Search Results (104)

It has long been recognised that airway smooth muscle cells (ASMCs) possess an abundance of M2 muscarinic receptors (M2Rs). However, the contribution of postjunctional M2Rs to contractions of airway smooth muscle (ASM) induced by the release of acetylcholine (ACh) from parasympathetic nerves was thought to be minimal. Instead, it was believed that these responses were exclusively mediated by activation of M3Rs. However, evidence is emerging that postjunctional M2Rs may have a greater role than previously realised. In this review, we discuss ACh signalling in airways, highlighting the well-established autoinhibitory role of prejunctional M2Rs and the putative roles of postjunctional M2Rs to cholinergic contractions of ASM. The cellular mechanisms that underpin M2R-dependent contractions of ASM are reviewed, with a particular emphasis on the role of ion channels in these responses. The regulation of M2R signalling pathways by β-adrenoceptor activation is also considered, along with the potential involvement of postjunctional M2Rs in airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Full article

Non-small cell lung cancer (NSCLC) is operated commonly by diverse genetic alterations, and oncogenic fusions represent a significant therapeutic role. Common fusions include ALK, ROS1, RET, and NTRK, signaling pathways in tumorigenesis. Recent advances in investigating tumor molecular biology include underlying fusions, including chromosomal rearrangements, highlighting their role as oncogenic drivers. The development of targeted therapies, such as tyrosine kinase inhibitors (TKIs), has impacted most patients’ NSCLC treatment. Despite the greater profiles, such as remarkable efficiency and tolerable side effects compared to traditional chemotherapy, challenges, such as acquired mutations, lead to more ongoing research-optimized future NSCLC therapies. Full article

Current lung cancer screening guidelines in the United States fail to identify many individuals at risk of developing the disease. Additionally, existing healthcare infrastructure has been leveraged to establish IPN clinics, a promising approach to addressing the limitations of current screening guidelines. Early-stage lung cancer is frequently diagnosed because of the incidental detection of pulmonary nodules on clinically indicated chest CT scans, particularly in the absence of formal screening programs. While artificial intelligence (AI) systems for lung cancer detection have demonstrated significant advancements in medicine, their clinical validation in screening settings remains limited. This review will discuss the pivotal trials underpinning the United States Preventive Services Task Force (USPSTF) recommendations for lung cancer screening, which have shaped the current guidelines for at-risk populations. We will explore recent studies investigating the role of AI in enhancing lung cancer screening efforts, highlighting how AI has the potential to improve early detection, streamline workflows, and reduce false positives and negatives in screening processes. This review will present the lung cancer screening rates at our institution, with a specific focus on the validation and integration of AI-driven technologies into our established screening programs. Using AI algorithms, we have validated enhanced detection capabilities through retrospective analysis of historical patient data, demonstrating significant improvements in identifying high-risk individuals and early-stage malignancies. These AI models, validated through rigorous cross-validation methods and clinical trials, have proven to outperform traditional screening approaches in sensitivity and specificity. The integration of these AI technologies within the lung cancer screening framework not only optimizes existing programs but also expands access to screening, improving early detection rates and ultimately leading to better patient outcomes. Through continuous validation and refinement, we aim to solidify AI’s role in transforming lung cancer detection and patient care. Through ongoing validation and implementation, AI can play a crucial role in transforming lung cancer screening practices, ultimately contributing to earlier diagnosis and improved patient survival. Full article

Peanut allergy, a significant public health issue, poses challenges due to its potential for life-threatening anaphylaxis and profound impact on quality of life. Traditional management approaches, including allergen avoidance and epinephrine administration, are effective in mitigating acute symptoms but do not address the underlying allergy or long-term disease burden. Recent advances in immunotherapy and biologics, as well as innovative technologies such as gene editing and microbiome modulation, have introduced promising pathways for desensitization and sustained unresponsiveness. This review provides a comprehensive exploration of emerging therapies for peanut allergy, including oral, sublingual, and epicutaneous immunotherapy, biologic agents, gene-editing techniques, and novel drug therapies. We discuss their mechanisms, clinical efficacy, and associated challenges, emphasizing the potential for these innovations to revolutionize peanut allergy treatment. Despite significant progress, barriers such as adverse reactions, cost, and limited access remain. Addressing these challenges through further research and standardization could transform the future of peanut allergy management. Full article

