Large Groups Of Cells Research Articles

Diagnostic Agreement in Whole Slide Digital Images ofCervical Cytology and Cell Blocks.

Cell blocks (CB) are an established technique in non-gynecological cytology, but experience in gynecological cytology is still relatively limited. In this study, we compared the diagnostic agreement between liquid-based cytology (LBC) and CB using whole slide digital imaging (WSI). WSI of 82 specimens (41 LBC and 41 CB) were evaluated independently by three observers. The overall agreement was 0.463 for all 82 cases including both LBC and CB, 0.439 for LBC alone, and 0.484 for CB alone. Agreement was highest for HSIL, NILM, cancers and lower for borderline (ASC-US, ASC-H). There was no significant difference in agreement between LBC and CB. WSI of CB can be used for the diagnosis of cervical lesions and may be particularly useful in cases with high atypical cellularity or large hyperchromatic cell groups.

In Situ Magnetometry of Iron in Human Dopaminergic Neurons Using Superresolution MRI and Ion-Beam Microscopy

Paramagnetic transition metals play a crucial role as cofactors in various cellular catalytic processes. However, their high concentrations in reactive oxidation states can induce oxidative stress, resulting in cell dysfunction or death. Hence, it is vital to have methods to monitor metal concentrations and paramagnetic properties in cells for medicine and cell biology. Here we present a novel multimodal method for in-cell magnetometry enabling direct measurement of metal magnetic properties within individual cells in tissue, without prior isolation and at room temperature. Individual cell magnetic moments are measured using superresolution magnetic resonance imaging (MRI) microscopy at 9.4 T by detecting microscopic magnetic-field perturbations around the cells. The cellular metal content is quantified using ion-beam microscopy or synchrotron micro-x-ray fluorescence for the same cells. The metal magnetic susceptibility at 9.4 T is then obtained from the slope of the cell magnetic moments’ dependence on cell metal content. To estimate the susceptibility at lower fields, multifield MR relaxometry and biophysical modeling are employed, extrapolating the 9.4-T susceptibility values to fields as low as 3 T. We apply the new method to determine the susceptibility of iron accumulated in human dopaminergic neurons inside neuromelanin, the by-product of dopamine synthesis. The susceptibility of iron in neuromelanin is measured to be χρ=(2.98±0.19)×10−6 m3/kg providing unique insights into the biochemistry of iron inside dopaminergic neurons. The obtained value reveals a predominant monoatomic low-affinity iron-binding site within neuromelanin, indicating a higher neurotoxicity of iron than previously suggested. Furthermore, the measured susceptibility value establishes a quantitative relationship between cellular iron concentration and iron-sensitive MRI parameters, which can be noninvasively measured . This breakthrough paves the way for the detection of dopaminergic neuron density and iron load, requiring a standard clinical MRI scanner only. It promises to facilitate early diagnosis of Parkinson’s disease. In conclusion, our presented novel method enables the direct measurements of magnetic properties of paramagnetic metals within single cells with high sensitivity and across large cell groups within a macroscopic volume, providing invaluable information about the cellular biology of metals. Published by the American Physical Society 2024

Proportion of dead cells in phytoplankton modulates community structure

The growth and death of phytoplankton are two key processes that affect structure and function of marine ecosystem. However, current understanding is elaborated from the perspective of growth, and relatively little is known about the environment-driven death of phytoplankton. Our study is aimed to elucidate the differences in group-specific proportion of dead cells and their effects on community structure. Based on flow cytometry analysis, the proportion of dead cells among eukaryotic phytoplankton groups was analyzed in the oligotrophic South China Sea. The eukaryotic phytoplankton were divided into five groups (eukaryotic group 1, eukaryotic group 2, eukaryotic group 3, cryptophytes, and eukaryotic group 4) with successively larger cell size from pico to micro. The larger cells (from nano to micro size) had a higher proportion of dead cells and a lower relative abundance. Only the group of large cells showed a complete correspondence between the proportion of dead cells and abundance in the vertical profile. Above the deep chlorophyll maximum layer, death induced by nutrient limitation was apparent in most groups, and the larger the cell size, the greater the limitation. Below the deep chlorophyll maximum layer, all groups were light-limited, but differences in the degree of light limitation among groups were not significant. These results suggested that differences in cell size contribute to some extent to differences in the proportion of dead cells among groups, making the proportion of dead cells important in regulating community structure and thus further influencing the structure and function of pelagic marine ecosystems.

