Highly enriched carbon and oxygen isotopes in carbonate-derived CO at Gale crater, Mars.

Carbonate minerals are of particular interest in paleoenvironmental research as they are an integral part of the carbon and water cycles, both of which are relevant to habitability. Given that these cycles are less constrained on Mars than they are on Earth, the identification of carbonates has been a point of emphasis for rover missions. Here, we present carbon (δC) and oxygen (δO) isotope data from four carbonates encountered by the Curiosity rover within the Gale crater.

1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study.

Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge.

Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium).

Mental health outcomes across the reproductive life course among women with disabilities: a systematic review.

Purpose: This systematic review examined literature on mental health outcomes among women with disabilities living in high-income countries within the context of reproductive health, spanning menstruation through menopause.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched MEDLINE, CINAHL, and PsycINFO databases for studies published through June 2023. Eligible studies were observational, quantitative, and included a comparison group without disabilities.

The backbone constitution drives passive permeability independent of side chains in depsipeptide and peptide macrocycles inspired by -verticilide.

The number of peptide-like scaffolds found in late-stage drug development is increasing, but a critical unanswered question in the field is whether substituents (side chains) or the backbone drive passive permeability. The backbone is scrutinized in this study. Five series of macrocyclic peptidic compounds were prepared, and their passive permeability was determined (PAMPA, Caco-2), to delineate structure-permeability relationships.

Performance of ChatGPT-4 and Bard chatbots in responding to common patient questions on prostate cancer Lu-PSMA-617 therapy.

Background: Many patients use artificial intelligence (AI) chatbots as a rapid source of health information. This raises important questions about the reliability and effectiveness of AI chatbots in delivering accurate and understandable information.

Purpose: To evaluate and compare the accuracy, conciseness, and readability of responses from OpenAI ChatGPT-4 and Google Bard to patient inquiries concerning the novel Lu-PSMA-617 therapy for prostate cancer.

Backbone-Determined Antiarrhythmic Structure-Activity Relationships for a Mirror Image, Oligomeric Depsipeptide Natural Product.

Cyclic oligomeric depsipeptides (COD) are a structural class within naturally occurring compounds with a wide range of biological activity. Verticilide is a COD (24-membered ring) that was identified by its inhibition of insect ryanodine receptor (RyR). We have since found that the enantiomer of verticilide (-verticilide, ) is a potent inhibitor of mammalian RyR2, a cardiac calcium channel, and therefore a potential antiarrhythmic agent.

Codesign and Evaluation of Pain Science Messages on Social Media With Adolescents With a History of Chronic Pain.

Pain science education (PSE) is an important component of pediatric pain care; however, access to services is limited. To disseminate pain science concepts on social media, we partnered with adolescents with chronic pain to codesign content. We engaged 7 adolescent codesigners (aged 13-18 years) with lived experience of chronic pain to take part in 4 codesign workshops.

Bone Metastases.

Bone metastases occur frequently in common malignancies such as breast and prostate cancer. They are responsible for considerable morbidity and skeletal-related events. Fortunately, there are now several systemic, focal, and targeted therapies that can improve quality and length of life, including radionuclide therapies.

Is drug interference still an issue for pretransfusion testing of patients on anti CD38 and other monoclonal antibody therapies?

Certain therapies that target CD markers on some blood cells can affect pretransfusion testing. Key examples are anti-CD38, CD47 monoclonal antibody (mAb) therapies such as daratumumab (DARA) and magrolimab, which have presented a challenge for transfusion medicine laboratories around the globe. Scientists have been faced with not only introducing a protocol to provide safe blood to patients but also investigating the most effective method to remove the pretransfusion pan-agglutinating interference caused.

Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going.

Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies.

Theranostics and artificial intelligence: new frontiers in personalized medicine.

