Nuclear Cardiology Surrogate Biomarkers in Clinical Trials.

Nuclear cardiology offers a diverse range of imaging tools that provide valuable insights into myocardial perfusion, inflammation, metabolism, neuroregulation, thrombosis, and microcalcification. These techniques are crucial not only for diagnosing and managing cardiovascular conditions but also for gaining pathophysiologic insights. Surrogate biomarkers in nuclear cardiology, represented by detectable imaging changes, correlate with disease processes or therapeutic responses and can serve as endpoints in clinical trials when they demonstrate a clear link with these processes.

Randomized Control Trial Evaluating Different Modalities of Real-Time Surgical Feedback.

Introduction:: Surgical training is a constant exchange between trainers and trainees, and intraoperative surgical feedback is an integral part of learning. New technologies in robotic surgery allow for the delivery of visual aid and verbal feedback intraoperatively, but it has not yet been determined if feedback type affects the trainee learning process.

Methods:: 49 novice participants were recruited and randomized into four feedback groups: , , of verbal/visual, and no feedback ().

Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes.

The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury.

Basic Science and Pathogenesis.

Background: An emerging theory suggests a link between Alzheimer's disease (AD) and microbial infection. Notably, various microbes have been detected in the post-mortem brains of AD patients and murine models. However, there exists a gap in research concerning the presence and role of microbial infection in the AD retina, which shares common pathogenesis with the brain.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a progressive irreversible dementia characterized by beta-amyloid protein plaque deposition and hyperphosphorylation of tau forming neurofibrillary tangles, and neurodegeneration. An emerging theory posits that infections could be one of the triggering factors in AD development and progression. Multiple lines of evidence have linked Chlamydia pneumoniae (Cp), a gram-negative obligate intracellular bacterium with AD.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the foremost cause of global dementia, also characterized by retinal changes involving Aβ, hyperphosphorylated-tau (p-tau), neuronal degeneration, and tissue atrophy. Mitochondrial-driven reactive oxygen species (ROS) production, linked to synaptic dysfunction, is common to various neurodegenerative conditions, including AD. Despite synaptic dysfunction being an early predictor of cognitive decline in AD, its occurrence in the AD retina is unexplored.

Basic Science and Pathogenesis.

Background: This study identifies and quantifies diverse pathological tau forms in the retina at both early and advanced stages of Alzheimer's disease (AD) and assesses their correlation with disease status. In the pathogenesis of AD, the tau protein undergoes post-translational modifications, including hyperphosphorylation (p-tau). As the disease progresses, pathological tau can propagate as oligomers, aggregate into fibrils, and paired helical filaments (PHF), and ultimately form intraneuronal neurofibrillary tangles (NFTs).

Basic Science and Pathogenesis.

Background: Frontotemporal lobar degeneration (FTLD)- TAR DNA-binding protein 43 (TDP) type C is commonly associated with a clinical diagnosis of semantic dementia (SD). Although anterior temporal lobe (ATL) is one of the primary atrophy centers, it is yet to be defined which other areas are involved in the TDP-type C pathology early in the disease course.

Methods: We included 16 patients with autopsy-confirmed FTLD-TDP type C from the database of the UCSF Memory and Aging Center: 13 patients with semantic variant primary progressive aphasia (svPPA) and predominant left ATL atrophy, and 3 patients with semantic behavioral variant frontotemporal dementia (sbvFTD) and predominant right ATL atrophy.

Clinical Manifestations.

Background: Hispanic adults comprise 19% of the US population, yet <8% of Alzheimer's Disease and Related Dementia (ADRD) research cohorts. Hispanic adults in the US are 1.5 times more likely to develop ADRDs compared to Non-Hispanics.

Alternate definitions of adverse pathology to predict a very high risk of metastasis in men with intermediate- and low-risk prostate cancer.

Background: Adverse pathology (AP) is often used as an intermediate end point for long-term outcomes in men with prostate cancer (PCa) who are active surveillance candidates. The association between a commonly used AP definition and long-term outcomes was tested, which identified definitions more strongly linked to a high risk of metastasis.

Methods: Data were reviewed from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing radical prostatectomy (RP) from 1988 to 2020 at nine Veterans Affairs hospitals.

Single-neuron spiking variability in hippocampus dynamically tracks sensory content during memory formation in humans.

