Existing deep learning models for defining pathology from clinical imaging data rely on expert annotations and lack generalization capabilities in open clinical environments. Here we present a generalizable vision-language model for Annotation-Free pathology Localization (AFLoc). The core strength of AFLoc is extensive multilevel semantic structure-based contrastive learning, which comprehensively aligns multigranularity medical concepts with abundant image features to adapt to the diverse expressions of pathologies without the reliance on expert image annotations. We conducted primary experiments on a dataset of 220,000 pairs of image-report chest X-ray images and performed validation across 8 external datasets encompassing 34 types of chest pathology. The results demonstrate that AFLoc outperforms state-of-the-art methods in both annotation-free localization and classification tasks. In addition, we assessed the generalizability of AFLoc on other modalities, including histopathology and retinal fundus images. We show that AFLoc exhibits robust generalization capabilities, even surpassing human benchmarks in localizing five different types of pathological image. These results highlight the potential of AFLoc in reducing annotation requirements and its applicability in complex clinical environments.

Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a markedly increased risk of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Lipoprotein(a) [Lp(a)], a genetically determined lipoprotein with proatherogenic, prothrombotic, and proinflammatory properties, has emerged as a potential contributor to this excess cardiovascular burden. Growing evidence suggests that Lp(a) may represent a mechanistic link between chronic inflammation, immune dysregulation, and accelerated atherosclerosis in RA.

This narrative review synthesizes evidence from observational studies, mechanistic research, genetic analyses, biomarker investigations, and emerging therapeutic trials examining Lp(a) in RA. Relevant literature was identified through comprehensive searches of major biomedical databases, with emphasis on studies addressing pathophysiology, cardiovascular outcomes, disease activity, and treatment effects on Lp(a).

RA patients frequently exhibit elevated Lp(a) levels, particularly in the presence of active systemic inflammation. Lp(a) contributes to vascular injury through enhanced arterial wall retention, carriage of oxidized phospholipids, endothelial activation, and impaired fibrinolysis. Clinical studies associate elevated Lp(a) with subclinical atherosclerosis, arterial stiffness, and increased cardiovascular events in RA, independent of conventional lipid parameters. Inflammatory cytokines, particularly interleukin-6 (IL-6), appear to modulate Lp(a) metabolism, providing a biological rationale for the Lp(a)-lowering effects observed with IL-6 receptor blockade. Advances in standardized assays, genetic insights into LPA polymorphisms, and novel RNA-based therapies have revitalized interest in Lp(a) as both a biomarker and therapeutic target in RA.

Lp(a) occupies a critical intersection between inflammation and atherosclerosis in RA. Incorporating Lp(a) into cardiovascular risk stratification and exploring targeted therapies may enable more precise, integrated management of cardiovascular risk in RA patients, warranting dedicated prospective studies.

In everyday clinical and research practice, normative data of voice quality, such as fundamental frequency (Fo), serve as a reference standard for comparing individual voice assessments. To date, normative data in the Greek language have only been published for pediatric populations. This study aimed to provide normative data for adults, reporting the average Fo and cycle-to-cycle variation in the electroglottography (EGG) waveform (jitter) during sustained phonation, as well as the speaking time-varying Fo during reading, in a sample of native adult Greek speakers.

This is a cross-sectional study.

All participants were recruited at the Athens Naval Hospital and the Cyprus Institute for Neurology and Genetics. Candidates with neurological, musculoskeletal, cardiovascular, metabolic, and respiratory diseases were excluded. Additional exclusion criteria related to voice included the presence of a vocal disorder or a history of a laryngeal pathology. A combination of tasks (sustained phonation and reading of a standard text passage) was used to provide normative data on average Fo and jitter (%; sustained phonation), as well as speaking Fo (reading). In all participants, the voice was recorded and analyzed through EGG.

One hundred forty-four native Greek speakers (77 females) aged between 20 and 86 years (mean 48.40 years) were included in the study. The Mann-Whitney U test showed significant differences in median average Fo in sustained phonation (U = 4638.50, P < 0.001) between males (139.12 Hz, n = 67) and females (207.43 Hz, n = 76). Along the same line, the speaking Fo during reading (DF x 1) was statistically different (U = 4820.00, P < 0.001) in males (124.55 Hz) compared to females (200.98 Hz). No differences were found in jitter (U = 2889.00, P > 0.05) between males and females. In males, speaking Fo showed a progressive lowering or relative stability until around age 60, followed by an increase in older age, whereas in females it progressively decreased with age.

This is the first study to provide normative EGG data on Fo and jitter in adult Greek speakers. Deviations from these norms may help clinicians in early diagnosis, monitoring disorder severity, and evaluating treatment effectiveness, thereby supporting timely adjustments in therapeutic plans.

