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Biomedical subjects

Joshua Levy

Publications and source records attributed to Joshua Levy.

7 recordsLinked to original sources

Versatile wastewater monitoring of pathogens and antimicrobial resistance enabled by metatranscriptomics and long-read metagenomics.

Widespread interest in the development of population-wide pathogen and antimicrobial resistance (AMR) monitoring has revealed wastewater's microbial footprint as a marker of public health. Near-source wastewater remains a difficult sample type for microbiome analyses but represents a closer link to human health than the downstream products of its treatment. Few studies integrate methods for non-targeted monitoring applications, and critically, current methods cannot connect AMR genes to species, nor resolve full genomes. We address these challenges by developing a pipeline that enables untargeted metagenomics, metatranscriptomics, and novel long-read metagenomics (LRG). We achieve untargeted pathogen detection, limited by highly abundant resident species, while retaining microbial information with near-source sampling. Furthermore, LRG identifies antibiotic resistance gene-containing microbes and enables assembly of culture-independent genomes with previously unreported AMR genes. We establish an integrated approach to broadly monitor pathogens in wastewater, while demonstrating the importance of LRG to illuminate microbial AMR at the species level.

Journal Article↗

Histology-Based Virtual RNA Inference Identifies Pathways Associated With Metastasis Risk in Colorectal Cancer.

Colorectal cancer (CRC) remains a major health concern, with >150,000 new diagnoses and >50,000 deaths annually in the United States, underscoring an urgent need for improved screening, prognostication, disease management, and therapeutic approaches. The tumor microenvironment (TME)-comprising cancerous and immune cells interacting within the tumor's spatial architecture-plays a critical role in disease progression and treatment outcomes, reinforcing its importance as a prognostic marker for metastasis and recurrence risk. However, traditional methods for TME characterization, such as bulk transcriptomics and multiplex protein assays, lack sufficient spatial resolution. Although spatial transcriptomics (ST) allows for the high-resolution mapping of whole transcriptomes at near-cellular resolution, current ST technologies (eg, Visium and Xenium) are limited by high costs, low throughput, and issues with reproducibility, preventing their widespread application in large-scale molecular epidemiology studies. In this study, we refined and implemented virtual RNA inference (VRI) to derive ST-level molecular information directly from hematoxylin and eosin (H&E)-stained tissue images. Our VRI models were trained on the largest matched CRC ST data set to date, comprising 45 patients and >300,000 Visium spots from primary tumors. Using state-of-the-art deep learning models (UNI, ResNet-50, Vision Transformer, and Vision Mamba), we achieved a median Spearman's correlation coefficient of 0.546 between predicted and measured spot-level expression. As validation, VRI-derived gene signatures linked to specific tissue regions (tumor, interface, submucosa, stroma, serosa, muscularis, and inflammation) showed strong concordance with signatures generated via direct ST, and VRI performed accurately in estimating cell-type proportions spatially from H&E slides. In an expanded CRC cohort controlling for tumor invasiveness and clinical factors, we further identified VRI-derived gene signatures significantly associated with key prognostic outcomes, including metastasis status. Although certain tumor-related pathways are not fully captured by histology alone, our findings highlight the ability of VRI to infer a wide range of "histology-associated" biological pathways at near-cellular resolution without requiring ST profiling. Future efforts will extend this framework to expand TME phenotyping from standard H&E tissue images, with the potential to accelerate translational CRC research at scale.

Humans↗

Occupational low back pain.

Low back injury is one of the most common conditions in the workplace. The causes are multifactorial and must be sought during the physician's examination. Failure to perform a comprehensive history and physical examination ultimately can lead to treatment failure and injury recurrence. A comprehensive history and physical may help clinicians to differentiate organic and nonorganic causes of low back pain. Different diagnoses need specific rather than generalized treatment programs. Teaching clinicians the nuances of the history and physical examination in a setting with an injured worker is the goal of this article.

