Design and Characterization of a Gene-Encoding DNA Nanoparticle in a Cell-Free Transcription-Translation System.

DNA nanotechnology has made initial progress toward developing gene-encoded DNA origami nanoparticles (NPs) that display potential utility for future gene therapy applications. However, due to the challenges involved with gene delivery into cells including transport through the membrane, intracellular targeting, and inherent expression of nucleases along with interference from other active proteins, it can be difficult to more directly study the effect of DNA NP design on subsequent gene expression. In this work, we demonstrate an approach for studying the expression of gene-encoding DNA origami NPs without the use of cells.

Investigation of Flurbiprofen Pharmacokinetics in Rats Following Dermal Administration of Optimized Cyclodextrin-Based Nanogel.

Purpose: The main purpose of this study was to optimize a cyclodextrin-based nanogel of flurbiprofen (FP) for prolonged dermal administration and evaluate its stability, in vitro release, ex vivo skin permeation, and in vivo pharmacokinetic profile.

Methods: The nanogels were prepared via emulsification/solvent evaporation process and optimized through design of experiments. Optimal formulation was characterized via particle size (PS), polydispersity index (PDI), zeta potential (ZP), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), solubility, stability, in vitro release/ex vivo permeation studies and mathematical modeling, and pharmacokinetic studies conducted in rats.

Simulating 500 million years of evolution with a language model.

More than three billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here we show that language models trained at scale on evolutionary data can generate functional proteins that are far away from known proteins. We present ESM3, a frontier multimodal generative language model that reasons over the sequence, structure, and function of proteins.

Functional Annotation of Bipolar Disorder 2 Risk Location Implicates Novel Susceptibility Genes.

Introduction: Bipolar 2 disorder (BD2) is an independent disease with specific familial aggregation, significant functional impairment, specific treatment challenges and several distinctive clinical features. However, unlike bipolar 1 disorder, studies investigating causal and functional genes are lacking. This study aims to identify and prioritize causal genetic variants and genes for BD2 by analyzing brain-specific gene expression markers, to improve the understanding of its genetic underpinnings and support advancements in diagnosis, treatment and prognosis.

Predicting postoperative atrial fibrillation after cardiac surgery using the Naples prognostic score.

Introduction: The Naples prognostic score (NPS) is a novel indicator of nutritional and inflammatory statuses in cancer patients. Development of atrial fibrillation after cardiac surgery (POAF) is a common complication that increases the incidence of adverse events. Numerous studies have investigated predictors of POAF.

Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes.

Spontaneous preterm birth (sPTB) poses significant challenges, affecting neonatal health and neurodevelopmental outcomes worldwide. The specific effects of placental trophoblasts on the pathological development of sPTB subtypes-preterm premature rupture of fetal membranes (pPROM) and spontaneous preterm labor (sPTL)-are not fully understood, making it crucial to uncover these impacts for the development of effective therapeutic strategies. Using single-nucleus RNA sequencing, we investigated transcriptomic and cellular differences at the maternal-fetal interface in pPROM and sPTL placentas.

Ultrasonographic accuracy in evaluating response of clipped lymph nodes in targeted axillary dissection in breast cancer.

This study aimed to evaluate the diagnostic accuracy of ultrasonography in assessing the response of clipped axillary lymph nodes to neoadjuvant chemotherapy. Between February 2022 and September 2023, 43 patients who underwent axillary lymph node marking for targeted axillary dissection were retrospectively analyzed. Ultrasonography parameters such as the number, size, shape, cortical thickness, hilum status, and treatment response of the clipped lymph node were assessed.

Evaluation of hyoid bone position, shape, area, volume, and tongue volume.

Purpose: Our study aims to determine the position and types of the hyoid bone and to evaluate the morphometry of the hyoid bone and tongue according to sex.

Methods: Our study included cervical Computed Tomography (CT) images of 200 individuals (100 females, 100 males) between the ages of 18 and 84. Using the 3D Slicer software package, hyoid bone position, shape, area, volume and tongue volume measurements were made on these images.

Screening of Polymers for Oral Ritonavir Amorphous Solid Dispersions by Film Casting.

Drug-polymer interactions and miscibility promote the formation and performance of amorphous solid dispersions (ASDs) of poorly soluble drugs for improved oral bioavailability. The objective of this study was to employ drug-polymer interaction calculations and small-scale experimental characterization to screen polymers for potential ASDs of ritonavir. Seven polymers across four polymer types were screened as follows: an enteric one (EudragitS100), amphiphilic ones (HPMCAS-L, HPMCAS-H, and their 1:1 combination), hydrophilic ones (PEG-6000, PVP-VA), and a surfactant (Soluplus), including PVP-VA as a positive control, as the commercial ASD employs PVP-VA.

Myxoid glioneuronal tumor of the septum pellucidum in pediatric patients: a case report and comprehensive review of the literature.

Introduction: Myxoid glioneuronal tumor of the septum pellucidum is an uncommon clinical entity, previously referred to dysembryoplastic neuroepithelial tumor located in the septum pellucidum.

Methods: This study was conducted following PRISMA guidelines. A comprehensive literature search was performed in the PubMed/MEDLINE, Web of Science, and Scopus databases.

Macrophages in tumor cell migration and metastasis.

Tumor-associated macrophages (TAMs) are a phenotypically diverse, highly plastic population of cells in the tumor microenvironment (TME) that have long been known to promote cancer progression. In this review, we summarize TAM ontogeny and polarization, and then explore how TAMs enhance tumor cell migration through the TME, thus facilitating metastasis. We also discuss how chemotherapy and host factors including diet, obesity, and race, impact TAM phenotype and cancer progression.

Classification of Human Ovarian Follicle Morphology: Recommendations of the NICHD-Sponsored Ovarian Nomenclature Workshop.

Objective: To develop a consensus on histologic human ovarian follicle staging nomenclature, provide guidelines for follicle density calculation, and assess changes due to fixation to enhance communication among clinicians and ovarian biology researchers in order to gain a deeper understanding of human fertility.

Methods: Beginning in March 2021, the Ovarian Nomenclature Workshop's Follicle Classification Working Subgroup was organized by the Pediatric and Adolescent Gynecology program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Results: The Follicle Working Subgroup recommends consolidation and expansion of the current classification systems to include six stages of normal preantral follicles, five stages of normal antral follicles, as well as categories of corpus lutea, abnormal preantral follicles, abnormal antral follicles, and other distinct follicle types.

Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer.

Purpose: Breast cancer cells disseminate to distant sites via tumor microenvironment of metastasis (TMEM) doorways. The TIE2 inhibitor rebastinib blocks TMEM doorway function in the PyMT mouse model of breast cancer. We aimed to assess the safety and pharmacodynamics of rebastinib plus paclitaxel or eribulin in patients with HER2-negative metastatic breast cancer (MBC).

Intratumoral CXCL12 Gradients Contextualize Tumor Cell Invasion, Migration and Immune Suppression in Breast Cancer.

Although the CXCL12/CXCR4 pathway has been prior investigated for its prometastatic and immuno- suppressive roles in the tumor microenvironment, evidence on the spatiotemporal regulation of these hallmarks has been lacking. Here, we demonstrate that CXCL12 forms a gradient specifically around cancer cell intravasation doorways, also known as Tumor Microenvironment of Metastasis (TMEM) doorways, thus facilitating the chemotactic translocation of prometastatic tumor cells expressing CXCR4 toward the perivascular TMEM doorways for subsequent entry into peripheral circulation. Fur- thermore, we demonstrate that the CXCL12-rich micro-environment around TMEM doorways may cre- ate immunosuppressive niches, whereby CD8 T cells, despite being attracted to these regions, often exhibit reduced effector functions, limiting their efficacy.

Evaluation of ventriculoperitoneal shunt infections and risk factors in children.

Introduction: To evaluate the demographic, clinical, diagnostic, and treatment data of pediatric patients with ventriculoperitoneal shunt infection and risk factors for ventriculoperitoneal shunt infection and recurrence of ventriculoperitoneal shunt infection.

Methods: Patients aged 0-18 years who were diagnosed with ventriculoperitoneal shunt infection at Cukurova University Faculty of Medicine Hospital between 2016 and 2021 were included in the study. Demographic, clinical, laboratory, and treatment data of the patients were evaluated retrospectively.

Evaluation of potential links between phenotypic features and genetic variants in left ventricular outflow tract obstruction in hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging.

This study aimed to identify the phenotypic features contributing to the development of left ventricular outflow tract obstruction (LVOTO) in patients with hypertrophic cardiomyopathy (HCM) and to evaluate the genotype‒phenotype relationship. This cross-sectional study included 96 patients diagnosed with HCM (mean age: 56.9 ± 13.

A Multivalent DNA Nanoparticle/Peptide Hybrid Molecular Modality for the Modulation of Protein-Protein Interactions in the Tumor Microenvironment.

Despite success in the treatment of some blood cancers and melanoma, positive response to immunotherapies remains disappointingly low in the treatment of solid tumors. The context of the molecular crosstalk within the tumor microenvironment can result in dysfunctional immune cell activation, leading to tumor tolerance and progression. Although modulating these protein-protein interactions (PPIs) is vital for appropriate immune cell activation and recognition, targeting nonenzymatic PPIs has proven to be fraught with challenges.

Expressions of the satellite repeat HSAT5 and transposable elements are implicated in disease progression and survival in glioma.

The glioma genome encompasses a complex array of dysregulatory events, presenting a formidable challenge in managing this devastating disease. Despite the widespread distribution of repeat and transposable elements across the human genome, their involvement in glioma's molecular pathology and patient survival remains largely unexplored. In this study, we aimed to characterize the links between the expressions of repeat/transposable elements with disease progression and survival in glioma patients.

The NF1 gene mutations and co-mutations in lung adenocarcinomas with brain metastasis.

Background: The co-occurrence of lung adenocarcinoma and brain metastasis remains a significant cause of morbidity and mortality despite advancements in cancer treatment. The activity of neurofibromin, the product of Neurofibromatosis Type 1 gene (NF1), is crucial in regulating the RAS/MAPK pathway. The NF1 somatic mutations are significant in conditions such as melanoma, lung cancer, breast cancer, neuroblastoma, and central nervous system tumors.