FORMATION OF MULTINUCLEATED OSTEOCLASTS DEPENDS ON AN OXIDIZED SPECIES OF CELL SURFACE ASSOCIATED LA PROTEIN.

The bone-resorbing activity of osteoclasts plays a critical role in the life-long remodeling of our bones that is perturbed in many bone loss diseases. Multinucleated osteoclasts are formed by the fusion of precursor cells, and larger cells - generated by an increased number of cell fusion events - have higher resorptive activity. We find that osteoclast fusion and bone-resorption are promoted by reactive oxygen species (ROS) signaling and by an unconventional low molecular weight species of La protein, located at the osteoclast surface.

Exploratory Efficacy Evaluation of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: 32-Week Results from a Phase 2, Randomized, Placebo-Controlled Study.

Introduction: Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments.

Methods: This was a randomized, double-blind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment.

A guide to troubleshooting metal sacrificial anodes for organic electrosynthesis.

The development of reductive electrosynthetic reactions is often enabled by the oxidation of a sacrificial metal anode, which charge-balances the reductive reaction of interest occurring at the cathode. The metal oxidation is frequently assumed to be straightforward and innocent relative to the chemistry of interest, but several processes can interfere with ideal sacrificial anode behavior, thereby limiting the success of reductive electrosynthetic reactions. These issues are compounded by a lack of reported observations and characterization of the anodes themselves, even when a failure at the anode is observed.

The impact of estradiol supplementation on endometrial thickness and intrauterine insemination outcomes.

The impact of estrogen supplementation during the follicular/proliferative phase on the endometrial lining thickness (EMT) prior to intrauterine insemination (IUI) remains largely unstudied. Our study examined changes in EMT and rates of clinical pregnancy, miscarriage, and live birth for all patients who completed an IUI cycle at Stanford Fertility Center from 2017-2023 (n = 2281 cycles). Cycles with estradiol supplementation (n = 309) were compared to reference cycles without supplementation (n = 1972), with the reference cohort further categorized into cycles with a pre-ovulatory EMT of < 7 mm ("thin-lining", n = 536) and ≥ 7 mm ("normal-lining", n = 1436).

Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial.

Background: Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis.

Objective: To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis.

Methods: SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy.

Enabling Al sacrificial anodes in tetrahydrofuran electrolytes for reductive electrosynthesis.

Al is widely used as a sacrificial anode in organic electrosynthesis. However, there remains a notable knowledge gap in the understanding of Al anode interface chemistry under electrolysis conditions. We hypothesize that Al interfacial chemistry plays a pivotal role in the discernible bias observed in solvent selections for reductive electrosynthesis.

Maximizing signal-to-noise ratio and statistical power in ERP measurement: Single sites versus multi-site average clusters.

One important decision in every event-related potential (ERP) experiment is which electrode site(s) to use in quantifying the ERP component of interest. A common approach is to measure the ERP from a single electrode site, typically the site where the ERP component is largest. Alternatively, two or more electrode sites in a given spatial region are averaged together, and the ERP is measured from the resulting multi-site cluster.

Three-Component Cross-Electrophile Coupling: Regioselective Electrochemical Dialkylation of Alkenes.

The cross-electrophile dialkylation of alkenes enables the formation of two C(sp)-C(sp) bonds from readily available starting materials in a single transformation, thereby providing a modular and expedient approach to building structural complexity in organic synthesis. Herein, we exploit the disparate electronic and steric properties of alkyl halides with varying degrees of substitution to accomplish their selective activation and addition to alkenes under electrochemical conditions. This method enables regioselective dialkylation of alkenes without the use of a transition-metal catalyst and provides access to a diverse range of synthetically useful compounds.

Clinical high risk for psychosis syndrome is associated with reduced neural responding to unpleasant images.

Deficits in emotion processing are core features of psychotic disorders. Electrophysiology research in schizophrenia suggests deficits in sustained engagement with emotional content (indexed by the late positive potential [LPP]) may contribute to emotion processing impairments. Despite similar behavioral emotion processing dysfunction in those at clinical high risk (CHR) for psychosis, limited research has examined neural mechanisms of impaired emotion processing in the high-risk period, where research can inform risk models.

Improving the Mg Sacrificial Anode in Tetrahydrofuran for Synthetic Electrochemistry by Tailoring Electrolyte Composition.

Mg is commonly used as a sacrificial anode in reductive electrosynthesis. While numerous methodologies using a Mg sacrificial anode have been successfully developed, the optimization of the electrochemistry at the anode, i.e.

An and study on extracorporeal transducer optimization for high-intensity focused ultrasound to improve the safety and efficacy of breast tumor ablation.

Objective: To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer.

