The Asymmetry Within: A Renewed Look at Cupids Bow in Unilateral Cleft Lip.

The purpose of this study is to analyze the angular variations within Cupid's bow in patients with unoperated unilateral cleft lip (UCL). Angular features of Cupid's bow were quantified in standardized presurgical photographs of children with UCL by 5 medical professionals specializing in craniofacial anomalies. The peaks and valley of Cupid's bow were identified. A cleft side (CSA) and a noncleft side angle (NCSA) were delineated and measured by each expert. The data was pooled, and the angles were analyzed for symmetry. Cupid's bow asymmetry was defined as a difference between NCSA and CSA ≥3°. Of the 37 patients studied, 29 were found to have asymmetry of Cupid's bow with an average angle difference of 8.0° (95% CI: 6.6°-9.5°). Within this group,15 patients were found with acute asymmetry and 14 with obtuse asymmetry. Geometric analysis was performed on an example of a patient with acute asymmetry to demonstrate how correction of asymmetry can be considered during surgical repair. There is an asymmetry that exists in the Cupid's bow of a significant number of patients with unoperated UCL. This finding not only adds to our understanding of UCL but may also have important implications when selecting the method/technique of surgical repair.

Spatially Dependent Tissue Distribution of Thyroid Hormones by Plasma Thyroid Hormone Binding Proteins.

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings. (1) Contrary to postulations that TTR and/or ALB are the major local T4 contributors, the three THBPs may unload comparable amounts of T4 in Liver, a rapidly perfused organ; however, their contributions in slowly perfused tissues follow the order of abundances of T4TBG, T4TTR, and T4ALB. The T3 amounts unloaded from or loaded onto THBPs in a tissue acting as a T3 sink or source respectively follow the order of abundance of T3TBG, T3ALB, and T3TTR regardless of perfusion rate. (2) Any THBP alone is sufficient to maintain spatially uniform TH tissue distributions. (3) The TH amounts unloaded by each THBP species are spatially dependent and nonlinear in a tissue, with ALB being the dominant contributor near the arterial end but conceding to TBG near the venous end. (4) Spatial gradients of TH transporters and metabolic enzymes may modulate these contributions, producing spatially invariant or heterogeneous TH tissue concentrations depending on whether the blood-tissue TH exchange operates in near-equilibrium mode. In summary, our modeling provides novel insights into the differential roles of THBPs in local TH tissue distribution.

Age-Related Differences in Motor Skill Transfer with Brief Memory Reactivation.

Motor memories can be strengthened through online practice and offline consolidation. Offline consolidation involves the stabilization of memory traces in post-practice periods. Following initial consolidation of a motor memory, subsequent practice of the motor skill can lead to reactivation and reconsolidation of the memory trace. The length of motor memory reactivation may influence motor learning outcomes; for example, brief, as opposed to long, practice of a previously learned motor skill appears to optimize intermanual transfer in healthy young adults. However, the influence of aging on reactivation-based motor learning has been scarcely explored. Here, the effects of brief and long motor memory reactivation schedules on the retention and intermanual transfer of a visuomotor tracing task are explored in healthy older adults. Forty older adults practiced a virtual star-tracing task either three ("brief reactivation") or ten ("long reactivation") times per session over a two-week period. Comparison with a previously reported group of younger adults revealed significant age-related differences in the effect of the motor memory reactivation schedule on the intermanual transfer of the motor task. In older adults, unlike younger adults, no significant between-group differences were found by practice condition in the speed, accuracy, or skill of intermanual task transfer. That is, motor task transfer in healthy younger, but not older, adults appears to benefit from brief memory reactivation. These results support the use of age-specific motor training approaches and may inform motor practice scheduling, with possible implications for physical rehabilitation, sport, and music.

Applied strategies of neuroplasticity.

Various levels of somatotopic organization are present throughout the human nervous system. However, this organization can change when needed based on environmental demands, a phenomenon known as neuroplasticity. Neuroplasticity can occur when learning a new motor skill, adjusting to life after blindness, or following a stroke. Following an injury, these neuroplastic changes can be adaptive or maladaptive, and often occur regardless of whether rehabilitation occurs or not. But not all movements produce neuroplasticity, nor do all rehabilitation interventions. Here, we focus on research regarding how to maximize adaptive neuroplasticity while also minimizing maladaptive plasticity, known as applied neuroplasticity. Emphasis is placed on research exploring how best to apply neuroplastic principles to training environments and rehabilitation protocols. By studying and applying these principles in research and clinical practice, it is hoped that learning of skills and regaining of function and independence can be optimized.

