Brain-derived textiloma post glioblastoma resection and application of oxidized regenerated cellulose: A pilot, bedside-to-bench, translational study.

Oxidized regenerated cellulose (ORC; marketed as Surgicel® and Tabotamp®) is routinely used as an intraoperative hemostatic agent. Rarely, residual ORC has been associated with a foreign body reaction generating cystic or granulomatous lesions (i.e.

Prediction of peptide structural conformations with AlphaFold2.

Protein structure prediction artificial intelligence/machine learning (AI/ML) approaches has sparked substantial research interest in structural biology and adjacent disciplines. More recently, AlphaFold2 (AF2) has been adapted for the prediction of multiple structural conformations in addition to single-state structures. This novel avenue of research has focused on proteins (typically 50 residues in length or greater), while multi-conformation prediction of shorter peptides has not yet been explored in this context.

Generative artificial intelligence performs rudimentary structural biology modeling.

Natural language-based generative artificial intelligence (AI) has become increasingly prevalent in scientific research. Intriguingly, capabilities of generative pre-trained transformer (GPT) language models beyond the scope of natural language tasks have recently been identified. Here we explored how GPT-4 might be able to perform rudimentary structural biology modeling.

Generative artificial intelligence performs rudimentary structural biology modeling.

Natural language-based generative artificial intelligence (AI) has become increasingly prevalent in scientific research. Intriguingly, capabilities of generative pre-trained transformer (GPT) language models beyond the scope of natural language tasks have recently been identified. Here we explored how GPT-4 might be able to perform rudimentary structural biology modeling.

Mathematical modeling of cancer immunotherapy for personalized clinical translation.

Encouraging advances are being made in cancer immunotherapy modeling, especially in the key areas of developing personalized treatment strategies based on individual patient parameters, predicting treatment outcomes and optimizing immunotherapy synergy when used in combination with other treatment approaches. Here we present a focused review of the most recent mathematical modeling work on cancer immunotherapy with a focus on clinical translatability. It can be seen that this field is transitioning from pure basic science to applications that can make impactful differences in patients' lives.

Research involving the recently deceased: ethics questions that must be answered.

Research involving recently deceased humans that are physiologically maintained following declaration of death by neurologic criteria-or 'research involving the recently deceased'-can fill a translational research gap while reducing harm to animals and living human subjects. It also creates new challenges for honouring the donor's legacy, respecting the rights of donor loved ones, resource allocation and public health. As this research model gains traction, new empirical ethics questions must be answered to preserve public trust in all forms of tissue donation and in the practice of medicine while respecting the legacy of the deceased and the rights of donor loved ones.

Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands.

The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins.

Integrated metabolic and genetic analysis reveals distinct features of human differentiated thyroid cancer.

Background: Differentiated thyroid cancer (DTC) affects thousands of lives worldwide each year. Typically, DTC is a treatable disease with a good prognosis. Yet, some patients are subjected to partial or total thyroidectomy and radioiodine therapy to prevent local disease recurrence and metastasis.

Preclinical optimization of a diode laser-based clamp-free partial nephrectomy in a large animal model.

Kidney cancer is a common urologic malignancy with either laparoscopic (LPN) or robotic partial nephrectomy as therapeutic options of choice for localized tumors. However, renal resection and suturing are challenging steps of the procedure that can lead to complications such as prolonged warm ischemia, bleeding, and urinary fistulas. LPN with a diode laser is an efficient technique due to its cutting and/or coagulation attributes.

Modeling of ACE2 and antibodies bound to SARS-CoV-2 provides insights into infectivity and immune evasion.

Given the COVID-19 pandemic, there is interest in understanding ligand-receptor features and targeted antibody-binding attributes against emerging SARS-CoV-2 variants. Here, we developed a large-scale structure-based pipeline for analysis of protein-protein interactions regulating SARS-CoV-2 immune evasion. First, we generated computed structural models of the Spike protein of 3 SARS-CoV-2 variants (B.

A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection.

