Design and Process Considerations for Preparation of Modified Release Ivermectin and Praziquantel Tablets by Wet Granulation.

Dosage forms containing Ivermectin (IVER) and Praziquantel (PRAZ) are important combination drug products in animal health. Understanding the relationship between products with differing in vitro release characteristics and bioequivalence could facilitate generics. The goal of this study was to create granulations for each active ingredient, with similar release mechanisms, but substantially different in vitro release rates, and then compressing these granulations into tablets with differing release rates.

Inflammatory disease progression shapes nanoparticle biomolecular corona-mediated immune activation profiles.

Polymeric nanoparticles (NPs) are promising tools used for immunomodulation and drug delivery in various disease contexts. The interaction between NP surfaces and plasma-resident biomolecules results in the formation of a biomolecular corona, which varies patient-to-patient and as a function of disease state. This study investigates how the progression of acute systemic inflammatory disease influences NP corona compositions and the corresponding effects on innate immune cell interactions, phenotypes, and cytokine responses.

Computationally Efficient Polarizable MD Simulations: A Simple Water Model for the Classical Drude Oscillator Polarizable Force Field.

An improvement in the computational efficiency of polarizable force field simulations is made through the development of a polarizable Drude water model, SWM3, in combination with the use of Lennard-Jones Particle Mesh Ewald (LJPME) for the treatment of long-range LJ interactions. The experimental bulk properties, density, heat of vaporization, dielectric constant, and self-diffusion constant of the SWM3 model are accurately replicated at ambient condition. The temperature dependence of the bulk properties is also captured except for the density.

Improving estimation efficiency for survival data analysis by integrating a coarsened time-to-event outcome from an external study.

In the era of big data, increasing availability of data makes combining different data sources to obtain more accurate estimations a popular topic. However, the development of data integration is often hindered by the heterogeneity in data forms across studies. In this paper, we focus on a case in survival analysis where we have primary study data with a continuous time-to-event outcome and complete covariate measurements, while the data from an external study contain an outcome observed at regular intervals, and only a subset of covariates is measured.

Jansen metaphyseal chondrodysplasia: analysis of craniofacial manifestations.

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by constitutive activation of parathyroid hormone type 1 receptor (PTH1R). We sought to characterize the craniofacial phenotype of patients with the disease. Six patients with genetically confirmed JMC underwent comprehensive craniofacial phenotyping revealing a distinct facial appearance that prompted a cephalometric analysis demonstrating a pattern of mandibular retrognathia.

Extended-release buprenorphine induction in opioid non-tolerant incarcerated individuals.

Background: Buprenorphine maintenance treatment remains unavailable in most jails in the US. We provide data on a four-day rapid sublingual buprenorphine (SL-B) induction strategy followed by a weekly dose of extended-release injectable buprenorphine (XR-B) with incarcerated individuals with opioid use disorder (OUD) who were not opioid tolerant.

Methods: Between October 2020 to April 2024, = 65 individuals with an opioid use disorder in jails participating in a larger randomized, controlled trial received SL-B and XR-B prior to release.

The polypharmacy combination of the BCL-2 inhibitor venetoclax (VEN) and the FLT3 inhibitor gilteritinib (GIL) is more active in acute myeloid leukemia cells than novel polypharmacologic BCL-2/FLT3 VEN-GIL hybrid single-molecule inhibitors.

Current treatments for acute myeloid leukemias (AMLs) cure fewer than 30 % of patients. This low efficacy is due, in part, to the inter-patient and intra-patient heterogeneity of AMLs; accordingly, all current AML treatment regimens involve drug combinations (polypharmacy). A recently-completed clinical trial in relapsed/refractory AML using a combination of two newer targeted antileukemics, the BCL-2 inhibitor venetoclax (VEN) plus the FLT3 inhibitor gilteritinib (GIL), yielded highly promising results for this two-drug polypharmacy combination.

Preserving the Academic Mission Amid Radiologist Shortages and Financial Pressures.

Academic radiology practices are navigating unprecedented operational and financial challenges, including a growing radiologist shortage, escalating imaging volumes, and mounting financial pressures driven by rising salaries, increasing practice expenses, and declining reimbursements. To address these challenges, academic department leaders must prioritize securing enhanced hospital professional service agreements and renegotiating outpatient imaging agreements. These strategic initiatives are essential to sustaining academic missions and ensuring long-term success.

Trends in Osteoporosis Drug Therapy Receipt Among Commercial and Medicare Advantage Enrollees in the United States, 2011-2022.

Context: A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis.

Objective: The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis.

Methods: This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022.

Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping.

Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls.

ShaderNN: A Lightweight and Efficient Inference Engine for Real-time Applications on Mobile GPUs.

Inference using deep neural networks on mobile devices has been an active area of research in recent years. The design of a deep learning inference framework targeted for mobile devices needs to consider various factors, such as the limited computational capacity of the devices, low power budget, varied memory access methods, and I/O bus bandwidth governed by the underlying processor's architecture. Furthermore, integrating an inference framework with time-sensitive applications - such as games and video-based software to perform tasks like ray tracing denoising and video processing - introduces the need to minimize data movement between processors and increase data locality in the target processor.

