PARP inhibitors differentially regulate immune responses in distinct genetic backgrounds of high-grade serous tubo-ovarian carcinoma models.

Immune checkpoint inhibitors (ICIs) have revolutionized treatment for several tumor indications without demonstrated benefit for ovarian cancer patients. To improve the therapeutic ratio of ICIs in ovarian cancer patients, several different clinical trials are testing combinations with poly (ADP-ribose) polymerase (PARP) inhibitors. Comparing the immunomodulatory effects of clinically advanced PARP inhibitors may help to identify the best partner to combine with ICIs.

Prevalence of High-Risk CTA-Based Carotid Plaque-RADS Subtypes in Patients With Embolic Stroke of Undetermined Source.

Background: A modified computed tomography angiography (CTA)-based Carotid Plaque Reporting and Data System (Plaque-RADS) classification was applied to a cohort of patients with embolic stroke of undetermined source to test whether high-risk Plaque-RADS subtypes are more prevalent on the ipsilateral side of stroke. With the widespread use of CTA for stroke evaluation, a CTA-based Plaque-RADS would be valuable for generalizability.

Methods: A retrospective observational cross-sectional study was conducted at a single integrated health system comprised of 3 hospitals with a comprehensive stroke center between October 1, 2015, and April 1, 2017.

Acute beneficial effects of a functional energy shot on cognitive performance and mood states during cognitively demanding task performance: a randomized, double-blind, placebo-controlled, crossover trial.

Introduction: Functional beverages are increasingly popular but it is important to validate their purported effects through research. The aim of the current study was to investigate the effects of a new functional energy shot on cognitive performance and mood states in healthy adults, with a focus on measuring mental energy enhancement and attenuation of negative effects associated with extended performance of mentally demanding tasks.

Methods: This study was a randomized, double-blind, placebo-controlled, crossover trial.

Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative.

Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.

Methods: We conducted a retrospective cohort study of individuals <21 years seeking care at 24 health systems across the U.

A Case of Pulmonary Sarcoidosis With Multiple Endobronchial Polypoid Structures and Partial Airway Obstruction.

We present a case of a 42-year-old male with sarcoidosis manifesting as endobronchial mass-like lesions, a rare and atypical presentation of the disease. Sarcoidosis typically involves the respiratory system, but its occurrence as endobronchial polyps mimicking malignancy is uncommon. The diagnosis was confirmed through bronchoscopy and biopsy, revealing non-caseating granulomas.

Methylmercury in subarctic amphibians: environmental gradients, bioaccumulation, and estimated flux.

Rapid warming in polar regions is causing large changes to ecosystems, including altering environmentally available mercury (Hg). Although subarctic freshwater systems have simple vertebrate communities, Hg in amphibians remains unexplored. We measured total Hg (THg) in wetland sediments and methylmercury (MeHg) in multiple life-stages (eggs to adults) of wood frogs (Rana sylvatica) and larval boreal chorus frogs (Pseudacris maculata) from up to 25 wetlands near Churchill, Manitoba (Canada), during the summers of 2018-2019.

Real-world use of tafasitamab preceding CD19-directed chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma.

Potential CD19 antigen loss following CD19-directed therapy has raised concerns over sequential use of these therapies. Tafasitamab, a CD19-targeting immunotherapy, combined with lenalidomide, is approved for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) treatment in adults ineligible for autologous stem cell transplantation. This retrospective analysis examined characteristics and outcomes of adults with R/R DLBCL who received tafasitamab preceding CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in a real-world setting.

Estimating health state utilities for aromatic L-amino acid decarboxylase deficiency (AADCd) in the United States.

Background: AADCd is a rare neurometabolic disorder presenting in infancy. Children with AADCd have motor dysfunction and development delays that result in the need for lifelong care; quality of life is greatly impacted. Current characterizations of health-related quality of life and associated health state utilities (HSUs) may be underestimated in AADCd.

Balancing the risks: continuous vs. interrupted anticoagulation during TAVI - what does the evidence say?

