Cystic Fibrosis (CF) is a life-limiting, inherited condition in which a novel class of oral medicine, CFTR modulators, has revolutionised symptoms and health indicators, providing an opportunity to evaluate traditional treatment regimens with the hope of reducing burden. Additionally, there is cautious optimism that life expectancy for people with CF born today could ultimately compare to that of the general population. Given this potential, there is a need and requirement to optimise treatment to balance burden with the best clinical outcomes for each person with CF in an individualised manner.
View Article and Find Full Text PDFPlasmodium species have variable genome compositions: many have an A/T content >80%, while others are similar in composition to human cells. Here, we made a direct comparison of DNA replication dynamics in two Plasmodium species whose genomes differ by ∼20% A/T content. This yielded fundamental insights into how DNA composition may affect replication.
View Article and Find Full Text PDFAn increasing number of individuals receiving psoriasis biologics achieve clear/nearly clear skin (disease control). Clinical trial data indicate that some maintain disease control with lower doses, especially those with higher serum drug concentrations. This indicates the potential of model-informed precision dosing, an advanced therapeutic drug-monitoring technique, to guide dose minimization.
View Article and Find Full Text PDFImmune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICIs) cause morbidity and necessitate cessation of treatment. Comparing irAE treatments, we find that anti-tumor immunity is preserved in mice after extracorporeal photopheresis (ECP) but reduced with glucocorticosteroids, TNFα blockade, and α4β7-integrin inhibition. Local adiponectin production elicits a tissue-specific effect by reducing pro-inflammatory T cell frequencies in the colon while sparing tumor-specific T cell development.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic has led to the widespread use of anticoagulation (AC) and corticosteroids (CCS) for hospitalized patients, but real-world outcomes may differ from clinical trial findings due to diverse patient populations and treatment variability.
Objective: To evaluate the real-world impact of AC and CCS therapies on key clinical outcomes in hospitalized COVID-19 patients.
Design: Multicenter, retrospective observational cohort study conducted across 11 hospitals in a Midwest health system.
Background And Objective: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a poor prognosis. Antifibrotics slow the decline of pulmonary function after 12-months, but limited studies have examined the role of circulatory biomarkers in antifibrotic treated IPF patients.
Methods: Serum from 98 IPF participants, from the Australian Idiopathic Pulmonary Fibrosis Registry were collected at four time-points over 1 year post-antifibrotic treatment and analysed as two separate cohorts.
Neurosci Biobehav Rev
February 2025
Nocebo effects are a heterogenous phenomenon in which contextual cues trigger or exacerbate symptoms independently of active interventions. Suggestion, conditioning, and social observation are widely recognised as hallmark methods for inducing nocebo effects, but the extent to which nocebo effects are differentially influenced by suggestion type (e.g.
View Article and Find Full Text PDFBackground: Sleep plays a crucial role in cognitive performance and cognitive changes in aging. In the current study, we investigated the role of sleep duration genetics in cognitive changes over time and the moderating effect of age.
Methods: Participants were drawn from the Reference Abilities Neural Network and the Cognitive Reserve studies of Columbia University.
In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).
View Article and Find Full Text PDFMotivation: Mitochondria are essential for cellular metabolism and are inherently flexible to allow correct function in a wide range of tissues. Consequently, dysregulated mitochondrial metabolism affects different tissues in different ways leading to challenges in understanding the pathology of mitochondrial diseases. System-level metabolic modelling is useful in studying tissue-specific mitochondrial metabolism, yet despite the mouse being a common model organism in research, no mouse specific mitochondrial metabolic model is currently available.
View Article and Find Full Text PDFGerontol Geriatr Educ
February 2025
Ageism - stereotyping, prejudice, and discrimination based on chronological age - is a highly prevalent yet underrecognized form of social discrimination with detrimental effects on healthy aging. Combating ageism is essential for creating an age-friendly society; however, there is no consensus on the optimal approach for doing so. In this manuscript, we posit that community-based participatory research holds promise for addressing and reframing ageism, especially in underserved minoritized communities.
