Comparison of Lean, Obese, and Weight Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T Cell Populations.

Obesity is an established risk factor for breast cancer development and poor prognosis. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression, and TREM2, a transmembrane receptor expressed on macrophages in adipose tissue and tumors, is an emerging therapeutic target for cancer. A better understanding of the mechanisms for the obesity-breast cancer association and the potential benefits of weight loss could help inform treatment strategies.

Hospitalized upper extremity artery disease patients: treatment and long-term outcomes.

Background And Aims: Current knowledge about upper extremity artery disease (UEAD) is scarce. This study aimed to evaluate the prevalence, treatment patterns, and short- and long-term outcomes of patients suffering from UEAD.

Methods: Retrospective health claims data of patients who were hospitalized with a primary diagnosis of UEAD between 2010 and 2017 were analysed.

Modulatory Effects of Mdivi-1 on OxLDL-Induced Metabolic Alterations, Inflammatory Responses, and Foam Cell Formation in Human Monocytes.

Atherosclerosis, a major contributor to cardiovascular disease, involves lipid accumulation and inflammatory processes in arterial walls, with oxidized low-density lipoprotein (OxLDL) playing a central role. OxLDL is increased during aging and stimulates monocyte transformation into foam cells and induces metabolic reprogramming and pro-inflammatory responses, accelerating atherosclerosis progression and contributing to other age-related diseases. This study investigated the effects of Mdivi-1, a mitochondrial fission inhibitor, and S1QEL, a selective complex I-associated reactive oxygen species (ROS) inhibitor, on OxLDL-induced responses in monocytes.

Impact of Hypertension and Physical Exercise on Hemolysis Risk in the Left Coronary Artery: A Computational Fluid Dynamics Analysis.

: Hypertension increases the risk of developing atherosclerosis and arterial stiffness, with secondarily enhanced wall stress pressure that damages the artery wall. The coexistence of atherosclerosis and hypertension leads to artery stenosis and microvascular angiopathies, during which the intravascular mechanical hemolysis of red blood cells (RBCs) occurs, leading to increased platelet activation, dysfunction of the endothelium and smooth muscle cells due to a decrease in nitric oxide, and the direct harmful effects of hemoglobin and iron released from the red blood cells. This study analyzed the impact of hypertension and physical exercise on the risk of hemolysis in the left coronary artery.

Characterization of sub-micrometre-sized voids in fixed human brain tissue using scanning X-ray microdiffraction.

Using a 5 µm-diameter X-ray beam, we collected scanning X-ray microdiffraction in both the small-angle (SAXS) and the wide-angle (WAXS) regimes from thin sections of fixed human brain tissue from Alzheimer's subjects. The intensity of scattering in the SAXS regime of these patterns exhibits essentially no correlation with the observed intensity in the WAXS regime, indicating that the structures responsible for these two portions of the diffraction patterns, which reflect different length scales, are distinct. SAXS scattering exhibits a power-law behavior in which the log of intensity decreases linearly with the log of the scattering angle.

Trem2 deficiency attenuates breast cancer tumor growth in lean, but not obese or weight loss, mice and is associated with alterations of clonal T cell populations.

Obesity is an established risk factor for breast cancer development and worsened prognosis; however, the mechanisms for this association - and the potential benefits of weight loss - have not been fully explored. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression. An emerging therapeutic target for cancer is TREM2, a transmembrane receptor of the immunoglobulin superfamily that is expressed on macrophages in adipose tissue and tumors.

Brown Adipose Tissue Mimicking Head and Neck Cancer on PET Scan in a Patient on GLP-1 Drug.

To report a case of a patient undergoing GLP-1 receptor agonist therapy in which increased FDG uptake in brown adipose tissue (BAT) mimicked metastatic head and neck cancer on PET/CT imaging. A 61-year-old female with Class III obesity presented with a right-sided neck mass after significant weight loss following the use of the GLP-1 receptor agonist, Semaglutide. PET/CT revealed FDG uptake in the right level II lymph node and extensive BAT uptake throughout the neck and mediastinum, complicating the diagnosis.

A molecular switch from tumor suppressor to oncogene in ER+ve breast cancer: Role of androgen receptor, JAK-STAT, and lineage plasticity.

Cancers develop resistance to inhibitors of oncogenes mainly due to target-centric mechanisms such as mutations and splicing. While inhibitors or antagonists force targets to unnatural conformation contributing to protein instability and resistance, activating tumor suppressors may maintain the protein in an agonistic conformation to elicit sustainable growth inhibition. Due to the lack of tumor suppressor agonists, this hypothesis and the mechanisms underlying resistance are not understood.

Fecal microbial transplants as investigative tools in cancer.

The gut microbiome plays a critical role in the development, progression, and treatment of cancer. As interest in microbiome-immune-cancer interactions expands, the prevalence of fecal microbial transplant (FMT) models has increased proportionally. However, current literature does not provide adequate details or consistent approaches to allow for necessary rigor and experimental reproducibility.

Three-Dimensionally Printed Elastic Cardiovascular Phantoms for Carotid Angioplasty Training and Personalized Healthcare.

Atherosclerosis is becoming increasingly common in modern society. Owing to the increasing number of complex angioplasty procedures, there is an increasing need for training in cases where the risk of periprocedural complications is high. A procedure was developed to obtain three-dimensional (3D) models and printing of blood vessels.

Apixaban, edoxaban and rivaroxaban but not dabigatran are associated with higher mortality compared to vitamin-K antagonists: A retrospective German claims data analysis.