A minimal human physiologically based kinetic model of thyroid hormones and chemical disruption of plasma thyroid hormone binding proteins.

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are under homeostatic control by the hypothalamic-pituitary-thyroid axis and plasma TH binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB). THBPs buffer free THs against transient perturbations and distribute THs to tissues. TH binding to THBPs can be perturbed by structurally similar endocrine-disrupting chemicals (EDCs), yet their impact on circulating THs and health risks are unclear. In the present study, we constructed a human physiologically based kinetic (PBK) model of THs and explored the potential effects of THBP-binding EDCs. The model describes the production, distribution, and metabolism of T4 and T3 in the Body Blood, Thyroid, Liver, and Rest-of-Body (RB) compartments, with explicit consideration of the reversible binding between plasma THs and THBPs. Rigorously parameterized based on literature data, the model recapitulates key quantitative TH kinetic characteristics, including free, THBP-bound, and total T4 and T3 concentrations, TH productions, distributions, metabolisms, clearance, and half-lives. Moreover, the model produces several novel findings. (1) The blood-tissue TH exchanges are fast and nearly at equilibrium especially for T4, providing intrinsic robustness against local metabolic perturbations. (2) Tissue influx is limiting for transient tissue uptake of THs when THBPs are present. (3) Continuous exposure to THBP-binding EDCs does not alter the steady-state levels of THs, while intermittent daily exposure to rapidly metabolized TBG-binding EDCs can cause much greater disruptions to plasma and tissue THs. In summary, the PBK model provides novel insights into TH kinetics and the homeostatic roles of THBPs against thyroid disrupting chemicals.

Development and Psychometric Testing of the Bimanual Assessment Measure for People With Chronic Stroke.

IMPORTANCE: Few tools are available to assess bimanual deficits after stroke. OBJECTIVE: To develop the Bimanual Assessment Measure (BAM), which assesses a person's hand coordination in both preferred and prestroke roles (i.e., stabilizer or manipulator). DESIGN: Development and psychometric testing of the BAM. SETTING: Research laboratory. PARTICIPANTS: People with chronic stroke (n = 24), age-matched controls (n = 23), and occupational therapists (n = 40). OUTCOMES AND MEASURES: We assessed the BAM's internal consistency, reliability, and face and known-groups validity. RESULTS: Items were selected as meaningful tasks that represented a range of bimanual coordination requirements (e.g., symmetrical forces and timing, asymmetrical forces and timing, time-limited reactive movement). Focus groups of people with stroke and occupational therapists provided input into BAM development. The BAM was found to have excellent reliability and internal consistency and face and known-groups validity. CONCLUSIONS AND RELEVANCE: The BAM is a valid, reliable measure for people with chronic stroke that identifies bimanual coordination deficits beyond unimanual impairments and the potential capacity for people to return to prestroke hand roles (i.e., as a manipulator). What This Article Adds: This article introduces the BAM as a new assessment measure of bimanual functioning with the potential capacity to restore prestroke hand roles as either a manipulator or a stabilizer among people with chronic stroke.

Fresh tissue procurement and preparation for multicompartment and multimodal analysis of the prostate tumor microenvironment.

