Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

Sequential intranasal booster triggers class switching from intramuscularly primed IgG to mucosal IgA against SARS-CoV-2.

The persistent emergence of COVID-19 variants and recurrent waves of infection worldwide underscores the urgent need for vaccines that effectively reduce viral transmission and prevent infections. Current intramuscular (IM) COVID-19 vaccines inadequately protect the upper respiratory mucosa. In response, we have developed a nonadjuvanted, interferon-armed SARS-CoV-2 fusion protein vaccine with IM priming and intranasal (IN) boost sequential immunization.

Mechanisms of adaptive resistance to targeted therapy in RET-aberrant cancers.

The success of targeted therapies in oncogene-driven cancer is limited by adaptive or acquired treatment resistance, leading to disease progression. A recent study reports that YAP-dependent HER3 activation constitutes a therapeutic vulnerability of adaptive resistance to RET-targeted therapies in RET-altered cancers, highlighting a promising strategy to improve RET-inhibitor tumor responses.

TRAIL agonists rescue mice from radiation-induced lung, skin or esophageal injury.

Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.

PDGFRα inhibition reduces myofibroblast expansion in the fibrotic rim and enhances recovery after ischemic stroke.

Ischemic stroke is a major cause of adult disability. Early treatment with thrombolytics and/or thrombectomy can significantly improve outcomes; however, following these acute interventions, treatment is limited to rehabilitation therapies. Thus, the identification of therapeutic strategies that can help restore brain function in the post-acute phase remains a major challenge.

An Activin Receptor-Like Kinase 1-governed monocytic lineage shapes an immunosuppressive landscape in breast cancer metastases.

The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.

LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models.

Colorectal cancer (CRC) remains a leading cause of cancer death due to metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice.

EMPOWER PKD: Patient, Caregiver, and Researcher Priorities for Research in Polycystic Kidney Disease.

Background: Patient involvement in research can help to ensure that the evidence generated aligns with their needs and priorities. In the Establishing Meaningful Patient-Centered Outcomes With Relevance for Patients with Polycystic Kidney Disease (EMPOWER PKD) project we aimed to identify patient-important outcomes and discuss the impact of PKD on patients.

Methods: Nine focus groups were held with adult patients with PKD, caregivers, and clinical or research experts in PKD.

Dynamic electroosmotic flow and solute dispersion through a nanochannel filled with an electrolyte surrounded by a layer of a dielectric and immiscible liquid.

The present article deals with the modulation of oscillatory electroosmotic flow (EOF) and solute dispersion across a nanochannel filled with an electrolyte solution surrounded by a layer of a dielectric liquid. The dielectric permittivity of the liquid layer adjacent to supporting rigid walls is taken to be lower than that of the electrolyte solution. Besides, the aforesaid liquid layer may bear additional mobile charges, , free lipid molecules, charged surfactant molecules , which in turn lead to a nonzero charge along the liquid-liquid interface.

Impaired hydrogen sulfide biosynthesis underlies eccentric contraction-induced force loss in dystrophin-deficient skeletal muscle.

Eccentric contraction- (ECC) induced force loss is a hallmark of murine dystrophin-deficient (mdx) skeletal muscle that is used to assess efficacy of potential therapies for Duchenne muscular dystrophy. While virtually all key proteins involved in muscle contraction have been implicated in ECC force loss, a unifying mechanism that orchestrates force loss across such diverse molecular targets has not been identified. We showed that correcting defective hydrogen sulfide (H2S) signaling in mdx muscle prevented ECC force loss.

The Association Between COVID-19 Vaccination Uptake and Information-Seeking Behaviors Using the Internet: Nationwide Cross-Sectional Study.

Background: The COVID-19 pandemic, declared in March 2020, profoundly affected global health, societal, and economic frameworks. Vaccination became a crucial tactic in combating the virus. Simultaneously, the pandemic likely underscored the internet's role as a vital resource for seeking health information.

Broken Symmetry and Elastic Frustration in Isostructural Spin Crossover Crystals.

Symmetry-breaking spin-state transitions in two of three isostructural salts of MnIII spin-crossover cations, [MnIII(3-OMe-5-NO2-sal2323)]+, with heavy anions are reported. The ReO4-  salt undergoes two-step spin crossover which is coupled with a re-entrant symmetry-breaking structural phase transition between a high temperature phase (S = 2, C2/c), an intermediate ordered phase (S = 1/S = 2, P21/c), and a low temperature phase (S = 1, C2/c). The AsF6-  complex undergoes an abrupt transition between a high temperature phase (S = 2, C2/c) and a low temperature ordered phase (S = 1/S = 2, P-1).

Kinetic Control of Self-Assembly Pathway in Dual Dynamic Covalent Polymeric Systems.

Kinetically controlled self-assembly is garnering increasing interest in the field of supramolecular polymers and materials, yet examples involving dynamic covalent exchange remain relatively unexplored. Here we report an unexpected dynamic covalent polymeric system whose aqueous self-assembly pathway is strongly influenced by the kinetics of evaporation of water. The key design is to integrate dual dynamic covalent bonds-including disulfide bonds and boroxine/borate-into a dynamic equilibrium system of monomers, polymers, and materials.

