Untargeted Spatial Metabolomics and Spatial Proteomics on the Same Tissue Section.

An increasing number of spatial multiomic workflows have recently been developed. Some of these approaches have leveraged initial mass spectrometry imaging (MSI)-based spatial metabolomics to inform the region of interest (ROI) selection for downstream spatial proteomics. However, these workflows have been limited by varied substrate requirements between modalities or have required analyzing serial sections (i.

Detecting and classifying eco-anxiety: development of clinical cut-off scores for the climate change anxiety scale.

Background: Climate change anxiety, that is worry and fear in relation to the awareness of the impacts of climate change, is widely observed around the world. Some evidence suggests that while climate change anxiety can, at times, be adaptive, a growing body of research has reported that climate change anxiety is also related to a range of negative mental health outcomes and psychological distress. Currently, however, there is limited ability to assess for elevated levels of climate change anxiety and to identify those who may need support.

From Patient to Advocate: Navigating the Journey of Cancer Survival to Empowerment.

Cancer survivorship is a transformative journey, evolving from personal healing to advocacy. Survivors often shift from patients in need to empowered advocates, navigating emotional challenges while contributing to systemic changes in cancer care and public awareness. This dynamic role bridges clinical gaps and enhances support for patients worldwide.

Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting.

Single-cell multiomics provides comprehensive insights into gene regulatory networks, cellular diversity, and temporal dynamics. Here, we introduce nanoSPLITS (nanodroplet SPlitting for Linked-multimodal Investigations of Trace Samples), an integrated platform that enables global profiling of the transcriptome and proteome from same single cells via RNA sequencing and mass spectrometry-based proteomics, respectively. Benchmarking of nanoSPLITS demonstrates high measurement precision with deep proteomic and transcriptomic profiling of single-cells.

INF2 mutations cause kidney disease through a gain-of-function mechanism.

Heterozygosity for inverted formin-2 (INF2) mutations causes focal segmental glomerulosclerosis (FSGS) with or without Charcot-Marie-Tooth disease. A key question is whether the disease is caused by gain-of-function effects on INF2 or loss of function (haploinsufficiency). Despite established roles in multiple cellular processes, neither INF2 knockout mice nor mice with a disease-associated point mutation display an evident kidney or neurologic phenotype.

The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent. We show that ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated the disease in 7 PDXs.

Advancing flourishing as the north star of medical education: A call for personal and professional development as key to becoming physicians.

Over the past 15 years, multiple calls to transform medical education, and by extension, health sciences education, have addressed issues pertaining to learners' subjective experiences as well as the learning environment. By and large, these calls to transform share many of the same themes: greater engagement with the humanities, enhanced professional identity formation, leadership development, as well as systemic changes to enhance meaning, purpose, and belonging. However, the many initiatives and reforms underway in medical education have yet to fully reach their desired outcomes - particularly those focused on enhancing meaning, purpose, and belonging.

Using native and synthetic genes to disrupt inositol pyrophosphates and phosphate accumulation in plants.

Inositol pyrophosphates are eukaryotic signaling molecules that have been recently identified as key regulators of plant phosphate sensing and homeostasis. Given the importance of phosphate to current and future agronomic practices, we sought to design plants, which could be used to sequester phosphate, as a step in a phytoremediation strategy. To achieve this, we expressed diadenosine and diphosphoinositol polyphosphate phosphohydrolase (DDP1), a yeast (Saccharomyces cerevisiae) enzyme demonstrated to hydrolyze inositol pyrophosphates, in Arabidopsis thaliana and pennycress (Thlaspi arvense), a spring annual cover crop with emerging importance as a biofuel crop.

Proteome-Scale Tissue Mapping Using Mass Spectrometry Based on Label-Free and Multiplexed Workflows.

Multiplexed bimolecular profiling of tissue microenvironment, or spatial omics, can provide deep insight into cellular compositions and interactions in healthy and diseased tissues. Proteome-scale tissue mapping, which aims to unbiasedly visualize all the proteins in a whole tissue section or region of interest, has attracted significant interest because it holds great potential to directly reveal diagnostic biomarkers and therapeutic targets. While many approaches are available, however, proteome mapping still exhibits significant technical challenges in both protein coverage and analytical throughput.

Diet-Induced Obesity Induces Transcriptomic Changes in Neuroimmunometabolic-Related Genes in the Striatum and Olfactory Bulb.

The incidence of obesity has markedly increased globally over the last several decades and is believed to be associated with the easier availability of energy-dense foods, including high-fat foods. The reinforcing hedonic properties of high-fat foods, including olfactory cues, activate reward centers in the brain, motivating eating behavior. Thus, there is a growing interest in the understanding of the genetic changes that occur in the brain that are associated with obesity and eating behavior.

