Current Methods for Hyperpolarized [1-C]pyruvate MRI Human Studies.

MRI with hyperpolarized (HP) C agents, also known as HP C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of hyperpolarized agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-C]pyruvate - by far the most commonly used agent, which sits at a key metabolic junction in glycolysis.

Dimethylaminododecyl Methacrylate-Incorporated Dental Materials Could Be the First Line of Defense against .

Oral cavity is an essential reservoir for . We aimed to investigate the antibacterial effects of dimethylaminododecyl methacrylate (DMADDM) against . Modified giomers were prepared by introducing 0%, 1.

Fluorescence-guided photoimmunotherapy using targeted nanotechnology and ML7710 to manage peritoneal carcinomatosis.

Fluorescence-guided intervention can bolster standard therapies by detecting and treating microscopic tumors before lethal recurrence. Tremendous progress in photoimmunotherapy and nanotechnology has been made to treat metastasis. However, many are lost in translation due to heterogeneous treatment effects.

Calvaria defect regeneration via human periodontal ligament stem cells and prevascularized scaffolds in athymic rats.

Background: Vascularization plays an important role in dental and craniofacial regenerations. Human periodontal ligament stem cells (hPDLSCs) are a promising cell source and, when co-cultured with human umbilical vein endothelial cells (hUVECs), could promote vascularization. The objectives of this study were to develop a novel prevascularized hPDLSC-hUVEC-calcium phosphate construct, and investigate the osteogenic and angiogenic efficacy of this construct with human platelet lysate (hPL) in cranial defects in rats for the first time.

Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3.

Background: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel.

Strategies for rapid production of crystallization quality coatomer WD40 domains.

The vesicular secretion of soluble cargo proteins from the endoplasmic reticulum (ER) is accompanied by the export of ER-resident membrane proteins that are co-packaged in secretory vesicles. The cytosolic coatomer protein complex I (COPI) utilizes the N-terminal WD40 domains of α-COPI and β'-COPI subunits to bind these membrane protein "clients" for ER retrieval. These "αWD40" and "β'WD40" domains are structural homologs that demonstrate distinct selectivity for client proteins.

Locoregional Thermal and Chemical Tumor Ablation: Review of Clinical Applications and Potential Opportunities for Use in Low- and Middle-Income Countries.

This review highlights opportunities to develop accessible ablative therapies to reduce the cancer burden in LMICs.

CryoEM structure of a therapeutic antibody (favezelimab) bound to human LAG3 determined using a bivalent Fab as fiducial marker.

Lymphocyte activation gene 3 protein (LAG3) is an inhibitory receptor that is upregulated on exhausted T cells in tumors. LAG3 is a major target for cancer immunotherapy with many anti-LAG3 antibodies in clinical trials. However, there is no structural information on the epitopes recognized by these antibodies.

Analysis of Radiation Therapy Quality Assurance in NRG Oncology RTOG 0848.

Purpose: NRG/Radiation Therapy Oncology Group 0848 is a 2-step randomized trial to evaluate the benefit of the addition of concurrent fluoropyrimidine and radiation therapy (RT) after adjuvant chemotherapy (second step) for patients with resected pancreatic head adenocarcinoma. Real-time quality assurance (QA) was performed on each patient who underwent RT. This analysis aims to evaluate adherence to protocol-specified contouring and treatment planning and to report the types and frequencies of deviations requiring revisions.

Injectable periodontal ligament stem cell-metformin-calcium phosphate scaffold for bone regeneration and vascularization in rats.

Objectives: Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial for dental and craniofacial repairs. The objectives of this study were to: (1) develop a novel injectable CPC scaffold encapsulating human periodontal ligament stem cells (hPDLSCs) and metformin (Met) for bone engineering; (2) test bone regeneration efficacy in vitro and in vivo.

Methods: hPDLSCs were encapsulated in degradable alginate fibers, which were then mixed into CPC paste.

Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy.

Circulating drugs in the peritoneal cavity is an effective strategy for advanced ovarian cancer treatment. Photoimmunotherapy, an emerging modality with potential for the treatment of ovarian cancer, involves near-infrared light activation of antibody-photosensitizer conjugates (photoimmunoconjugates) to generate cytotoxic reactive oxygen species. Here, a microfluidic cell culture model is used to study how fluid flow-induced shear stress affects photoimmunoconjugate delivery to ovarian cancer cells.

Novel Dental Low-Shrinkage-Stress Composite with Antibacterial Dimethylaminododecyl Methacrylate Monomer.

Objectives: Current dental resins exhibit polymerization shrinkage causing microleakage, which has the potential to cause recurrent caries. Our objectives were to create and characterize low-shrinkage-stress (LSS) composites with dimethylaminododecyl methacrylate (DMADDM) as an antibacterial agent to combat recurrent caries.

Methods: Triethylene glycol divinylbenzyl ether and urethane dimethacrylate were used to reduce shrinkage stress.