Background/Objectives: Streptococcus pneumoniae with, or following, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased mortality, particularly in older adults. However, vaccination can be an effective preventative measure. This Phase 3 study (NCT05158140) assessed the immunogenicity and safety of co-administering the SARS-CoV-2 vaccine mRNA-1273 with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or the 15-valent pneumococcal conjugate vaccine (PCV15). Methods: Participants were healthy adults ≥50 years of age who had previously received a two-dose primary series of mRNA-1273 ≥5 months before the first study visit and may have received a booster dose of mRNA-1273 ≥4 months prior to the first study visit. Participants were randomized (1:1:1:1) to receive mRNA-1273 concomitantly with PPSV23 or PCV15 on Day 1 followed by placebo on Day 30, or sequentially with mRNA-1273 and placebo on Day 1 and PPSV23 or PCV15 on Day 30. The primary study endpoints were pneumococcal-serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and SARS-CoV-2-specific binding antibody GMTs at 30 days after vaccination, as well as safety and tolerability following vaccination. Results: In total, 850 adults participated in the study. Serotype-specific OPA GMTs at 30 days post-vaccination with PPSV23 or PCV15 were generally comparable between the concomitant and sequential groups. SARS-CoV-2-specific GMTs increased in all groups from pre-vaccination to 30 days post-vaccination with mRNA-1273, with a consistent response between concomitant and sequential groups. Safety profiles were comparable across study groups. Conclusions: Co-administration of mRNA-1273 with PPSV23 or PCV15 in healthy adults ≥50 years of age was immunogenic and well tolerated. Full article

Tick bites and tick-related diseases are on the rise. Diagnostic tests that identify well-characterised tick-borne pathogens (TBPs) possess limited capacity to address the causation of symptoms associated with poorly characterised tick-related illnesses, such as debilitating symptom complexes attributed to ticks (DSCATT) in Australia. Identification of local signals in tick-bitten skin that can be detected systemically in blood would have both clinical (diagnostic or prognostic) and research (mechanistic insight) utility, as a blood sample is more readily obtainable than tissue biopsies. We hypothesised that blood samples may reveal signals which reflect relevant local (tissue) events and that the time course of these signals may align with local pathophysiology. As a first step towards testing this hypothesis, we compared molecular signatures in skin biopsies taken from the tick-bite location of human participants, as published in our previous study, together with peripheral blood signatures obtained concurrently. This approach captures differentially expressed molecules across multiple omics datasets derived from peripheral blood (including cellular and cell-free transcriptomics, proteomics, metabolomics, and DNA methylation), and skin biopsies (spatial transcriptomics). Our original data revealed that extracellular matrix organisation and platelet degranulation pathways were upregulated in the skin within 72 h of a tick bite. The same signals appeared in blood, where they then remained elevated for three months, displaying longitudinally consistent alterations of biological functions. Despite the limited sample size, these data represent proof-of-concept that molecular events in the skin following a tick bite can be detectable systemically. This underscores the potential value of blood samples, akin to a liquid biopsy, to capture biomarkers reflecting local tissue processes. Full article

Background/Objectives: Patient and family involvement in bedside handover is a requirement of the national standards on patient safety and quality in Australia. To ensure patient-and-family-centred care, it is essential to understand how patients and families perceive their involvement in nursing bedside handover and what difficulties they face when participating. This study aimed to explore patient and family perceptions of their involvement in nursing bedside handover. Methods: We employed a qualitative descriptive study design with in-depth and semi-structured interviews. Using purposive and convenience sampling, 24 patients and family members were recruited from two adult hospitals in Western Australia between November 2021 and February 2022. The data were thematically analysed. Results: Participants had mixed experiences that overlapped with their individual perceptions, needs, and experiences. Their responses were grouped into three major themes with sub-themes: (1) discovering new nursing care approaches; (2) seeing the value of involvement in bedside handover; and (3) barriers hindering patient and family involvement in bedside handover. The findings revealed that patients and families valued their involvement in nursing bedside handover. However, several factors challenged their participation, including a lack of awareness about their right to participate, the timing of handovers, the nurse’s approach, and fear of asking questions. Conclusions: The findings serve as a guide for evidence-based practice and may significantly influence policy and practice in nursing bedside handover, potentially enhancing patient-and-family-centred care. While considered best practice, the consistent involvement of patients and their families in nursing bedside handover is not routinely achieved and is implemented to varying extents. Full article

