Stellarex Drug-Coated Balloon for the Treatment of Peripheral Artery Disease: Five-Year Results from the ILLUMENATE Pivotal Randomized Controlled Trial.

This study aimed to report the 5-year outcomes from the ILLUMENATE Pivotal randomized controlled trial of the lower dose (2 µg/mm) Stellarex drug-coated balloon (DCB) (Philips, formerly Spectranetics Corp, Colorado Springs, Colorado) compared with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic peripheral arterial disease. Long-term safety and effectiveness data for DCBs remains limited. The ILLUMENATE Pivotal was a prospective, randomized, multi-center, single-blinded study.

Mass online training of health care workers during COVID-19: approach, impact, and outcomes for over 10,000 health care providers.

Objectives: COVID-19 revealed major shortfalls in healthcare workers (HCWs) trained in acute and critical care worldwide, especially in low-resource settings. We aimed to assess mass online courses' efficacy in preparing HCWs to manage COVID-19 patients and to determine whether rapidly deployed e-learning can enhance their knowledge and confidence during a pandemic.

Study Design: Retrospective cohort study.

Outcomes of a Remote Cardiac Rehabilitation Program for Patients Undergoing Atrial Fibrillation Ablation: Pilot Study.

Background: Risk factor modification, in particular exercise and weight loss, has been shown to improve outcomes for patients with atrial fibrillation (AF). However, access to structured supporting programs is limited. Barriers include the distance from appropriate facilities, insurance coverage, work or home responsibilities, and transportation.

Chocolate Touch Versus Lutonix Drug-Coated Balloon for Femoropopliteal Lesions in Diabetes: The Chocolate Touch Study.

Background: The randomized Chocolate Touch Study demonstrated that in patients undergoing treatment of femoropopliteal artery lesions, the Chocolate Touch drug-coated balloon (DCB) was safe and had superior efficacy at 12 months compared with the Lutonix DCB. We report the prespecified diabetes subanalysis comparing outcomes among patients with and without diabetes mellitus (DM).

Methods: Patients with claudication or ischemic rest pain (Rutherford class 2-4) were randomized to Chocolate Touch or Lutonix DCB.

Comparison of Invasive Coronary Angiography Versus Computed Tomography Angiography to Assess Mehran Classification of In-Stent Restenosis in Bifurcation Percutaneous Coronary Intervention.

The Mehran classification is used to determine the presence of in-stent restenosis (ISR) and characterization of its subtypes in invasive coronary angiography (ICA). The utility of computed tomography angiography (CTA) for the assessment of Mehran classification is unknown. We aimed to compare the agreement and reproducibility of Mehran classification between ICA and CTA and evaluate the sensitivity and specificity of both imaging methods.

Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display.

The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1.

Does One's Socioeconomic Status Predispose to the Development of Stress-Induced Cardiomyopathy?

Introduction: Stress-induced cardiomyopathy (SIC) has a higher incidence in Caucasians (CAUCs) compared to African-Americans (AAs). Whether this is due to racial predisposition, selection bias, or environmental factors remains unclear.

Hypothesis: We hypothesize that people from lower socioeconomic strata (SES) have a lower incidence of SIC.

No Mortality Signal With Stellarex Low-Dose Paclitaxel DCB: ILLUMENATE Pivotal 4-Year Outcomes.

Background: Paclitaxel-coated balloons have shown safety and efficacy in the short- to intermediate-term; however, long-term data remain limited.

Objectives: To report late safety and efficacy outcomes for a low-dose paclitaxel drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions from a large randomized controlled trial (RCT).

Methods: ILLUMENATE Pivotal is a multicenter, single-blind RCT conducted across 43 US and EU centers to examine the safety and efficacy of the Stellarex DCB for the treatment of femoropopliteal disease.

Kernel recursive least square tracker and long-short term memory ensemble based battery health prognostic model.

A data-driven approach is developed to predict the future capacity of lithium-ion batteries (LIBs) in this work. The empirical mode decomposition (EMD), kernel recursive least square tracker (KRLST), and long short-term memory (LSTM) are used to derive the proposed approach. First, the LIB capacity data is split into local regeneration and monotonic global degradation using the EMD approach.

High Prevalence of Multidrug Resistance and Biofilm-Formation Ability Among Avian Isolated from Broilers in Iran.

The present study was conducted to determine the antimicrobial resistance pattern and biofilm-formation ability in 100 Avian-Pathogenic (APEC) isolated from colibacillosis-suspected broilers and 100 Avian Fecal (AFEC) isolates from healthy broilers in Hamedan, Iran. All isolates were screened by polymerase chain reaction for antimicrobial resistance genes, class 1 and 2 integrons, and biofilm-associated genes. Besides, we assessed the possible relationship between biofilm-formation ability antibiotic resistance patterns, genetic background, and the pathogenicity of APEC strains.

Dual-Antigen COVID-19 Vaccine Subcutaneous Prime Delivery With Oral Boosts Protects NHP Against SARS-CoV-2 Challenge.