While the development of different vaccines slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections has continued to fuel the COVID-19 pandemic. To secure at least partial protection in the majority of the population through 1 dose of a COVID-19 vaccine, delayed administration of boosters has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may induce breakthrough infections due to intermittent lapses in protection.

Dysregulation of the PRUNE2/PCA3 genetic axis in human prostate cancer: from experimental discovery to validation in two independent patient cohorts.

Background: We have previously shown that the long non-coding (lnc)RNA (; formerly ) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene (a homolog of the gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the / regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression.

Methods: The reciprocal and gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497).

Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy.

A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection.

While the development of different vaccines has slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections continues to fuel the pandemic. As a strategy to secure at least partial protection, with a single dose of a given COVID-19 vaccine to maximum possible fraction of the population, administration of subsequent doses (or boosters) has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may jeopardize the attainment of herd immunity due to intermittent lapses in protection.

Leveraging the scientific findings to develop therapeutic strategies for dormant breast cancer cells.

Breast cancer (BC) metastasis can occur decades before clinical diagnosis. During this time, the cancer cells (BCCs) can remain dormant for decades. This type of dormancy also occurs during remission where the dormant BCCs adapt cycling quiescence within the tissue microenvironment.

Genomic landscape of lymphatic malformations: a case series and response to the PI3Kα inhibitor alpelisib in an -of-1 clinical trial.

Background: Lymphatic malformations (LMs) often pose treatment challenges due to a large size or a critical location that could lead to disfigurement, and there are no standardized treatment approaches for either refractory or unresectable cases.

Methods: We examined the genomic landscape of a patient cohort of LMs ( = 30 cases) that underwent comprehensive genomic profiling using a large-panel next-generation sequencing assay. Immunohistochemical analyses were completed in parallel.

Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection.

Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed.

Translational Modeling Identifies Synergy between Nanoparticle-Delivered miRNA-22 and Standard-of-Care Drugs in Triple-Negative Breast Cancer.

Purpose: Downregulation of miRNA-22 in triple-negative breast cancer (TNBC) is associated with upregulation of eukaryotic elongation 2 factor kinase (eEF2K) protein, which regulates tumor growth, chemoresistance, and tumor immunosurveillance. Moreover, exogenous administration of miRNA-22, loaded in nanoparticles to prevent degradation and improve tumor delivery (termed miRNA-22 nanotherapy), to suppress eEF2K production has shown potential as an investigational therapeutic agent in vivo.

Methods: To evaluate the translational potential of miRNA-22 nanotherapy, we developed a multiscale mechanistic model, calibrated to published in vivo data and extrapolated to the human scale, to describe and quantify the pharmacokinetics and pharmacodynamics of miRNA-22 in virtual patient populations.

Spatial and temporal dynamics of HDACs class IIa following mild traumatic brain injury in adult rats.

The fundamental role of epigenetic regulatory mechanisms involved in neuroplasticity and adaptive responses to traumatic brain injury (TBI) is gaining increased recognition. TBI-induced neurodegeneration is associated with several changes in the expression-activity of various epigenetic regulatory enzymes, including histone deacetylases (HDACs). In this study, PET/CT with 6-([F]trifluoroacetamido)-1- hexanoicanilide ([F]TFAHA) to image spatial and temporal dynamics of HDACs class IIa expression-activity in brains of adult rats subjected to a weight drop model of diffuse, non-penetrating, mild traumatic brain injury (mTBI).

Structural models of SARS-CoV-2 Omicron variant in complex with ACE2 receptor or antibodies suggest altered binding interfaces.

There is enormous ongoing interest in characterizing the binding properties of the SARS-CoV-2 Omicron Variant of Concern (VOC) (B.1.1.

Protocol for design, construction, and selection of genome phage (gPhage) display libraries.

This protocol describes the genomic phage (gPhage) display platform, a large-scale antigen and epitope mapping technique. We constructed a gPhage display peptide library of a eukaryotic organism, (causative agent of Chagas disease), to map the antibody response landscape against the parasite. Here, we used an organism with a relatively large but intronless genome, although future applications could include other prevalent or (re)emerging infectious organisms carrying genomes with a limited number of introns.