The field of theranostics is rapidly advancing, driven by the goals of enhancing patient care. Recent breakthroughs in artificial intelligence (AI) and its innovative theranostic applications have marked a critical step forward in nuclear medicine, leading to a significant paradigm shift in precision oncology. For instance, AI-assisted tumor characterization, including automated image interpretation, tumor segmentation, feature identification, and prediction of high-risk lesions, improves diagnostic processes, offering a precise and detailed evaluation.

Changes in hospital mortality in patients with cancer during the COVID-19 pandemic (ISARIC-CCP-UK): a prospective, multicentre cohort study.

Background: Patients with cancer are at greater risk of dying from COVID-19 than many other patient groups. However, how this risk evolved during the pandemic remains unclear. We aimed to determine, on the basis of the UK national pandemic protocol, how factors influencing hospital mortality from COVID-19 could differentially affect patients undergoing cancer treatment.

Extended Cleavage Specificity of two Hematopoietic Serine Proteases from a Ray-Finned Fish, the Spotted Gar ().

The extended cleavage specificities of two hematopoietic serine proteases originating from the ray-finned fish, the spotted gar (), have been characterized using substrate phage display. The preference for particular amino acids at and surrounding the cleavage site was further validated using a panel of recombinant substrates. For one of the enzymes, the gar granzyme G, a strict preference for the aromatic amino acid Tyr was observed at the cleavable P1 position.

-Verticilide B1 Inhibits Type 2 Ryanodine Receptor Channels and is Antiarrhythmic in Mice.

Intracellular Ca leak from cardiac ryanodine receptor (RyR2) is an established mechanism of sudden cardiac death (SCD), whereby dysregulated Ca handling causes ventricular arrhythmias. We previously discovered the RyR2-selective inhibitor (+)-verticilide (-1), a 24-membered cyclooligomeric depsipeptide that is the enantiomeric form of a natural product (-(-)-verticilide). Here, we examined its 18-membered ring-size oligomer (-verticilide B1; "-B1") in RyR2 single channel and [H]ryanodine binding assays, and in cardiomyocytes and mice, a gene-targeted model of SCD.

Plasma steroid concentrations reflect acute disease severity and normalise during recovery in people hospitalised with COVID-19.

Objective: Endocrine systems are disrupted in acute illness, and symptoms reported following coronavirus disease 2019 (COVID-19) are similar to those found with clinical hormone deficiencies. We hypothesised that people with severe acute COVID-19 and with post-COVID symptoms have glucocorticoid and sex hormone deficiencies.

Design/patients: Samples were obtained for analysis from two UK multicentre cohorts during hospitalisation with COVID-19 (International Severe Acute Respiratory Infection Consortium/World Health Organisation [WHO] Clinical Characterization Protocol for Severe Emerging Infections in the UK study), and at follow-up 5 months after hospitalisation (Post-hospitalisation COVID-19 study).

The Extended Cleavage Specificity of Channel Catfish Granzyme-like II, A Highly Specific Elastase, Expressed by Natural Killer-like Cells.

The extended cleavage specificity of catfish granzyme-like II has been characterized using substrate phage display. The preference for particular amino acids at and surrounding the cleavage site was further validated by using a panel of recombinant substrates. This serine protease, which has previously been isolated as cDNA from a catfish natural killer-like cell line showed a preference for Ala in the P1 position of the substrate, and for multiple basic amino acids N-terminally of the cleavage site.

Rates of convergence for regression with the graph poly-Laplacian.

In the (special) smoothing spline problem one considers a variational problem with a quadratic data fidelity penalty and Laplacian regularization. Higher order regularity can be obtained via replacing the Laplacian regulariser with a poly-Laplacian regulariser. The methodology is readily adapted to graphs and here we consider graph poly-Laplacian regularization in a fully supervised, non-parametric, noise corrupted, regression problem.

The impact of imputation quality on machine learning classifiers for datasets with missing values.

Background: Classifying samples in incomplete datasets is a common aim for machine learning practitioners, but is non-trivial. Missing data is found in most real-world datasets and these missing values are typically imputed using established methods, followed by classification of the now complete samples. The focus of the machine learning researcher is to optimise the classifier's performance.