BACKGROUND: Prostatic cancers include a diverse microenvironment of tumor cells, cancer-associated fibroblasts, and immune components. This tumor microenvironment (TME) is a known driving force of tumor survival after treatment, but the standard-of-care tissue freezing or fixation in pathology practice limit the use of available approaches/tools to study the TME's functionality in tumor resistance. Thus, there is a need for approaches that satisfy both clinical and laboratory endpoints for TME study. Here we present methods for clinical case identification, tissue processing, and analytical workflow that are compatible with standard histopathology while enabling molecular and functional interrogation of prostate TME components. METHODS: We first performed a small retrospective review to identify cases where submission of alternate prostate tissue slices and a parallel live tissue processing protocol complement traditional histopathology and enable viable multicompartment analysis of the TME. Then, we tested its compatibility with commonly employed methods to study the microenvironment including quantification of components both in situ and after tissue dissociation. We also evaluated tissue digestion conditions and cell isolation techniques to aid various molecular and functional endpoints. RESULTS: We identified Gleason Grade Group 3+ clinical cases where tumor volume was sufficient to allow slicing of unfixed tissue and distribution of alternating tissue slices to standard-of-care histopathology and viable multi-modal TME analyses. No single method was found that preserved cellular sub-types for all downstream readouts; instead, tissues were further divided so techniques could be catered to each endpoint. For instance, we show that incorporating the protease dispase into tissue dissociation improves viability for culture and functional analyses but hinders immune cell analysis by flow cytometry. We also found that flow activated cell sorting provides highly pure cell populations for quantitative reverse-transcription polymerase chain reaction and RNA-seq while isolation using antibody-labeled paramagnetic particles facilitated functional coculture experiments. CONCLUSIONS: The identification of candidate cases and use of these techniques enable translational research and the development of molecular and functional assays to facilitate prostate TME study without compromising standard-of-care histopathological diagnosis. This allows bridging clinical histopathology and further interrogation of the prostate TME and promises to advance our understanding of tumor biology and unveil new predictive and prognostic markers of prostate cancer progression.

Reward and plasticity: Implications for neurorehabilitation.

Neuroplasticity follows nervous system injury in the presence or absence of rehabilitative treatments. Rehabilitative interventions can be used to modulate adaptive neuroplasticity, reducing motor impairment and improving activities of daily living in patients with brain lesions. Learning principles guide some rehabilitative interventions. While basic science research has shown that reward combined with training enhances learning, this principle has been only recently explored in the context of neurorehabilitation. Commonly used reinforcers may be more or less rewarding depending on the individual or the context in which the task is performed. Studies in healthy humans showed that both reward and punishment can enhance within-session motor performance; but reward, and not punishment, improves consolidation and retention of motor skills. On the other hand, neurorehabilitative training after brain lesions involves complex tasks (e.g., walking and activities of daily living). The contribution of reward to neurorehabilitation is incompletely understood. Here, we discuss recent research on the role of reward in neurorehabilitation and the needed directions of future research.

Crowdsourcing in Cognitive and Systems Neuroscience.

Behavioral research in cognitive and human systems neuroscience has been largely carried out in-person in laboratory settings. Underpowering and lack of reproducibility due to small sample sizes have weakened conclusions of these investigations. In other disciplines, such as neuroeconomics and social sciences, crowdsourcing has been extensively utilized as a data collection tool, and a means to increase sample sizes. Recent methodological advances allow scientists, for the first time, to test online more complex cognitive, perceptual, and motor tasks. Here we review the nascent literature on the use of online crowdsourcing in cognitive and human systems neuroscience. These investigations take advantage of the ability to reliably track the activity of a participant's computer keyboard, mouse, and eye gaze in the context of large-scale studies online that involve diverse research participant pools. Crowdsourcing allows for testing the generalizability of behavioral hypotheses in real-life environments that are less accessible to lab-designed investigations. Crowdsourcing is further useful when in-laboratory studies are limited, for example during the current COVID-19 pandemic. We also discuss current limitations of crowdsourcing research, and suggest pathways to address them. We conclude that online crowdsourcing is likely to widen the scope and strengthen conclusions of cognitive and human systems neuroscience investigations.

Engineering Epithelial-Mesenchymal Microtissues to Study Cell-Cell Interactions in Development.

