5-FU Weakens Defensive Functions of the Junctional Epithelium.

Aim: To investigate additional factors contributing to the pathophysiology of chemotherapy-induced oral mucositis and periodontitis beyond the systemic immune suppression caused by the chemotherapeutic agent 5-Fluorouracil (5-FU).

Methods: 5-Fluorouracil was topically delivered to the non-keratinized, rapidly proliferating junctional epithelium (JE) surrounding the dentition, and acts as an immunologic and functional barrier to bacterial ingression. Various techniques, including EdU incorporation, quantitative immunohistochemistry (qIHC), histology, enzymatic activity assays, and micro-computed tomographic (μCT) imaging, were employed to analyze the JE at multiple time points following topical 5-FU treatment.

Real-World Treatment Patterns and Clinical Outcomes in Patients With Multiple Myeloma Previously Treated With Lenalidomide and an Anti-CD38 Monoclonal Antibody.

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

Materials And Methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

Autophagy related 7 (ATG7) regulates food intake and liver health during asparaginase exposure.

Amino acid starvation by the chemotherapy agent asparaginase is a potent activator of the integrated stress response (ISR) in liver and can upregulate autophagy in some cell types. We hypothesized that autophagy related 7 (ATG7), a protein that is essential for autophagy and an ISR target gene, was necessary during exposure to asparaginase to maintain liver health. We knocked down Atg7 systemically (Atg7) or in hepatocytes only (ls-Atg7KO) in mice before exposure to pegylated asparaginase for 5 d.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Detecting Hemorrhagic Myocardial Infarction With 3.0-T CMR: Insights Into Spatial Manifestation, Time-Dependence, and Optimal Acquisitions.

Background: Hemorrhagic myocardial infarction (hMI) can rapidly diminish the benefits of reperfusion therapy and direct the heart toward chronic heart failure. T2∗ cardiac magnetic resonance (CMR) is the reference standard for detecting hMI. However, the lack of clarity around the earliest time point for detection, time-dependent changes in hemorrhage volume, and the optimal methods for detection can limit the development of strategies to manage hMI.

Digital Solutions for the Optimization of Pharmacologic Therapy for Heart Failure.

Data from large-scale, randomized, controlled trials demonstrate that contemporary treatments for heart failure (HF) can substantially improve morbidity and mortality. Despite this, observed outcomes for patients living with HF are poor, and they have not improved over time. The are many potential reasons for this important problem, but inadequate use of optimal medical therapy for patients with HF, an important component of guideline-directed medical therapy, in routine practice is a principal and modifiable contributor.

Mitigating the Risk of QTc Prolongation When Using Haloperidol for Acute Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents and Young Adults.

: Cannabinoid Hyperemesis Syndrome (CHS), associated with long-term cannabinoid use, has been increasingly observed in emergency room visits as more states in the U.S. have legislatively permitted medical and recreational marijuana use.

Integrated Analysis of Single-Cell and Bulk RNA Data Reveals Complexity and Significance of the Melanoma Interactome.

Despite significant strides in anti-melanoma therapies, resistance and recurrence remain major challenges. A deeper understanding of the underlying biology of these challenges is necessary for developing more effective treatment paradigms. Melanoma single-cell data were retrieved from the Broad Single Cell Portal (SCP11).

Endoscopic Ultrasound-Guided Treatments for Pancreatic Cancer: Understanding How Endoscopic Ultrasound Has Revolutionized Management of Pancreatic Cancer.

Pancreatic cancer is associated with high rates of morbidity and mortality. Endoscopic ultrasound (EUS)-guided biopsy has become the standard diagnostic modality per the guidelines. The use of EUS has been growing for providing various treatments in patients with pancreatic cancers: biliary and gallbladder drainage for those with malignant biliary obstruction, gastroenterostomy for malignant gastric outlet obstruction, celiac plexus/ganglia neurolysis for pain control, radiofrequency ablation, placement of fiducial markers, and injection of local chemotherapeutic agents.

Role of PI3 Kinases in Cell Signaling and Soleus Muscle Atrophy During Three Days of Unloading.

During skeletal muscle unloading, phosphoinositide 3-kinase (PI3K), and especially PI3K gamma (PI3Kγ), can be activated by changes in membrane potential. Activated IP3 can increase the ability of Ca to enter the nucleus through IP3 receptors. This may contribute to the activation of transcription factors that initiate muscle atrophy processes.

The Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect.

Bone marrow transplantation (BMT) is mainly performed to restore an anti-tumor immune response, called the graft-versus-tumor (GVT) effect, against leukemia, myeloma and lymphoma. This GVT reactivity is driven by donor T cells, and it can also cause lethal graft-versus-host disease (GVHD). We previously demonstrated that the colonization of mice with helminths preserves the GVT response while suppressing GVHD.

Characterizing Curing Efficiency of EGCG-Encapsulated Halloysite Nanotube Modified Adhesives for Durable Dentin-Resin Interfaces.

Matrix metalloproteinase (MMP)-induced collagen degradation at the resin-dentin interface remains a significant challenge for maintaining the longevity of dental restorations. This study investigated the effects of epigallocatechin-3-gallate (EGCG), a potent MMP inhibitor, on dental adhesive curing efficiency when encapsulated in halloysite nanotubes (HNTs). EGCG-loaded HNTs were incorporated into a commercial dental adhesive (Adper Scotchbond Multi-Purpose) at 7.

Time Dependent Effects of Cerebellar tDCS on Cerebello-cortical Connectivity Networks in Young Adults.

The cerebellum is involved in non-motor processing, supported by topographically distinct cerebellar activations and closed-loop circuits between the cerebellum and the cortex. Disruptions to cerebellar function may negatively impact prefrontal function and processing. Cerebellar resources may be important for offloading cortical processing, providing crucial scaffolding for normative performance and function.

Lead time trajectory of blood-based protein biomarkers for detection of pancreatic cancer based on repeat testing.

In the current study, we assessed whether repeated measurements of a panel of protein biomarkers with relevance to pancreatic ductal adenocarcinoma (PDAC) improves lead time performance for earlier detection over a single timepoint measurement. Specifically, CA125, CEA, LRG1, REG3A, THBS2, TIMP1, TNRFSF1A as well as CA19-9 were assayed in serially collected pre-diagnostic plasma from 242 PDAC cases and 242 age- and sex-matched non-case control participants in the PLCO cohort. We compared performance estimates of a parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history, to that of a single-threshold (ST) method.

Chemically defined and dynamic click hydrogels support hair cell differentiation in human inner ear organoids.

The mechanical properties in the inner ear microenvironment play a key role in its patterning during embryonic development. To recapitulate inner ear development in vitro, three-dimensional tissue engineering strategies including the application of representative tissue models and scaffolds are of increasing interest. Human inner ear organoids are a promising model to recapitulate developmental processes; however, the current protocol requires Matrigel that contains ill-defined extracellular matrix components.

Activity of Platinum Chemotherapy in Men With Prostate Cancer With and Without DNA Damage Repair Mutations.

Introduction: Alterations in homologous recombination repair (HRR) genes occur in 20%-30% of men with metastatic castration-resistant prostate cancer (mCRPC) which may increase sensitivity to platinum chemotherapy. Specifically, exceptional responses to platinum chemotherapy have been reported among patients with BRCA mutations. This study aimed to evaluate the efficacy of platinum chemotherapy in patients with mCRPC with and without HRR.

Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction.

Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.

Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

Patient-reported outcome trajectories the first 24 months after surgery for cervical spondylotic myelopathy: a Quality Outcomes Database study.

Objective: Cervical spondylotic myelopathy (CSM) shows varying levels of improvement after surgical treatment. While some patients improve soon after surgery, others may take months to years to show any signs of improvement. The goal of this study was to evaluate postoperative improvement, patient-reported outcomes, and patient satisfaction up to 2 years after surgical treatment for CSM, which will help optimize the current treatment strategies and effectively manage patient expectations.

Development and validation of a high-throughput qPCR platform for the detection of soil-transmitted helminth infections.

Background: Historically, soil-transmitted helminth (STH) control and prevention strategies have relied on mass drug administration efforts targeting preschool and school-aged children. While these efforts have succeeded in reducing morbidity associated with STH infection, recent modeling efforts have suggested that expanding intervention to treatment of the entire community could achieve transmission interruption in some settings. Testing the feasibility of such an approach requires large-scale clinical trials, such as the DeWorm3 cluster randomized trial.

Ten simple rules for good model-sharing practices.

Computational models are complex scientific constructs that have become essential for us to better understand the world. Many models are valuable for peers within and beyond disciplinary boundaries. However, there are no widely agreed-upon standards for sharing models.