Leadless Pacemaker vs. Transvenous Pacemaker in End Stage Kidney Disease: Insights from the Nationwide Readmission Database.

: Leadless pacemakers offer a safe and effective alternative pacing strategy. However, limited data are available for patients with end stage renal disease (ESRD), a population of significant relevance. Using the Nationwide Readmission Database, we extracted data from all adult patients with ESRD who underwent traditional transvenous or leadless pacemaker implantation between 2016 and 2021.

Administration of AICAR, an AMPK Activator, Prevents and Reverses Diabetic Polyneuropathy (DPN) by Regulating Mitophagy.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in both Type 1 (T1D) and Type 2 (T2D). While there are no specific medications to prevent or treat DPN, certain strategies can help halt its progression. In T1D, maintaining tight glycemic control through insulin therapy can effectively prevent or delay the onset of DPN.

The PANDA score: External validation and modification of a simple upfront prediction tool for poor outcomes despite successful stroke thrombectomy.

Background: While endovascular thrombectomy (EVT) has become standard of care for patients' acute ischemic stroke (AIS) due to large vessel occlusion (LVO), many patients still suffer profound neurological disability, also termed futile recanalization (FR). The BAND score, which incorporates baseline disability, age, stroke severity, and treatment time window, is derived as a simple tool for upfront prediction of FR prior to EVT. This study aims to externally validate the BAND score and to incorporate upfront imaging biomarkers into the prediction tool.

Quantitative LC-MS/MS Analysis of Endogenous Isomeric Metabolites Biliverdin IX Alpha, Beta, and Delta in Cell Culture Supernatant, Cell Pellet, and Lung Tissue.

() utilizes heme as an iron source from the host during infection. Biliverdin beta and delta (BVIXβ and BVIXδ) are generated by HemO, specific to , while biliverdin alpha is generated from the bacterial BphO system and by mammalian heme oxygenases. Here, we have developed and characterized a quantitative LC-MS/MS assay for the separation of three endogenous isomers, BVIXα, BVIXβ, and BVIXδ.

Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown.

Individualized brain radiomics-based network tracks distinct subtypes and abnormal patterns in prodromal Parkinson's disease.

Individuals in the prodromal phase of Parkinson's disease (PD) exhibit significant heterogeneity and can be divided into distinct subtypes based on clinical symptoms, pathological mechanisms, and brain network patterns. However, little has been done regarding the valid subtyping of prodromal PD, which hinders the early diagnosis of PD. Therefore, we aimed to identify the subtypes of prodromal PD using the brain radiomics-based network and examine the unique patterns linked to the clinical presentations of each subtype.

Correlation of Histologic Features with Gene Alterations in Pleural Mesothelioma.

Histologic features, including architectural patterns, cytologic features, and 2021 World Health Organization nuclear grade have been shown to have prognostic significance in epithelioid diffuse pleural mesothelioma (DPM). Biphasic and sarcomatoid DPM, regardless of morphology, have worse outcomes. These prognostic findings are well-established but correlation of architectural patterns, cytologic features, and nuclear grade with genetic alterations has not been well studied.

Blunted Ventral Striatal Reactivity to Social Reward Is Associated with More Severe Motivation and Pleasure Deficits in Psychosis.

Background And Hypothesis: Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are undoubtedly complex, converging lines of evidence suggest that social motivation and pleasure (MAP) deficits play a central role. Yet most neuroimaging studies have focused on monetary rewards, precluding decisive inferences.

Machine Learning and Statistical Analyses of Sensor Data Reveal Variability Between Repeated Trials in Parkinson's Disease Mobility Assessments.

Mobility tasks like the Timed Up and Go test (TUG), cognitive TUG (cogTUG), and walking with turns provide insights into the impact of Parkinson's disease (PD) on motor control, balance, and cognitive function. We assess the test-retest reliability of these tasks in 262 PD participants and 50 controls by evaluating machine learning models based on wearable-sensor-derived measures and statistical metrics. This evaluation examines total duration, subtask duration, and other quantitative measures across two trials.

Sexual Dimorphism of Ethanol-Induced Mitochondrial Dynamics in Purkinje Cells.

The cerebellum, a key target of ethanol's toxic effects, is associated with ataxia following alcohol consumption. However, the impact of ethanol on Purkinje cell (PC) mitochondria remains unclear. To investigate how ethanol administration affects mitochondrial dynamics in cerebellar Purkinje cells, we employed a transgenic mouse model expressing mitochondria-targeted yellow fluorescent protein in Purkinje cells (PC-mito-eYFP).

Predictive Value of Inflammatory Scores for Left Atrium Thrombosis in Ischemic Stroke Without Atrial Fibrillation.

: Studies have shown that inflammation markers can be used as prognostic tools in predicting acute ischemic stroke. In this study, we conducted a comparison of several inflammation scores in predicting left atrial thrombosis (LAT) in patients with ischemic stroke without AF. : In this single-center, retrospective study, we included 303 consecutive patients with ischemic stroke.