Background: Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials.

Methods: Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020.

Revisiting the Roles of Catalytic Residues in Human Ornithine Transcarbamylase.

Human ornithine transcarbamylase (hOTC) is a mitochondrial transferase protein involved in the urea cycle and is crucial for the conversion of toxic ammonia to urea. Structural analysis coupled with kinetic studies of rat, bovine, and other transferase proteins has identified residues that play key roles in substrate recognition and conformational changes but has not provided direct evidence for all of the active residues involved in OTC function. Here, computational methods were used to predict the likely active residues of hOTC; the function of these residues was then probed with site-directed mutagenesis and biochemical characterization.

FXR Agonism with Bile Acid Mimetic Reduces Pre-Clinical Triple-Negative Breast Cancer Burden.

Bariatric surgery is associated with improved outcomes for several cancers, including breast cancer (BC), although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Patients with greater expression of the bile acid receptor FXR displayed improved survival in specific aggressive BC subtypes.

Complications and Outcomes in 39,864 Patients Receiving Standard Care Plus Mechanical Circulatory Support or Standard Care Alone for Infarct-Associated Cardiogenic Shock.

Background: Temporary mechanical circulatory support devices (tMCS) are increasingly being used in patients with infarct-associated cardiogenic shock (AMICS). Evidence on patient selection, complications and long-term outcomes is lacking. We aim to investigate differences in clinical characteristics, complications and outcomes between patients receiving no tMCS or either intra-aortic balloon pump (IABP), veno-arterial extracorporeal membrane oxygenation (V-A ECMO) or Impella for AMICS, with a particular focus on long-term outcomes.

Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS.

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment.

Prediction of Hemodynamic-Related Hemolysis in Carotid Stenosis and Aiding in Treatment Planning and Risk Stratification Using Computational Fluid Dynamics.

Atherosclerosis affects human health in many ways, leading to disability or premature death due to ischemic heart disease, stroke, or limb ischemia. Poststenotic blood flow disruption may also play an essential role in artery wall impairment linked with hemolysis related to shear stress. The maximum shear stress in the atherosclerotic plaque area is the main parameter determining hemolysis risk.

Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer.

Mononuclear phagocytes (MPs) play a crucial role in tissue homeostasis; however, MPs also contribute to tumor progression and resistance to immune checkpoint blockade (ICB). Targeting MPs could be an effective strategy to enhance ICB efficacy. We report that protein kinase C delta (PKCδ), a serine/threonine kinase, is abundantly expressed by MPs in human and mouse tumors.

In-patient characteristics of peripheral artery disease in Germany.

Peripheral artery disease (PAD) frequently leads to hospital admission. Sex related differences in in-patient care are a current matter of debate. Data were provided from the German national in-patient sample provided by the Federal Bureau of Statistics (DESTATIS).

Contemporary secondary prevention in survivors of ST-elevation myocardial infarction with and without chronic kidney disease: a retrospective analysis.

Background: Survivors of myocardial infarction have an elevated risk of long-term mortality. We sought to evaluate guideline-directed medical treatment and its impact on long-term mortality in survivors of ST-elevation myocardial infarction (STEMI) according to their chronic kidney disease (CKD) stage.

Methods: Using German health insurance claims data, 157 663 hospitalized survivors of STEMI were identified.

Survival of Patients with Acute Coronary Syndrome and Hematologic Malignancies-A Real-World Analysis.

Background: The impact of the encounter between coronary heart disease (CHD) and cancer, and in particular hematologic malignancies (HM), remains poorly understood.

Objective: The aim of this analysis was to clarify how HM affects the prognosis of acute coronary syndrome (ACS). We analyzed German health insurance data from 11 regional Ortskrankenkassen (AOK) of patients hospitalized for ACS between January 2010 and December 2018, matched by age, sex and all comorbidities for short- and long-term survival and major adverse cardiac events (MACE).

Can the resting state peak alpha frequency explain the relationship between temporal resolution power and psychometric intelligence?

The temporal resolution power (TRP) hypothesis states that individuals with higher TRP, as reflected by a higher performance on several psychophysical timing tasks, perform better on intelligence tests due to their ability to process information faster and coordinate their mental operations more effectively. It is proposed that these differences in TRP are related to the rate of a master clock based on neural oscillations. The present study aimed to investigate whether the peak alpha frequency (PAF) measured via electroencephalography (EEG) reflects a psychophysiological measure of this rate and its potential role in explaining the relationship between TRP and psychometric intelligence.

Reducing particulate emissions by using advanced engine oil nanoadditives based on molybdenum disulfide and carbon nanotubes.

Nanoadditives can be used to enhance lubricating properties of engine oils. Although many additives have been developed, molybdenum disulfide and carbon nanotubes have attracted significant attention. In this study, we demonstrate that hybrid nanostructures based on these unique materials (MoS/CNTs) positively affect engine oil lubricating properties.

Contemporary Treatment and Outcome of Patients with Ischaemic Lower Limb Amputation: A Focus on Sex Differences.

Objective: Chronic limb threatening ischaemia (CLTI) has a devastating prognosis with high rates of lower limb amputation (LLA) and deaths. This is an illustration of contemporary management and the long term fate of patients after ischaemic LLA, particularly with respect to sex, using real world data.

Methods: This was a multisectoral cross sectional and longitudinal analysis of health claims data from the largest German health insurance database (AOK).