We are entering an era in which therapeutic proteins are assembled using building block-like strategies, with no standardized schema to discuss these formats. Existing nomenclatures, like AbML, sacrifice human readability for precision. Therefore, considering even a dozen such formats, in combination with hundreds of possible targets, can create confusion and increase the complexity of drug discovery.
View Article and Find Full Text PDFIntroduction: Interstitial lung diseases consist of a range of lung disorders, the most prevalent being idiopathic pulmonary fibrosis (IPF). IPF is a chronic, progressive disease, resulting in loss of lung function and potentially significant impacts on quality of life. There is an increasing need to address unmet needs in this population as there is evidence that unmet needs may impact quality of life and health outcomes.
View Article and Find Full Text PDFCharacterizing the diet of imperiled species using minimally invasive methods is crucial to understanding their ecology and conservation requirements. Here, we apply a DNA metabarcoding approach to study the diet of the eastern massasauga rattlesnake (), a Federally Threatened snake found throughout the Great Lakes region. Eighty-three fecal samples collected across 10 different massasauga populations located in Michigan, USA, were sequenced, with 70 samples containing prey DNA.
View Article and Find Full Text PDFPostinfantile giant cell hepatitis (PIGCH), also known as syncytial giant cell hepatitis, continues to be a poorly defined and rare disease presentation in the adult population. Although a common finding in neonates, there is limited literature on the disease process, causes, and treatment success of PIGCH in adults. A strong association between autoimmune disorders and PIGCH, considerably so in the case of autoimmune hepatitis, has been established.
View Article and Find Full Text PDFAgeing causes a decline in leukocyte function and blunted leukocyte responses to resistance exercise. Systemic hypoxia exposure augments the leukocyte response to resistance exercise in young adults, yet this response remains uncharacterised in older adults. This study characterised the effects of normobaric hypoxia on the acute leukocyte and inflammatory cytokine responses to resistance exercise in older adults.
View Article and Find Full Text PDFHigh energy consumption and high cost have been the obstacles for large-scale deployment of all state-of-the-art CO capture technologies. Finding a transformational way to improve mass transfer and reaction kinetics of the CO capture process is timely for reducing carbon footprints. In this work, commercial single-walled carbon nanotubes (CNTs) were activated with nitric acid and urea under ultrasonication and hydrothermal methods, respectively, to prepare N-doped CNTs with the functional group of -COOH, which possesses both basic and acid functionalities.
View Article and Find Full Text PDFInfluenza A virus exhibits high rates of replicative failure due to a variety of genetic defects. Most influenza virions cannot, when acting as individual particles, complete the entire viral life cycle. Nevertheless influenza is incredibly successful in the suppression of innate immune detection and the production of interferons, remaining undetected in >99% of cells in tissue-culture models of infection.
View Article and Find Full Text PDFBackground: At the onset of the pandemic, there was poor public awareness and inaction in response to COVID-19; it is less known whether this translated to subsequent infections.
Objectives: To explore whether adults who perceived COVID-19 as less of a threat and who were not taking early actions were more likely to become infected over the following year.
Research Design: Survey data from the ongoing (COVID-19 & Chronic Conditions (C3) anonymized for review) cohort study.
Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed. Missing from these measurements, however, is the ability to routinely and easily spatially localise these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are 'tagged' with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions.
View Article and Find Full Text PDFInvestigative interviews by police are socially and cognitively demanding encounters, likely presenting significant challenges to those on the autism spectrum. Behavioral and communication differences mean that autistic people may also be more likely to be perceived as deceptive in the context of an investigative interview. In the present study, 32 autistic and 33 (age and IQ-matched) non-autistic adults took part in a novel virtual burglary scenario in either an 'innocent' or 'guilty' condition.
View Article and Find Full Text PDFSystemic sclerosis (SSc) -related calcinosis can be a debilitating, constantly painful, poorly understood vascular complication of calcium hydroxyapatite deposition in soft tissue structures that affects approximately 40% of both limited and diffuse cutaneous SSc subtypes. This publication describes the iterative and multitiered international qualitative investigations that yielded remarkable insights into natural history, daily experience, and complications of SSc-calcinosis providing pivotal information for health management. Patient-driven question development and field testing, according to Food and Drug Administration guidance, propelled the development of a patient-reported outcome measure for SSc-calcinosis, the Mawdsley Calcinosis Questionnaire.
View Article and Find Full Text PDFBackground: Autistic girls are underdiagnosed compared to autistic boys, even when they experience similar clinical impact. Research suggests that girls present with distinct symptom profiles across a variety of domains, such as language, which may contribute to their underdiagnosis. In this study, we examine sex differences in the temporal dynamics of natural conversations between naïve adult confederates and school-aged children with or without autism, with the goal of improving our understanding of conversational behavior in autistic girls and ultimately improving identification.
