Preventing Site-Specific Calpain Proteolysis of Junctophilin-2 Protects Against Stress-Induced Excitation-Contraction Uncoupling and Heart Failure Development.

Background: Excitation-contraction (E-C) coupling processes become disrupted in heart failure (HF), resulting in abnormal Ca homeostasis, maladaptive structural and transcriptional remodeling, and cardiac dysfunction. Junctophilin-2 (JP2) is an essential component of the E-C coupling apparatus but becomes site-specifically cleaved by calpain, leading to disruption of E-C coupling, plasmalemmal transverse tubule degeneration, abnormal Ca homeostasis, and HF. However, it is not clear whether preventing site-specific calpain cleavage of JP2 is sufficient to protect the heart against stress-induced pathological cardiac remodeling in vivo.

Mammal responses to global changes in human activity vary by trophic group and landscape.

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely.

Tropoelastin Improves Post-Infarct Cardiac Function.

Background: Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to collagen, the extracellular matrix protein elastin has high elasticity and may have more favorable properties within the cardiac scar.

Longitudinal Assessment of Posttreatment Diffuse Glioma Tissue Volumes with Three-dimensional Convolutional Neural Networks.

Neural networks were trained for segmentation and longitudinal assessment of posttreatment diffuse glioma. A retrospective cohort (from January 2018 to December 2019) of 298 patients with diffuse glioma (mean age, 52 years ± 14 [SD]; 177 men; 152 patients with glioblastoma, 72 patients with astrocytoma, and 74 patients with oligodendroglioma) who underwent two consecutive multimodal MRI examinations were randomly selected into training ( = 198) and testing ( = 100) samples. A posttreatment tumor segmentation three-dimensional nnU-Net convolutional neural network with multichannel inputs (T1, T2, and T1 postcontrast and fluid-attenuated inversion recovery [FLAIR]) was trained to segment three multiclass tissue types (peritumoral edematous, infiltrated, or treatment-changed tissue [ED]; active tumor or enhancing tissue [AT]; and necrotic core).

Under-5-Minute Immunoblot Assays by Vortex Fluidic Device Acceleration.

Unlocking the potential of personalized medicine in point-of-care settings requires a new generation of biomarker and proteomic assays. Ideally, assays could inexpensively perform hundreds of quantitative protein measurements in parallel at the bedsides of patients. This goal greatly exceeds current capabilities.

Interinstitutional Portability of a Deep Learning Brain MRI Lesion Segmentation Algorithm.

Purpose: To assess how well a brain MRI lesion segmentation algorithm trained at one institution performed at another institution, and to assess the effect of multi-institutional training datasets for mitigating performance loss.

Materials And Methods: In this retrospective study, a three-dimensional U-Net for brain MRI abnormality segmentation was trained on data from 293 patients from one institution (IN1) (median age, 54 years; 165 women; patients treated between 2008 and 2018) and tested on data from 51 patients from a second institution (IN2) (median age, 46 years; 27 women; patients treated between 2003 and 2019). The model was then trained on additional data from various sources: 285 multi-institution brain tumor segmentations, 198 IN2 brain tumor segmentations, and 34 IN2 lesion segmentations from various brain pathologic conditions.

Neural correlates of metacognition across the adult lifespan.

Metacognitive accuracy describes the degree of overlap between the subjective perception of one's decision accuracy (i.e. confidence) and objectively observed performance.

Efficacy of Selpercatinib in -Altered Thyroid Cancers.

Background: mutations occur in 70% of medullary thyroid cancers, and fusions occur rarely in other thyroid cancers. In patients with -altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown.

Methods: We enrolled patients with -mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated fusion-positive thyroid cancer, in a phase 1-2 trial of selpercatinib.

Influences of Immunocastration on Endocrine Parameters, Growth Performance and Carcass Quality, as Well as on Boar Taint and Penile Injuries.

Castration of male pigs without anesthesia is a significant welfare issue. Improvac, a GnRH vaccine induces an endogenous immune response leading to a decrease in testicular steroids. Consequences of different vaccination schemes on testicular function and carcass quality were evaluated in immunocastrated boars (IC), surgical castrates (SC), and entire males (EM).

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.

Background: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.

Methods: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age.

Symmetric-Key Encryption Based on Bioaffinity Interactions.

The research presented here shows a bridge between biochemistry and cryptography. Enzyme-based assays were used in a new methodology linked to ciphers and cipher systems. Three separate enzyme assays, alkaline phosphatase (ALP) (E.

International Porphyria Molecular Diagnostic Collaborative: an evidence-based database of verified pathogenic and benign variants for the porphyrias.

With the advent of precision and genomic medicine, a critical issue is whether a disease gene variant is pathogenic or benign. Such is the case for the three autosomal dominant acute hepatic porphyrias (AHPs), including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, each resulting from the half-normal enzymatic activities of hydroxymethylbilane synthase, coproporphyrinogen oxidase, and protoporphyrinogen oxidase, respectively. To date, there is no public database that documents the likely pathogenicity of variants causing the porphyrias, and more specifically, the AHPs with biochemically and clinically verified information.

Preliminary Definitions for Sacroiliac Joint Pathologies in the OMERACT Juvenile Idiopathic Arthritis Magnetic Resonance Imaging Score (OMERACT JAMRIS-SIJ).

Objective: To develop definitions for the assessment of magnetic resonance imaging (MRI) pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis.

Methods: An Outcome Measures in Rheumatology (OMERACT) consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists.

Results: Two domains, inflammation and structural, were identified.

E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator.

Junctophilin-2 (JP2) is a structural protein required for normal excitation-contraction (E-C) coupling. After cardiac stress, JP2 is cleaved by the calcium ion-dependent protease calpain, which disrupts the E-C coupling ultrastructural machinery and drives heart failure progression. We found that stress-induced proteolysis of JP2 liberates an N-terminal fragment (JP2NT) that translocates to the nucleus, binds to genomic DNA, and controls expression of a spectrum of genes in cardiomyocytes.

Targeting Calpain for Heart Failure Therapy: Implications From Multiple Murine Models.

Heart failure remains a major cause of morbidity and mortality in developed countries. There is still a strong need to devise new mechanism-based treatments for heart failure. Numerous studies have suggested the importance of the Ca-dependent protease calpain in cardiac physiology and pathology.

Preclinical evaluation of an MR-compatible microwave ablation system and comparison with a standard microwave ablation system in an ex vivo bovine liver model.

Objective: Evaluation of a newly developed MR-compatible microwave ablation system with focus on ablation performance and comparison with a corresponding standard microwave ablation system.

Materials And Methods: A total of 52 ablations were performed with a non-cooled microwave ablation system in an ex vivo bovine liver model using the following settings: [A] 16G-standard antenna, 2 cm active tip, 2.4 m cable; [B] MR-compatible 16G-antenna, 2 cm active tip, 2.

Mapping Plasmodium falciparum Mortality in Africa between 1990 and 2015.

Background: Malaria control has not been routinely informed by the assessment of subnational variation in malaria deaths. We combined data from the Malaria Atlas Project and the Global Burden of Disease Study to estimate malaria mortality across sub-Saharan Africa on a grid of 5 km from 1990 through 2015.

Methods: We estimated malaria mortality using a spatiotemporal modeling framework of geolocated data (i.