Anticoagulation therapy is a critical component of post-transcatheter aortic valve implantation (TAVI) management, aimed at reducing the risk of thromboembolic events and mortality. This review examines the efficacy of continuous versus interrupted anticoagulation strategies in TAVI patients, focusing on mortality, stroke rates, and composite events. A literature review was conducted, analyzing recent studies that evaluate the impact of different anticoagulation regimens on clinical outcomes in TAVI patients.

Translation of PET radiotracers for cancer imaging: recommendations from the National Cancer Imaging Translational Accelerator (NCITA) consensus meeting.

Background: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation.

Methods: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation.

Pharmacokinetics of Nivolumab and Erythropoietin in a Rat Model of Diet-Induced Obesity.

Purpose: To investigate how obesity affects the pharmacokinetics of biologics in a rat model.

Method: Male Long-Evans rats were fed a high-fat diet from the age of 3 weeks and development of obesity was monitored by measuring body size and composition (fat and lean mass). The animals received nivolumab (1 and 8 mg/kg) or recombinant human erythropoietin (rHuEPO, 1000 IU/kg) by intravenous or subcutaneous injection.

Microstructure response of concentrated suspensions to flow reversal.

We study experimentally at the macroscopic and microstructure scale a dense suspension of non-Brownian neutrally buoyant spherical particles experiencing periodic reversals of flow at constant rate between parallel plates and tracked individually. We first characterize the quasi-steady state reached at the end of half periods. The volume fraction of particles increases from the walls to the center as a result of migration induced by the nonuniform strain rate.

Mapping the topography of spatial gene expression with interpretable deep learning.

Spatially resolved transcriptomics technologies provide high-throughput measurements of gene expression in a tissue slice, but the sparsity of these data complicates analysis of spatial gene expression patterns. We address this issue by deriving a topographic map of a tissue slice-analogous to a map of elevation in a landscape-using a quantity called the isodepth. Contours of constant isodepths enclose domains with distinct cell type composition, while gradients of the isodepth indicate spatial directions of maximum change in expression.

The relationship between cannabis and cardiovascular disease: clearing the haze.

Cannabis has been consumed for centuries, but global regulatory changes over the past three decades have increased the availability and consumption of cannabis. Cannabinoids are touted to have therapeutic potential for many diseases and could be a replacement for opioids for analgesia and sedation. However, cannabinoids can cause substantial adverse cardiovascular events that would mitigate any potential benefit.

Practice patterns for acquiring neuroimaging after pediatric in-hospital cardiac arrest.

Aims: To determine which patient and cardiac arrest factors were associated with obtaining neuroimaging after in-hospital cardiac arrest, and among those patients who had neuroimaging, factors associated with which neuroimaging modality was obtained.

Methods: Retrospective cohort study of patients who survived in-hospital cardiac arrest (IHCA) and were enrolled in the ICU-RESUS trial (NCT02837497).

Results: We tabulated ultrasound (US), CT, and MRI frequency within 7 days following IHCA and identified patient and cardiac arrest factors associated with neuroimaging modalities utilized.

Cellulose-based poly(ionic liquid)s: Correlations between degree of substitution and alkyl side chain length with conductive and morphological properties.

Ion transport in solid polymer electrolytes is crucial for applications like energy conversion and storage, as well as carbon dioxide capture. However, most of the materials studied in this area are petroleum-based. Natural materials (biopolymers) have the potential to act as alternatives to petroleum-based products and, when derived with ionic liquid (IL) functionalities, present a sustainable alternative for conductive materials by offering tunable morphological, thermal, and mechanical properties.

Safety and Effectiveness of Microwave Ablation of Liver Tumors. Initial Real-World Results from the Multinational NOLA Registry.

Purpose: To investigate the safety and effectiveness of microwave ablation (MWA) for treating liver tumors using real-world data from a multicenter registry (NOLA: NEUWAVE Observational Liver Ablation).