Astrocytes in ischemic stroke: Crosstalk in central nervous system and therapeutic potential.

In the central nervous system (CNS), a large group of glial cells called astrocytes play important roles in both physiological and disease conditions. Astrocytes participate in the formation of neurovascular units and interact closely with other cells of the CNS, such as microglia and neurons. Stroke is a global disease with high mortality and disability rate, most of which are ischemic stroke. Significant strides in understanding astrocytes have been made over the past few decades. Astrocytes respond strongly to ischemic stroke through a process known as activation or reactivity. Given the important role played by reactive astrocytes (RAs) in different spatial and temporal aspects of ischemic stroke, there is a growing interest in the potential therapeutic role of astrocytes. Currently, interventions targeting astrocytes, such as mediating astrocyte polarization, reducing edema, regulating glial scar formation, and reprogramming astrocytes, have been proven in modulating the progression of ischemic stroke. The aforementioned potential interventions on astrocytes and the crosstalk between astrocytes and other cells of the CNS will be summarized in this review.

Cis-inhibition suppresses basal Notch signaling during sensory organ precursor selection

The emergence of the sensory organ precursor (SOP) from an equivalence group in Drosophila is a paradigm for studying single-cell fate specification through Notch-mediated lateral inhibition. Yet, it remains unclear how only a single SOP is selected from a relatively large group of cells. We show here that a critical aspect of SOP selection is controlled by cis-inhibition (CI), whereby the Notch ligands, Delta (Dl), cis-inhibit Notch receptors in the same cell. Based on the observation that the mammalian ligand Dl-like 1 cannot cis-inhibit Notch in Drosophila, we probe the role of CI in vivo. We develop a mathematical model for SOP selection where Dl activity is independently regulated by the ubiquitin ligases Neuralized and Mindbomb1. We show theoretically and experimentally that Mindbomb1 induces basal Notch activity, which is suppressed by CI. Our results highlight the trade-off between basal Notch activity and CI as a mechanism for singling out a SOP from a large equivalence group.

Electric field-guided collective motility initiation of large epidermal cell groups.

Recent research has elucidated mechanochemical pathways of single cell polarization, but much less is known about collective motility initiation in adhesive cell groups. We used galvanotactic assays of zebrafish keratocyte cell groups, pharmacological perturbations, electric field switches, particle imaging velocimetry, and cell tracking to show that large cell groups initiate motility in minutes toward the cathode. Interestingly, while PI3K-inhibited single cells are biased toward the anode, inhibiting PI3K does not affect the cathode-directed cell group migration. We observed that control groups had the fastest cathode-migrating cell at the front, while the front cells in PI3K-inhibited groups were the slowest. Both control and PI3K-inhibited groups rapidly repolarized when the electric field direction was reversed, and the group migration continued after the electric field was switched off. Inhibiting myosin disrupted the cohesiveness of keratocyte groups and abolished the collective directionality and ability to switch direction when the electric field is reversed. Our data are consistent with a model according to which cells in the group sense the electric field individually and mechanical integration of the cells results in coherent group motility.

Liquid-based cytology: Technical aspects.

Liquid-based cytology (LBC) is a monolayer slide preparation technology that has outperformed conventional Pap smears because of improved fixation, decreased obscuring factors, and standardized cell transfer. In LBC, samples are collected by completely immersing the sampling device into the company vial containing preservative fluid, whereby the cells are preserved and fixed simultaneously unlike conventional smears where the sample is smeared onto the glass slide and fixed separately. To date, two major liquid-based preparation methods are known – ThinPrep and SurePath. These two methods are different in their principles of cell harvesting but produce similar preparations. SurePath works on the principle of density gradient sedimentation. In this, a sample is vortexed and strained to break the mucus and large cell groups and then is treated through a density gradient centrifugation process to remove blood and debris. The cell pellet is resuspended and is allowed to sediment onto a glass slide. This is followed by staining on the PrepStain instrument. Government Medical College and Hospital, Nagpur, India, uses the SurePath method which was approved by FDA in the USA in 1999. Our institution uses Rovers Cervex-Brush to collect the cells from the transformation zone. This chapter describes the principle of SurePath and the processing of cervicovaginal specimen using the fully automated system in the laboratory.