TwinF interface inhibitor FP802 prevents retinal ganglion cell loss in a mouse model of amyotrophic lateral sclerosis.

Motor neuron loss is well recognized in amyotrophic lateral sclerosis (ALS), but research on retinal ganglion cells (RGCs) is limited. Ocular symptoms are generally not considered classic ALS symptoms, although RGCs and spinal motor neurons share certain cell pathologies, including hallmark signs of glutamate neurotoxicity, which may be triggered by activation of extrasynaptic NMDA receptors (NMDARs). To explore potential novel strategies to prevent ALS-associated death of RGCs, we utilized inhibition of the TwinF interface, a new pharmacological principle that detoxifies extrasynaptic NMDARs by disrupting the NMDAR/TRPM4 death signaling complex.

An outbreak of Shiga toxin-producing (STEC) O157:H7 associated with contaminated lettuce and the cascading risks from climate change, the United Kingdom, August to September 2022.

Shiga-toxin producing (STEC) O157 is a food-borne pathogen which causes gastrointestinal illness in humans. Ruminants are considered the main reservoir of infection, and STEC exceedance has been associated with heavy rainfall. In September 2022, a large outbreak of STEC O157:H7 was identified in the United Kingdom (UK).

Evaluating the before operational stress program: comparing in-person and virtual delivery.

Introduction: Public safety personnel (PSP) are at increased risk for posttraumatic stress injuries (PTSI). Before Operational Stress (BOS) is a mental health program for PSP with preliminary support mitigating PTSI. The current study compared the effectiveness of delivering BOS in-person by a registered clinician (i.

Interleukin-35 alleviates neuropathic pain and induces an anti-inflammatory shift in spinal microglia in nerve-injured male mice.

Immune cells are critical in promoting neuroinflammation and neuropathic pain and in facilitating pain resolution, depending on their inflammatory and immunoregulatory cytokine response. Interleukin (IL)-35, secreted by regulatory immune cells, is a member of the IL-12 family with a potent immunosuppressive function. In this study, we investigated the effects of IL-35 on pain behaviors, spinal microglia phenotype following peripheral nerve injury, and in vitro microglial cultures in male and female mice.

Development and Validation of the Ease of Imagery Questionnaire.

The present series of studies aimed to develop and provide initial validation of the Ease of Imagery Questionnaire (EIQ)-a measure assessing ease of imaging different positive and negative imagery content reflective of valence and engaging or disengaging in adverse situations. Five studies were conducted to collectively examine the questionnaire's factor structure and concurrent validity. Study 1 ( = 336) and Study 2 ( = 207) informed the development of 16 items of the EIQ, with a four-factor structure supported in Studies 3 ( = 219), 4 ( = 135), and 5 ( = 184) using confirmatory factor analysis.

Assessing Team Performance: A Mixed-Methods Analysis Using Interprofessional Simulation.

Introduction: Optimizing the performance of emergency department (ED) teams impacts patient care, but the utility of current, team-based performance assessment tools to comprehensively measure this impact is underexplored. In this study we aimed to 1) evaluate ED team performance using current team-based assessment tools during an interprofessional in situ simulation and 2) identify characteristics of effective ED teams.

Methods: This mixed-methods study employed case study methodology based on a constructivist paradigm.

A method for the analysis of the oligomerization profile of the Huntington's disease-associated, aggregation-prone mutant huntingtin protein by isopycnic ultracentrifugation.

Conformational diseases, such as Alzheimer's, Parkinson's and Huntington's diseases as well as ataxias and fronto-temporal disorders, are part of common class of neurological disorders characterised by the aggregation and progressive accumulation of mutant proteins which display aberrant conformation. In particular, Huntington's disease (HD) is caused by mutations leading to an abnormal expansion in the polyglutamine (poly-Q) tract of the huntingtin protein (HTT), leading to the formation of inclusion bodies in neurons of affected patients. Furthermore, recent experimental evidence is challenging the conventional view of the disease by revealing the ability of mutant HTT to be transferred between cells by means of extracellular vesicles (EVs), allowing the mutant protein to seed oligomers involving both the mutant and wild type forms of the protein.

Ingested Foreign Bodies in the Sigmoid Colon Requiring Earlier Intervention in Patients With Prior Hysterectomy.

The use of dentures and dental plates is widespread in the adult population. Accidental ingestion of these foreign objects is not uncommon, with the majority of patients having an uneventful passage of the object through the gastrointestinal tract. Of those patients requiring intervention, endoscopy is the most common, followed by surgical removal.