Type 1 Diabetes (T1D) is a progressive autoimmune disease often identified in childhood or adolescence, with early stages detectable through pre-diabetic markers such as autoantibodies and subclinical beta-cell dysfunction. The identification of the pre-T1D stage is critical for preventing complications, such as diabetic ketoacidosis, and for enabling timely interventions that may alter disease progression. This review examines the multifaceted approach to managing T1D risk in adolescents and teens, emphasizing early detection, nutritional interventions, beta-cell preservation strategies, and psychosocial support. Screening for T1D-associated autoantibodies offers predictive insight into disease risk, particularly when combined with education and family resources that promote lifestyle adjustments. Although nutritional interventions alone are not capable of preventing T1D, certain lifestyle interventions, such as weight management and specific nutritional choices, have shown the potential to preserve insulin sensitivity, reduce inflammation, and mitigate metabolic strain. Pharmacological strategies, including immune-modulating drugs like teplizumab, alongside emerging regenerative and cell-based therapies, offer the potential to delay disease onset by protecting beta-cell function. The social and psychological impacts of a T1D risk diagnosis are also significant, affecting adolescents’ quality of life, family dynamics, and mental health. Supportive interventions, including counseling, cognitive-behavioral therapy (CBT), and group support, are recommended for managing the emotional burden of pre-diabetes. Future directions call for integrating universal or targeted screening programs within schools or primary care, advancing research into nutrition and psychosocial support, and promoting policies that enhance access to preventive resources. Advocacy for the insurance coverage of screening, nutritional counseling, and mental health services is also crucial to support families in managing T1D risk. By addressing these areas, healthcare systems can promote early intervention, improve beta-cell preservation, and support the overall well-being of adolescents at risk of T1D. Full article

The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology. Our analysis confirmed that differentiated cells have a proteomic profile more similar to healthy primary aortic smooth muscle cells than iPSCs. We also identified sex-based differences in iPSC-derived vascular smooth muscle cells in pathways related to ATP binding, glycogen metabolic process, and cadherin binding as well as multiple proteins relevant to cardiovascular pathophysiology and disease. Additionally, we explored the role of autosomal and sex chromosomes in protein regulation, identifying that proteins on autosomal chromosomes also show sex-based regulation that may affect the protein expression of proteins from autosomal chromosomes. This work supports the biological relevance of iPSC-derived vascular smooth muscle cells as a model for disease, and further exploration of the pathways identified here can lead to the discovery of sex-specific pharmacological targets for cardiovascular disease. Full article

Drawing on Karl Marx’s ecological concepts of the “metabolic rift” and the “emancipation of senses”, this paper explores an alternative ecocinema that integrates the ecological with the social and the economic. Early Hollywood films, such as Sunrise: A Song of Two Humans (1927) and The Good Earth (1937), represent the metabolic rift in human relationships as a byproduct of the metabolic rift with nature created in the process of urbanization; hence, they can be regarded as precursors to an alternative ecocinema, which I refer to as “metabolic cinema”. The Story of the Golden Bell (Jinling Zhuan), a comedy film produced during the Chinese Great Leap Forward in 1958, offers an intriguing case for socialist metabolic cinema as a multisensory medianature that participates in and facilitates the metabolic process between humans and nature, as well as the social metabolism among humans, despite the period’s notorious ecological record. The film not only consciously moves away from the visual-centric model associated with capitalist consumerism by using the aural to rectify the once-aberrant visual but also demonstrates how romantic love, as one of the human senses, must be emancipated along with other senses through denouncing utilitarianism and commercialism and, subsequently, returning to need-based labor as the universal condition for the metabolic interaction between humans and nature. Full article

Background: Bone hemangiomas are rare benign vascular tumors, comprising less than 1% of all bone tumors. They are predominantly found in the vertebral body or skull; rib hemangiomas are particularly rare and are often misdiagnosed as malignant tumors. Given the high malignancy rate of primary rib tumors, understanding rib hemangiomas is crucial to avoid misdiagnosis. Methods: A systematic review was conducted according to PRISMA standards. A comprehensive literature search was performed in PubMed, EMBASE, Web of Science, and Scopus. Data on patient demographics, tumor characteristics, and clinical presentation were analyzed using STATA/SE 17. Results: From 306 articles, 40 studies including 43 patients met the inclusion criteria. Rib hemangiomas showed a bimodal age distribution, with peaks in patients younger than 30 years (mean age 21.43 ± 5.60 years) and ≥30 years (mean age 59.96 ± 9.70 years). Females were more affected (62.79%) than males (37.21%), with a ratio of 1.69:1. The tumors were most frequently located in mid-thoracic ribs (4–8) and predominantly on the left side of the thorax. The mean tumor size was 7.27 cm, with 76.19% exhibiting osteolytic changes. Clinically, 63.41% of cases were asymptomatic, while symptomatic cases mainly presented with pain. Conclusions: Rib hemangiomas, though rare, should be considered in the differential diagnosis of thoracic tumors. They present as well-demarcated lytic lesions with distinct imaging features, and they typically require complete surgical excision, which may be aided with preoperative embolization. Their accurate diagnosis involves a combination of radiologic and clinical evaluation. Further studies are needed to understand the disease’s pathophysiology and to refine diagnostic and treatment protocols. Full article