View Article and Find Full Text PDFBackground: Nocebo responding involves the experience of adverse health outcomes in response to contextual cues. These deleterious responses impact numerous features of mental and physical health but are characterized by pronounced heterogeneity. Suggestion is widely recognized as a contributing factor to nocebo responding but the moderating role of trait responsiveness to verbal suggestions (suggestibility) in nocebo responding remains poorly understood.
View Article and Find Full Text PDFObjectives: To compare the manual dexterity and composure under pressure of people in different hospital staff roles using a buzz wire game.
Design: Prospective, observational, comparative study (Tremor study).
Setting: Leeds Teaching Hospitals NHS Trust, Leeds, UK, during a three week period in 2024.
Extracell Vesicles Circ Nucl Acids
July 2024
Aim: Extracellular communication via the transfer of vesicles and nanoparticles is now recognized to play an important role in tumor microenvironment interactions. Cancer cells upregulate and secrete abundant levels of and that can alter gene expression in donor and recipient cells. In this study, we sought to identify targets of and and conclusively demonstrate that microRNAs (miRNAs) can be functionally transferred from donor to recipient cells.
View Article and Find Full Text PDFConsiderable variation exists in the delivery of acute stroke care and stroke outcomes across settings and population groups. This is attributable in part to variation in resources among emergency departments in the United States, most notably in rural regions. Structural constraints of the US health care system, including the geographic distribution of where patients live relative to the location of hospitals and certified stroke centers, will continue to mean that many patients with stroke initially present to community emergency departments that have fewer stroke-related resources.
View Article and Find Full Text PDFWe report the findings of a genome-wide association study (GWAS) meta-analysis of endometriosis consisting of a large portion (31%) of non-European samples across 14 biobanks worldwide as part of the Global Biobank Meta-Analysis Initiative (GBMI). We identified 45 significant loci using a wide phenotype definition, seven of which are previously unreported and detected first genome-wide significant locus ( ) among only African-ancestry. Our narrow phenotypes and surgically confirmed case definitions for endometriosis analyses replicated the known loci near , , and .
View Article and Find Full Text PDFBackground And Objectives: Stroke in young adults has a lifelong impact on activities of daily life, including driving, leisure, and community-based activities; social participation; and reduced productivity. The needs of young people with stroke (YPwS) are likely to vary across different countries, and the development of age-adapted information and interventions is therefore critical in addressing those needs. This study aims to (1) identify the unmet needs of people with stroke aged 18 to 55 years across countries with varied income levels and cultural backgrounds and (2) determine their preferred means to access knowledge and information about stroke in the young.
View Article and Find Full Text PDFIn the United States, Black people face harsher health and social consequences of addiction compared to people who are not Black. These differential consequences are largely attributable to systemic racism. While addiction treatment may mitigate health disparities related to substance use, Black people also experience structural barriers and direct interpersonal racism which contribute to inequitable access and treatment outcomes.
View Article and Find Full Text PDFBackground: Predicting future brain health is a complex endeavor that often requires integrating diverse data sources. The neural patterns and interactions identified through neuroimaging serve as the fundamental basis and early indicators that precede the manifestation of observable behaviors or psychological states.
New Method: In this work, we introduce a multimodal predictive modeling approach that leverages an imaging-informed methodology to gain insights into future behavioral outcomes.
The di-π-methane (DPM) rearrangement is an important organic photorearrangement that converts 1,4-diene-containing compounds to vinyl cyclopropanes, often resulting in extensive, synthetically valuable restructuring of the substrate's carbon framework. We investigated the influence of Lewis and Brønsted acids on the DPM rearrangement of dibenzobarrelenes. These studies have culminated in the identification of a dual chiral Brønsted acid-iridium photosensitizer system that enables the first highly enantioselective catalytic all-carbon DPM rearrangement.
View Article and Find Full Text PDFRecent advances in cystic fibrosis (CF) treatments have led to improved survival, with life expectancy for Australians living with CF at 57yo. As life expectancy improves, long-term cardiovascular disease risk factors (as for the general population) will become an issue in these patients. We hypothesized that increased leukocyte expression of vasoconstriction and pro-fibrotic mediators may contribute to CF severity in adults with CF.
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