Network-Based Identification of Key Toxic Compounds in Airborne Chemical Exposome.

Air pollution is a leading contributor to the global disease burden. However, the complex nature of the chemicals to which humans are exposed through inhalation has obscured the identification of the key compounds responsible for diseases. Here, we develop a network topology-based framework to identify key toxic compounds in the airborne chemical exposome.

A Proposed mHealth Intervention to Address Patient Barriers to Colposcopy Attendance: Qualitative Interview Study of Clinic Staff and Patient Perspectives.

Background: Cervical cancer disparities persist among minoritized women due to infrequent screening and poor follow-up. Structural and psychosocial barriers to following up with colposcopy are problematic for minoritized women. Evidence-based interventions using patient navigation and tailored telephone counseling, including the Tailored Communication for Cervical Cancer Risk (TC3), have modestly improved colposcopy attendance.

[Diagnosis and therapy of chronic hepatitis D: Czech national guideline].

For the first time, a separate Czech guideline focuses exclusively on hepatitis D virus (HDV) infection. Until recently, HDV infection was only mentioned in guidelines concerning hepatitis B virus (HBV) infection, in chapters on HBV/HDV co-infection. The guideline is based on the July 2023 recommendations from the European Association for the Study of the Liver.

[Cytomegalovirus coinfection].

The rapid advancement of modern pharmacological and surgical therapeutic interventions is often accompanied by potential disruptions to the immune system, both permanent and transient. Consequently, life-threatening infectious complications may emerge, which were either absent or exceedingly rare in the past. Observational studies have identified pneumocystis and cytomegalovirus pneumonia as one of the most prevalent coinfections.

[Pneumocystis pneumonia].

In parallel with the introduction of modern therapeutic and pharmacological interventions that have successfully resolved many diseases and conditions, previously deemed incompatible with life, there has been a significant increase in the number of patients experiencing secondary immunodeficiency. As a result, these patients are highly susceptible to various opportunistic infections. Among these infections, pneumocystis pneumonia (PCP) stands out as one of the most frequent and potentially life-threatening ones, necessitating prompt diagnosis and treatment.

Geographical Disparities in Research Misconduct: Analyzing Retraction Patterns by Country.

This study examines disparities in research retractions due to misconduct, identifying countries with the highest retraction counts and those disproportionately represented relative to population and publication output. The findings emphasize the need for improved research integrity measures.

Eliciting Preferences for the Uptake of Smoking Cessation Apps: Discrete Choice Experiment.

Background: If the most evidence-based and effective smoking cessation apps are not selected by smokers wanting to quit, their potential to support cessation is limited.

Objective: This study sought to determine the attributes that influence smoking cessation app uptake and understand their relative importance to support future efforts to present evidence-based apps more effectively to maximize uptake.

Methods: Adult smokers from the United Kingdom were invited to participate in a discrete choice experiment.

Absorptivity Is an Important Determinant in the Toxicity Difference between Aristolochic Acid I and Aristolochic Acid II.

Inadvertent exposure to aristolochic acids (AAs) is causing chronic renal disease worldwide, with aristolochic acid I (AA-I) identified as the primary toxic agent. This study employed chemical methods to investigate the mechanisms underlying the nephrotoxicity and carcinogenicity of AA-I. Aristolochic acid II (AA-II), which has a structure similar to that of AA-I, was investigated with the same methods for comparison.

An event-based account of conformity: evidence from attention manipulations targeting event-file encoding and retrieval.

Previous findings have raised doubt in whether comparable conformity effects can be obtained for information from humans and computers or other systems of little or no social importance. In the present study, we compared the impact of "other choices" (i.e.

Oxygen-Passivated Sulfur Vacancies in Monolayer MoS for Enhanced Piezoelectricity.

Modern-day applications demand onboard electricity generation that can be achieved using piezoelectric phenomena. Reducing the dimensionality of materials is a pathway to enhancing the piezoelectric properties. Transition-metal dichalcogenides have been shown to exhibit high piezoelectricity.

Analogue-Sensitive Inhibition of Histone Demethylases Uncovers Member-Specific Function in Ribosomal Protein Synthesis.

Lysine demethylases (KDMs) catalyze the oxidative removal of the methyl group from histones using earth-abundant iron and the metabolite 2-oxoglutarate (2OG). KDMs have emerged as master regulators of eukaryotic gene expression and are novel drug targets; small-molecule inhibitors of KDMs are in the clinical pipeline for the treatment of human cancer. Yet, mechanistic insights into the functional heterogeneity of human KDMs are limited, necessitating the development of chemical probes for precision targeting.

The Combined Effect of Multisensory Stimulation and Therapist Support on Physical and Mental Health of Older Adults Living in Nursing Homes: Pilot Randomized Controlled Trial.

Background: Increasing life expectancy has led to a rise in nursing home admissions, a context in which older adults often experience chronic physical and mental health conditions, chronic pain, and reduced well-being. Nonpharmacological approaches are especially important for managing older adults' chronic pain, mental health conditions (such as anxiety and depression), and overall well-being, including sensory stimulation (SS) and therapist support (TS). However, the combined effects of SS and TS have not been investigated.