Humans↗

Using a metaperspective to clarify the structural-narrative debate in family therapy.

The debate in family therapy between structural and narrative therapists often seems irreconcilable. Drawing from work in theoretical sociology that identifies the basic structure of existing social theory, a metaperspective is introduced to clarify a discussion between leading figures in the debate. Disparate views of family interactions are examined in terms of more fundamental disagreements about the center of attention in therapy. Narrative and structural modes of presentation are examined as separate traditions that could not be further apart conceptually. Efforts to identify common ground are discussed in terms of more significant differences that are minimized by drawing out similarities. This analysis provides a framework for standing outside entrenched arguments to see more clearly the unique contributions of each approach.

Family↗

Radiation phantom with humanoid shape and adjustable thickness (RPHAT).

A new radiation phantom with humanoid shape and adjustable thickness (RPHAT) has been developed. Unlike the RANDO phantom which is a fixed thickness, this newly designed phantom has adjustable thickness to address the range of thicknesses of real-world patients. RPHAT allows adjustment of the body thickness by being sliced in the coronal (instead of axial) direction. Centre slices are designed so that more sections can be added or removed while maintaining the anthropomorphic shape. A prototype of the new phantom has been successfully used in a study investigating peripheral dose delivery, where the amount of scatter within the patient, and therefore the patient thickness, plays a critical role in dose deposition. This newly designed phantom is an important tool to improve the quality of radiation therapy.

Humans↗

Correcting immune imbalance: the use of Prosorba column treatment for immune disorders.

The treatment of selected refractory autoimmune diseases has been complemented by the use of Protein A (Prosorba column) immunoadsorption. US Food and Drug Administration-approved clinical applications include idiopathic thrombocytopenia purpura (ITP) and rheumatoid arthritis (RA). Other common off label uses include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Less common experimental uses in diseases in which efficacy has been reported include autoimmune CNS syndromes, peripheral neuropathies, autoimmune pancytopenia, hemolytic anemia and solid organ transplant rejection. Prosorba column treatment is generally well tolerated but a small proportion of treated patients experience chills, fever, tremor, hypotension and rash. The mechanism of action suggested for the efficacy of the column is the restoration of normal immune balance and normal tolerance. Observations in ITP has suggested that column treatment stimulates a rise in anti-idiotype antibody directed against antiplatelet antibodies, effecting a decrease in pathogenic antiplatelet antibodies and immune complexes.

Animals↗

Cooking classes outperform cooking demonstrations for college sophomores.

OBJECTIVE: To determine if cooking classes improve subjects' knowledge, attitudes, and behaviors toward cooking. DESIGN: Comparison of outcomes of 2 treatment groups (demonstration vs hands-on cooking classes) using pre- and posttests. SETTING: University cooking laboratories. PARTICIPANTS: First-semester sophomores (n = 65) who were 25% male with a mean age of 19.7 years. INTERVENTION: The intervention group (n = 33) attended 4 2-hour cooking classes, based on Social Learning Theory, and a supermarket tour. The demonstration group (n = 32) attended a cooking demonstration. Subjects completed 6 surveys. MAIN OUTCOME MEASURES: Changes in attitudes, knowledge, and behaviors regarding cooking. ANALYSIS: Descriptive statistics were used to compare demographic variables. Analysis of covariance and chi-square analyses were used to compare outcome variables. RESULTS: Analysis revealed no gender differences. Participants displayed positive shifts on attitude scales. The intervention group had a pattern of larger positive shifts (0.4-0.7 vs 0.1-0.5 gain), some of which were statistically significant. Participants displayed positive, but not statistically significant, shifts in knowledge and some behaviors. CONCLUSION AND IMPLICATIONS: The intervention group experienced more statistically significant gains in attitudes and appeared to have a better pattern of gains in cooking-related knowledge and behaviors. Given limited resources, demonstration cooking classes could reach larger audiences in varied settings, but the impact would likely be weaker than that of cooking classes.

Adult↗