Collective elastic properties of mechanical metamaterials

Recent studies of the unusual frequency–wavenumber dependences and the related phenomena of the negative effective mass and stiffness in phononic metamaterials unveiled many futuristic opportunities for the acoustical and heat transfer engineering [1], [2], [3], [4], [5]. They also facilitated investigations of quasistatic responses of architected material systems in a quest for negative elastic moduli [6], [7], [8], [9], [10] and other unusual basic properties [11], [12], [13], [14], [15] expected at uniform loading conditions. In this letter, we show that materials with discrete internal structure may also demonstrate strong dependences of their effective (continuum equivalent) mechanical properties on the wavenumber/spatial frequency of static sinusoidal pressure waves. The Fourier mode stiffness, a ratio of the periodic load amplitude and a response amplitude is a quadratic function of the load’s wavenumber in continuum materials. However, in discrete periodic lattices, we show it to be a squared sine function of the wavenumber, which flattens down when the wavelength becomes comparable with a unit cell size. As a result, comparing similarly loaded continuum and lattice materials leads to a varying dependence of the effective longitudinal and shear moduli on the wavenumber. Practically, this means that both material design and static load patterning can influence an effective elastic modulus of a mechanical metamaterial, and it can be seen from collective responses of a large group of unit cells.

HDirect-MAP: projection-free single-cell modeling of response to checkpoint immunotherapy.

There is a lack of robust generalizable predictive biomarkers of response to immune checkpoint blockade in multiple types of cancer. We develop hDirect-MAP, an algorithm that maps T cells into a shared high-dimensional (HD) expression space of diverse T cell functional signatures in which cells group by the common T cell phenotypes rather than dimensional reduced features or a distorted view of these features. Using projection-free single-cell modeling, hDirect-MAP first removed a large group of cells that did not contribute to response and then clearly distinguished T cells into response-specific subpopulations that were defined by critical T cell functional markers of strong differential expression patterns. We found that these grouped cells cannot be distinguished by dimensional-reduction algorithms but are blended by diluted expression patterns. Moreover, these identified response-specific T cell subpopulations enabled a generalizable prediction by their HD metrics. Tested using five single-cell RNA-seq or mass cytometry datasets from basal cell carcinoma, squamous cell carcinoma and melanoma, hDirect-MAP demonstrated common response-specific T cell phenotypes that defined a generalizable and accurate predictive biomarker.

Propensity for Early Metastatic Spread in Breast Cancer: Role of Tumor Vascularization Features and Tumor Immune Infiltrate

Simple SummaryNeoangiogenesis and different components of tumor microenvironment exert crucial roles in early metastatic spreading of breast cancer. Due to the paucity of available factors for breast cancer that can estimate the risk of metastasis or response to a given treatment, there is an important need for new, additional biomarkers of the tumor stroma that can be prognostic and predictive at the early stages of the disease. This review is focused on the current understanding of breast tumor environment characteristics (tumor vasculature and immune infiltrate) in order to incorporate them in diagnostic algorithms together with the assessment of hormone receptors (ER and PR) and of HER2 status.Breast cancer is a complex and highly heterogeneous disease consisting of various subtypes. It is classified into human epidermal growth receptor 2 (HER-2)-enriched, luminal A, luminal B and basal-like/triple negative (TNBC) breast cancer, based on histological and molecular features. At present, clinical decision-making in breast cancer is focused only on the assessment of tumor cells; nevertheless, it has been recognized that the tumor microenvironment (TME) plays a critical biologic role in breast cancer. This is constituted by a large group of immune and non-immune cells, but also by non-cellular components, such as several cytokines. TME is deeply involved in angiogenesis, immune-evasion strategies, and propensity for early metastatic spread, impacting on prognosis and prediction of response to specific treatments. In this review, we focused our attention on the early morphological changes of tumor microenvironment (tumor vasculature features, presence of immune and non-immune cells infiltrating the stroma, levels of cytokines) during breast cancer development. At the same time, we correlate these characteristics with early metastatic propensity (defined as synchronous metastasis or early recurrence) with particular attention to breast cancer subtypes.

Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers

BackgroundThe clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated.MethodsImmunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs.ResultsThirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01).ConclusionLarge cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.

Taking Cellular Heterogeneity Into Consideration When Modeling Astrocyte Involvement in Amyotrophic Lateral Sclerosis Using Human Induced Pluripotent Stem Cells.

Astrocytes are a large group of glial cells that perform a variety of physiological functions in the nervous system. They provide trophic, as well as structural, support to neuronal cells. Astrocytes are also involved in neuroinflammatory processes contributing to neuronal dysfunction and death. Growing evidence suggests important roles for astrocytes in non-cell autonomous mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Understanding these mechanisms necessitates the combined use of animal and human cell-based experimental model systems, at least in part because human astrocytes display a number of unique features that cannot be recapitulated in animal models. Human induced pluripotent stem cell (hiPSC)-based approaches provide the opportunity to generate disease-relevant human astrocytes to investigate the roles of these cells in ALS. These approaches are facing the growing recognition that there are heterogenous populations of astrocytes in the nervous system which are not functionally equivalent. This review will discuss the importance of taking astrocyte heterogeneity into consideration when designing hiPSC-based strategies aimed at generating the most informative preparations to study the contribution of astrocytes to ALS pathophysiology.

DIAGNOSTIC CAPABILITIES OF FINE NEEDLE ASPIRATION OF LYMPH NODES METASTASES OF PRIMARY PULMONARY LYMPHOEPITHELIAL CARCINOMAS

Introduction. Primary pulmonary lymphoepithelial carcinoma is a poorly differentiated squamous cell carcinoma admixed with variable amounts of lymphoplasmacytic infiltrate, frequently associated with EBV. It is a rare cancer and have a better prognosis than other non-small cell lung cancer. The tumor can mimic metastatic non-keratinizing SCC of the naso-pharynx, poorly differentiated non-small cell carcinoma and NUT carcinoma arising in the lung, and non-Hodgkin lymphomas. Materials and methods. A 75-year-old man presented with peripheral mass of left lower lobe, maximal diameter was 5.1 cm, involving lingula and medial pleura, with mediastinal, and retroperitoneal lymphadenopathy revealed by computer tomography. Fine needle aspiration-EBUS was performed from hilar and interlobar lymph nodes. Papanicolaou smears and cell blocks were prepared. Additional CT-guided cor-needle biopsy and FNA were performed from lung lesion later. Results. A few large malignant epithelial cells, consistent with non-small lung cancer, were found on a background of lymphocytes in fine-needle aspiration from lymph nodes. Immunostain results: Pan-CK (AE1/AE3), p63 and Ki67 were positive in malignant cells, leukocyte common antigen (CD45) was positive in lymphocytes (negative in tumor cells), and negative markers were TTF1, chromogranin and synaptophysin. Cytological diagnosis was metastatic non-small lung cancer, favor squamous cell carcinoma. Biopsy and aspiration from left lung showed syncytial groups of large malignant epithelial cells with scant cytoplasm and prominent nucleoli on a background of prominent inflammatory infiltrate,consistent with lymphoepithelial carcinoma. Conclusion. It is impossible to correctly diagnose metastasis of lymphoepithelial carcinoma in lymph node by FNA only without FNA or biopsy of primary lesion, because cytological features and immunostains are identical to non-keratinizing squamous cell carcinoma.

The covariance perceptron: A new paradigm for classification and processing of time series in recurrent neuronal networks.

