Perinatal exposure to methadone or buprenorphine impairs hippocampal-dependent cognition and brain development in juvenile rats.

The opioid crisis continues to escalate, disproportionately affecting women of reproductive age. Traditionally the first line of treatment for pregnant women with opioid use disorder is the mu-opioid receptor agonist methadone. However, in recent years, the use of buprenorphine as a replacement therapy has increased as it has fewer side-effects and longer duration of action.

Intra-tumoral YAP and TAZ heterogeneity drives collective NSCLC invasion that is targeted by SUMOylation inhibitor TAK-981.

Non-small cell lung cancer (NSCLC) collective invasion is supported by cooperativity of proliferative (follower) and invasive (leader) cells. H1299-isolated follower cells exhibit higher Yes-associated protein (YAP) expression, while leader cells were found to express elevated transcriptional coactivator with PDZ-binding motif (TAZ/WWTR1) expression. Suppressing TAZ (not YAP) in leader cells reduced invasion.

Development and Validation of Claims-Based Algorithms for Conjunctivitis and Keratitis.

Background: Ocular surface disorders have been reported among patients with various medical conditions, including atopic dermatitis (AD). Nonetheless, validated algorithms to identify conjunctivitis and keratitis in claims data are lacking.

Objective: Develop validated, claims-based algorithms for conjunctivitis and keratitis among patients with AD using medical records.

The pro-oncogenic noncanonical activity of a RAS•GTP:RanGAP1 complex facilitates nuclear protein export.

Canonical RAS signaling, including PI3K/AKT- and RAF/MEK-dependent activities, results mainly from RAS•GTP interaction with its effectors at the plasma membrane. Here, we identified a fundamental, oncogenic, noncanonical RAS•GTP activity that increases XPO1-dependent export of nuclear protein cargo into the cytoplasm and is independent of PI3K/AKT and RAF/MEK signaling. This RAS-dependent step acts downstream from XPO1 binding to nuclear protein cargo and is mediated by a perinuclear protein complex between RAS•GTP and RanGAP1 that facilitates hydrolysis of Ran•GTP to Ran•GDP, which promotes release of nuclear protein cargo into the cytoplasm.

Tenascin-C in the early lung cancer tumor microenvironment promotes progression through integrin αvβ1 and FAK.

Pre-cancerous lung lesions are commonly initiated by activating mutations in the RAS pathway, but do not transition to lung adenocarcinomas (LUAD) without additional oncogenic signals. Here, we show that expression of the extracellular matrix protein Tenascin-C (TNC) is increased in and promotes the earliest stages of LUAD development in oncogenic KRAS-driven lung cancer mouse models and in human LUAD. TNC is initially expressed by fibroblasts and its expression extends to tumor cells as the tumor becomes invasive.

Two-photon excitation two-dimensional fluorescence spectroscopy (2PE-2DFS) of the fluorescent nucleobase 6-MI.

Base stacking is fundamentally important to the stability of double-stranded DNA. However, few experiments can directly probe the local conformations and conformational fluctuations of the DNA bases. Here we report a new spectroscopic approach to study the local conformations of DNA bases using the UV-absorbing fluorescent guanine analogue, 6-methyl isoxanthopterin (6-MI), which can be used as a site-specific probe to label DNA.

Molecular Dynamical and Quantum Mechanical Exploration of the Site-Specific Dynamics of Cy3 Dimers Internally Linked to dsDNA.

Performing spectroscopic measurements on biomolecules labeled with fluorescent probes is a powerful approach to locating the molecular behavior and dynamics of large systems at specific sites within their local environments. The indocarbocyanine dye Cy3 has emerged as one of the most commonly used chromophores. The incorporation of Cy3 dimers into DNA enhances experimental resolution owing to the spectral characteristics influenced by the geometric orientation of excitonically coupled monomeric units.

Hand-Specific External Fixation for Treatment of Complex Proximal Interphalangeal Joint Injuries.

Background: Complex proximal interphalangeal joint (PIPJ) fractures are challenging injuries to treat. There are multiple established treatment methods available for these injuries, including dynamic external fixation. This study reports the outcomes of complex PIPJ fractures treated with a hand-specific external fixation device.

Tumor-Intrinsic Enhancer of Zeste Homolog 2 Controls Immune Cell Infiltration, Tumor Growth, and Lung Metastasis in a Triple-Negative Breast Cancer Model.

Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBCs.

Application of multiple validated algorithms for identifying incident breast cancer among individuals with atopic dermatitis.

Purpose: Validated algorithms (VAs) in insurance claims databases are often used to estimate the prevalence and incidence of comorbidities and evaluate safety signals. However, although they are then used in different data sources or subpopulations from those in which they were developed the replicability of these VAs are rarely tested, making their application and performance in these settings potentially unknown. This paper describes testing multiple VAs used to identify incident breast cancer cases in a general population and in an indication-specific population, patients with atopic dermatitis (AD).

Spectroscopic approaches for studies of site-specific DNA base and backbone 'breathing' using exciton-coupled dimer-labeled DNA.

DNA regulation and repair processes require direct interactions between proteins and DNA at specific sites. Local fluctuations of the sugar-phosphate backbones and bases of DNA (a form of DNA 'breathing') play a central role in such processes. Here we review the development and application of novel spectroscopic methods and analyses - both at the ensemble and single-molecule levels - to study structural and dynamic properties of exciton-coupled cyanine and fluorescent nucleobase analogue dimer-labeled DNA constructs at key positions involved in protein-DNA complex assembly and function.

Subpopulation commensalism promotes Rac1-dependent invasion of single cells via laminin-332.

Phenotypic heterogeneity poses a significant hurdle for cancer treatment but is under-characterized in the context of tumor invasion. Amidst the range of phenotypic heterogeneity across solid tumor types, collectively invading cells and single cells have been extensively characterized as independent modes of invasion, but their intercellular interactions have rarely been explored. Here, we isolated collectively invading cells and single cells from the heterogeneous 4T1 cell line and observed extensive transcriptional and epigenetic diversity across these subpopulations.

Association between allergic conditions and COVID-19 susceptibility and outcomes.

Background: The relationship between underlying type 2 inflammation and immune response to COVID-19 is unclear.

Objective: To assess the relationships between allergic conditions and COVID-19 susceptibility and outcomes.

Methods: In the Optum database, adult patients with and without major allergic conditions (asthma, atopic dermatitis [AD], allergic rhinitis, food allergy, anaphylaxis, or eosinophilic esophagitis) and patients with and without severe asthma/AD were identified.

Lessons Learned: Evaluation of Fracture Liaison Service Quality Improvement Efforts in a Large Academic Healthcare System.

Background: The Fracture Liaison Service (FLS) care model, a care coordination program for patients experiencing a fragility fracture, is proven to improve management of patients with an osteoporotic fracture, but treatment initiation gaps persist.

Objective: We describe the evolution of a centralized FLS within a university-based healthcare system, including impact of adding clinical pharmacist consultation, and describe circumstances surrounding continued care gaps.

Design: Cohort analysis of osteoporosis medication initiation before FLS, after initial implementation, and after addition of pharmacist consultation.

Studies of DNA 'Breathing' by Polarization-Sweep Single-Molecule Fluorescence Microscopy of Exciton-Coupled (iCy3) Dimer-Labeled DNA Fork Constructs.

Local fluctuations of the sugar-phosphate backbones and bases of DNA (often called DNA 'breathing') play a variety of critical roles in controlling the functional interactions of the DNA genome with the protein complexes that regulate it. Here, we present a single-molecule fluorescence method that we have used to measure and characterize such conformational fluctuations at and near biologically important positions in model DNA replication fork constructs labeled with exciton-coupled cyanine [(iCy3)] dimer probes. Previous work has shown that the constructs that we tested here exhibit a broad range of spectral properties at the ensemble level, and these differences can be structurally and dynamically interpreted using our present methodology at the single-molecule level.

Using transition density models to interpret experimental optical spectra of exciton-coupled cyanine (iCy3)2 dimer probes of local DNA conformations at or near functional protein binding sites.

Exciton-coupled chromophore dimers are an emerging class of optical probes for studies of site-specific biomolecular interactions. Applying accurate theoretical models for the electrostatic coupling of a molecular dimer probe is a key step for simulating its optical properties and analyzing spectroscopic data. In this work, we compare experimental absorbance and circular dichroism (CD) spectra of 'internally-labeled' (iCy3)2 dimer probes inserted site-specifically into DNA fork constructs to theoretical calculations of the structure and geometry of these exciton-coupled dimers.