A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function

\ua9 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF

A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function.

Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF

Measurement of the Ratio of b Quark Production Cross Sections in Antiproton-Proton Collisions at 630 GeV and 1800 GeV

We report a measurement of the ratio of the bottom quark production cross section in antiproton-proton collisions at 630 GeV to 1800 GeV using bottom quarks with transverse momenta greater than 10.75 GeV identified through their semileptonic decays and long lifetimes. The measured ratio sigma(630)/sigma(1800) = 0.171 +/- .024 +/- .012 is in good agreement with next-to-leading order (NLO) quantum chromodynamics (QCD)

Visualization and measurement of capillary-driven blood flow using spectral domain optical coherence tomography

Capillary-driven flow (CD-flow) in microchannels plays an important role in many microfluidic devices. These devices, the most popular being those based in lateral flow, are becoming increasingly used in health care and diagnostic applications. CD-flow can passively pump biological fluids as blood, serum or plasma, in microchannels and it can enhance the wall mass transfer by exploiting the convective effects of the flow behind the meniscus. The flow behind the meniscus has not been experimentally identified up to now because of the lack of high-resolution, non-invasive, cross-sectional imaging means. In this study, spectral-domain Doppler optical coherence tomography is used to visualize and measure the flow behind the meniscus in CD-flows of water and blood. Microchannels of polydimethylsiloxane and glass with different cross-sections are considered. The predictions of the flow behind the meniscus of numerical simulations using the power-law model for non-Newtonian fluids are in reasonable agreement with the measurements using blood as working fluid. The extension of the Lucas-Washburn equation to non-Newtonian power-law fluids predicts well the velocity of the meniscus of the experiments using blood.close3

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Immune checkpoint inhibitors (ICIs) have revolutionized our approach to cancer treatment in the past decade. While monoclonal antibodies to CTLA‐4 and PD‐1/PD‐L1 have produced remarkable and durable responses in a subset of patients, the majority of patients will still develop primary or adaptive resistance. With complex mechanisms of resistance limiting the efficacy of checkpoint inhibitor monotherapy, it is critical to develop combination approaches to allow more patients to benefit from immunotherapy. In this review, I approach the current landscape of ICI research from the perspective of sarcomas, a rare group of bone and soft tissue cancers that have had limited benefit from checkpoint inhibitor monotherapy, and little investigation of biomarkers to predict responses. By surveying the various mechanisms of resistance and treatment modalities being explored in other solid tumors, I outline how ICIs will undoubtedly serve as the critical foundation for future directions in modern immunotherapy