Parallel multiOMIC analysis reveals glutamine deprivation enhances directed differentiation of renal organoids.

Metabolic pathways play a critical role in driving differentiation but remain poorly understood in the development of kidney organoids. In this study, parallel metabolite and transcriptome profiling of differentiating human pluripotent stem cells (hPSCs) to multicellular renal organoids revealed key metabolic drivers of the differentiation process. In the early stage, transitioning from hPSCs to nephron progenitor cells (NPCs), both the glutamine and the alanine-aspartate-glutamate pathways changed significantly, as detected by enrichment and pathway impact analyses.

Differential metabolic profiles by Hispanic ethnicity among male Tucson firefighters.

Introduction: Firefighters face regular exposure to known and probable human carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), benzene, and formaldehyde, leading to an increased risk of various cancers compared to the general population. Hispanic and black firefighters are at increased risk of additional cancers not elevated in non-Hispanic white firefighters, yet biological pathways underlying these differences are unknown.

Objectives: The study objectives were to evaluate differences in the urinary metabolome between Hispanic and non-Hispanic firefighters, pre-and post-fireground exposure.

Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types.

Background: There is uncertainty around clinical applicability of tumor mutational burden (TMB) across cancer types, in part because of inconsistency between TMB measurements from different platforms. The KEYNOTE 158 trial supported United States Food and Drug Administration (FDA) approval of the Foundation Medicine test (FoundationOneCDx) at TMB≥10 mut/Mb as a companion diagnostic (CDx) for single-agent pembrolizumab in second+line. Using a large real-world dataset with validated survival endpoint data, we evaluated clinical validity of TMB measurement by the test in over 8000 patients across 24 cancer types who received single-agent immune checkpoint inhibitor (ICI).

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Peanut (Arachis hypogaea L.) growth and photosynthetic response to high and low temperature extremes.

In some peanut (Arachis hypogaea L.) producing regions, growth and photosynthesis-limiting low and high temperature extremes are common. Heat acclimation potential of photosynthesis and respiration is a coping mechanism that is species-dependent and should be further explored for peanut.

Author Correction: Systematic protein-protein interaction mapping for clinically relevant human GPCRs.

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Real-World Patient-Reported and Neurocognitive Outcomes in the Year After Axicabtagene Ciloleucel.

Axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell therapy, has significantly improved clinical outcomes in adult patients with relapsed/refractory large B-cell lymphoma. However, few studies have examined patient-reported outcomes (PROs) or neurocognitive performance in patients treated with axi-cel. Moreover, no longitudinal PRO study has reported on patients treated with axi-cel as standard of care in the United States, to our knowledge.

Evolution of Lipid Metabolism in the Injured Mouse Spinal Cord.

Following spinal cord injury (SCI), there is a short-lived recovery phase that ultimately plateaus. Understanding changes within the spinal cord over time may facilitate targeted approaches to prevent and/or reverse this plateau and allow for continued recovery. Untargeted metabolomics revealed distinct metabolic profiles within the injured cord during recovery (7 days postinjury [DPI]) and plateau (21 DPI) periods in a mouse model of severe contusion SCI.

A split intein and split luciferase-coupled system for detecting protein-protein interactions.

Elucidation of protein-protein interactions (PPIs) represents one of the most important methods in biomedical research. Recently, PPIs have started to be exploited for drug discovery purposes and have thus attracted much attention from both the academic and pharmaceutical sectors. We previously developed a sensitive method, Split Intein-Mediated Protein Ligation (SIMPL), for detecting binary PPIs via irreversible splicing of the interacting proteins being investigated.

Personalized Medicine in Histiocytic Disorders: Novel Targets in Patients Without MAPK Alterations.

Purpose: BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective.

Methods: We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations.

The Radiosurgery Society Working Groups on GRID, LATTICE, Microbeam, and FLASH Radiotherapies: Advancements Symposium and Subsequent Progress Made.

Purpose: Since the inaugural workshop "Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy." hosted by the National Cancer Institute and sponsored by the Radiosurgery Society (RSS), growing collaborations and investigations have ensued among experts, practitioners, and researchers. The RSS GRID, LATTICE, Microbeam and FLASH (GLMF) Working Groups were formed as a framework for these efforts and have focused on advancing the understanding of the biology, technical/physical parameters, trial design, and clinical practice of these new radiation therapy modalities.

Proton Therapy for Spinal Tumors: A Consensus Statement From the Particle Therapy Cooperative Group.

Purpose: Proton beam therapy (PBT) plays an important role in the management of primary spine tumors. The purpose of this consensus statement was to summarize safe and optimal delivery of PBT for spinal tumors.