View Article and Find Full Text PDFBackground: Air pollution exposure is a significant risk factor for morbidity and mortality, especially for those with pre-existing chronic disease. Previous studies highlighted the risks that long-term particulate matter exposure has for readmissions. However, few studies have evaluated source and component specific associations particularly among vulnerable patient populations.
View Article and Find Full Text PDFBackground: Innate immune responses play essential roles in skeletal muscle recovery after injury. Programmed cell death protein 1 (PD-1) contributes to skeletal muscle regeneration by promoting macrophage proinflammatory to anti-inflammatory phenotype transition. Interferon (IFN)-γ induces proinflammatory macrophages that appear to hinder myogenesis in vitro.
View Article and Find Full Text PDFLoss of function mutations in the gene encoding dystrophin elicits a hypersensitive fear response in mice and humans. In the dystrophin-deficient mdx mouse, this behaviour is partially protected by oestrogen, but the mechanistic basis for this protection is unknown. Here, we show that female mdx mice remain normotensive during restraint stress compared to a hypotensive and hypertensive response in male mdx and male/female wildtype mice, respectively.
View Article and Find Full Text PDFBackground: Previous studies of short-term ambient air pollution exposure and asthma morbidity in the United States have been limited to a small number of cities and/or pollutants and with limited consideration of effects across ages.
Objectives: To estimate acute age group-specific effects of fine and coarse particulate matter (PM), major PM components, and gaseous pollutants on emergency department (ED) visits for asthma during 2005-2014 across the United States.
Methods: We acquired ED visit and air quality data in regions surrounding 53 speciation sites in 10 states.
In addition to the reduction of suboptimal welfare, there is now a need to provide farmed animals with positive opportunities to provide confidence that they have experienced a life worth living. Diversification of the environment through environmental enrichment strategies is one suggested avenue for providing animals with opportunities for positive experiences. The provision of more stimulating environmental conditions has been widely implemented in other animal production industries, based on evidenced welfare benefits.
View Article and Find Full Text PDFDuchenne muscular dystrophy (DMD) is a lethal muscle disease caused by absence of the protein dystrophin, which acts as a structural link between the basal lamina and contractile machinery to stabilize muscle membranes in response to mechanical stress. In DMD, mechanical stress leads to exaggerated membrane injury and fiber breakdown, with fast fibers being the most susceptible to damage. A major contributor to this injury is muscle contraction, controlled by the motor protein myosin.
View Article and Find Full Text PDFObjectives: The aim of this review was to summarize current evidence from the United States on the effectiveness of practices and interventions for preventing, recognizing, and controlling occupationally acquired infectious diseases in Emergency Medical Service (EMS) clinicians.
Report And Methods: PubMed, Embase, CINAHL, and SCOPUS were searched from January 1, 2006 through March 15, 2022 for studies in the United States that involved EMS clinicians and firefighters, reported on one or more workplace practices or interventions that prevented or controlled infectious diseases, and included outcome measures. Eleven (11) observational studies reported on infection prevention and control (IPC) practices providing evidence that hand hygiene, standard precautions, mandatory vaccine policies, and on-site vaccine clinics are effective.
Barriers to the ready adoption of biocatalysis into asymmetric synthesis for early stage medicinal chemistry are addressed, using ketone reduction by alcohol dehydrogenase as a model reaction. An efficient substrate screening approach is used to show the wide substrate scope of commercial alcohol dehydrogenase enzymes, with a high tolerance to chemical groups employed in drug discovery (heterocycle, trifluoromethyl and nitrile/nitro groups) observed. We use our screening data to build a preliminary predictive pharmacophore-based screening tool using Forge software, with a precision of 0.
View Article and Find Full Text PDFSafer gambling messages are one potential input to a public health approach toward reducing gambling-related harm, and yet there is no strong evidence supporting current messages such as "gamble responsibly" or "keep the fun in the game". Furthermore, sports betting is increasing in popularity in multiple jurisdictions, such as Australia and the US, increasing the need to design effective messaging campaigns for race and sports betting. Compared to other gambling formats, such as electronic gambling machines, the level of potential skill involved in race and sports betting may raise unique issues regarding the design of effective messages.
View Article and Find Full Text PDFEating behaviours affect food intakes and are involved in the aetiology of obesity. There has been impetus to translate findings about children's eating behaviour into intervention and policy programs. However, measurement limitations have hindered our capacity to understand and influence children's eating behaviours.
View Article and Find Full Text PDFBackground Aims: Allogeneic hematopoietic stem cell transplant is a curative approach for many malignant and non-malignant hematologic conditions. Despite advances in its prevention and treatment, the morbidity and mortality related to graft-versus-host disease (GVHD) remains. The mechanisms by which currently used pharmacologic agents impair the activation and proliferation of potentially alloreactive T cells reveal pathways essential for the detrimental activities of these cell populations.
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