Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b.

Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 μm to 12 μm with the JWST's Mid-Infrared Instrument.

Federated benchmarking of medical artificial intelligence with MedPerf.

Medical artificial intelligence (AI) has tremendous potential to advance healthcare by supporting and contributing to the evidence-based practice of medicine, personalizing patient treatment, reducing costs, and improving both healthcare provider and patient experience. Unlocking this potential requires systematic, quantitative evaluation of the performance of medical AI models on large-scale, heterogeneous data capturing diverse patient populations. Here, to meet this need, we introduce MedPerf, an open platform for benchmarking AI models in the medical domain.

Low Doses of Deoxynivalenol and Zearalenone Alone or in Combination with a Mycotoxin Binder Affect ABCB1 mRNA and ABCC2 mRNA Expression in the Intestines of Pigs.

Mycotoxin binders, in combination with enzymes degrading some mycotoxins, contribute to feed detoxification. Their use reduces economic losses and the negative impacts of mycotoxins on animal health and productivity in farm animals. The aim of this study was to evaluate the efficacy of a mycotoxin detoxifier on the expression of the ATP-binding cassette efflux transporters ABCB1 mRNA and ABCC2 mRNA, which transport xenobiotics and thus have a barrier function, in the tissues of pigs exposed to low doses of deoxynivalenol (DON, 1 mg/kg feed) and zearalenone (ZEN, 0.

American College of Rheumatology and Food and Drug Administration Summit: Summary of the Meeting, May 17-18, 2022.

The American College of Rheumatology and the US Food and Drug Administration co-sponsored a public meeting in May 2022 about challenges in the clinical development of drugs for rheumatoid arthritis (RA) and psoriatic arthritis (PsA), focusing on innovative clinical trial designs, outcome measures, and data collection methods. Recommendations include early dose-ranging studies and use of active comparators. Challenges and opportunities in assessing long-term safety by leveraging real-world data from electronic health records (EHRs) and claims data are discussed, along with insights from European registries and the evolving role of real-world evidence and artificial intelligence in regulatory evaluations.

Using Machine Learning to Determine a Suitable Patient Population for Anakinra for the Treatment of COVID-19 Under the Emergency Use Authorization.

A randomized, double-blind, placebo-controlled study (SAVEMORE trial) provided data to support an Emergency Use Authorization (EUA) of anakinra in hospitalized adults with positive results of direct severe acute respiratory syndrome-coronavirus 2 viral testing with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR). Currently, the suPAR assay is not commercially available in the United States. An alternative method was needed to identify patients that best reflect the population in the clinical trial selected based on suPAR level ≥ 6 ng/mL at baseline.

Presence of kratom in opioid overdose deaths: findings from coroner postmortem toxicological report.

Background: Kratom () use in the United States is becoming increasingly popular and its legal status varies widely from state to state. Multiple reports of adverse events associated with kratom use have ranged from liver injury, seizures, psychiatric disturbance, and rarely death.

Methods: This study investigated coroner autopsy reports from Kern County in California for the year 2020 which included qualitative data on substances from blood toxicological reports.

Orthogonal assay and QSAR modelling of Tox21 PPARγ antagonist in vitro high-throughput screening assay.

Disruption of signalling mediated by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is associated with risk of cancer, metabolic diseases, and endocrine disruption. The purpose of this study was to identify environmental chemicals acting as PPARγ antagonists. Data from the Tox21 PPARγ antagonism assay were replicated using a reporter system in HEK293 cells.

Exosomes as biomarkers and therapy in type 2 diabetes mellitus and associated complications.

Type 2 diabetes mellitus (T2DM) is one of the most prevalent metabolic disorders worldwide. However, T2DM still remains underdiagnosed and undertreated resulting in poor quality of life and increased morbidity and mortality. Given this ongoing burden, researchers have attempted to locate new therapeutic targets as well as methodologies to identify the disease and its associated complications at an earlier stage.

Reflections from the OARSI 2022 clinical trials symposium: The pain of OA-Deconstruction of pain and patient-reported outcome measures for the benefit of patients and clinical trial design.

Objective: Osteoarthritis (OA) drug development is hampered by a number of challenges. One of the main challenges is the apparent discordance between pain and structure, which has had a significant impact on drug development programs and has led to hesitance among stakeholders. Since 2017, the Clinical Trials Symposium (CTS) has been hosted under the Osteoarthritis Research Society International (OARSI) leadership.

New approach methods to improve human health risk assessment of thyroid hormone system disruption-a PARC project.

Current test strategies to identify thyroid hormone (TH) system disruptors are inadequate for conducting robust chemical risk assessment required for regulation. The tests rely heavily on histopathological changes in rodent thyroid glands or measuring changes in systemic TH levels, but they lack specific new approach methodologies (NAMs) that can adequately detect TH-mediated effects. Such alternative test methods are needed to infer a causal relationship between molecular initiating events and adverse outcomes such as perturbed brain development.