Learning in neuronal networks has developed in many directions, in particular to reproduce cognitive tasks like image recognition and speech processing. Implementations have been inspired by stereotypical neuronal responses like tuning curves in the visual system, where, for example, ON/OFF cells fire or not depending on the contrast in their receptive fields. Classical models of neuronal networks therefore map a set of input signals to a set of activity levels in the output of the network. Each category of inputs is thereby predominantly characterized by its mean. In the case of time series, fluctuations around this mean constitute noise in this view. For this paradigm, the high variability exhibited by the cortical activity may thus imply limitations or constraints, which have been discussed for many years. For example, the need for averaging neuronal activity over long periods or large groups of cells to assess a robust mean and to diminish the effect of noise correlations. To reconcile robust computations with variable neuronal activity, we here propose a conceptual change of perspective by employing variability of activity as the basis for stimulus-related information to be learned by neurons, rather than merely being the noise that corrupts the mean signal. In this new paradigm both afferent and recurrent weights in a network are tuned to shape the input-output mapping for covariances, the second-order statistics of the fluctuating activity. When including time lags, covariance patterns define a natural metric for time series that capture their propagating nature. We develop the theory for classification of time series based on their spatio-temporal covariances, which reflect dynamical properties. We demonstrate that recurrent connectivity is able to transform information contained in the temporal structure of the signal into spatial covariances. Finally, we use the MNIST database to show how the covariance perceptron can capture specific second-order statistical patterns generated by moving digits.

Short Chain Fatty Acid Transporter/Receptor Expression and Signaling in Enteric Glial Cells

Abstract Objectives The enteric nervous system (ENS) independently coordinates gastrointestinal functions such as motility, secretion, and absorption. Enteric glial cells (EGCs), the largest group of cells within the ENS, secrete neurotrophic factors that support enteric neurons and epithelial growth factors that promote integrity of the intestinal epithelial barrier. Although numerous studies have examined the effect of short chain fatty acids (SCFAs) on functional properties of several intestinal cell types, including enterocytes, enteroendocrine cells, and gut immune cells, no studies to date have examined if and how SCFA influence EGCs. We sought to determine: (1) if EGCs have the capacity to respond to SCFAs; (2) signaling pathways downstream of SCFA transporters/receptors are active in EGCs. Methods Experiments were performed in a stably transformed enteroglial cell line (Ruhl et al., 1998). Cells were treated with propionate (0–10 mM), butyrate (0–5 mM), AR420626 (an FFAR3 agonist), or an FFAR2 agonist. Activation of transporters and receptors was assessed using Western blotting for acetylation and phosphorylation state of proteins downstream of the receptors. Expression of SCFA transporters and receptors was assessed using quantitative PCR. Results Basal expression of monocarboxylate transporter (MCT)-1 and MCT-4, as well as the G-protein coupled receptors FFAR2 and FFAR3 was detected, with expression levels of MCT-1 the highest. GPR109a and Olfr920 were not present in these cells. Butyrate treatment for 2 hours significantly elevated levels of acetylated histone H2B and H3 (P &amp;lt; 0.05), but not histone H2A, suggesting that this SCFA is transported across the plasma membrane to exert intracellular effects. Neither SCFAs nor AR420626 blocked forskolin-induced phosphorylation of protein kinase A (PKA), suggesting that FFAR3 signaling is not active in EGCs. Butyrate, but not the FFAR2 agonist, significantly increased phosphorylation of protein kinase C (PKC) (P &amp;lt; 0.05), suggesting that signaling pathways independent of FFAR2 are triggered by SCFA in EGCs. Conclusions Our preliminary evidence suggests that SCFAs are internalized by EGCs and affect intracellular signaling events. Future studies will determine the implications of histone deacetylation and PKC activation by SCFA on EGC function. Funding Sources University of Winnipeg Major Research Grant.

Is the Role of Ideologists Central in Terrorist Networks? A Social Network Analysis of Indonesian Terrorist Groups.

