Nonlinearity of the post-spinel transition and its expression in slabs and plumes worldwide.

Phase transitions in the mantle control its internal dynamics and structure. The post-spinel transition marks the upper-lower mantle boundary, where ringwoodite dissociates into bridgmanite plus ferropericlase, and its Clapeyron slope regulates mantle flow across it. This interaction has previously been assumed to have no lateral spatial variations, based on the assumption of a linear post-spinel boundary in pressure and temperature.

Towards device technologies non-invasive to our daily lives.

Recent advances in non-invasive technologies have shown disruptive potential for biomedical applications. However, while surgically non-invasive, they may introduce other types of limitations which interfere with the patient’s quality of life, from impracticalities and discomfort in daily life to social stigma.

Emerging insights into the impact of systemic metabolic changes on tumor-immune interactions.

Tumors are inherently embedded in systemic physiology, which contributes metabolites, signaling molecules, and immune cells to the tumor microenvironment. As a result, any systemic change to host metabolism can impact tumor progression and response to therapy. In this review, we explore how factors that affect metabolic health, such as diet, obesity, and exercise, influence the interplay between cancer and immune cells that reside within tumors.

Patterns of Treatment and Real-World Outcomes of Patients With Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations Receiving Mobocertinib: The EXTRACT Study.

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.

Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).

Adherence to the Mediterranean Diet and the Risk of Head and Neck Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies.

Background/objectives: Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence rates and significant mortality. While tobacco use, alcohol consumption, and viral infections are established risk factors, the role of dietary patterns, particularly adherence to the Mediterranean diet (MD), in HNC prevention has gained increasing attention. The aim of the current systematic review and meta-analysis is to investigate the association between adherence to the MD and the risk of HNC.

Restoration of Genuine Sensation and Proprioception of Individual Fingers Following Transradial Amputation with Targeted Sensory Reinnervation as a Mechanoneural Interface.

: Tactile gnosis derives from the interplay between the hand's tactile input and the memory systems of the brain. It is the prerequisite for complex hand functions. Impaired sensation leads to profound disability.

The Response Regulator OmpR Negatively Controls the Expression of Genes Implicated in Tilimycin and Tilivalline Cytotoxin Production in .

toxigenic strains represent a critical health threat, mainly due to their link to antibiotic-associated hemorrhagic colitis. This serious condition results from the bacteria's ability to produce tilimycin and tilivalline cytotoxins. Our research highlights the pivotal role of OmpR, a key regulator within the EnvZ/OmpR two-component system, in controlling the virulence factors associated with .

Uniform volumetric single-cell processing for organ-scale molecular phenotyping.

Extending single-cell analysis to intact tissues while maintaining organ-scale spatial information poses a major challenge due to unequal chemical processing of densely packed cells. Here we introduce Continuous Redispersion of Volumetric Equilibrium (CuRVE) in nanoporous matrices, a framework to address this challenge. CuRVE ensures uniform processing of all cells in organ-scale tissues by perpetually maintaining dynamic equilibrium of the tissue's gradually shifting chemical environment.

Tenzing Assisted Delivery of Aspiration (TADA) technique for thrombectomy of medium vessel occlusions using the Freeclimb 54 catheter: multicenter experience.

Background: Medium vessel occlusions (MeVOs) account for 25-40% of acute ischemic stroke. The Tenzing 5 (Route 92 Medical, San Mateo, California, USA) and FreeClimb 54 (Route 92 Medical, San Mateo, California, USA) catheter is a novel delivery-aspiration catheter combination designed to facilitate aspiration thrombectomy (AT) of MeVOs. We report our clinical experience using the Tenzing assisted delivery of aspiration (TADA) technique with FreeClimb 54 for first-line AT of MeVO.

Regulation of PD-L1 glycosylation and advances in cancer immunotherapy.

Protein glycosylation plays a versatile role in regulating homeostasis, such as cell migration, protein sorting, and the immune response. Drugs aimed at targeting glycosylation have strong implications for immunity enhancement, diagnosis, and cancer regression. Programmed death-ligand 1 (PD-L1), expressed in cancer or antigen-presenting cells, binds to programmed cell death protein 1 (PD-1) and suppresses T cells.

Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2s), five (mosaic-5), or seven (mosaic-7) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges.

Myelin ensheathment and drug responses of oligodendrocytes are modulated by stiffness of artificial axons.