A broadband thermal emission spectrum of the ultra-hot Jupiter WASP-18b.

Close-in giant exoplanets with temperatures greater than 2,000 K ('ultra-hot Jupiters') have been the subject of extensive efforts to determine their atmospheric properties using thermal emission measurements from the Hubble Space Telescope (HST) and Spitzer Space Telescope. However, previous studies have yielded inconsistent results because the small sizes of the spectral features and the limited information content of the data resulted in high sensitivity to the varying assumptions made in the treatment of instrument systematics and the atmospheric retrieval analysis. Here we present a dayside thermal emission spectrum of the ultra-hot Jupiter WASP-18b obtained with the NIRISS instrument on the JWST.

Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.

Objective: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders.

Methods: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA.

Linear Interval Approximation of Sensor Characteristics with Inflection Points.

The popularity of smart sensors and the Internet of Things (IoT) is growing in various fields and applications. Both collect and transfer data to networks. However, due to limited resources, deploying IoT in real-world applications can be challenging.

A method for in vitro data and structure curation to optimize for QSAR modelling of minimum absolute potency levels and a comparative use case.

Large screening programs such as the US Tox21 are releasing experimental in vitro results for many endpoints of relevance for human health. In (Q)SAR modelling, it is essential to clearly define the endpoint (OECD QSAR Validation Principle 1) and extract the most robust data points according to the definition. We have developed a comprehensive data curation procedure to interpret in vitro experimental data sets for (Q)SAR development, with modules for selecting actives according to quality of curve fittings, magnitude of activity and 'absolute' potency cut-offs, requiring non-cytotoxicity at activity concentration; extracting only very robust inactives; selecting only substances tested in high purity; and accounting for assay signal interference.

Smart Data Placement Using Storage-as-a-Service Model for Big Data Pipelines.

Big data pipelines are developed to process data characterized by one or more of the three big data features, commonly known as the three Vs (volume, velocity, and variety), through a series of steps (e.g., extract, transform, and move), making the ground work for the use of advanced analytics and ML/AI techniques.

Early Release Science of the exoplanet WASP-39b with JWST NIRISS.

The Saturn-mass exoplanet WASP-39b has been the subject of extensive efforts to determine its atmospheric properties using transmission spectroscopy. However, these efforts have been hampered by modelling degeneracies between composition and cloud properties that are caused by limited data quality. Here we present the transmission spectrum of WASP-39b obtained using the Single-Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph (NIRISS) instrument on the JWST.

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec G395H.

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems. Access to the chemical inventory of an exoplanet requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based and high-resolution ground-based facilities. Here we report the medium-resolution (R ≈ 600) transmission spectrum of an exoplanet atmosphere between 3 and 5 μm covering several absorption features for the Saturn-mass exoplanet WASP-39b (ref.

Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules. Here we report a broad-wavelength 0.

Prevalence of low bone mineral density at axial sites and fracture risk in Bulgarian population.

Background: Osteoporosis is a common chronic disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of the bone, which are associated with increased risk of fragility fractures. Currently the most popular tool is the fracture risk assessment model FRAX to calculate the 10-year probability of major osteoporotic fractures (MOF) and hip fractures (HF).

Objective: To investigate the prevalence of low BMD at axial sites and fracture risk in Bulgarian population.

FDA/Arthritis Foundation osteoarthritis drug development workshop recap: Assessment of long-term benefit.

Objective: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market.

Design: Summary of the one-day workshop held virtually on June 22nd, 2021.

Results: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit.

Identification of substances with a carcinogenic potential in spray-formulated engine/brake cleaners and lubricating products, available in the European Union (EU) - based on IARC and EU-harmonised classifications and QSAR predictions.

Spray-formulated engine/brake cleaners and lubricating agents are widely used to maintain machines. The occupational exposure to their aerosols is evident. To assess the carcinogenic potential of these products, we identified such products available in the European Union (EU).

Pretrained Transformer Language Models Versus Pretrained Word Embeddings for the Detection of Accurate Health Information on Arabic Social Media: Comparative Study.

Background: In recent years, social media has become a major channel for health-related information in Saudi Arabia. Prior health informatics studies have suggested that a large proportion of health-related posts on social media are inaccurate. Given the subject matter and the scale of dissemination of such information, it is important to be able to automatically discriminate between accurate and inaccurate health-related posts in Arabic.

UV absorption by silicate cloud precursors in ultra-hot Jupiter WASP-178b.

Aerosols have been found to be nearly ubiquitous in substellar atmospheres. The precise temperature at which these aerosols begin to form in exoplanets has yet to be observationally constrained. Theoretical models and observations of muted spectral features indicate that silicate clouds play an important role in exoplanets between at least 950 and 2,100 K (ref.