Levels of Trimethylamine N-Oxide Remain Elevated Long Term After Left Ventricular Assist Device and Heart Transplantation and Are Independent From Measures of Inflammation and Gut Dysbiosis.

Background: Trimethylamine N-oxide (TMAO)-a gut-derived metabolite-is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis.

Methods: We enrolled 341 patients.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

Background: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.

Methods: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis.

Circulating HPV DNA in the Management of Oropharyngeal and Cervical Cancers: Current Knowledge and Future Perspectives.

Human papillomaviruses (HPVs) are associated with invasive malignancies, including almost 100% of cervical cancers (CECs), and 35-70% of oropharyngeal cancers (OPCs). HPV infection leads to clinical implications in related tumors by determining better prognosis and predicting treatment response, especially in OPC. Currently, specific and minimally invasive tests allow for detecting HPV-related cancer at an early phase, informing more appropriately therapeutical decisions, and allowing for timely disease monitoring.

Benefits and Harms of Hypertension and High-Normal Labels: A Randomized Experiment.

Background: Recent US guidelines lowered the threshold for diagnosing hypertension while other international guidelines use alternative/no labels for the same group (blood pressure [BP], <140/90 mm Hg). We investigated potential benefits and harms of hypertension and high-normal BP labels, compared with control, among people at lower risk of cardiovascular disease.

Methods: We conducted a randomized experiment using a national sample of Australians (n=1318) 40 to 50 years of age recruited from an online panel.

Preparation and Characterization of a Novel Poly(vinylidene fluoride-co-hexafluoropropylene)/Poly(ethersulfone) Blend Membrane Fabricated Using an Innovative Method of Mixing Electrospinning and Phase Inversion.

In this work, a novel polymeric membrane was innovated in terms of composition and preparation techniques. A blend of poly(vinylidene fluoride-co-hexafluoropropylene) (PcH) and poly(ethersulfone) (PES) (18 wt.% total polymer concentration) was prepared using a N-methylpyrrolidone (NMP) and N, N-Dimethylformamide (DMF) solvents mixture, while Lithium chloride (0.

Intermittently Scanned Continuous Glucose Monitoring Data of Polish Patients from Real-Life Conditions: More Scanning and Better Glycemic Control Compared to Worldwide Data.

Randomized trials and observational studies have shown that the use of FreeStyle Libre intermittently scanned continuous glucose monitoring system (isCGMS) is associated with improved glycemic indices and quality of life. In this retrospective, real-world data analysis, we described country-specific glucometrics among isCGMS users from Poland and compared them with international data. The analyzed time period for the Polish data ranged between August 2016 and August 2020, and the analyzed time period for the international data ranged from September 2014 to August 2020.

T Cells Specific for a Mycobacterial Glycolipid Expand after Intravenous Bacillus Calmette-Guérin Vaccination.

Intradermal vaccination with bacillus Calmette-Guérin (BCG) protects infants from disseminated tuberculosis, and i.v. BCG protects nonhuman primates (NHP) against pulmonary and extrapulmonary tuberculosis.

The relationship between development assistance for health and public health financing in 134 countries between 2000 and 2015.

This paper utilizes causal time-series and panel techniques to examine the relationship between development assistance for health (DAH) and domestic health spending, both public and private, in 134 countries between 2000 and 2015. Data on 237 656 donor transactions from the Institute for Health Metrics and Evaluation's DAH and Health Expenditure datasets are merged with economic, demographic and health data from the World Bank Databank and World Health Organization's Global Health Observatory. Arellano-Bond system GMM estimation is used to assess the effect of changes in DAH on domestic health spending and health outcomes.

No Impact of NRAS Mutation on Features of Primary and Metastatic Melanoma or on Outcomes of Checkpoint Inhibitor Immunotherapy: An Italian Melanoma Intergroup (IMI) Study.

It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt.

Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease.

Background: Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in 5 trials across the spectrum of cardiometabolic disease.

Methods: Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation), SOLID-TIMI 52 (Stabilization of Plaques Using Darapladib), SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trials were included in this analysis.

Injectable Hydrogels for Sustained Codelivery of Subunit Vaccines Enhance Humoral Immunity.

Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system's natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform.

The Dually Negative Effect of Industrial Polluting Enterprises on China's Air Pollution: A Provincial Panel Data Analysis Based on Environmental Regulation Theory.

Although the Chinese government has promulgated a series of policies to mitigate air pollution, the air quality in a number of Chinese cities still has the potential to be improved. As the major source of air pollution, enterprises in the industrial and energy sectors are the most difficult to regulate in terms of polluting emissions. This paper aims to investigate what factors influence the intensity of environmental regulations on polluting enterprises based on environmental regulation theory and an empirical test.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling.

