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Recent years have seen an explosion of interest in understanding the mechanisms of phosphate ester hydrolysis in biological systems, using a range of computational approaches, each with different advantages and limitations. In this contribution, we present the empirical valence bond (EVB) approach as a powerful tool for modeling biochemical reactivity, using the example of organophosphate hydrolys
Background Exertional breathlessness is a key symptom in cardiorespiratory disease and can be quantified using incremental exercise testing, but its prognostic significance is unknown. We evaluated the ability of abnormally high breathlessness intensity during incremental cycle exercise testing to predict all-cause, respiratory, and cardiac mortality. Study design and methods Longitudinal cohort s
Obstetric anal sphincter injury (OASI) is a serious complication to vaginal birth, with the primary risk factors being primiparity and instrumental birth. Rates of OASI vary across countries, affecting up to 4% of primiparous women for spontaneous births and 6% to 24% for instrumental births in the United States, Canada, and Europe.
The evolution of sexual dimorphism is widely acknowledged as a manifestation of sex-specific genetic architecture. Although empirical studies suggested that sexual dimorphism evolves as a joint consequence of constraints arising from genetic architecture and sexually divergent selection, it remains unclear whether and how these established microevolutionary processes scale up to the macroevolution
Background Pancreatic ductal adenocarcinoma (PDAC) represents a major clinical challenge due to its tumor microenvironment, which exhibits immune-suppressive properties that facilitate cancer progression, metastasis, and therapy resistance. Interleukin 1 (IL-1) signaling has been implicated as a driver in this process. Mechanistically, both IL-1α and IL-1β bind to the IL-1 receptor type 1, forming
Nanoscale detection and control of the magnetic order underpins a spectrum of condensed-matter research and device functionalities involving magnetism. The key principle involved is the breaking of time-reversal symmetry, which in ferromagnets is generated by an internal magnetization. However, the presence of a net magnetization limits device scalability and compatibility with phases, such as sup
Introduction: Teledermatoscopy (TDS) has proven to be effective and reliable for diagnosis of skin malignancies. The factors that determine the success of implementation of TDS are largely unknown. Objectives: To investigate barriers to implementation of TDS in primary health care (PHC) at center and individual level. Methods: Following introduction of TDS, cross-sectional quantitative data and fr
In many species, polymorphic genomic inversions underlie complex phenotypic polymorphisms and facilitate local adaptation in the face of gene flow. Multiple polymorphic inversions can co-occur in a genome, but the prevalence, evolutionary significance, and limits to complexity of genomic inversion landscapes remain poorly understood. Here, we examine genome-wide genetic variation in one of Europe’
During the coronavirus disease 2019 (COVID-19) pandemic, Sweden emphasized voluntary guidelines over mandates. We exploited a rapid change and reversal of the Public Health Agency of Sweden's COVID-19 testing guidelines for vaccinated and recently infected individuals as a quasi-experiment to examine sociodemographic differences in the response to changes in pandemic guidelines. We analyzed daily
Background: The Finnish Shaft of the Humerus (FISH) trial compared open reduction and internal plate fixation (ORIF) with functional bracing in adult patients with displaced, closed humeral shaft fractures. Here, we compare the results of the patients in the randomized clinical trial (RCT [the randomized cohort]) with those of the cohort of patients who were also eligible but declined randomizatio
AIMS: Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection aga
Background: High body mass index (BMI) has been shown to have an association with chronic widespread pain (CWP), both in Rheumatoid arthritis (RA) and in other pain conditions such as fibromyalgia. Research on the adipose tissue and it’s adipokines, for example the well described leptin, is emerging. The objective of this study was to determine if there is an association between leptin levels in b
Background: Home mechanical ventilation (HMV), noninvasive ventilation and invasive ventilation outside a hospital setting, is a key treatment to improve outcomes in chronic hypoventilation. Research Question: What are the temporal trends observed over 27 years in Sweden regarding the incidence, prevalence, diagnostic spectrum, and patient characteristics associated with HMV? Study Design and Meth
Background: With a trend toward de-escalation of axillary surgery in breast cancer, prediction models incorporating imaging modalities can help reassess the need for surgical axillary staging. Although mammography is routinely performed for breast cancer imaging, its potential in nodal staging remains underutilized. This study aims to employ advancements in deep learning (DL) to comprehensively ev
This article introduces a mode of thought called dystopian optimism in response to the question of how critical marketing can be made more optimistic. Dystopian optimism counters both the utopian-optimistic belief that the climate crisis can be solved from within the current growth-capitalist system, and the dystopian pessimism of terminal marketing. We propose degrowth as a means to revitalise cr
G-quadruplexes (G4s) have long been implicated in the regulation of chromatin packaging and gene expression. These processes require or are accelerated by the separation of related proteins into liquid condensates on DNA/RNA matrices. While cytoplasmic G4s are acknowledged scaffolds of potentially pathogenic condensates, the possible contribution of G4s to phase transitions in the nucleus has only
The retinal pigment epithelium is a monolayer of pigmented, hexagonal cells connected by tight junctions. These cells compose part of the outer blood-retina barrier, protect the eye from excessive light, have important secretory functions, and support the function of photoreceptors, ensuring the coordination of a variety of regulatory mechanisms. It is the degeneration of the pigment epithelium th