1.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycemic agents that selectively inhibit glucose reabsorption in the renal proximal tubules, thereby promoting urinary glucose excretion and reducing blood glucose levels. In recent years, accumulating evidence from large-scale clinical trials has demonstrated that SGLT2i not only exert robust glucose-lowering effects but also confer significant protective benefits on the cardiovascular, renal, and nervous systems. However, the precise molecular mechanisms underlying these multi-system benefits remain incompletely understood.2.

Mitochondria are central organelles responsible for cellular energy metabolism, redox homeostasis, and calcium handling, and they play a pivotal role in the pathogenesis and progression of various chronic diseases.3.

Emerging studies indicate that SGLT2i can markedly improve mitochondrial function through multiple mechanisms, including enhancement of mitochondrial quality control, modulation of mitochondrial energy metabolism, reinforcement of antioxidant defenses, and improvement of calcium homeostasis.4.

These mitochondria-centered mechanisms may underlie the protective effects of SGLT2i on the cardiovascular, renal, and neurological systems. In this review, we systematically summarize the regulatory effects of SGLT2i on mitochondrial function and discuss their potential therapeutic implications in related diseases, aiming to provide novel insights and a theoretical foundation for future basic research and clinical applications.

Cannabidiol (CBD), the primary non-psychoactive component of cannabis, is renowned for its antiepileptic, analgesic, and anti-inflammatory properties. Emerging evidence highlights its potential as an anti-tumor agent, yet significant heterogeneity in preclinical studies and an incomplete mechanistic understanding impede its clinical translation.

This review aims to systematically evaluate the anti-tumor efficacy, underlying mechanisms, and safety profile of CBD, and to discuss the challenges and future directions for its application in oncology.

A systematic review.

We integrated recent high-quality research to assess CBD's effects across various cancer types. The analysis encompassed its mechanisms in tumor cell biology and the tumor microenvironment (TME), a comparison of monotherapy versus combination therapy efficacy, its role in managing cancer-related symptoms, and its pharmacokinetic/pharmacodynamic properties. Advances in nano-based drug delivery systems were also reviewed.

CBD demonstrates multi-target anti-tumor effects, including inhibiting proliferation, inducing apoptosis, suppressing metastasis, and remodeling the TME via immunomodulation. It exhibits broad-spectrum efficacy in vitro and in vivo, shows synergistic effects in combination therapy, and can alleviate cancer-related symptoms. Safety data indicate a favorable tolerability profile. However, current evidence relies predominantly on preclinical models.

CBD holds substantial promise as an anti-tumor agent. This review provides a theoretical foundation for its rational development. Future work should focus on validating these findings in clinical trials, optimizing targeted drug delivery systems, and establishing standardized treatment protocols.

G protein-coupled receptor kinases (GRKs) are a class of serine/threonine kinases that shut down active signaling mediated by agonist-bound G protein-coupled receptors. Of all the diseases that arise from dysfunctional G protein-coupled receptor-GRK interactions, this review will focus on the roles of the 2 most highly expressed GRKs in heart failure (HF)-GRK2 and GRK5. Both are upregulated in human and mouse HF heart samples. Because both GRK2 and GRK5 are expressed in all cardiac cell types-cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and cardiomyocytes-it is essential to examine their role in these individual cell types for identifying specific cardiomyopathies and targeting them accordingly. Seminal work from our laboratory over the last 3 decades has uncovered multiple crucial aspects of GRK2- and GRK5-mediated interactions that lead to HF. Based on that, several GRK2 and GRK5 inhibitors have been identified/generated that have high potency and have been tested in multiple animal models of HF. One of the GRK2 inhibitors, paroxetine, has also been evaluated in 2 clinical trials. Similarly, potent GRK5 inhibitors have also been recently generated, and it remains to be seen how they affect cardiac structure and function in vivo. Lastly, assessing cell-specific fine differences in GRK2 and GRK5 inhibition will pave the way for identifying ideal patient cohorts for clinical trials in which selective GRK2 and GRK5 inhibitors can be evaluated as a new class of drugs for HF. SIGNIFICANCE STATEMENT: G protein-coupled receptor kinases 2 and 5 play a central role in heart failure (HF) onset and progression. They have critical significance in all cardiac cells, which contribute to the pathophysiology of HF, namely, cardiomyocytes, cardiac fibroblasts, endothelial cells, and vascular smooth muscle cells. Dysfunction in their canonical G protein-coupled receptor-related function or noncanonical function must be sufficiently investigated and addressed to evaluate their inhibitors as a new class of drugs for HF.