Intercellular signaling drives human development, but there is a paucity of in vitro models that recapitulate important tissue architecture while remaining operationally simple and scalable. As an example, formation of the upper lip and palate requires the orchestrated proliferation and fusion of embryonic facial growth centers and is dependent on paracrine epithelial-mesenchymal signaling through multiple pathways including the Sonic Hedgehog (SHH), transforming growth factor-beta (Tgf-ß), bone morphogenic protein (BMP), and epidermal growth factor (EGF) pathways. We have developed a robust, throughput-compatible microphysiological system to model intercellular signaling including epithelial-mesenchymal interactions that is useful for studying both normal and abnormal orofacial development. We describe the construction and operation of an engineered microplate created using CNC micromilling of 96-well microtiter plates capable of containing up to 20 epithelial-mesenchymal microtissues. A dense three-dimensional mesenchyme is created by embedding cells (O9-1, 3T3) in a biomimetic hydrogel. An epithelial layer is then overlayed on the microtissue by loading cells in engineered microchannels that flank the microtissue. The result is an engineering epithelial-mesenchymal interface that is both on and perpendicular to the imaging plane making it suitable for high-content imaging and analysis. The resulting microtissues and device are compatible with diverse analytical techniques including fluorescent and luminescent cell health and enzymatic reporter assays, gene expression analyses, and protein staining. This tractable model and approach promise to shed light on critical processes in intercellular signaling events in orofacial development and beyond.

Enhancing motor learning in people with stroke via memory reactivation during sleep.

PURPOSE: Investigate the use of repetitive delivery of task-related auditory cues, known as targeted memory reactivation (TMR), throughout a 1-hour daytime nap to enhance motor learning in individuals with chronic stroke. RESEARCH METHOD: Participants with a history of stroke at least 6 months prior were recruited to perform a novel overhand throwing task to randomly appearing target locations using the nonparetic upper extremity immediately before and after a 1-hour daytime nap. Half of the participants received TMR during the nap. RESULTS: Participants who received TMR demonstrated a greater overall reduction in absolute and variable spatial errors relative to the NoTMR control group. Both groups demonstrated similar generalization of skill to 2 untrained variants of the trained task, but not to a novel untrained task. CONCLUSIONS: This study suggests that TMR may enhance motor learning after stroke. Future studies should investigate whether TMR can lead to improvements of the paretic upper extremity during clinically based rehabilitation interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Microphysiological Approach to Evaluate Effectors of Intercellular Hedgehog Signaling in Development.

Paracrine signaling in the tissue microenvironment is a central mediator of morphogenesis, and modeling this dynamic intercellular activity in vitro is critical to understanding normal and abnormal development. For example, Sonic Hedgehog (Shh) signaling is a conserved mechanism involved in multiple developmental processes and strongly linked to human birth defects including orofacial clefts of the lip and palate. SHH ligand produced, processed, and secreted from the epithelial ectoderm is shuttled through the extracellular matrix where it binds mesenchymal receptors, establishing a gradient of transcriptional response that drives orofacial morphogenesis. In humans, complex interactions of genetic predispositions and environmental insults acting on diverse molecular targets are thought to underlie orofacial cleft etiology. Consequently, there is a need for tractable in vitro approaches that model this complex cellular and environmental interplay and are sensitive to disruption across the multistep signaling cascade. We developed a microplate-based device that supports an epithelium directly overlaid onto an extracellular matrix-embedded mesenchyme, mimicking the basic tissue architecture of developing orofacial tissues. SHH ligand produced from the epithelium generated a gradient of SHH-driven transcription in the adjacent mesenchyme, recapitulating the gradient of pathway activity observed in vivo. Shh pathway activation was antagonized by small molecule inhibitors of epithelial secretory, extracellular matrix transport, and mesenchymal sensing targets, supporting the use of this approach in high-content chemical screening of the complete Shh pathway. Together, these findings demonstrate a novel and practical microphysiological model with broad utility for investigating epithelial-mesenchymal interactions and environmental signaling disruptions in development.

Chronic Poststroke Deficits in Gross and Fine Motor Control of the Ipsilesional Upper Limb.

