Coronary Angiography-Derived Murray Law-Based Quantitative Flow Ratio (μQFR) After De Novo Drug-Coated Balloon Angioplasty.

Background: Drug-coated balloon (DCB) angioplasty has emerged as a stentless alternative for de novo coronary artery disease. However, the prognostic value of post-procedural angiography-derived physiology, particularly three-dimensional (3D) Murray-law quantitative flow ratio (μQFR), after DCB in native vessels remains unclear.

Objectives: To quantify the prognostic value of immediate post-DCB 3D-μQFR for predicting lesion failure in de novo coronary disease.

Disparities in ST-elevation myocardial infarction diagnosis and management among patients with mental health conditions.

Aims: Patients with mental health conditions (MHCs) experience delayed diagnosis and management. We aimed to assess whether these patients had longer treatment delays and poorer outcomes despite a dedicated ST-elevation myocardial infarction (STEMI) fast-track protocol.

Methods And Results: We analysed data from EVALFAST prospective registry of confirmed STEMI patients admitted directly to the catheterization laboratory at Fribourg Hospital since June 2008.

Harnessing Immunogenic Cell Death to Boost the Impact of Radiation Therapy.

Harnessing radiotherapy (RT) to effectively eliminate cancer cells has been a cornerstone of clinical oncology for decades. Beyond its well-established cytotoxic effects, RT triggers a diverse array of tumor cell death modalities, including apoptosis, necrosis, mitotic catastrophe, and, under specific conditions, immunogenic forms such as necroptosis and pyroptosis. Although apoptosis serves as a homeostatic and immunologically silent process that removes over 200 billion cells daily in our body, lytic forms of regulated cell death, such as necroptosis and pyroptosis, have evolved to detect and combat pathogens, thereby acting as potent danger signals that alert and mobilise immune responses.

Improving large language models accuracy for aortic stenosis treatment via Heart Team simulation: a prompt design analysis.

Aims: Large language models (LLMs) have shown potential in clinical decision support, but the influence of prompt design on their performance, particularly in complex cardiology decision-making, is not well understood.

Methods And Results: We retrospectively reviewed 231 patients evaluated by our Heart Team for severe aortic stenosis, with treatment options including surgical aortic valve replacement, transcatheter aortic valve implantation, or medical therapy. We tested multiple prompt-design strategies using zero-shot (0-shot), Chain-of-Thought (CoT), and Tree-of-Thought (ToT) prompting, combined with few-shot prompting, free/guided-thinking, and self-consistency.

The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models.

Reovirus type 3 Dearing (RT3D) is an oncolytic, double-stranded RNA virus. To identify potential RT3D drug-viral sensitizer, here we use a high-throughput screen of therapeutic agents and find a PARP-1 inhibitor, talazoparib, as a top hit. RT3D interacts with retinoic acid-induced gene-1 (RIG-I) and activates PARP-1, with consequent PARylation of components of the extrinsic apoptosis pathway.

Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion.

Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen for synergistic drug-virotherapy combinations and find that the reovirus type III Dearing strain (Rt3D)-palbociclib combination augments oncolytic virus-induced stress responses and increases interferon production and signaling. Data from RIG-I agonist and ER stress-inducing agents further confirms the crosstalk between RNA-sensing and ER stress in inducing cancer cell death and interferon production.

Diagnostic Accuracy of Angiography-Derived Murray Law-Based Quantitative Flow Ratio (μQFR) Versus Pressure-Derived Fractional Flow Reserve (FFR) in Moderate to Severe Calcified Coronary Lesions-The DIAMOND Study.

Background: Murray law-based Quantitative Flow Ratio (μQFR) is an innovative AI-driven method for evaluating coronary lesions using contrast flow velocity estimates. Unlike traditional approaches, μQFR does not require pressure wires or hyperemia induction. However, its accuracy compared to Fractional Flow Reserve (FFR) for calcified lesions (ACC/AHA classification B2 or C) remains underexplored.

PIP-mediated oligomerization of the endosomal sodium/proton exchanger NHE9.

The strict exchange of Na for H ions across cell membranes is a reaction carried out in almost every cell. Na/H exchangers that perform this task are physiological homodimers, and whilst the ion transporting domain is highly conserved, their dimerization differs. The Na/H exchanger NhaA from Escherichia coli has a weak dimerization interface mediated by a β-hairpin domain and with dimer retention dependent on cardiolipin.

Durable versus biodegradable polymer drug-eluting stents in all-comers.

Background: Drug-eluting stents (DESs) have become the gold standard of coronary angioplasty since their inception in 2002. Biodegradable polymer DESs (BP-DESs) have been postulated to be superior to durable polymer DESs (DP-DESs) due to their more biocompatible polymer. To date, no study has shown the superiority of one type of polymer compared with the other.