This study aimed to evaluate the effectiveness of warm compress and cold compress in managing peripheral intravenous catheter (PIVC)-induced pain and phlebitis. A quantitative, pre-experimental 2-group pre-test post-test design was adopted, involving 60 purposively selected patients. Participants were divided into 2 groups on the basis of 2 different interventions: Group A (warm compress) and Group B (cold compress). Data were collected using a sociodemographic and clinical variables interview, Numerical Pain Rating Scale, and Visual Infusion Phlebitis (VIP) Scale. In Group A, the mean pain score decreased from 4.37 ± 1.00 to 1.97 ± 1.73, and the mean phlebitis score decreased from 3.20 ± 0.76 to 1.03 ± 0.89. In Group B, the mean pain score reduced from 4.33 ± 0.92 to 1.03, and the mean phlebitis score dropped from 3.24 ± 0.74 to 1.00 ± 0.53. The cold compress demonstrated slightly more effectiveness in relieving pain, whereas the warm compress showed marginally better outcomes in reducing phlebitis severity. No clinical variables were associated with post-test pain levels. However, a significant association was observed between the phlebitis score and type of drug administered (P = .04), suggesting that certain medications, such as antibiotics or inotropes, may influence the development or severity of phlebitis.

BACKGROUND: IRRAflow is a novel active cerebrospinal fluid (CSF) exchange system for the treatment of hemorrhagic strokes and intracranial infections. It is a closed system that irrigates various medications dissolved in irrigation solutions at a speed of up to 180 mL/h, expediting resolution. Disrupting this closed system to withdraw CSF samples or infuse medications is necessary in certain circumstances. We report our novel approach for maintaining the sterility of the closed IRRAflow system using a needleless extension and assess the compatibility and safety of this technology throughout treatment. METHODS: We used a needleless extension to withdraw CSF samples and deliver medications to 5 patients treated with the IRRAflow system. We used 1 stopcock with a 3-way valve, 2 neutral needleless connectors, and 2 antiseptic caps. The stopcock was connected between the irrigation and drainage ports of the catheter. The needleless connectors were mounted at the 12 o'clock position of the attached stopcock and the irrigation port with antiseptic caps covering the distal ends. To initiate fluid exchange, the 2 needleless connectors were separated. The extra stopcock valve was connected between the drainage arm, the cassette, and the irrigation arm. The needleless connectors remained mounted at the 12 o'clock position of the stopcock and irrigation port throughout treatment. RESULTS: The needleless connectors mounted on the 12 o'clock position of the stopcock and irrigation port on the drainage and irrigation arms, respectively, provided efficient management of fluid exchange, CSF fluid sampling, and medication delivery. Our needleless extension was compatible with the IRRAflow device and prevented secondary infections despite repeated CSF sampling and medication delivery. CONCLUSION: The needleless extension facilitated a simple and safe interaction with the closed IRRAflow system without compromising the sterile environment during CSF sampling and medication delivery.

BACKGROUND: Neuroscience nurses generate new knowledge through research. Establishing research priorities is essential to support evidence-based nursing practice and direct research agendas. The purpose of this scoping review was to describe the nursing interventions and outcomes of adult 18 years of age or older nonintensive care or rehabilitation hospitalized patients with acute ischemic stroke (AIS) and identify gaps in the evidence. METHODS: Scoping review was followed, which included creation of a structured review protocol, a comprehensive librarian-assisted literature search of studies from 2010 to 2023, and the use of systematic review software. Reviewers performed title, abstract, and full-text review of studies meeting the inclusion criteria. A structured data extraction form was used to record characteristics of included studies, as well as nursing interventions and outcomes for hospitalized patients with AIS. RESULTS: Of the 797 studies identified from the literature search, 35 studies met the inclusion criteria. Nursing interventions included specific activities related to motor functioning (13), patient and family education (7), dysphagia (8), workflow (3), management of hyperglycemia (3) and fever (3), and discharge planning (1). Clinical outcomes included measures of disability (20), mortality (17), neurological deficits (15), adverse events and complications (14), and length of stay (14). Additional less frequently reported outcomes included time (9), patient satisfaction (6), and unplanned emergency department visits and readmissions (1). No studies reported metrics related to return on investment or costs related to nursing interventions. Across all interventions, motor functioning appears to have a positive impact on length of stay, neurological deficits, disability, and timing. CONCLUSION: This review provides a summary of nursing interventions and outcomes for adult hospitalized patients with AIS from a small sample of studies over 20 years. Gaps in the literature are noted to help inform the American Association of Neuroscience Nurses on the need for future research.