This study aims to describe how group leaders operate with their social ties of jihadi terrorists, using social network analysis. Data was collected through documents and interviews from terrorist detainees who were involved in jihadi terrorism activities in Indonesia. We found that relational trust with operational leaders plays an important role in terrorist social networks. More specifically, operational leaders possess a higher degree of centrality and betweenness centrality compared to ideological leaders, as operational leaders happened to possess stronger social ties (with close friends or respected authorities). Furthermore, we also found that terrorist networks in Indonesia consist of a large group of cells with low density, where members are not strongly connected to each other. The only bridges that were strong in these social networks were those involving operational leaders. This study confirmed previous studies that terrorist groups operate in a cell system, but lead to a novel finding that ideological leaders may play a limited or indirect influence in operational networks.

Abstract A55: Pancreatic stellate cells promote pancreatic cancer invasion and metastasis by secretion of soluble factors and through contact-mediated mechanisms

Abstract Pancreatic ductal adenocarcinoma (PDAC) is rarely detected early, instead presenting in patients as advanced metastatic disease once symptoms are evident. Given the central role of metastasis in pancreatic tumor progression and mortality, there is an urgent need for further investigation of how PDAC metastasizes and for novel treatment strategies targeting PDAC metastasis. A prominent histopathologic feature of PDAC is a desmoplastic, fibrotic stroma consisting of extracellular matrix components, immune cells, and activated fibroblasts termed “pancreatic stellate cells” (PSCs) that often compose a majority of cellular content in many PDAC tumors. Data from recent studies demonstrate multiple phenotypic PSC populations in the stroma (Ohlund et al., 2017); however, the influence of individual PSC populations on metastasis and disease progression is not fully understood. We hypothesized that PSCs promote pancreatic tumor metastasis through secretion of soluble factors and accompany these metastasizing tumor cells to distal sites using collective invasion mechanisms. Tumor spheroids were formed by centrifugation of HPAC cells (a human PDAC cell line) in low adhesion round bottom plates. Spheroids were embedded in both collagen- and Matrigel-based matrices and z-stacks were collected every 24hrs for 72hrs using a Lecia SP8 confocal microscope. Live cell imaging was performed in an incubation chamber for 72hrs using a Leica SP8 confocal microscope. Human pancreatic stellate cells were isolated from surgically resected tumor specimens at Emory University Hospital under IRB-approved protocols and grown to ~70% confluency before supernatants were collected. Utilizing innovative 3D invasion assays, we demonstrate the ability of human PSC conditioned media to initiate and promote invasion of HPAC pancreatic tumor spheroids. HPAC spheroids exposed to 10% PSC supernatants showed significantly decreased roundness in comparison to media alone. Further investigation of possible soluble factors mediating this interaction indicated a protein-based interaction, although alternative mechanisms by which metastasis may be initiated were also identified. Phenotypic analysis of invasion through live cell imaging led to observations of unique invasion mechanisms by which hyperactive cells at the leading edge seemingly guide invasion of large groups of cells. Additionally, we observed co-culture interactions between PSCs and HPAC cells. In comparison to HPAC cells alone, ratios of 10:1 PSCs to HPAC cells increased circularity (less invasive) while inverse ratios decreased circularity of spheroids (more invasive). This study supports the hypothesis that PSCs can promote collective invasion and migration of pancreatic tumor cells through both contact-dependent and -independent means. Further identification of mechanisms mediating this interaction may reveal novel therapeutic targets for the treatment of PDAC and present new strategies for targeting metastasis of this deadly disease. Citation Format: Michael B. Ware, Jerry Yue, Bassel El-Rayes, Shishir K. Maithel, Juan Sarmiento, Gregory B. Lesinski. Pancreatic stellate cells promote pancreatic cancer invasion and metastasis by secretion of soluble factors and through contact-mediated mechanisms [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A55.

Biomechanical modeling of invasive breast carcinoma under a dynamic change in cell phenotype: collective migration of large groups of cells.

