NEDD4-Mediated GSNOR Degradation Aggravates Cardiac Hypertrophy and Dysfunction.

Background: The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the pathogenesis of pressure overload-induced cardiac hypertrophy, by modulating GSNOR levels, thereby demonstrating significant therapeutic potential.

Cryoballoon Pulmonary Vein Isolation With Versus Without Additional Right Atrial Linear Ablation for Persistent Atrial Fibrillation: The CRALAL Randomized Clinical Trial.

Background: Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with those with paroxysmal AF. We investigate whether additional linear ablation from the superior vena cava to the right atrial septum and cavotricuspid isthmus ablation improves the rhythm outcome of patients with persistent AF undergoing cryoballoon PVI (Cryo-PVI).

Methods: In this investigator-initiated, multicenter, randomized clinical trial, 289 patients with persistent AF refractory to antiarrhythmic drug therapy were randomized 1:1 to either Cryo-PVI with additional right atrium (RA) linear ablation or Cryo-PVI alone.

A foldon-free prefusion F trimer vaccine for respiratory syncytial virus to reduce off-target immune responses.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and older people. Current RSV subunit vaccines are based on a fusion protein that is stabilized in the prefusion conformation and linked to a heterologous foldon trimerization domain to obtain a prefusion F (preF) trimer. Here we show that current RSV vaccines induce undesirable anti-foldon antibodies in non-human primates, mice and humans.

Trastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study.

Purpose: This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC).

Patients And Methods: Part 1 determined the recommended dose for expansion of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate by independent central review.

A practical guide to using oral Janus kinase inhibitors for atopic dermatitis from the International Eczema Council.

Background: Janus kinase inhibitors (JAKi) have the potential to alter the landscape of atopic dermatitis (AD) management dramatically, owing to promising efficacy results from phase III trials and their rapid onset of action. However, JAKi are not without risk, and their use is not appropriate for all patients with AD, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD.

Objectives: To provide a consensus expert opinion statement from the International Eczema Council (IEC) that provides a pragmatic approach to prescribing JAKi, including choosing appropriate patients and dosing, clinical and laboratory monitoring and advice about long-term use.

mRNA-delivery of IDO1 suppresses T cell-mediated autoimmunity.

Indoleamine-2,3-dioxygenase (IDO)1 degrades tryptophan, obtained through dietary intake, into immunoregulatory metabolites of the kynurenine pathway. Deficiency or blockade of IDO1 results in the enhancement of autoimmune severity in rodent models and increased susceptibility to developing autoimmunity in humans. Despite this, therapeutic modalities that leverage IDO1 for the treatment of autoimmunity remain limited.

The influence of peritumoral parenchyma on local tumor progression of hepatocellular carcinoma after thermal ablation: a retrospective multicenter study.

Background: With the increasing importance of thermal ablation (TA) in hepatocellular carcinoma (HCC) treatment, local tumor progression (LTP) has become a nonignorable recurrence type after ablation.

Purposes: To analyze the influence of peritumoral liver parenchyma on LTP and to explore the possible reasons for this influence.

Methods: Ablated HCCs with peritumoral parenchymal biopsy and ablation margins greater than 5 mm were included from two hospitals.

Genome-Wide Association Analysis Identifies Important Haplotypes and Candidate Gene for Body Size Traits in Pekin Ducks.

Body size is an important growth indicator in ducks and is a primary selection criterion for physical improvement. An excessively rapid growth rate in meat ducks can result in excessive body size, which may hinder subsequent processing and slaughter operations. However, only a few molecular markers related to body size have been studied in meat ducks.

Efficacious human metapneumovirus vaccine based on AI-guided engineering of a closed prefusion trimer.

The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces.

Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.

Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study.

Background: Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited.

Objective: To compare weight change across common first-line antidepressant treatments by emulating a target trial.

Design: Observational cohort study over 24 months.

A Description and Safety Overview of Irreversible Electroporation for Prostate Tissue Ablation in Intermediate-Risk Prostate Cancer Patients: Preliminary Results from the PRESERVE Trial.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion.

Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies.

The Morphologic Patella Entry Point Into the Proximal Trochlea Is More Lateral in Recurrent Dislocators Than Controls as Measured by Entry Point-Trochlear Groove Angle.

Purpose: To create a metric for evaluating the degree of laterality of the patella's entry into the trochlea, the entry point-trochlear groove (EP-TG) angle, and to evaluate if this laterality is associated with recurrent patella instability.

Methods: The time frame of the study was January 2020 to February 2023. The inclusion criteria were patients treated by the senior author (J.

Covert Cerebrovascular Changes in People With Heart Disease: A Systematic Review and Meta-Analysis.

Background And Objectives: To determine the prevalence of silent brain infarction (SBI) and cerebral small vessel disease (CSVD) in adults with atrial fibrillation (AF), coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (PFO), with comparisons between those with and without recent stroke and an exploration of associations between heart disease and SBI/CSVD.

Methods: Medline, Embase, and Cochrane Library were systematically searched for hospital-based or community-based studies reporting SBI/CSVD in people with heart disease. Data were extracted from eligible studies.

Photon-counting CT in Thoracic Imaging: Early Clinical Evidence and Incorporation Into Clinical Practice.

Photon-counting CT (PCCT) is an emerging advanced CT technology that differs from conventional CT in its ability to directly convert incident x-ray photon energies into electrical signals. The detector design also permits substantial improvements in spatial resolution and radiation dose efficiency and allows for concurrent high-pitch and high-temporal-resolution multienergy imaging. This review summarizes key differences in PCCT image acquisition and image reconstruction compared with conventional CT; early evidence for the clinical benefit of PCCT for high-spatial-resolution diagnostic tasks in thoracic imaging, such as assessment of airway and parenchymal diseases, as well as benefits of high-pitch and multienergy scanning; anticipated radiation dose reduction, depending on the diagnostic task, and increased utility for routine low-dose thoracic CT imaging; adaptations for thoracic imaging in children; potential for further quantitation of thoracic diseases; and limitations and trade-offs.

Demonstrating Bioequivalence for Two Dose Strengths of Niraparib and Abiraterone Acetate Dual-Action Tablets Versus Single Agents: Utility of Clinical Study Data Supplemented with Modeling and Simulation.

Background And Objective: The combination of niraparib and abiraterone acetate (AA) plus prednisone is under investigation for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). Regular-strength (RS) and lower-strength (LS) dual-action tablets (DATs), comprising niraparib 100 mg/AA 500 mg and niraparib 50 mg/AA 500 mg, respectively, were developed to reduce pill burden and improve patient experience. A bioequivalence (BE)/bioavailability (BA) study was conducted under modified fasting conditions in patients with mCRPC to support approval of the DATs.

Effect of YC-1102 on the Improvement of Obesity in High-Fat Diet-Induced Obese Mice.

Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of , on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the oral administration of YC-1102 (100, 150, and 200 mg/kg body weight) daily to mice for eight weeks.