Dissecting regulatory T cell expansion using polymer microparticles presenting defined ratios of self-antigen and regulatory cues.

Biomaterials allow for the precision control over the combination and release of cargo needed to engineer cell outcomes. These capabilities are particularly attractive as new candidate therapies to treat autoimmune diseases, conditions where dysfunctional immune cells create pathogenic tissue environments during attack of self-molecules termed self-antigens. Here we extend past studies showing combinations of a small molecule immunomodulator co-delivered with self-antigen induces antigen-specific regulatory T cells.

Exploiting Unique Features of Microneedles to Modulate Immunity.

Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses-often more protective or therapeutic-compared to conventional needle delivery.

The Roles of Zinc Finger Proteins in Colorectal Cancer.

Despite colorectal cancer remaining a leading worldwide cause of cancer-related death, there remains a paucity of effective treatments for advanced disease. The molecular mechanisms underlying the development of colorectal cancer include altered cell signaling and cell cycle regulation that may result from epigenetic modifications of gene expression and function. Acting as important transcriptional regulators of normal biological processes, zinc finger proteins also play key roles in regulating the cellular mechanisms underlying colorectal neoplasia.

Transforming bioengineering with unbiased teams and tools.

Scientific bias originates from both researchers and techniques. Evidence-based strategies to mitigate this bias include the assembly of diverse teams, development of rigorous experimental designs, and use of unbiased analytical techniques. Here, we highlight potential starting points to decrease bias in bioengineering research.

Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma.

Background: In an analysis of the primary outcome of this phase 3 trial, patients with early relapsed or refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, as second-line treatment had significantly longer event-free survival than those who received standard care. Data were needed on longer-term outcomes.

Methods: In this trial, we randomly assigned patients with early relapsed or refractory large B-cell lymphoma in a 1:1 ratio to receive either axi-cel or standard care (two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had a response).

Common Analysis of Direct RNA SequencinG CUrrently Leads to Misidentification of 5-Methylcytosine Modifications at GCU Motifs.

RNA modifications, such as méthylation, can be detected with Oxford Nanopore Technologies direct RNA sequencing. One commonly used tool for detecting 5-methylcytosine (mC) modifications is Tombo, which uses an "Alternative Model" to detect putative modifications from a single sample. We examined direct RNA sequencing data from diverse taxa including virus, bacteria, fungi, and animals.

3D-Autologous Culture Method for Precision Oncology.

The 3D-autologous culture method (3D-ACM) for patient-derived cancer samples utilizes a patient's own body fluid or serum to prepare a 3D scaffold and for the culture medium. 3D-ACM enables tumor cells and/or tissues from an individual patient to proliferate in vitro, in a microenvironment that is very similar to their original, in vivo surroundings. The purpose is to maximally preserve in culture the native biological properties of a tumor.

Tuning innate immune function using microneedles containing multiple classes of toll-like receptor agonists.

Microneedle arrays (MNAs) are patches displaying hundreds of micron-scale needles that can penetrate skin. As a result, these arrays efficiently and painlessly access this immune cell-rich niche, motivating significant clinical interest in MNA-based vaccines. Our lab has developed immune polyelectrolyte multilayers (iPEMs), nanostructures built entirely from immune signals employing electrostatic self-assembly.

Degradable hydrogel fibers encapsulate and deliver metformin and periodontal ligament stem cells for dental and periodontal regeneration.

Human periodontal ligament stem cells (hPDLSCs) are promising cells for dental and periodontal regeneration. This study aimed to develop novel alginate-fibrin fibers that encapsulates hPDLSCs and metformin, to investigate the effect of metformin on the osteogenic differentiation of hPDLSCs, and to determine the regulatory role of the Shh/Gli1 signaling pathway in the metformin-induced osteogenic differentiation of hPDLSCs for the first time. CCK8 assay was used to evaluate hPDLSCs.

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials.

Importance: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.

Objective: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).

Design, Setting, And Participants: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group).

KeyLoop retractor for global gasless laparoscopy: evaluation of safety and feasibility in a porcine model.

Background: Many surgeons in low- and middle-income countries have described performing surgery using gasless (lift) laparoscopy due to inaccessibility of carbon dioxide and reliable electricity, but the safety and feasibility of the technique has not been well documented. We describe preclinical testing of the in vivo safety and utility of KeyLoop, a laparoscopic retractor system to enable gasless laparoscopy.

Methods: Experienced laparoscopic surgeons completed a series of four laparoscopic tasks in a porcine model: laparoscopic exposure, small bowel resection, intracorporeal suturing with knot tying, and cholecystectomy.

Harnessing Biomaterials to Study and Direct Antigen-Specific Immunotherapy.

Immunotherapies are an evolving treatment paradigm for addressing cancer, autoimmunity, and infection. While exciting, most of the existing therapies are limited by their specificity─unable to differentiate between healthy and diseased cells at an antigen-specific level. Biomaterials are a powerful tool that enable the development of next-generation immunotherapies due to their tunable synthesis properties.