OBJECTIVES: Individuals with stroke often experience contralesional and ipsilesional arm motor deficits. The aim of this study was to compare fine and gross motor hand dexterity of the ipsilesional hand post-stroke with controls, normative values, and the contralesional hand. DESIGN: Data were collected from right-handed individuals with chronic stroke (n = 20), age-/sex-matched controls (n = 10), and normative values (n = 20) performing the Nine-Hole Peg Test and the Box and Blocks Test. RESULTS: Individuals with stroke demonstrated poorer performance with the ipsilesional arm relative to both the control group (mean difference [95% confidence interval]: Nine-Hole Peg Test [seconds], 3.4 [-0.5 to 7.3]; Box and Blocks Test [number of blocks], -12.3 [-20.3 to -4.2]) and normative values (mean difference [95% confidence interval]: Nine-Hole Peg Test [seconds], 6.5 [4.0-9.1]; Box and Blocks Test (number of blocks), -15.3 [-20.1 to -10.5]). Ipsilesional arm performance was significantly better than performance with the contralesional arm (mean difference [95% confidence interval]: Nine-Hole Peg Test [seconds], -9.4 [-20.2 to 1.4]; Box and Blocks Test (number of blocks), 33.2 [20.9-45.5]). CONCLUSION: These findings identify residual deficits in fine and gross dexterity of the ipsilesional hand in commonly used outcome measures of hand manipulation among individuals with chronic stroke. Possible underlying mechanisms and clinical relevance are discussed.

A bioengineered organotypic prostate model for the study of tumor microenvironment-induced immune cell activation.

The prostate tumor microenvironment (TME) is strongly immunosuppressive; it is largely driven by alteration in cell phenotypes (i.e. tumor-associated macrophages and exhausted cytotoxic T cells) that result in pro-tumorigenic conditions and tumor growth. A greater understanding into how these altered immune cell phenotypes are developed and could potentially be reversed would provide important insights into improved treatment efficacy for prostate cancer. Here, we report a microfluidic model of the prostate TME that mimics prostate ducts across various stages of prostate cancer progression, with associated stroma and immune cells. Using this platform, we exposed immune cells to a benign prostate TME or a metastatic prostate TME and investigated their metabolism, gene and cytokine expression. Immune cells exposed to the metastatic TME showed metabolic differences with a higher redox ratio indicating a switch to a more glycolytic metabolic profile. These cells also increased expression of pro-tumor response cytokines that have been shown to increase cell migration and angiogenesis such as Interleukin-1 (IL-1) a and Granulocyte-macrophage colony-stimulating factor (GM-CSF). Lastly, we observed decreased TLR, STAT signaling and TRAIL expression, suggesting that phenotypes derived from exposure to the metastatic TME could have an impaired anti-tumor response. This platform could provide a valuable tool for studying immune cell phenotypes in in vitro tumor microenvironments.

Engineered Perineural Vascular Plexus for Modeling Developmental Toxicity.

There is a vital need to develop in vitro models of the developing human brain to recapitulate the biological effects that toxic compounds have on the brain. To model perineural vascular plexus (PNVP) in vitro, which is a key stage in embryonic development, human embryonic stem cells (hESC)-derived endothelial cells (ECs), neural progenitor cells, and microglia (MG) with primary pericytes (PCs) in synthetic hydrogels in a custom-designed microfluidics device are cocultured. The formation of a vascular plexus that includes networks of ECs (CD31+, VE-cadherin+), MG (IBA1+), and PCs (PDGFRß+), and an overlying neuronal layer that includes differentiated neuronal cells (ßIII Tubulin+, GFAP+) and radial glia (Nestin+, Notch2NL+), are characterized. Increased brain-derived neurotrophic factor secretion and differential metabolite secretion by the vascular plexus and the neuronal cells over time are consistent with PNVP functionality. Multiple concentrations of developmental toxicants (teratogens, microglial disruptor, and vascular network disruptors) significantly reduce the migration of ECs and MG toward the neuronal layer, inhibit formation of the vascular network, and decrease vascular endothelial growth factor A (VEGFA) secretion. By quantifying 3D cell migration, metabolic activity, vascular network disruption, and cytotoxicity, the PNVP model may be a useful tool to make physiologically relevant predictions of developmental toxicity.

Sensorimotor performance is improved by targeted memory reactivation during a daytime nap in healthy older adults.

Sensorimotor consolidation occurs during sleep. However, the benefit of sleep-based consolidation decreases with age due to decreased sleep quality and quantity. This study aimed to enhance sensorimotor performance through repetitive delivery of task-based auditory cues during sleep, known as targeted memory reactivation (TMR). Healthy older adults performed a non-dominant arm throwing task before and after a 1 h nap. While napping, half of participants received TMR throughout the hour. Participants who received TMR during sleep demonstrated a greater overall change in throwing accuracy from the start of the first to the end of the second throwing task session. However, there was no generalization of throwing accuracy to variants of the task or to a novel dart throwing task. Findings support the use of TMR during sleep to enhance task-specific sensorimotor performance in healthy older adults despite age-related decreases in sleep quality and quantity. Future research is needed to evaluate the effects of TMR on rehabilitation protocols.