Materials And Methods: Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as acoustic model. The udders of female goats were used as acoustic model.

Uncovering the magnitude of African pangolin poaching with extensive nanopore DNA genotyping of seized scales.

Trade in pangolins is illegal, and yet tons of their scales and products are seized at various ports. These large seizures are challenging to process and comprehensively genotype for upstream provenance tracing and species identification for prosecution. We implemented a scalable DNA barcoding pipeline in which rapid DNA extraction and MinION sequencing were used to genotype a substantial proportion of pangolin scales subsampled from 2 record shipments seized in Singapore in 2019 (37.

Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis.

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis.

Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behçet's Syndrome.

Background: Since US FDA approval in 2014, apremilast has consistently demonstrated a favorable benefit-risk profile in 706,585 patients (557,379 patient-years of exposure) worldwide across approved indications of plaque psoriasis, psoriatic arthritis, and Behçet's syndrome; however, long-term exposure across these indications has not been reported.

Objective: The aim of this study was to conduct a pooled analysis of apremilast data from 15 clinical studies with open-label extension phases, focusing on long-term safety.

Methods: We analyzed longer-term safety and tolerability of apremilast 30 mg twice daily across three indications for up to 5 years, focusing on adverse events of special interest, including thrombotic events, malignancies, major adverse cardiac events (MACE), serious infections, and depression.

Electrochemical Preparation of Sm(II) Reagent Facilitated by Weakly Coordinating Anions.

Samarium diiodide (SmI ) is widely used as a strong one-electron reducing agent and is often employed to form C-C bonds in complex systems. Despite their utility, SmI and related salts suffer from several drawbacks that render the use of Sm reducing agents in large-scale synthesis impractical. Here, we report factors influencing the electrochemical reduction of Sm(III) to Sm(II), towards the goal of electrocatalytic Sm(III) reduction.

Screening for Social Determinants of Health Among Medicare Beneficiaries in Primary Care During the Covid-19 Pandemic in Prince George's County, Maryland.

Primary care providers in Prince George's County, Maryland reported inconsistencies in their ability to identify and refer patients with social care needs. This project aimed to improve health outcomes of Medicare beneficiaries by implementing social determinant of health (SDOH) screening to identify unmet needs and improve rates of referral to appropriate services. Buy-in was achieved from providers and frontline staff via stakeholder meetings at a private primary care group practice.

Efficacy and Safety of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: Results from a Phase 2, Randomized, Placebo-Controlled Study.

Background: Palmoplantar pustulosis (PPP) is a pruritic, painful, recurrent, and chronic dermatitis with limited therapeutic options.

Objective: To evaluate the efficacy and safety of apremilast for the treatment of Japanese patients with PPP and inadequate response to topical treatment.

Methods: This phase 2, randomized, double-blind, placebo-controlled study enrolled patients with Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score ≥ 12 and moderate or severe pustules/vesicles on the palm or sole (PPPASI pustule/vesicle severity score ≥ 2) at screening and baseline with an inadequate response to topical treatment.

Contemporary Care and Outcomes of Critically-ill Children With Clinically Diagnosed Myocarditis.

Purpose: To describe contemporary management and outcomes in children with myocarditis who are admitted to a cardiac intensive care unit (CICU) and to identify the characteristics associated with mortality.

Methods: All patients in the Pediatric Cardiac Critical Care Consortium (PC) registry between August 2014 and June 2021 who were diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated the factors associated with in-hospital mortality.

Elevated body mass index in modified natural cycle frozen euploid embryo transfers is not associated with live birth rate.

Purpose: To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos.

Methods: This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m) category: normal weight (18.

Pregnancy and neonatal outcomes of letrozole versus natural cycle frozen embryo transfer of autologous euploid blastocyst.

Purpose: To investigate the pregnancy and neonatal outcomes of letrozole-stimulated frozen embryo transfer (LTZ-FET) cycles compared with natural FET cycles (NC-FET).

Methods: Our retrospective cohort included all LTZ-FET (n = 161) and NC-FET (n = 575) cycles that transferred a single euploid autologous blastocyst from 2016 to 2020 at Stanford Fertility Center. The LTZ-FET protocol entailed 5 mg of daily letrozole for 5 days starting on cycle day 2 or 3.

The Effect of Human Growth Hormone on Endometrial Growth in Controlled Ovarian Hyperstimulation Cycles.

This study aims to compare endometrial growth before and after the addition of human growth hormone (hGH) in controlled ovarian hyperstimulation (COH) cycles. A 5-year retrospective cohort study of patients treated with hGH to improve oocyte development during COH cycles was conducted. Each patient’s cycle without hGH immediately preceding cycle(s) with hGH was used for patients to serve as their own controls.