Methods And Materials: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee consisting of radiation oncologists and medical physicists with specific expertise in spinal irradiation developed expert recommendations discussing treatment planning considerations and current approaches in the treatment of primary spinal tumors.

Cotton morphological traits tracking through spatiotemporal registration of terrestrial laser scanning time-series data.

Understanding the complex interactions between genotype-environment dynamics is fundamental for optimizing crop improvement. However, traditional phenotyping methods limit assessments to the end of the growing season, restricting continuous crop monitoring. To address this limitation, we developed a methodology for spatiotemporal registration of time-series 3D point cloud data, enabling field phenotyping over time for accurate crop growth tracking.

Characterization of Caulimovirid-like Sequences from Upland Cotton ( L.) Exhibiting Terminal Abortion in Georgia, USA.

In this study, we investigated the potential involvement of endogenous viral elements (EVEs) in the development of apical tissue necrosis, resulting in the terminal abortion of upland cotton ( L.) in Georgia. The high-throughput sequence analysis of symptomatic and asymptomatic plant tissue samples revealed near-complete EVE-Georgia (EVE-GA) sequences closely related to caulimoviruses.

Effect of Aerosol Size on Glass Transition Temperature.

The amorphous phase state of suspended nanoparticles affects their atmospheric lifetimes and environmental impact. Influence of relative humidity and chemical composition on the glass-to-liquid transition is well-known. However, the influence of the particle size on the phase transition remains uncertain.

Impact of fish oil supplementation on plasma levels of highly unsaturated fatty acid-containing lipid classes and molecular species in American football athletes.

Background: Previous studies have linked sports-related concussions and repeated subconcussive head impacts in contact sport athletes to elevated brain injury biomarkers. Docosahexaenoic acid (DHA), the primary omega-3 (n-3) highly unsaturated fatty acid (HUFA) in the brain, has shown neuroprotective effects in animal models after brain injury, but clinical research has shown mixed results.

Methods: We conducted a randomized, double-blind, placebo-controlled study on 29 Division 1 collegiate American football players, exploring the impact of DHA (2.

A comprehensive measure of Golgi sphingolipid flux using NBD C-ceramide: evaluation of sphingolipid inhibitors.

Measurements of sphingolipid metabolism are most accurately performed by LC-MS. However, this technique is expensive, not widely accessible, and without the use of specific probes, it does not provide insight into metabolic flux through the pathway. Employing the fluorescent ceramide analogue NBD-C-ceramide as a tracer in intact cells, we developed a comprehensive HPLC-based method that simultaneously measures the main nodes of ceramide metabolism in the Golgi.

Identification of a family of species-selective complex I inhibitors as potential anthelmintics.

Soil-transmitted helminths (STHs) are major pathogens infecting over a billion people. There are few classes of anthelmintics and there is an urgent need for new drugs. Many STHs use an unusual form of anaerobic metabolism to survive the hypoxic conditions of the host gut.

Temporal associations of plasma levels of the secreted phospholipase A family and mortality in severe COVID-19.

Previous research suggests that group IIA-secreted phospholipase A (sPLA-IIA) plays a role in and predicts lethal COVID-19 disease. The current study reanalyzed a longitudinal proteomic data set to determine the temporal relationship between levels of several members of a family of sPLA isoforms and the severity of COVID-19 in 214 ICU patients. The levels of six secreted PLA isoforms, sPLA-IIA, sPLA-V, sPLA-X, sPLA-IB, sPLA-IIC, and sPLA-XVI, increased over the first 7 ICU days in those who succumbed to the disease but attenuated over the same time period in survivors.

Diffusional and Biochemical Limitations to Photosynthesis Under Water Deficit for Field-Grown Cotton.

Water deficit stress limits net photosynthetic rate (A), but the relative sensitivities of underlying processes such as thylakoid reactions, ATP production, carbon fixation reactions, and carbon loss processes to water deficit stress in field-grown upland cotton require further exploration. Therefore, the objective of the present study was to assess (1) the diffusional and biochemical mechanisms associated with water deficit-induced declines in A and (2) associations between water deficit-induced variation in oxidative stress and energy dissipation for field-grown cotton. Water deficit stress was imposed for three weeks during the peak bloom stage of cotton development, causing significant reductions in leaf water potential and A.

Individual and Geospatial Determinants of Health Associated With School-Based Human Papillomavirus Immunization in Alberta: Population-Based Cohort Study.

Background: Human papillomavirus (HPV) infection causes nearly all cervical cancer cases and is a cause of anogenital and oropharyngeal cancers. The incidence of HPV-associated cancers is inequitable, with an increased burden on marginalized groups in high-income countries. Understanding how immunization status varies by material and social deprivation, health system, and geospatial factors is valuable for prioritizing and planning HPV immunization interventions.