Myelination is a key biological process wherein glial cells such as oligodendrocytes wrap myelin around neuronal axons, forming an insulative sheath that accelerates signal propagation down the axon. A major obstacle to understanding myelination is the challenge of visualizing and reproducibly quantifying this inherently three-dimensional process in vitro. To this end, we previously developed artificial axons (AAs), a biocompatible platform consisting of 3D-printed hydrogel-based axon mimics designed to more closely recapitulate the micrometer-scale diameter and sub-kilopascal mechanical stiffness of biological axons.

Automating alloy design and discovery with physics-aware multimodal multiagent AI.

The design of new alloys is a multiscale problem that requires a holistic approach that involves retrieving relevant knowledge, applying advanced computational methods, conducting experimental validations, and analyzing the results, a process that is typically slow and reserved for human experts. Machine learning can help accelerate this process, for instance, through the use of deep surrogate models that connect structural and chemical features to material properties, or vice versa. However, existing data-driven models often target specific material objectives, offering limited flexibility to integrate out-of-domain knowledge and cannot adapt to new, unforeseen challenges.

Measuring self-similarity in empirical signals to understand musical beat perception.

Experiencing music often entails the perception of a periodic beat. Despite being a widespread phenomenon across cultures, the nature and neural underpinnings of beat perception remain largely unknown. In the last decade, there has been a growing interest in developing methods to probe these processes, particularly to measure the extent to which beat-related information is contained in behavioral and neural responses.

Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions.

Background: We developed a United States-based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results: The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients.

Synthetic data in generalizable, learning-based neuroimaging.

Synthetic data have emerged as an attractive option for developing machine-learning methods in human neuroimaging, particularly in magnetic resonance imaging (MRI)-a modality where image contrast depends enormously on acquisition hardware and parameters. This retrospective paper reviews a family of recently proposed methods, based on synthetic data, for generalizable machine learning in brain MRI analysis. Central to this framework is the concept of domain randomization, which involves training neural networks on a vastly diverse array of synthetically generated images with random contrast properties.

Machine learning for antimicrobial peptide identification and design.

Artificial intelligence (AI) and machine learning (ML) models are being deployed in many domains of society and have recently reached the field of drug discovery. Given the increasing prevalence of antimicrobial resistance, as well as the challenges intrinsic to antibiotic development, there is an urgent need to accelerate the design of new antimicrobial therapies. Antimicrobial peptides (AMPs) are therapeutic agents for treating bacterial infections, but their translation into the clinic has been slow owing to toxicity, poor stability, limited cellular penetration and high cost, among other issues.

Evaluating the impact of ESICM 2023 guidelines and the new global definition of ARDS on clinical outcomes: insights from MIMIC-IV cohort data.

Background: In 2023, the European Society of Intensive Care Medicine (ESICM) recommended updated criteria for acute respiratory distress syndrome (ARDS). In 2024, Matthay et al. updated the global ARDS definition in AJRCCM, titled "A New Global Definition of Acute Respiratory Distress Syndrome.

Leveraging mRNA technology for antigen based immuno-oncology therapies.

The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response.

Embracing the Future of Clinical Trials in Radiotherapy: An NRG Oncology CIRO Technology Retreat Whitepaper on Pioneering Technologies and AI-Driven Solutions.

This white paper examines the potential of pioneering technologies and artificial intelligence (AI)-driven solutions in advancing clinical trials involving radiotherapy. As the field of radiotherapy evolves, the integration of cutting-edge approaches such as radiopharmaceutical dosimetry, FLASH radiotherapy, image-guided radiation therapy (IGRT), and AI promises to improve treatment planning, patient care, and outcomes. Additionally, recent advancements in quantum science, linear energy transfer/relative biological effect (LET/RBE), and the combination of radiotherapy and immunotherapy create new avenues for innovation in clinical trials.

Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines.

Through-the-sensor sub-bottom imaging using the self-noise of an autonomous underwater vehiclea).

This work demonstrates the feasibility of performing through-the-sensor (TTS) sub-bottom imaging using low-frequency ([100 Hz-1kHz]) self-noise generated by the propulsion of an autonomous underwater vehicle (AUV) acting as a source of opportunity. The self-noise was recorded by a short towed horizontal line array (11.4 m aperture) by the same AUV while it operated ∼35 m above the seabed along a range-dependent section at the New England shelf break.

Epstein-Barr virus BALF0/1 subverts the Caveolin and ERAD pathways to target B cell receptor complexes for degradation.

Epstein-Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host B cells to support lytic replication. We previously identified that EBV lytic replication results in selective depletion of plasma membrane (PM) B cell receptor (BCR) complexes, composed of immunoglobulin and the CD79A and CD79B signaling chains.