According to recent studies, cancer is an evolving complex ecosystem. It means that tumor cells are well differentiated and involved in heterotypic interactions with their microenvironment competing for available resources to proliferate and survive. In this paper, we propose a chemo-mechanical model for the growth of specific subtypes of an invasive breast carcinoma. The model suggests that a carcinoma is a heterogeneous entity comprising cells of different phenotypes, which perform different functions in a tumor. Every cell is represented by an elastic polygon changing its form and size under pressure from the tissue. The mechanical model is based on the elastic potential energy of the tissue including the effects of contractile forces within the cell perimeter and the elastic resistance to stretching or compressing the cell with respect to the reference area. A tissue can evolve via mechanisms of cell division and intercalation. The phenotype of each cell is determined by its environment and can dynamically change via an epithelial-mesenchymal transition and vice versa. The phenotype defines the cell adhesion to the adjacent tissue and the ability to divide. In this part, we focus on the forms of collective migration of large groups of cells. Numerical simulations show the different architectural subtypes of invasive carcinoma. For each communication, we examine the dynamics of the cell population and evaluate the complexity of the pattern in terms of the synergistic paradigm. The patterns are compared with the morphological structures previously identified in clinical studies.

A LATE DIAGNOSIS OF A PRIMARY INTEROSSEOUS SQUAMOUS CELL CARCINOMA: A CASE REPORT

<h3>Background</h3> Primary intraosseous squamous cell carcinoma is a rare malignant central jaw tumor derived from odontogenic epithelial remnants. It predominantly affects the mandible, although both jawbones may be involved. <h3>Objective(s)</h3> The purpose of this article was to represent the clinical, radiologic, and microscopic characteristics of a late diagnosed primary interosseous squamous cell carcinoma (PIOSCC). This case adds to the very few cases of PIOSCC in the literature. <h3>Study Design</h3> This case report describes a 60-year-old man who was initially misdiagnosed with a periapical infection related to the right lower wisdom tooth, that is, an infected odontogenic cyst of the mandible. After 4 months, the patient presented to a private dental clinic with a large swelling at the right side of the mandible. <h3>Results</h3> Extraoral examination revealed a swelling with paresthesia in the right mandibular angle. A panoramic radiograph was requested and revealed a complete erosion of the right ramus with an extension of the lesion to the body of the mandible. Advanced imaging revealed a large, ill-defined, right facial soft tissue mass lesion measuring 8.8 × 4.5 × 5 cm. The microscopic examination revealed fibrofatty tissue infiltrated by a tumor mass formed of solid groups of large pleomorphic atypical squamous cells with high nuclear-to-cytoplasmic ratio and focal intracytoplasmic keratin formation. The diagnosis was PIOSCC. <h3>Discussion/Conclusions</h3> Radiologic and clinical characteristics of PIOSCCs are similar to those of benign odontogenic cysts and tumors. In certain cases, early-stage PIOSCC may mimic routine dental disorders, such as periapical and periodontal disease, which may lead to misdiagnosis or delayed diagnosis. Clinicians must be aware that PIOSCC may initially present as a routine dental disorder, and that unsuccessful treatment may be a sign of underlying malignancy.

A Comprehensive Methodology to Evaluate Losses and Process Variations in Silicon Solar Cell Manufacturing

Novel, high-throughput metrology methods are used in this paper for detailed performance loss analysis of approximately 400 industrial crystalline silicon solar cells, all coming from the same production line. The characterization sequence combines traditional global cell measurements (e.g., current–voltage, Suns- ${V}_{\text{OC}}$ ) with camera-based cell imaging of voltage distribution and power dissipation from photoluminescence and lock-in thermography, respectively. Spatial variations in current collection are visualized using a high-speed external quantum efficiency and reflectance measurement technique. A nondestructive transfer length method (TLM) measurement technique is also implemented, featuring circular TLM structures hidden within the busbars of the cells. The variance of individual loss parameters and their impact on cell performance are quantified for this large group of cells. Based on correlations performed across parameters, recombination losses in the bulk and rear surface of the cell are shown to be the primary limiting factor for the cell efficiency. The nature of these distributions and correlations provide important insights about loss mechanisms in industrial solar cells, helping to prioritize efforts for optimizing the performance of the production line. Additionally, many of the parameters extracted from these techniques can be tied back to incoming material quality issues (e.g., poor bulk carrier lifetime, nonuniform wafer doping) and to individual unit processes (e.g., texturing, phosphorus diffusion, silicon nitride deposition, metallization), allowing the data to be used directly for process control in manufacturing. All of the datasets are made available for download.