RIPK1 is required for ZBP1-driven necroptosis in human cells.

Necroptosis initiated by the host sensor Z-NA binding protein 1 (ZBP1) is essential for host defense against a growing number of viruses, including herpes simplex virus 1 (HSV-1). Studies with HSV-1 and other necroptogenic stimuli in murine settings have suggested that ZBP1 triggers necroptosis by directly complexing with the kinase RIPK3. Whether this is also the case in human cells, or whether additional co-factors are needed for ZBP1-mediated necroptosis, is unclear.

Sex differences in ST-segment elevation myocardial infarction patients treated by primary percutaneous intervention.

Introduction: The impact of sex on coronary artery disease prognosis is debated. It has been postulated that women receive less prompt treatment compared with men, potentially adversely affecting their prognosis by significantly increasing the risk of morbidity and mortality. We aim to investigate the influence of sex on the timing and clinical outcomes of ST-segment elevation myocardial infarction (STEMI) patients using a controlled Swiss registry.

RIPK1 is essential for Herpes Simplex Virus-triggered ZBP1-dependent necroptosis in human cells.

Necroptosis initiated by the host sensor Z-NA Binding Protein-1 (ZBP1) is essential for host defense against a growing number of viruses, including Herpes Simplex Virus-1 (HSV-1). Studies with HSV-1 and other necroptogenic stimuli in murine settings have suggested that ZBP1 triggers necroptosis by directly complexing with the kinase RIPK3. Whether this is also the case in human cells, or whether additional co-factors are needed for ZBP1-mediated necroptosis, is unclear.

Impact of protein and small molecule interactions on kinase conformations.

Protein kinases act as central molecular switches in the control of cellular functions. Alterations in the regulation and function of protein kinases may provoke diseases including cancer. In this study we investigate the conformational states of such disease-associated kinases using the high sensitivity of the kinase conformation (KinCon) reporter system.

Autocrine glutamate signaling drives cell competition in Drosophila.

Cell competition is an evolutionarily conserved quality control process that eliminates suboptimal or potentially dangerous cells. Although differential metabolic states act as direct drivers of competition, how these are measured across tissues is not understood. Here, we demonstrate that vesicular glutamate transporter (VGlut) and autocrine glutamate signaling are required for cell competition and Myc-driven super-competition in the Drosophila epithelia.

Experience with a novel high frequency optical coherence tomography device for intracoronary imaging: a case series.

Introduction: Intravascular imaging, especially optical coherence tomography (OCT), has significantly improved percutaneous coronary intervention (PCI), yet its routine clinical application faces challenges. This case series introduces the Gentuity® High-Frequency Optical Coherence Tomography (HF-OCT), a novel device designed to enhance intracoronary imaging with a significantly faster pullback and smaller catheter size, potentially offering enhanced navigability in complex lesions. We aimed to assess the image quality of Gentuity® HF-OCT in complex vessel conditions, as well as presenting a case series to illustrate the application of the device in various clinical scenarios.

Structure and mechanism of the K/H exchanger KefC.

Intracellular potassium (K) homeostasis is fundamental to cell viability. In addition to channels, K levels are maintained by various ion transporters. One major family is the proton-driven K efflux transporters, which in gram-negative bacteria is important for detoxification and in plants is critical for efficient photosynthesis and growth.

A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic cell death (ICD). Although the catalytic function of RIPK1 is required to trigger cell death, its non-catalytic scaffold function mediates strong pro-survival signaling. Accordingly, cancer cells can hijack RIPK1 to block necroptosis and evade immune detection.

Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity.

Most metastatic cancers remain incurable due to the emergence of apoptosis-resistant clones, fuelled by intratumour heterogeneity and tumour evolution. To improve treatment, therapies should not only kill cancer cells but also activate the immune system against the tumour to eliminate any residual cancer cells that survive treatment. While current cancer therapies rely heavily on apoptosis - a largely immunologically silent form of cell death - there is growing interest in harnessing immunogenic forms of cell death such as necroptosis.

Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death.

Cell death and inflammation are closely linked arms of the innate immune response to combat infection and tissue malfunction. Recent advancements in our understanding of the intricate signals originating from dying cells have revealed that cell death serves as more than just an end point. It facilitates the exchange of information between the dying cell and cells of the tissue microenvironment, particularly immune cells, alerting and recruiting them to the site of disturbance.

Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair.

Cell death coordinates repair programs following pathogen attack and tissue injury. However, aberrant cell death can interfere with such programs and cause organ failure. Cellular FLICE-like inhibitory protein (cFLIP) is a crucial regulator of cell death and a substrate of Caspase-8.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.