Materials And Methods: NOLA is approved to enroll up to 1,500 adults treated with MWA and follow them for five years. Initial data for 615 patients treated across 24 tertiary healthcare centers in the United States (14), Europe (8), and Asia (2), from January 2020 to October 2022, are summarized herein.

The impact of ACOG's 39-week rule on fetal death rates in the United States: A systematic review.

Objective: The "39-week rule," implemented in August 2009, strongly discouraged early term deliveries before 39 weeks without accepted ACOG delivery indications. In this study, we evaluated fetal death rates before and after the 39-week rule in the United States (US) by review of published series.

Study Design: Systematic literature searches were performed in PubMed, Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus databases (January 2009-June 2023).

Pembrolizumab in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) and non-MSI-H/non-dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results.

Objective: We report updated results with longer follow-up in patients with MSI-H/dMMR endometrial cancer (EC) in cohort D (advanced EC of any MSI/dMMR status) and cohort K (any MSI-H/dMMR advanced solid tumor, except colorectal) of the phase 2 KEYNOTE-158 study (NCT02628067) and the first results from patients with non-MSI-H/non-dMMR advanced EC (cohort D).

Methods: Patients received pembrolizumab 200 mg Q3W for ≥35 cycles. The primary endpoint was objective response rate (ORR) per RECIST v1.

Can gamification improve children's performance in mental rotation?

A common obstacle in cognitive development research is that many cognitive tasks can be long, repetitive, and hence seemingly boring for children. The current study examined whether incorporating gamification elements could make a classic mental rotation task more child-friendly and engaging for young children. A total of 100 children aged 6 to 9 years participated in two mental rotation tasks, where one included gamification elements and the other did not.

How do restrictions on opioid prescribing, harm reduction, and treatment coverage policies relate to opioid overdose deaths in the United States in 2013-2020? An application of a new state opioid policy scale.

Background: Identifying the most effective state laws and provisions to reduce opioid overdose deaths remains critical.

Methods: Using expert ratings of opioid laws, we developed annual state scores for three domains: opioid prescribing restrictions, harm reduction, and Medicaid treatment coverage. We modeled associations of state opioid policy domain scores with opioid-involved overdose death counts in 3133 counties, and among racial/ethnic subgroups in 1485 counties (2013-2020).

Effect of siponimod on retinal thickness, a marker of neurodegeneration, in participants with SPMS: Findings from the EXPAND OCT substudy.

Background: People with MS show abnormal thinning of the retinal layers, which is associated with clinical disability and brain atrophy, and is a potential surrogate marker of neurodegeneration and treatment effects.

Objective: To evaluate the utility of retinal thickness as a surrogate marker of neurodegeneration and treatment effect in participants with secondary progressive MS (SPMS) from the optical coherence tomography (OCT) substudy of the EXPAND Phase 3 clinical trial (siponimod versus placebo).

Methods: In the OCT substudy population (n = 159), treatment effects on change in the average thickness of the retinal layer, peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (GCIPL) were analyzed by high-definition spectral domain OCT at months 3, 12, and 24.

Dysregulated Clot Mechanics and Kinetics Impacted by Injury Severity, Predict Mortality After Trauma.

Introduction: Coagulopathy following traumatic injury impairs stable blood clot formation and exacerbates mortality from hemorrhage. Understanding how these alterations impact blood clot stability is critical to improving resuscitation. Furthermore, the incorporation of machine learning algorithms to assess clinical markers, coagulation assays and biochemical assays allows us to define the contributions of these factors to mortality.

Variable impacts of land-based climate mitigation on habitat area for vertebrate diversity.

Pathways to achieving net zero carbon emissions commonly involve deploying reforestation, afforestation, and bioenergy crops across millions of hectares of land. It is often assumed that by helping to mitigate climate change, these strategies indirectly benefit biodiversity. Here, we modeled the climate and habitat requirements of 14,234 vertebrate species and show that the impact of these strategies on species' habitat area tends not to arise through climate mitigation, but rather through habitat conversion.