Recent scientific research has shown that the ketogenic diet may have potential benefits in a variety of medical fields, which has led to the diet receiving a substantial amount of attention. Clinical and experimental research on brain tumors has shown that the ketogenic diet has a satisfactory safety profile. This safety profile has been established in a variety of applications, including the management of obesity and the treatment of drug-resistant epileptic cases. However, in human studies, the impact of ketogenic therapy on the growth of tumors and the life expectancy of patients has not provided results that are well characterized. Consequently, our purpose is to improve the comprehension of these features by succinctly presenting the developments and conclusions that have been gained from the most recent study that pertains to this non-pharmacological technique. According to the findings of our study, patients with brain tumors who stick to a ketogenic diet are more likely to experience improved survival rates. However, it is required to conduct additional research on humans in order to more accurately define the anti-tumor efficiency of this diet as well as the underlying processes that support the therapeutic effects of this dieting regimen. Full article

Objective: The objective of the study was to establish an AI-driven decision support system by identifying the most important features in the severity of disease for Intensive Care Unit (ICU) with Mechanical Ventilation (MV) requirement, ICU, and InterMediate Care Unit (IMCU) admission for hospitalized patients with COVID-19 in South Florida. The features implicated in the risk factors identified by the model interpretability can be used to forecast treatment plans faster before critical conditions exacerbate. Methods: We analyzed eHR data from 5371 patients diagnosed with COVID-19 from South Florida Memorial Healthcare Systems admitted between March 2020 and January 2021 to predict the need for ICU with MV, ICU, and IMCU admission. A Random Forest classifier was trained on patients’ data augmented by SMOTE, collected at hospital admission. We then compared the importance of features utilizing different model interpretability analyses, such as SHAP, MDI, and Permutation Importance. Results: The models for ICU with MV, ICU, and IMCU admission identified the following factors overlapping as the most important predictors among the three outcomes: age, race, sex, BMI, diarrhea, diabetes, hypertension, early stages of kidney disease, and pneumonia. It was observed that individuals over 65 years (‘older adults’), males, current smokers, and BMI classified as ‘overweight’ and ‘obese’ were at greater risk of severity of illness. The severity was intensified by the co-occurrence of two interacting features (e.g., diarrhea and diabetes). Conclusions: The top features identified by the models’ interpretability were from the ‘sociodemographic characteristics’, ‘pre-hospital comorbidities’, and ‘medications’ categories. However, ‘pre-hospital comorbidities’ played a vital role in different critical conditions. In addition to individual feature importance, the feature interactions also provide crucial information for predicting the most likely outcome of patients’ conditions when urgent treatment plans are needed during the surge of patients during the pandemic. Full article

This paper addresses the potential for technology to support husbandry and enrichment opportunities that enhance the welfare of zoo and sanctuary-housed nocturnal and crepuscular species. This topic was investigated through the medium of a multidisciplinary workshop (Moon Jam) that brought together species experts, zoo designers, Animal-Computer Interaction researchers and post-graduate students in collaborative discussions and design sessions. We explain the context through an examination of existing research and current practices, and report on specific challenges raised and addressed during the Moon Jam, highlighting and discussing key themes that emerged. Finally, we offer a set of guidelines to support the integration of technology into the design of animal husbandry and enrichment that support wellbeing, to advance the best practices in keeping and managing nocturnal and crepuscular animals. Full article

We present a Bayesian adaptive design for dose finding in oncology trials with application to a first-in-human trial. The design is based on the escalation with overdose control principle and uses an intermediate grade 2 toxicity in addition to the traditional binary indicator of dose-limiting toxicity (DLT) to guide the dose escalation and de-escalation. We model the dose–toxicity relationship using the proportional odds model. This assumption satisfies an important ethical concern when a potentially toxic drug is first introduced in the clinic; if a patient experiences grade 2 toxicity at the most, then the amount of dose escalation is lower relative to that wherein if this patient experienced a maximum of grade 1 toxicity. This results in a more careful dose escalation. The performance of the design was assessed by deriving the operating characteristics under several scenarios for the true MTD and expected proportions of grade 2 toxicities. In general, the trial design is safe and achieves acceptable efficiency of the estimated MTD for a planned sample size of twenty patients. At the time of writing this manuscript, twelve patients have been enrolled to the trial. Full article