The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1.

Background: Myotonic dystrophy type 1 (DM1) is a multisystemic, CTG repeat expansion disorder characterized by a slow, progressive decline in skeletal muscle function. A biomarker correlating RNA mis-splicing, the core pathogenic disease mechanism, and muscle performance is crucial for assessing response to disease-modifying interventions. We evaluated the Myotonic Dystrophy Splice Index (SI), a composite RNA splicing biomarker incorporating 22 disease-specific events, as a potential biomarker of DM1 muscle weakness.

Twenty years of advances in prediction of nucleic acid-binding residues in protein sequences.

Computational prediction of nucleic acid-binding residues in protein sequences is an active field of research, with over 80 methods that were released in the past 2 decades. We identify and discuss 87 sequence-based predictors that include dozens of recently published methods that are surveyed for the first time. We overview historical progress and examine multiple practical issues that include availability and impact of predictors, key features of their predictive models, and important aspects related to their training and assessment.

Modeling the Health and Economic Impact of Pharmacologic Therapies for MASLD in the United States.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition leading to chronic liver disease which generates substantial health care costs. Our aim was to model the impact on disease and economic burden of a hypothetical pharmacologic therapy which halts MASLD fibrosis progression.

Methods: The U.

Fibrotic extracellular matrix preferentially induces a partial Epithelial-Mesenchymal Transition phenotype in a 3-D agent based model of fibrosis.

One of the main drivers of fibrotic diseases is epithelial-mesenchymal transition (EMT): a transdifferentiation process in which cells undergo a phenotypic change from an epithelial state to a pro-migratory state. The cytokine transforming growth factor-β1 (TGF-β1) has been previously shown to regulate EMT. TGF-β1 binds to fibronectin (FN) fibrils, which are the primary extracellular matrix (ECM) component in renal fibrosis.

Characterization of a novel oronasal-restricted nicotine vaping self-administration model in mice.

Nicotine use remains one of the leading causes of preventable deaths in the United States and, while the prevalence of combustible cigarette use has declined over the past few years, the popularity of electronic nicotine delivery systems continues to rise. Vaping is not without risks, and its long-term effects, particularly in vulnerable populations, remain largely unknown. This study introduces a novel, oronasal-restricted, nicotine vapor self-administration mouse model to investigate the impact of nicotine concentration, genotype, sex, and age on self-administration and behavioral response to nicotine.

Posttraumatic Stress Disorder Is Associated With Endothelial Dysfunction in Women With HIV.

Background: HIV induced endothelial dysfunction (ED) contributes to cardiovascular disease (CVD) in women with HIV (WWH). Although psychosocial stress has been implicated in the development of CVD in HIV, its impact on ED in WWH remains unknown.

Objectives: The authors hypothesized that posttraumatic stress disorder (PTSD) and HIV interact to contribute to ED in WWH.

Characterization of Pediatric Extrathoracic Aerosol Deposition with Air-Jet Dry Powder Inhalers.

The use of air-jet dry powder inhalers (DPIs) offers a number of advantages for the administration of pharmaceutical aerosols, including the ability to achieve highly efficient and potentially targeted aerosol delivery to the lungs of children using the oral or trans-nasal routes of administration. To better plan targeted lung delivery of pharmaceutical aerosols with these inhalers, more information is needed on the extrathoracic (ET) depositional loss in pediatric subjects when using relatively small (e.g.

Obinutuzumab Infusion-Related Reactions: Multicenter Retrospective Evaluation of Incidence, Severity, and Risk Factors.

Introduction: Despite standard prevention strategies, obinutuzumab carries a significant risk of infusion-related reactions (IRRs) for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Reported rates of IRRs vary in phase III clinical trials evaluating obinutuzumab-containing regimens. Although obinutuzumab has a higher rate of severe (grade 3 and higher) IRRs than rituximab, clinical risk factors predicting IRR have not been identified, and therefore strata informing patient-specific risk of IRR have not been applied in practice.

Sulfonium Moieties as Ammonium Bioisosteres: Novel Ligands for the Alpha7 Nicotinic Acetylcholine Receptor.

In the pressing quest of novel treatments for chronic pain, α7 nAChR silent agonists show efficacy as anti-inflammatory modulators and represent a promising strategy. Recent findings reveal that a sulfonium ion can replace the quaternary ammonium nitrogen as an alternative pharmacophore for nAChR silent activation. This study reports the design, synthesis, and electrophysiological evaluation of a new series of sulfonium-based derivatives inspired by the archetypal silent agonist NS6740.

Limited preventive care among Medicaid enrollees with HIV in the US South.

Routine preventive care (RPC) services are recommended for people with HIV, who have higher risk of certain preventable conditions. We used a pooled cross-section of patient-years to examine receipt of 5 annual RPC services among Medicaid enrollees in the US South. Data were person-level administrative claims (Medicaid Analytic eXtract, 2008-2012) and county-level characteristics for 16 Southern states plus District of Columbia.

Functional capacity at rehabilitation discharge predicts physical activity characteristics twenty-four weeks later for people with total knee arthroplasty: a secondary analysis of a randomized controlled trial.

