized, double-blind BLISS-LN study (GSK BEL114054; NCT01639339) were performed to assess belimumab efficacy on kidney-related outcomes in newly diagnosed and relapsed LN subgroups and according to the use of glucocorticoid (GC) pulses at induction.

Methods: BLISS-LN randomized 448 patients with active LN to monthly intravenous belimumab 10 mg/kg or placebo plus standard therapy.

Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study.

Background And Objectives: In the BLISS-LN study, belimumab improved kidney outcomes in adult patients with active lupus nephritis. This 28-week open-label extension of BLISS-LN assessed belimumab's safety and efficacy.

Design, Setting, Participants, & Measurements: Eligible patients completing BLISS-LN received monthly intravenous belimumab 10 mg/kg plus standard therapy.

Electrical Conductance of Charged Nanopores.

A nanopore's response to an electrical potential drop is characterized by its electrical conductance, . For the last two decades, it has been thought that at low electrolyte concentrations, , the conductance is concentration-independent such that . It has been recently demonstrated that surface charge regulation changes the dependency to , whereby the slope typically takes the values α = 1/3 or 1/2.

ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma.

Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is typically initiated by inactivation of the von Hippel Lindau (VHL) gene, which results in the constitutive activation of the hypoxia inducible factors, HIF-1α and HIF-2α. Using a high throughput screen, we identify novel compounds that decrease HIF-1/2α levels and induce ferroptosis by targeting Iron Sulfur Cluster Assembly 2 (ISCA2), a component of the late mitochondrial Iron Sulfur Cluster (L-ISC) assembly complex. ISCA2 inhibition either pharmacologically or using siRNA decreases HIF-2α protein levels by blocking iron-responsive element (IRE)-dependent translation, and at higher concentrations, also decreases HIF-1α translation through unknown mechanisms.

Efficacy and Safety of Belimumab in Patients With Lupus Nephritis: Subgroup Analyses of a Phase 3 Randomized Trial in the East Asian Population.

Rationale & Objective: Belimumab improved kidney outcomes in patients with active lupus nephritis (LN) in BLISS-LN, leading to its approval in the United States and the European Union. As data on treatment of East Asian patients with LN are limited, we evaluated the efficacy and safety of belimumab in the BLISS-LN East Asian subgroup.

Study Design: Prespecified subgroup analysis of BLISS-LN, a phase 3, placebo-controlled, randomized 104-week trial.

Conditions for electroneutrality breakdown in nanopores.

It has recently been suggested that a breakdown of electroneutrality occurs in highly confined nanopores that are encompassed by a dielectric material. This work elucidates the conditions for this breakdown. We show that the breakdown within the pore results from the response of the electric field within the dielectric.

A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis.

We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more.

Tril dampens Nodal signaling through Pellino2- and Traf6-mediated activation of Nedd4l.

Toll-like receptor 4 (Tlr) interactor with leucine-rich repeats (Tril) functions as a Tlr coreceptor to mediate innate immunity in adults. In embryos, Tril triggers degradation of the transforming growth factor β (Tgf-ß) family inhibitor, Smad7. This enhances bone morphogenetic protein (Bmp) signaling to enable ventral mesoderm to commit to a blood fate.

Bipolar Nanochannels: A Systematic Approach to Asymmetric Problems.

Nanofluidic diodes are capable of rectifying the electrical current by several orders of magnitude. In the current state of affairs, determining the rectification factor is not possible as it depends on many system parameters. In this work, we systematically scan the effects of geometry and excess counterion concentrations (i.

Multidisciplinary intensive outpatient rehabilitation program for patients with moderate-to-advanced Parkinson's disease.

Background: Intensive, multi-disciplinary, rehabilitation programs for patients with Parkinson's disease (PWPs) have shown to be effective. However, most programs are based on in-patient service, which is expensive.

Objective: To demonstrate the feasibility of a multidisciplinary, intensive, outpatient rehabilitation program (MIOR) for moderate to advanced Parkinson's Disease (H&Y≥2).

Ion transport in nanopores with highly overlapping electric double layers.

Investigation of ion transport through nanopores with highly overlapping electric double layers is extremely challenging. This can be attributed to the non-linear Poisson-Boltzmann equation that governs the behavior of the electrical potential distribution as well as other characteristics of ion transport. In this work, we leverage the approach of Schnitzer and Yariv [Phys.

A theoretical model of collective cell polarization and alignment.

Collective cell polarization and alignment play important roles in tissue morphogenesis, wound healing and cancer metastasis. How cells sense the direction and position in these processes, however, has not been fully understood. Here we construct a theoretical model based on describing cell layer as a nemato-elastic medium, by which the cell polarization, cell alignment and cell active contraction are explicitly expressed as functions of components of the nematic order parameter.

Erratum: Approximate time-dependent current-voltage relations for currents exceeding the diffusion limit [Phys. Rev. E 101, 043113 (2020)].

This corrects the article DOI: 10.1103/PhysRevE.101.

Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis.

Background: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown.

Methods: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.

Relationship between velocities, tractions, and intercellular stresses in the migrating epithelial monolayer.

The relationship between velocities, tractions, and intercellular stresses in the migrating epithelial monolayer are currently unknown. Ten years ago, a method known as monolayer stress microscopy (MSM) was suggested from which intercellular stresses could be computed for a given traction field. The core assumption of MSM is that intercellular stresses within the monolayer obey a linear and passive constitutive law.