During memory formation, the hippocampus is presumed to represent the content of stimuli, but how it does so is unknown. Using computational modelling and human single-neuron recordings, we show that the more precisely hippocampal spiking variability tracks the composite features of each individual stimulus, the better those stimuli are later remembered. We propose that moment-to-moment spiking variability may provide a new window into how the hippocampus constructs memories from the building blocks of our sensory world.

Circulatory age-associated B cells: Their distinct transcriptomic characteristics and clinical significance in drug-naïve patients with rheumatoid arthritis.

Age-associated B cells (ABCs) have been implicated in the pathogenesis of autoimmune diseases. However, the global gene expression and clinical significance of circulatory ABCs in rheumatoid arthritis (RA) remain poorly understood. Here, single-cell RNA sequencing identified nine B cell subsets in peripheral blood of RA patients, including ABCs.

Intermittent fasting as a treatment for obesity in young people: a scoping review.

Intermittent fasting focuses on the timing of eating rather than diet quality or energy intake, with evidence supporting its effects on weight loss and improvements in cardiometabolic outcomes in adults with obesity. However, there is limited evidence for its feasibility and efficacy in young people. To address this, a scoping review was conducted to examine intermittent fasting regimens in individuals aged 10 to 25 for the treatment of obesity focusing on methodology, intervention parameters, outcomes, adherence, feasibility, and efficacy.

Phenotyping atherosclerotic plaque and perivascular adipose tissue: signalling pathways and clinical biomarkers in atherosclerosis.

Computed tomography coronary angiography provides a non-invasive evaluation of coronary artery disease that includes phenotyping of atherosclerotic plaques and the surrounding perivascular adipose tissue (PVAT). Image analysis techniques have been developed to quantify atherosclerotic plaque burden and morphology as well as the associated PVAT attenuation, and emerging radiomic approaches can add further contextual information. PVAT attenuation might provide a novel measure of vascular health that could be indicative of the pathogenetic processes implicated in atherosclerosis such as inflammation, fibrosis or increased vascularity.

The human zinc-binding cysteine proteome.

Zinc is an essential micronutrient that regulates a wide range of physiological processes, most often through zinc binding to protein cysteine residues. Despite being critical for modulation of protein function, the cysteine sites in the majority of the human proteome that are subject to zinc binding remain undefined. Here, we develop ZnCPT, a deep and quantitative mapping of the zinc-binding cysteine proteome.

PEG-Polymeric Nanocarriers Alleviate the Immunosuppressive Effects of Free 4-Thiazolidinone-Based Chemotherapeutics on T Lymphocyte Function and Cytokine Production.

Purpose: Our study aimed to assess the effects of anticancer 4-thiazolidinone-based free water-insoluble therapeutics Les-3288 and Les-3833 and their waterborne complexes with branched PEG-containing polymeric carriers (A24-PEG550 and A24-PEG750) on immune response.

Methods: Human peripheral blood was used to study in vitro lymphocyte proliferative function, leukocyte phagocytic activity and respiratory burst, and cytokine production.

Results: The binding of the polymer to the anticancer drug Les-3288, which is intended to mitigate the immunosuppressive effects of the free drug on the proliferative activity of T lymphocytes and T-dependent B cells, demonstrated comparable efficacy for both A24-PEG750 and A24-PEG550 nanocarriers.

Cardiac events and dynamic echocardiographic and electrocardiogram changes following osimertinib treatment in lung cancer.

Osimertinib is first-line treatment for epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC) and has been associated with cardiotoxicity. However, the nature of cardiac remodeling and associated risk factors remains incompletely understood. Retrospective analysis of NSCLC patients with ≥1 echocardiogram post-osimertinib between 2007 and 2022 was performed.

Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations.

Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.

How to Predict Recurrence After Resection of Hepatocellular Carcinoma.

Background/aim: Predictors of recurrence following resection of hepatocellular carcinoma (HCC) are not fully established. This study investigated potential risk factors and prognostic scores for this situation.

Patients And Methods: In 297 patients undergoing resection of HCC between 2000 and 2021, risk scores and potential additional risk factors for intrahepatic and extrahepatic recurrence were assessed.

Rapid identification and phenotyping of nonalcoholic fatty liver disease patients using a machine-based approach in diverse healthcare systems.

Nonalcoholic fatty liver disease (NAFLD) is the most common global cause of chronic liver disease and remains under-recognized within healthcare systems. Therapeutic interventions are rapidly advancing for its inflammatory phenotype, nonalcoholic steatohepatitis (NASH) at all stages of disease. Diagnosis codes alone fail to recognize and stratify at-risk patients accurately.