We have developed a dual-antigen COVID-19 vaccine incorporating genes for a modified SARS-CoV-2 spike protein (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to increase the potential for MHC class II responses. The vaccine antigens are delivered by a human adenovirus serotype 5 platform, hAd5 [E1-, E2b-, E3-], previously demonstrated to be effective in the presence of Ad immunity. Vaccination of rhesus macaques with the hAd5 S-Fusion + N-ETSD vaccine by subcutaneous prime injection followed by two oral boosts elicited neutralizing anti-S IgG and T helper cell 1-biased T-cell responses to both S and N that protected the upper and lower respiratory tracts from high titer (1 x 10 TCID) SARS-CoV-2 challenge.

Rapid Identification of Neutralizing Antibodies against SARS-CoV-2 Variants by mRNA Display.

The increasing prevalence of SARS-CoV-2 variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly-reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identified a set of antibodies against SARS-CoV-2 spike (S) proteins and characterized the structures of nAbs that recognized epitopes in the S1 subunit of the S glycoprotein. These structural studies revealed distinct binding modes for several antibodies, including targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interacts with angiotensin- converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1.

Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice.

We have developed a COVID-19 vaccine, hAd5 S-Fusion + N-ETSD, that expresses SARS-CoV-2 spike (S) and nucleocapsid (N) proteins with modifications to increase immune responses delivered using a human adenovirus serotype 5 (hAd5) platform. Here, we demonstrate subcutaneous (SC) prime and SC boost vaccination of CD-1 mice with this dual-antigen vaccine elicits T-helper cell 1 (Th1) biased T-cell and humoral responses to both S and N that are greater than those seen with hAd5 S wild type delivering only unmodified S. We then compared SC to intranasal (IN) prime vaccination with SC or IN boosts and show that an IN prime with an IN boost is as effective at generating Th1 biased humoral responses as the other combinations tested, but an SC prime with an IN or SC boost elicits greater T cell responses.

Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy.

Background: Therapeutic regimens designed to augment the immunological response of a patient with breast cancer (BC) to tumor tissue are critically informed by tumor mutational burden and the antigenicity of expressed neoepitopes. Herein we describe a neoepitope and cognate neoepitope-reactive T-cell identification and validation program that supports the development of next-generation immunotherapies.

Methods: Using GPS Cancer, NantOmics research, and The Cancer Genome Atlas databases, we developed a novel bioinformatic-based approach which assesses mutational load, neoepitope expression, human leukocyte antigen (HLA)-binding prediction, and in vitro confirmation of T-cell recognition to preferentially identify targetable neoepitopes.

An ACE2 Triple Decoy that neutralizes SARS-CoV-2 shows enhanced affinity for virus variants.

The SARS-CoV-2 variants replacing the first wave strain pose an increased threat by their potential ability to escape pre-existing humoral protection. An angiotensin converting enzyme 2 (ACE2) decoy that competes with endogenous ACE2 for binding of the SARS-CoV-2 spike receptor binding domain (S RBD) and inhibits infection may offer a therapeutic option with sustained efficacy against variants. Here, we used Molecular Dynamics (MD) simulation to predict ACE2 sequence substitutions that might increase its affinity for S RBD and screened candidate ACE2 decoys in vitro.

Reassessment of clinical variables in cardiac resynchronization defibrillator patients at the time of first replacement: Death after replacement of CRT (DARC) score.

Introduction: Cardiac resynchronization defibrillator (CRT-D) as primary prevention is known to reduce mortality. At the time of replacement, higher age and comorbidities may attenuate the benefit of implantable cardioverter-defibrillator (ICD) therapy. The purpose of this study was to evaluate the progression of comorbidities after implantation and their association with mortality following CRT-D generator replacement.

Clinical outcomes of patients with and without chronic kidney disease undergoing endovascular revascularization of infrainguinal peripheral artery disease: Insights from the XLPAD registry.

Objectives: The purpose of the present study was to define clinical outcomes of chronic kidney disease (CKD) patients undergoing endovascular revascularization of infrainguinal peripheral artery disease (PAD).

Background: CKD is an established predictor of advanced PAD. However, clinical outcomes for these patients following endovascular revascularization remain inadequately defined.

2021 ACC/AHA/SVM/ACP Advanced Training Statement on Vascular Medicine (Revision of the 2004 ACC/ACP/SCAI/SVMB/SVS Clinical Competence Statement on Vascular Medicine and Catheter-Based Peripheral Vascular Interventions).

Supplemental Digital Content is available in the text.

Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery.

Generating mammalian cells with specific mitochondrial DNA (mtDNA)-nuclear DNA (nDNA) combinations is desirable but difficult to achieve and would be enabling for studies of mitochondrial-nuclear communication and coordination in controlling cell fates and functions. We developed 'MitoPunch', a pressure-driven mitochondrial transfer device, to deliver isolated mitochondria into numerous target mammalian cells simultaneousl. MitoPunch and MitoCeption, a previously described force-based mitochondrial transfer approach, both yield stable isolated mitochondrial recipient (SIMR) cells that permanently retain exogenous mtDNA, whereas coincubation of mitochondria with cells does not yield SIMR cells.

Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates.

Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (ρ0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration.