COVID-19 Infection Percentage Estimation from Computed Tomography Scans: Results and Insights from the International Per-COVID-19 Challenge.

COVID-19 analysis from medical imaging is an important task that has been intensively studied in the last years due to the spread of the COVID-19 pandemic. In fact, medical imaging has often been used as a complementary or main tool to recognize the infected persons. On the other hand, medical imaging has the ability to provide more details about COVID-19 infection, including its severity and spread, which makes it possible to evaluate the infection and follow-up the patient's state. CT scans are the most informative tool for COVID-19 infection, where the evaluation of COVID-19 infection is usually performed through infection segmentation. However, segmentation is a tedious task that requires much effort and time from expert radiologists. To deal with this limitation, an efficient framework for estimating COVID-19 infection as a regression task is proposed. The goal of the Per-COVID-19 challenge is to test the efficiency of modern deep learning methods on COVID-19 infection percentage estimation (CIPE) from CT scans. Participants had to develop an efficient deep learning approach that can learn from noisy data. In addition, participants had to cope with many challenges, including those related to COVID-19 infection complexity and crossdataset scenarios. This paper provides an overview of the COVID-19 infection percentage estimation challenge (Per-COVID-19) held at MIA-COVID-2022. Details of the competition data, challenges, and evaluation metrics are presented. The best performing approaches and their results are described and discussed.

Exact solutions via Prabhakar fractional approach to investigate heat transfer and flow features of hybrid nanofluid subject to shape and slip effects.

The core devotion of this study is to develop a generalized model by means of a recently proposed fractional technique in order to anticipate the enhancement in the thermal efficiency of engine oil because of the dispersion of graphene and magnesia nanoparticles. In addition to investigating the synergistic attributes of the foregoing particles, this work evaluates shape impacts for column, brick, tetrahedron, blade, and lamina-like shapes. In the primary model, the flow equation is coupled with concentration and energy functions. This classical system is transmuted into a fractional environment by generalizing mathematical expressions of thermal and diffusion fluxes by virtue of the Prabhakar fractional operator. In this study, ramped flow and temperature slip conditions are simultaneously applied for the first time to examine the behavior of a hybrid nanofluid. The mathematical analysis of this problem involves the incorporation of dimension-independent parameters into the model and the execution of the Laplace transform for the consequent equations. By doing so, exact solutions are derived in the form of Mittag-Leffler functions. Multiple illustrations are developed by dint of exact solutions to chew over all aspects of temperature variations and flow dynamics. For the preparation of these illustrations, the details of parametric ranges are as follows: [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]. The contribution of differently shaped nanoparticles, volume proportions, and fractional parameters in boosting the heat-transferring attributes of engine oil is also anticipated. In this regard, results for Nusselt number are provided in tabular form. Additionally, a brief analysis of shear stress is carried out for fractional parameters and various combinations of magnesia, graphene, and engine oil. This investigation anticipates that engine oil's hybridization with magnesia and graphene would result in a 33% increase in its thermal performance, which evidently improves its industrial significance. The enhancement in Schmidt number yields an improvement in the mass transfer rate. An increment in collective volume fraction leads to raising the profile of the thermal field. However, the velocity indicates a decreasing behavior. Nusselt number reaches its highest value ([Formula: see text]) for the lamina shape of considered particles. When the intensity of the buoyancy force augments, it causes the velocity to increase.

EZH2 T367 phosphorylation activates p38 signaling through lysine methylation to promote breast cancer progression.

Triple-negative breast cancers (TNBCs) are frequently poorly differentiated with high propensity for metastasis. Enhancer of zeste homolog 2 (EZH2) is the lysine methyltransferase of polycomb repressive complex 2 that mediates transcriptional repression in normal cells and in cancer through H3K27me3. However, H3K27me3-independent non-canonical functions of EZH2 are incompletely understood. We reported that EZH2 phosphorylation at T367 by p38α induces TNBC metastasis in an H3K27me3-independent manner. Here, we show that cytosolic EZH2 methylates p38α at lysine 139 and 165 leading to enhanced p38α stability and that p38 methylation and activation require T367 phosphorylation of EZH2. Dual inhibition of EZH2 methyltransferase and p38 kinase activities downregulates pEZH2-T367, H3K27me3, and p-p38 pathways in vivo and reduces TNBC growth and metastasis. These data uncover a cooperation between EZH2 canonical and non-canonical mechanisms and suggest that inhibition of these pathways may be a potential therapeutic strategy.

Using a Deep Learning Model to Explore the Impact of Clinical Data on COVID-19 Diagnosis Using Chest X-ray.

The coronavirus pandemic (COVID-19) is disrupting the entire world; its rapid global spread threatens to affect millions of people. Accurate and timely diagnosis of COVID-19 is essential to control the spread and alleviate risk. Due to the promising results achieved by integrating machine learning (ML), particularly deep learning (DL), in automating the multiple disease diagnosis process. In the current study, a model based on deep learning was proposed for the automated diagnosis of COVID-19 using chest X-ray images (CXR) and clinical data of the patient. The aim of this study is to investigate the effects of integrating clinical patient data with the CXR for automated COVID-19 diagnosis. The proposed model used data collected from King Fahad University Hospital, Dammam, KSA, which consists of 270 patient records. The experiments were carried out first with clinical data, second with the CXR, and finally with clinical data and CXR. The fusion technique was used to combine the clinical features and features extracted from images. The study found that integrating clinical data with the CXR improves diagnostic accuracy. Using the clinical data and the CXR, the model achieved an accuracy of 0.970, a recall of 0.986, a precision of 0.978, and an F-score of 0.982. Further validation was performed by comparing the performance of the proposed system with the diagnosis of an expert. Additionally, the results have shown that the proposed system can be used as a tool that can help the doctors in COVID-19 diagnosis.

A Generic Approach for Classification of Psychological Disorders Diagnosis using EEG.

Electroencephalogram (EEG) is a widely used technique to diagnose psychological disorders. Until now, most of the studies focused on the diagnosis of a particular psychological disorder using EEG. We propose a generic approach to diagnose the different type of psychological disorders with high accuracy. The proposed approach is tested on five different datasets and three psychological disorders. Electrodes having higher signal to noise ratio are selected from the raw EEG signals. Multiple linear and non-linear features are then extracted from the selected electrodes. After feature selection, machine learning is used to diagnose the psychological disorders. We kept the same generic approach for all the datasets and diseases and achieved 93%, 85% and 80% F1 score on Schizophrenia, Epilepsy and Parkinson disease, respectively.

Significance of Shape Factor in Heat Transfer Performance of Molybdenum-Disulfide Nanofluid in Multiple Flow Situations; A Comparative Fractional Study.

In this modern era, nanofluids are considered one of the advanced kinds of heat transferring fluids due to their enhanced thermal features. The present study is conducted to investigate that how the suspension of molybdenum-disulfide (MoS2) nanoparticles boosts the thermal performance of a Casson-type fluid. Sodium alginate (NaAlg) based nanofluid is contained inside a vertical channel of width d and it exhibits a flow due to the movement of the left wall. The walls are nested in a permeable medium, and a uniform magnetic field and radiation flux are also involved in determining flow patterns and thermal behavior of the nanofluid. Depending on velocity boundary conditions, the flow phenomenon is examined for three different situations. To evaluate the influence of shape factor, MoS2 nanoparticles of blade, cylinder, platelet, and brick shapes are considered. The mathematical modeling is performed in the form of non-integer order operators, and a double fractional analysis is carried out by separately solving Caputo-Fabrizio and Atangana-Baleanu operators based fractional models. The system of coupled PDEs is converted to ODEs by operating the Laplace transformation, and Zakian's algorithm is applied to approximate the Laplace inversion numerically. The solutions of flow and energy equations are presented in terms of graphical illustrations and tables to discuss important physical aspects of the observed problem. Moreover, a detailed inspection on shear stress and Nusselt number is carried out to get a deep insight into skin friction and heat transfer mechanisms. It is analyzed that the suspension of MoS2 nanoparticles leads to ameliorating the heat transfer rate up to 9.5%. To serve the purpose of achieving maximum heat transfer rate and reduced skin friction, the Atangana-Baleanu operator based fractional model is more effective. Furthermore, it is perceived that velocity and energy functions of the nanofluid exhibit significant variations because of the different shapes of nanoparticles.

Unsteady MHD natural convection flow of Casson fluid incorporating thermal radiative flux and heat injection/suction mechanism under variable wall conditions.

Unsteady magnetohydrodynamic flow of Casson fluid over an infinite vertical plate is examined under ramped temperature and velocity conditions at the wall. Thermal radiation flux and heat injection/suction terms are also incorporated in the energy equation. The electrically conducting fluid is flowing through a porous material and these phenomena are governed by partial differential equations. After employing some adequate dimensionless variables, the solutions are evaluated by dint of Laplace transform. In addition, the physical contribution of substantial parameters such as Grashof number, radiation parameter, heat injection/suction parameter, porosity parameter, Prandtl number, and magnetic parameter is appropriately elucidated with the aid of graphical and tabular illustrations. The expressions for skin friction and Nusselt number are also derived to observe wall shear stress and rate of heat transfer. A graphical comparison between solutions corresponding to ramped and constant conditions at the wall is also provided. It is observed that graphs of the solutions computed under constant conditions are always superior with respect to graphs of ramped conditions. The magnetic field decelerates the flow, whereas the radiative flux leads to an upsurge in the flow. Furthermore, the shear stress is a decreasing function of the magnetic parameter.

Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer.

Enhancer of Zeste Homologue 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that is critical for determining cell identity. An epigenetic writer, EZH2 has a well-defined role in transcriptional repression by depositing trimethyl marks on lysine 27 of histone H3. However, there is mounting evidence that histone methyltransferases like EZH2 exert histone methyltransferase-independent functions. The relevance of these functions to breast cancer progression and their regulatory mechanisms are only beginning to become understood. Here, we review the current understanding of EZH2 H3K27me3-independent, noncanonical, functions and their regulation in breast cancer.

Heat Transfer Enhancement in Unsteady MHD Natural Convective Flow of CNTs Oldroyd-B Nanofluid under Ramped Wall Velocity and Ramped Wall Temperature.

This article analyzes heat transfer enhancement in incompressible time dependent magnetohydrodynamic (MHD) convective flow of Oldroyd-B nanofluid with carbon nanotubes (CNTs). Single wall carbon nanotubes (SWCNTs) and multi-wall carbon nanotubes (MWCNTs) are immersed in a base fluid named Sodium alginate. The flow is restricted to an infinite vertical plate saturated in a porous material incorporating the generalized Darcy's law and heat suction/injection. The governing equations for momentum, shear stress and energy are modelled in the form of partial differential equations along with ramped wall temperature and ramped wall velocity boundary conditions. Laplace transformation is applied to convert principal partial differential equations to ordinary differential equations first and, later, complex multivalued functions of Laplace parameter are handled with numerical inversion to obtain the solutions in real time domain. Expression for Nusselt number is also obtained to clearly examine the difference in rate of heat transfer. A comparison for isothermal wall condition and ramped wall condition is also made to analyze the difference in both profiles. A graphical study is conducted to analyze how the fluid profiles are significantly affected by several pertinent parameters. Rate of heat transfer increases with increasing volume fraction of nanoparticle while shear stress reduces with elevation in retardation time. Moreover, flow gets accelerated with increase in Grashof number and Porosity parameter. For every parameter, a comparison between solutions of SWCNTs and MWCNTs is also presented.

An exact analysis of unsteady MHD free convection flow of some nanofluids with ramped wall velocity and ramped wall temperature accounting heat radiation and injection/consumption.

This article investigates the influence of ramped wall velocity and ramped wall temperature on time dependent, magnetohydrodynamic (MHD) natural convection flow of some nanofluids close to an infinitely long vertical plate nested in porous medium. Combination of water as base fluid and three types of nanoparticles named as copper, titanium dioxide and aluminum oxide is taken into account. Impacts of non linear thermal radiation flux and heat injection/consumption are also evaluated. The solutions of principal equations of mass and heat transfer are computed in close form by applying Laplace transform. The physical features of connected parameters are discussed and elucidated with the assistance of graphs. The expressions for Nusselt number and skin friction are also calculated and control of pertinent parameters on both phenomenons is presented in tables. A comparative study is performed for ramped wall and isothermal wall to evaluate the application extent of both boundary conditions.

Next-generation sequencing identifies recurrent copy number variations in invasive breast carcinomas from Ghana.

African and African-American (AA) women have higher incidence of triple-negative breast cancers (TNBC) with high histological grade and aggressive clinical behavior, but the reasons are not fully understood. We recently found that the oncogenic protein EZH2 is overexpressed in Ghanaian breast cancer patients, with 16% of the tumors expressing cytoplasmic EZH2. Understanding the molecular underpinnings of these aggressive tumors may lead to the identification of potential targetable oncogenic drivers. We characterized the copy number variations of 11 Ghanaian breast tumor patients by targeted multiplexed PCR-based DNA next-generation sequencing (NGS) over 130 cancer-relevant genes. While the DNA quality was not optimal for mutation analysis, 90% of the tumors had frequent recurrent copy number alterations (CNAs) of 17 genes: SDHC, RECQL4, TFE3, BCL11A, BCL2L1, PDGFRA, DEK, SMUG1, AKT3, SMARCA4, VHL, KLF6, CCNE1, G6PD, FGF3, ABL1, and CCND1, with the top oncogenic functions being mitotic G1-G1/S-phase regulation, gene transcription, apoptosis, and PI3K/AKT pathway. The most common recurrent high-level CNAs were gains of RECQL4 and SDHC, in 50% and 60% of cases, respectively. Network analyses revealed a significant predicted interaction among 12 of the 17 (70.6%) genes with high-level CNAs (p = 5.7E-07), which was highly correlated with EZH2 expression (r = 0.4-0.75). By immunohistochemistry, RECQL4 and SDHC proteins were upregulated in 53 of 86 (61.6%) and 48 of 86 (56%) of Ghanaian invasive carcinoma tissue samples. In conclusion, our data show that invasive carcinomas from Ghana exhibit recurrent CNAs in 17 genes, with functions in oncogenic pathways, including PI3K/AKT and G1-G1/S regulation, which may have implications for the biology and treatment of invasive carcinomas in African and AA women.

Unsteady Radiative Natural Convective MHD Nanofluid Flow Past a Porous Moving Vertical Plate with Heat Source/Sink.

In this research article, we investigated a comprehensive analysis of time-dependent free convection electrically and thermally conducted water-based nanofluid flow containing Copper and Titanium oxide (Cu and TiO 2 ) past a moving porous vertical plate. A uniform transverse magnetic field is imposed perpendicular to the flow direction. Thermal radiation and heat sink terms are included in the energy equation. The governing equations of this flow consist of partial differential equations along with some initial and boundary conditions. The solution method of these flow interpreting equations comprised of two parts. Firstly, principal equations of flow are symmetrically transformed to a set of nonlinear coupled dimensionless partial differential equations using convenient dimensionless parameters. Secondly, the Laplace transformation technique is applied to those non-dimensional equations to get the close form exact solutions. The control of momentum and heat profile with respect to different associated parameters is analyzed thoroughly with the help of graphs. Fluid accelerates with increasing Grashof number (Gr) and porosity parameter (K), while increasing values of heat sink parameter (Q) and Prandtl number (Pr) drop the thermal profile. Moreover, velocity and thermal profile comparison for Cu and TiO 2 -based nanofluids is graphed.

Mesenchymal Stem/Stromal Cell Engulfment Reveals Metastatic Advantage in Breast Cancer.

Twenty percent of breast cancer (BC) patients develop distant metastasis for which there is no cure. Mesenchymal stem/stromal cells (MSCs) in the tumor microenvironment were shown to stimulate metastasis, but the mechanisms are unclear. Here, we identified and quantified cancer cells engulfing stromal cells in clinical samples of BC metastasis by dual immunostaining for EZH2 and ALDH1 expression. Using flow cytometry and a microfluidic single-cell paring and retrieval platform, we show that MSC engulfment capacity is associated with BC cell metastatic potential and generates cells with mesenchymal-like, invasion, and stem cell traits. Whole-transcriptome analyses of selectively retrieved engulfing BC cells identify a gene signature of MSC engulfment consisting of WNT5A, MSR1, ELMO1, IL1RL2, ZPLD1, and SIRPB1. These results delineate a mechanism by which MSCs in the tumor microenvironment promote metastasis and provide a microfluidic platform with the potential to predict BC metastasis in clinical samples.

p38-mediated phosphorylation at T367 induces EZH2 cytoplasmic localization to promote breast cancer metastasis.

Overexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. EZH2 has been mainly studied as the catalytic component of the Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how EZH2 drives metastasis despite the low H3K27me3 levels observed in ER- breast cancer is unknown. Here we show that in human invasive carcinomas and distant metastases, cytoplasmic EZH2 phosphorylated at T367 is significantly associated with ER- disease and low H3K27me3 levels. p38-mediated EZH2 phosphorylation at T367 promotes EZH2 cytoplasmic localization and potentiates EZH2 binding to vinculin and other cytoskeletal regulators of cell migration and invasion. Ectopic expression of a phospho-deficient T367A-EZH2 mutant is sufficient to inhibit EZH2 cytoplasmic expression, disrupt binding to cytoskeletal regulators, and reduce EZH2-mediated adhesion, migration, invasion, and development of spontaneous metastasis. These results point to a PRC2-independent non-canonical mechanism of EZH2 pro-metastatic function.

Mesenchymal Stem Cell-Induced DDR2 Mediates Stromal-Breast Cancer Interactions and Metastasis Growth.

Increased collagen deposition by breast cancer (BC)-associated mesenchymal stem/multipotent stromal cells (MSC) promotes metastasis, but the mechanisms are unknown. Here, we report that the collagen receptor discoidin domain receptor 2 (DDR2) is essential for stromal-BC communication. In human BC metastasis, DDR2 is concordantly upregulated in metastatic cancer and multipotent mesenchymal stromal cells. In MSCs isolated from human BC metastasis, DDR2 maintains a fibroblastic phenotype with collagen deposition and induces pathological activation of DDR2 signaling in BC cells. Loss of DDR2 in MSCs impairs their ability to promote DDR2 phosphorylation in BC cells, as well as BC cell alignment, migration, and metastasis. Female ddr2-deficient mice homozygous for the slie mutation show inefficient spontaneous BC metastasis. These results point to a role for mesenchymal stem cell DDR2 in metastasis and suggest a therapeutic approach for metastatic BC.

Tissue-based identification of stem cells and epithelial-to-mesenchymal transition in breast cancer.

Pathologists have recognized breast cancer heterogeneity for decades, but its causes were unknown. In recent years, basic science and translational studies have demonstrated that cancer stem cells contribute to the heterogeneous histologic and functional characteristics of breast cancer. Even more recently, the ability of breast epithelial cells to undergo an epithelial-to-mesenchymal transition has been linked to the acquisition of stem cells properties and enhanced tumor invasion, metastasis, and resistance to available treatments. The stem cells and cells undergoing epithelial-to-mesenchymal transition are attractive targets for therapy and breast cancer prevention. Despite current challenges, their identification in breast tissue samples would enable pathologists to discover and validate prognostic and predictive markers as well as identify markers of increased risk for breast cancer.

Pazopanib inhibits the activation of PDGFRß-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells.

Brain metastases occur in more than one-third of metastatic breast cancer patients whose tumors overexpress HER2 or are triple negative. Brain colonization of cancer cells occurs in a unique environment, containing microglia, oligodendrocytes, astrocytes, and neurons. Although a neuroinflammatory response has been documented in brain metastasis, its contribution to cancer progression and therapy remains poorly understood. Using an experimental brain metastasis model, we characterized the brain metastatic microenvironment of brain tropic, HER2-transfected MDA-MB-231 human breast carcinoma cells (231-BR-HER2). A previously unidentified subpopulation of metastasis-associated astrocytes expressing phosphorylated platelet-derived growth factor receptor ß (at tyrosine 751; p751-PDGFRß) was identified around perivascular brain micrometastases. p751-PDGFRß(+) astrocytes were also identified in human brain metastases from eight craniotomy specimens and in primary cultures of astrocyte-enriched glial cells. Previously, we reported that pazopanib, a multispecific tyrosine kinase inhibitor, prevented the outgrowth of 231-BR-HER2 large brain metastases by 73%. Here, we evaluated the effect of pazopanib on the brain neuroinflammatory microenvironment. Pazopanib treatment resulted in 70% (P = 0.023) decrease of the p751-PDGFRß(+) astrocyte population, at the lowest dose of 30 mg/kg, twice daily. Collectively, the data identify a subpopulation of activated astrocytes in the subclinical perivascular stage of brain metastases and show that they are inhibitable by pazopanib, suggesting its potential to prevent the development of brain micrometastases in breast cancer patients.

Raf kinase inhibitor RKIP inhibits MDA-9/syntenin-mediated metastasis in melanoma.

Melanoma differentiation associated gene-9 (MDA-9), also known as syntenin, functions as a positive regulator of melanoma progression and metastasis. In contrast, the Raf kinase inhibitor, RKIP, a negative modulator of RAF-stimulated MEKK activation, is strongly downregulated in metastatic melanoma cells. In this study, we explored a hypothesized inverse relationship between MDA-9 and RKIP in melanoma. Tumor array and cell line analyses confirmed an inverse relationship between expression of MDA-9 and RKIP during melanoma progression. We found that MDA-9 transcriptionally downregulated RKIP in support of a suggested cross-talk between these two proteins. Furthermore, MDA-9 and RKIP physically interacted in a manner that correlated with a suppression of FAK and c-Src phosphorylation, crucial steps necessary for MDA-9 to promote FAK/c-Src complex formation and initiate signaling cascades that drive the MDA-9-mediated metastatic phenotype. Finally, ectopic RKIP expression in melanoma cells overrode MDA-9-mediated signaling, inhibiting cell invasion, anchorage-independent growth, and in vivo dissemination of tumor cells. Taken together, these findings establish RKIP as an inhibitor of MDA-9-dependent melanoma metastasis, with potential implications for targeting this process therapeutically.

Regulation of RKIP function by Helicobacter pylori in gastric cancer.

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world's population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP's S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells.

TPI-287, a new taxane family member, reduces the brain metastatic colonization of breast cancer cells.

Brain metastases of breast and other cancers remain resistant to chemotherapeutic regimens that are effective systemically, in part due to the blood-brain barrier. We report that TPI-287, a new microtubule-stabilizing agent, displays in vitro cytotoxic activity similar to taxanes and epothilones. Unlike the taxanes, TPI-287 is permeable through the blood-brain barrier. Brain-to-plasma ratios of TPI-287 after a single injection typically exceeded one and were as high as 63.8 in the rat and 14.1 in the mouse. A brain-tropic derivative of the MDA-MB-231 triple-negative breast cancer cell line, 231-BR, was used to test whether TPI-287 may be efficacious at preventing or treating brain metastases. TPI-287 had growth inhibitory effects comparable with paclitaxel when 231-BR tumor cells were injected into the mammary fat pad. Brain metastatic colonization was determined by intracardiac injection of 231-BR cells, with treatment beginning on day 3 to 4 postinjection, culminating in a histologic count of brain metastases in brains necropsied days 25 to 28 postinjection. In this assay, paclitaxel, ixabepilone, and nab paclitaxel did not have significant inhibitory activity. TPI-287 was ineffective in the same assay using a 6 mg/kg every week schedule; however an 18 mg/kg dose delivered on days 3, 7, and 11 significantly reduced the outgrowth of brain metastases (55% reduction, P = 0.028) and reduced proliferation in brain metastases (16% reduction, P = 0.008). When TPI-287 treatment was delayed until days 18, 22, and 26 postinjection, efficacy was reduced (17% reduction, not significant). These data suggest that TPI-287 may have efficacy when administered early in the course of the disease.