Modeling chemical effects on breast cancer: the importance of the microenvironment in vitro.

Accumulating evidence suggests that our ability to predict chemical effects on breast cancer is limited by a lack of physiologically relevant in vitro models; the typical in vitro breast cancer model consists of the cancer cell and excludes the mammary microenvironment. As the effects of the microenvironment on cancer cell behavior becomes more understood, researchers have called for the integration of the microenvironment into in vitro chemical testing systems. However, given the complexity of the microenvironment and the variety of platforms to choose from, identifying the essential parameters to include in a chemical testing platform is challenging. This review discusses the need for more complex in vitro breast cancer models and outlines different approaches used to model breast cancer in vitro. We provide examples of the microenvironment modulating breast cancer cell responses to chemicals and discuss strategies to help pinpoint what components should be included in a model.

Systematic Review Investigating the Effects of Nonpharmacological Interventions During Sleep to Enhance Physical Rehabilitation Outcomes in People With Neurological Diagnoses.

OBJECTIVE: Conduct a systematic review of nonpharmacological interventions applied during sleep to enhance physical rehabilitation outcomes of individuals with a neurological diagnosis. DATA SOURCES: Three online databases were searched for original research. STUDY SELECTION: Intervention studies were included that used outcome measures of impairment, activity, and/or participation. DATA EXTRACTION: Two reviewers independently screened 2287 titles and abstracts, reviewed 101 full texts, extracted data, and assessed study quality and risk of bias for 9 included studies. DATA SYNTHESIS: All included studies were randomized controlled trials involving continuous positive airway pressure (CPAP) with inpatient individuals with stroke and sleep apnea. Several studies also included long-term outpatient follow-ups. Results in terms of outcomes based on impairment, activity, and participation were mixed. However, several studies found that the use of CPAP following stroke and sleep apnea during early stroke recovery had benefits relative to no CPAP. CONCLUSIONS: The only nonpharmacological intervention to be administered during sleep in a neurological population to improve physical rehabilitation outcomes was found to be CPAP. This review was complicated by the variety of outcome measures used, lack of physical rehabilitation description, and CPAP compliance. In general, participants who had acceptable to good CPAP compliance saw the largest improvements in physical rehabilitation outcomes. Several other promising methods of brain stimulation during sleep are discussed.

Mammary adipose stromal cells derived from obese women reduce sensitivity to the aromatase inhibitor anastrazole in an organotypic breast model.

Aromatase inhibitors are the preferred treatment for certain women with estrogen receptor (ER)-positive breast cancer, but evidence suggests that women with obesity experience aromatase inhibitor resistance at higher rates. To compare how stromal cells derived from women who are lean or obese influence response to the aromatase inhibitor (anastrazole), we incorporated patient-derived stroma in a previously characterized MCF7-derived in vitro duct model. Coculture with adipose stromal cells enabled the metabolism of testosterone (T) to E2, which induced estrogen response element activity, epithelial proliferation, and hyperplasia in MCF7 cells. The effects of T were inhibited by the ER antagonist tamoxifen and aromatase inhibitor anastrazole and were increased by the aromatase inducer dexamethasone. Primary mammary adipose stromal cells derived from women with obesity displayed increased aromatase mRNA compared with lean controls. MCF7-derived ducts cocultured with obese stromal cells exhibited higher maximal aromatization-induced ER transactivation and reduced anastrazole sensitivity, a difference not seen in 2-dimensional coculture. Finally, tamoxifen was more effective than anastrazole at reducing aromatization-induced ER transactivation and proliferation. These findings suggest that patient-specific responses to hormone therapies can be modeled and studied organotypically in vitro and add to evidence advocating obesity as a parameter to consider when identifying treatments for patients with ER-positive breast cancer.-Morgan, M. M., Arendt, L. M., Alarid, E. T., Beebe, D. J., Johnson, B. P. Mammary adipose stromal cells derived from obese women reduce sensitivity to the aromatase inhibitor anastrazole in an organotypic breast model.