Anti-cancer uses of non-oncology drugs have occasionally been found, but such discoveries have been serendipitous. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. We used PRISM, a molecular barcoding method, to screen drugs against cell lines in pools.

Data-driven segmentation of audiometric phenotypes across a large clinical cohort.

Pure tone audiograms are used to assess the degree and underlying source of hearing loss. Audiograms are typically categorized into a few canonical types, each thought to reflect distinct pathologies of the ear. Here, we analyzed 116,400 patient records from our clinic collected over a 24-year period and found that standard categorization left 46% of patient records unclassified.

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare variants implicated in LQT5 was sought through an international multicenter collaboration.

Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries.

A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia.

Inhibition of the Menin (MEN1) and MLL (MLL1, KMT2A) interaction is a potential therapeutic strategy for MLL-rearranged (MLL-r) leukemia. Structure-based design yielded the potent, highly selective, and orally bioavailable small-molecule inhibitor VTP50469. Cell lines carrying MLL rearrangements were selectively responsive to VTP50469.

Longitudinal Trajectories of Parenting Stress Among Ethnic Minority Adolescent Mothers.

Objectives: Parenting stress has been linked with negative outcomes for parents and their infants (e.g., parental depression, negative parenting behaviors, poor attachment).

Targeted drug delivery via caveolae-associated protein PV1 improves lung fibrosis.

Systemic administration of bio-therapeutics can result in only a fraction of drug reaching targeted tissues, with the majority of drug being distributed to tissues irrelevant to the drug's site of action. Targeted delivery to specific organs may allow for greater accumulation, better efficacy, and improved safety. We investigated how targeting plasmalemma vesicle-associated protein (PV1), a protein found in the endothelial caveolae of lungs and kidneys, can promote accumulation in these organs.

Trajectories of Symptom Change in the Treatment for Adolescents With Depression Study.

Objective: Depression is the most prominent mental health disorder among youth and has a profound impact with respect to morbidity and mortality if not addressed. The Treatment for Adolescent Depression Study (TADS) is one of the largest randomized controlled trials that compared the effectiveness of four treatments: cognitive-behavioral therapy (CBT); fluoxetine (FLX); combined cognitive-behavioral and fluoxetine treatment (COMB); and placebo (PBO). However, meaningful heterogeneous treatment courses are masked by these group mean comparisons of treatment impact.

PESA: Probabilistic Efficient Storage Algorithm for Time-Domain Spectrum Measurements.

Wireless communication is an essential part of daily life for users globally with applications in medical devices, cellular phones, Internet of Things nodes, and others. Accordingly, there is a need to understand the patterns and properties of radio frequency spectrum use by acquiring accurate spectrum utilization measurements. However, the massive storage volume needed to execute spectrum surveys-especially when a fast sampling rate is used-is an impeding factor in terms of cost and ease-of-access.

Advanced diffusion imaging for assessing normal white matter development in neonates and characterizing aberrant development in congenital heart disease.

Background: Elucidating developmental trajectories of white matter (WM) microstructure is critically important for understanding normal development and regional vulnerabilities in several brain disorders. Diffusion Weighted Imaging (DWI) is currently the method of choice for in-vivo white matter assessment. A majority of neonatal studies use the standard Diffusion Tensor Imaging (DTI) model although more advanced models such as the Neurite Orientation Dispersion and Density Imaging (NODDI) model and the Gaussian Mixture Model (GMM) have been used in adult population.

Smartphone-Based Geofencing to Ascertain Hospitalizations.

Background: Ascertainment of hospitalizations is critical to assess quality of care and the effectiveness and adverse effects of various therapies. Smartphones, mobile geolocators that are ubiquitous, have not been leveraged to ascertain hospitalizations. Therefore, we evaluated the use of smartphone-based geofencing to track hospitalizations.

An evaluation of the use of covariates to assist in class enumeration in linear growth mixture modeling.

This study examined whether the inclusion of covariates that predict class membership improves class identification in a growth mixture modeling (GMM). We manipulated the degree of class separation, sample size, the magnitude of covariate effect on class membership, the covariance between the intercept and the slope, and fit two models with covariates and an unconditional model. We concluded that correct class identification in GMM requires large sample sizes and class separation, and that unconditional GMM performs better than GMM with covariates if the sample size and class separation are sufficiently large.

Comparison of unsupervised classification methods for brain tumor segmentation using multi-parametric MRI.

Tumor segmentation is a particularly challenging task in high-grade gliomas (HGGs), as they are among the most heterogeneous tumors in oncology. An accurate delineation of the lesion and its main subcomponents contributes to optimal treatment planning, prognosis and follow-up. Conventional MRI (cMRI) is the imaging modality of choice for manual segmentation, and is also considered in the vast majority of automated segmentation studies.