Coronary artery disease is the leading cause of morbidity and mortality worldwide. Selected patients with obstructive coronary artery disease benefit from revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. #link# Many (but not all) studies have demonstrated increased survival and greater freedom from adverse cardiovascular events after complete revascularization (CR) than after incomplete revascularization (ICR) in patients with multivessel disease. However, achieving CR after PCI or CABG surgery might not be feasible owing to patient comorbidities, anatomical factors, and technical or procedural considerations. These factors also mean that comparisons between CR and ICR are subject to multiple confounders and are difficult to understand or apply to real-world clinical practice. In this Review, we summarize and critically appraise the evidence linking various types of ICR to adverse outcomes in patients with multivessel disease and stable ischaemic heart disease, non-ST-segment elevation acute coronary syndrome or ST-segment elevation myocardial infarction, with or without cardiogenic shock. In addition, we provide practical recommendations for revascularization in patients with high-risk multivessel disease to optimize their long-term clinical outcomes and identify areas requiring future clinical investigation.It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripheral adenosine A1 receptor (pADORA1) signaling; however, it remains unclear whether systemic and adipose tissue metabolism would also be under the control of central (c) ADORA1 signaling. Here, we use tissue-specific pharmacology and metabolic tools to clarify the roles of cADORA1 signaling in energy and adipocyte physiology. We found that cADORA1 signaling reduces body weight while also inducing adipose tissue lipolysis. cADORA1 signaling also increases adipose tissue sympathetic norepinephrine content. In contrast, pADORA1 signaling facilitates a high-fat diet-induced obesity (DIO). We propose here a novel mechanism in which cADORA1 and pADORA1 signaling hinder and aggravate DIO, respectively.Hydrogen sulfide (H2S) is constitutively generated in the human body and works as a gasotransmitter in synaptic transmission. In this study, we aimed to evaluate the roles of endogenous H2S in generating eupnea at the respiratory center. We employed an in situ arterially perfused preparation of decerebrated rats and recorded the central respiratory outputs. When the H2S-producing enzyme cystathionine β-synthase (CBS) was inhibited, respiration switched from the 3-phase eupneic pattern, which consists of inspiration, postinspiration, and expiration, to gasping-like respiration, which consists of inspiration only. On the other hand, when H2S synthesis was inhibited via cystathionine γ-lyase (CSE) or when H2S synthesis was activated via CBS, eupnea remained unchanged. These results suggest that H2S produced by CBS has crucial roles in maintaining the neuronal network to generate eupnea. The mechanism of respiratory pattern generation might be switched from a network-based system to a pacemaker cell-based system in low H2S conditions.Although gold-standard histological assessment is subjective it remains central to diagnosis and clinical trial protocols and is crucial for the evaluation of any preclinical disease model. Objectivity and reproducibility are enhanced by quantitative analysis of histological images but current methods require application-specific algorithm training and fail to extract understanding from the histological context of observable features. We reinterpret histopathological images as disease landscapes to describe a generalisable framework defining topographic relationships in tissue using geoscience approaches. The framework requires no user-dependent training to operate on all image datasets in a classifier-agnostic manner but is adaptable and scalable, able to quantify occult abnormalities, derive mechanistic insights, and define a new feature class for machine-learning diagnostic classification. check details demonstrate application to inflammatory, fibrotic and neoplastic disease in multiple organs, including the detection and quantification of occult lobular enlargement in the liver secondary to hilar obstruction. We anticipate this approach will provide a robust class of histological data for trial stratification or endpoints, provide quantitative endorsement of experimental models of disease, and could be incorporated within advanced approaches to clinical diagnostic pathology.Chronic myeloid leukemia is a hematological cancer driven by the oncoprotein BCR-ABL1, and lifelong treatment with tyrosine kinase inhibitors extends patient survival to nearly the life expectancy of the general population. Despite advances in the development of more potent tyrosine kinase inhibitors to induce a durable deep molecular response, more than half of patients relapse upon treatment discontinuation. This clinical finding supports the paradigm that leukemia stem cells feed the neoplasm, resist tyrosine kinase inhibition, and reactivate upon drug withdrawal depending on the fitness of the patient’s immune surveillance. This concept lends support to the idea that treatment-free remission is not achieved solely with tyrosine kinase inhibitors and that new molecular targets independent of BCR-ABL1 signaling are needed in order to develop adjuvant therapy to more efficiently eradicate the leukemia stem cell population responsible for chemoresistance and relapse. Future efforts must focus on the identification of new targets to support the discovery of potent and safe small molecules able to specifically eradicate the leukemic stem cell population. In this review, we briefly discuss molecular maintenance in leukemia stem cells in chronic myeloid leukemia and provide a more in-depth discussion of the dual-specificity kinase DYRK2, which has been identified as a novel actionable checkpoint in a critical leukemic network. DYRK2 controls the activation of p53 and proteasomal degradation of c-MYC, leading to impaired survival and self-renewal of leukemia stem cells; thus, pharmacological activation of DYRK2 as an adjuvant to standard therapy has the potential to induce treatment-free remission.