Objective: To determine the association between performance-based and patient-reported functional capacity at the conclusion of 12-week rehabilitation with average daily step counts and peak walking cadence 38 weeks following total knee arthroplasty (TKA).

Design: Secondary analysis of an RCT.

Setting: Veterans Affairs Medical Center.

The functions of papillomavirus E2 proteins.

All papillomaviruses encode an E2 protein and it is essential for the viral life cycle. E2 has three domains; a carboxyl-terminal DNA binding and dimerization domain, an amino-terminal protein interaction domain and a hinge region linking these two. Following homo-dimerization human papillomavirus E2 binds to four 12bp palindromic DNA sequences located in the non-coding long control region (LCR) of the viral genome.

Ultrafast Dissociation Dynamics of the Sensitive Explosive Ethylene Glycol Dinitrate.

Ethylene glycol dinitrate (EGDN) is a nitrate ester explosive widely used in military ordnance and missile systems. This study investigates the decomposition dynamics of the EGDN cation using a comprehensive approach that combines femtosecond time-resolved mass spectrometry (FTRMS) experiments with electronic structure and molecular dynamics computations. We identify three distinct dissociation time scales for the metastable EGDN cation of approximately 40-60 fs, 340-450 fs, and >2 ps.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Characterization of a novel PET radioligand for mitochondrial complex I in nonhuman primate.

The role of mitochondrial complex I (MC-I) dysfunction is well-documented across a range of neurodegenerative disorders. Recently, a novel positron emission tomography (PET) radioligand, [F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [F]CNL02, using nonhuman primate as a model system.

Drivers of Palliative Care and Hospice Use Among Patients With Advanced Lung Cancer.

Purpose: Despite rigorous evidence of improved quality of life and longer survival, disparities in the utilization of palliative and hospice care persist for racial and ethnic minority patients with cancer. This study evaluated the impact of psychosocial factors on utilization of these services.

Methods: Patients with advanced lung cancer were recruited at a large academic urban hospital.

Surgical Management of Fibrosing Mediastinitis Presenting as Superior Vena Cava Syndrome.

Fibrosing mediastinitis is a rare chronic inflammatory condition characterized by excessive fibrotic process in the mediastinum. Although various infectious processes are more common causes, it can also be related to several malignancies. We report a case of a 28-year-old woman with fibrosing mediastinitis related to an aggressive primary gray-zone lymphoma causing complete occlusion of the superior vena cava (SVC) and the innominate veins.

Extracavitary Cardiac Calcific Amorphous Tumors Compressing Biventricular Outflow Tracts.

Extracavitary cardiac calcific amorphous tumors/masses are extremely rare. We present a case report of a 62-year-old man with end-stage renal disease who presented with extracavitary cardiac calcific amorphous tumors/masses compressing the biventricular outflow tracts, resulting in hemodynamic compromise and progressive limitation of activities. The patient was successfully treated with surgery, with complete resolution of symptoms and markedly improved quality of life.

THE WHO, WHAT, AND HOW OF INTERAGENCY CRIMINAL JUSTICE-BEHAVIORAL HEALTH TEAMS: Developing and Sustaining Collaborations.

Interagency teams are considered an evidence-based change practice, but there is a paucity of research examining them in criminal justice (CJ) and behavioral health (BH) reform contexts. This study draws on qualitative interviews ( = 52) and survey data ( = 791) from BH and CJ leaders across the United States to examine who is on them, what they do, and effective strategies for building and sustaining them. Findings indicated that CJ-BH interagency teams often incorporate agencies from a range of CJ, BH, social service, and health agencies.

Internalizing Psychiatric Symptoms in People With Mosaicism for Trisomy 21.

People with mosaicism for trisomy 21 have been shown to exhibit many of the same phenotypic traits present in people with non-mosaic Down syndrome, but with varying symptom severity. However, the behavioral phenotype of people with mosaic Down syndrome (mDS) has not been well characterized. This study aimed to examine the prevalence of self-report and caregiver-report symptoms of depression and anxiety among a sample of 62 participants with mDS aged 12-46 and assess their association with the percentage of trisomy 21 in blood and/or buccal mucosa cells.

A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.

Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.

Development of CPAP Overlay Interfaces for Efficient Administration of Aerosol Surfactant Therapy to Preterm Infants.

The administration of surfactant aerosol therapy to preterm infants receiving continuous positive airway pressure (CPAP) respiratory support is highly challenging due to small flow passages, relatively high ventilation flow rates, rapid breathing and small inhalation volumes. To overcome these challenges, the objective of this study was to implement a validated computational fluid dynamics (CFD) model and develop an overlay nasal prong interface design for use with CPAP respiratory support that enables high efficiency powder aerosol delivery to the lungs of preterm infants when needed (i.e.

The impact of aging on neutrophil functions and the contribution to periodontitis.

The increasing aging population and aging-associated diseases have become a global issue for decades. People over 65 show an increased prevalence and greater severity of periodontitis, which poses threats to overall health. Studies have demonstrated a significant association between aging and the dysfunction of neutrophils, critical cells in the early stages of periodontitis, and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion.