7 days vs 61.7 days, P= .01). The difference in the summary measure of guideline concordance across groups was not statistically significant (P=.38). E-consults were faster than face-to-face consults and similarly guideline-concordant compared with both face-to-face consults and no endocrinology input for workups resulting in FNA. Decisions about the appropriate use of e-consults for thyroid nodules should take into account these data while also considering the potential benefits of direct patient-endocrinologist interaction for complex situations.E-consults were faster than face-to-face consults and similarly guideline-concordant compared with both face-to-face consults and no endocrinology input for workups resulting in FNA. Decisions about the appropriate use of e-consults for thyroid nodules should take into account these data while also considering the potential benefits of direct patient-endocrinologist interaction for complex situations.Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline related to deficits in synaptic transmission and plasticity. We report in APP/PS1 mice, a double transgenic mouse model of AD, that females displayed an early burden of Aβ plaques load in the stratum moleculare of the dentate gyrus (DG) together with prominent neuroinflammatory activation of astrocytes and microglia. Robust deficits in hippocampus-dependent memory tasks were observed in APP/PS1 female mice as early as 3 months of age. We then studied the functional properties of the lateral perforant path (LPP) to DG granule cells. Remarkably DG granule cells displayed higher intrinsic excitability in APP/PS1 female mice. We showed that the long term potentiation of population spike amplitude induced by high frequency stimulation (HFS) at LPP-DG granule cells synapse is impaired in APP/PS1 female mice. HFS induced plasticity of intrinsic excitability in DG granule cells without inducing noticeable modification of synaptic strength. Furthermore, the enhanced intrinsic excitability was potentiated to a greater extent in APP/PS1 as compared to control mice following HFS. Our study shows that changes in the intrinsic excitability of DG granule cells in AD contribute to the dysfunctional transfer of information from the entorhinal cortex to the hippocampus. A variety of transgenic and knock-in mice that express mutant alleles of Amyloid precursor protein (APP) have been used to model the effects of amyloid-beta (Aβ) on circuit function in Alzheimer's disease (AD); however phenotypes described in these mice may be affected by expression of mutant APP or proteolytic cleavage products independent of Aβ. In addition, the effects of mutant APP expression are attributed to elevated expression of the amyloidogenic, 42-amino acid-long species of Aβ (Aβ42) associated with amyloid plaque accumulation in AD, though elevated concentrations of Aβ40, an Aβ species produced with normal synaptic activity, may also affect neural function. To explore the effects of elevated expression of Aβ on synaptic function in vivo, we assessed visual system plasticity in transgenic mice that express and secrete Aβ throughout the brain in the absence of APP overexpression. Transgenic mice that express either Aβ40 or Aβ42 were assayed for their ability to appropriately demonstrate ocular d of modulating synaptic plasticity, likely independent of any aggregation. These findings may have implications for the role of soluble species of Aβ in both development and disease settings.Although polyploid cells were first described nearly two centuries ago, their ability to proliferate has only recently been demonstrated. It also becomes increasingly evident that a subset of tumor cells, polyploid giant cancer cells (PGCCs), play a critical role in the pathophysiology of breast cancer (BC), among other cancer types. In BC, PGCCs can arise in response to therapy-induced stress. Their progeny possess cancer stem cell (CSC) properties and can repopulate the tumor. By modulating the tumor microenvironment (TME), PGCCs promote BC progression, chemoresistance, metastasis, and relapse and ultimately impact the survival of BC patients. Given their pro- tumorigenic roles, PGCCs have been proposed to possess the ability to predict treatment response and patient prognosis in BC. Traditionally, DNA cytometry has been used to detect PGCCs.. K02288 research buy The field will further derive benefit from the development of approaches to accurately detect PGCCs and their progeny using robust PGCC biomarkers. In this review, we present the current state of knowledge about the clinical relevance of PGCCs in BC. We also propose to use an artificial intelligence-assisted image analysis pipeline to identify PGCC and map their interactions with other TME components, thereby facilitating the clinical implementation of PGCCs as biomarkers to predict treatment response and survival outcomes in BC patients. Finally, we summarize efforts to therapeutically target PGCCs to prevent chemoresistance and improve clinical outcomes in patients with BC.EV-miRNAs are microRNA (miRNA) molecules encapsulated in extracellular vesicles (EVs), which play crucial roles in tumor pathogenesis, progression, and metastasis. Recent studies about EV-miRNAs have gained novel insights into cancer biology and have demonstrated a great potential to develop novel liquid biopsy assays for various applications. Notably, compared to conventional liquid biomarkers, EV-miRNAs are more advantageous in representing host-cell molecular architecture and exhibiting higher stability and specificity. Despite various available techniques for EV-miRNA separation, concentration, profiling, and data analysis, a standardized approach for EV-miRNA biomarker development is yet lacking. In this review, we performed a substantial literature review and distilled an integrated workflow encompassing important steps for EV-miRNA biomarker development, including sample collection and EV isolation, EV-miRNA extraction and quantification, high-throughput data preprocessing, biomarker prioritization and model construction, functional analysis, as well as validation. With the rapid growth of "big data", we highlight the importance of efficient mining of high-throughput data for the discovery of EV-miRNA biomarkers and integrating multiple independent datasets for in silico and experimental validations to increase the robustness and reproducibility. Furthermore, as an efficient strategy in systems biology, network inference provides insights into the regulatory mechanisms and can be used to select functionally important EV-miRNAs to refine the biomarker candidates. Despite the encouraging development in the field, a number of challenges still hinder the clinical translation. We finally summarize several common challenges in various biomarker studies and discuss potential opportunities emerging in the related fields.