Sharp Border Research Articles

Heterozygosity for loss-of-function variants in LZTR1 is associated with isolated multiple café-au-lait macules

PurposePathogenic LZTR1 variants cause schwannomatosis and dominant/recessive Noonan syndrome (NS). We aim to establish an association between heterozygous loss-of-function LZTR1 alleles and isolated multiple café-au-lait macules (CaLMs). MethodsA total of 849 unrelated participants with multiple CaLMs, lacking pathogenic/likely pathogenic NF1 and SPRED1 variants, underwent RASopathy gene panel sequencing. Data on 125 individuals with heterozygous LZTR1 variants were collected for characterizing their clinical features and the associated molecular spectrum. In vitro functional assessment was performed on a representative panel of missense variants and small in-frame deletions. ResultsAnalysis revealed heterozygous LZTR1 variants in 6.0% (51/849) of participants, exceeding the general population prevalence. LZTR1-related CaLMs varied in number, displayed sharp or irregular borders, and were generally isolated but occasionally associated with features recurring in RASopathies. In 2 families, CaLMs and schwannomas co-occurred. The molecular spectrum mainly consisted of truncating variants, indicating loss-of-function. These variants substantially overlapped with those occurring in schwannomatosis and recessive NS. Functional characterization showed accelerated protein degradation or mislocalization, and failure to downregulate mitogen-activated protein kinase signaling. ConclusionOur findings expand the phenotypic variability associated with LZTR1 variants, which, in addition to conferring susceptibility to schwannomatosis and causing dominant and recessive NS, occur in individuals with isolated multiple CaLMs.

A Comparative Study of Efficacy between Oral Tranexamic Acid with Fluocinolone-Based Triple Combination Cream Versus Fluocinolone-Based Triple Combination Cream Alone in Melasma

Introduction: Melasma is an acquired, chronic, recurrent hyper-pigmentary disorder characterized by symmetric light-brown to bluish-gray macules and patches with irregular, sharp borders. The term “melasma” is derived from the Greek word “melas,” meaning black, while “chloasma” refers to its occurrence during pregnancy, derived from “chloazein,” meaning green. Clinically, melasma predominantly affects the face, including the forehead, cheeks, temples, upper lip, chin, and nose. Methods: This cross-sectional study was conducted on 60 clinically diagnosed cases of melasma attending the Skin and VD outpatient department of Combined Military Hospital (CMH), Dhaka, Bangladesh from January 2020 to June 2020. Result: Ages of the patient at onset of melasma, in majority (56.67%) cases were between 20-25 years and 90% study population was female. Most (56.67%) of the patients were housewife. Regarding the distribution of melasma 50% were found malar, 46.67% centro-facial and 3.33% mandibular. By 12 weeks, Group A's mean MASI score further reduced to 6.995 ± 6.056, and Group B's score decreased significantly to 2.19 ± 2.378. The P value of 0.00 confirms a statistically significant difference between the groups at 12 weeks. Conclusion: In conclusion, our study demonstrates that oral tranexamic acid in combination with fluocinolone-based triple combination cream is significantly more effective in treating facial melasma than the cream alone.

Genotype-relevant neuroimaging features in low-grade epilepsy-associated tumors.

Low-grade epilepsy-associated tumors are the second most common histopathological diagnoses in cases of drug-resistant focal epilepsy. However, the connection between neuroimaging features and genetic alterations in these tumors is unclear, prompting an investigation into genotype-relevant neuroimaging characteristics. This study retrospectively analyzed neuroimaging and surgical specimens from 46 epilepsy patients with low-grade epilepsy-associated neuroepithelial tumors that had genetic mutations identified through panel sequencing to investigate their relationship to genotypes. Three distinct neuroimaging groups were established: Group 1 had indistinct borders and iso T1-weighted and slightly high or high T2-weighted signal intensities without a diffuse mass effect, associated with 93.8% sensitivity and 100% specificity to BRAF V600E mutations; Group 2 exhibited sharp borders and very or slightly low T1-weighted and very high T2-weighted signal intensities with a diffuse mass effect and 100% sensitivity and specificity for FGFR1 mutations; and Group 3 displayed various characteristics. Histopathological diagnoses including diffuse low-grade glioma and ganglioglioma showed no clear association with genotypes. Notably, postoperative seizure-free rates were higher in Group 1 tumors (BRAF V600E) than in Group 2 tumors (FGFR1). These findings suggest that tumor genotype may be predicted by neuroimaging before surgery, providing insights for personalized treatment approaches.

Spatial Single-cell Analysis Decodes Cortical Layer and Area Specification.

The human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas1,2. The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization3,4. While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation5,6,7,8. Here, we utilized multiplexed error-robust fluorescence in situ hybridization (MERFISH)9, augmented with deep-learning-based cell segmentation, to examine the molecular, cellular, and cytoarchitectural development of human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing 16 million single cells, spans eight cortical areas across four time points in the second and third trimesters. We uncovered an early establishment of the six-layer structure, identifiable in the laminar distribution of excitatory neuronal subtypes by mid-gestation, long before the emergence of cytoarchitectural layers. Notably, while anterior-posterior gradients of neuronal subtypes were generally observed in most cortical areas, a striking exception was the sharp molecular border between primary (V1) and secondary visual cortices (V2) at gestational week 20. Here we discovered an abrupt binary shift in neuronal subtype specification at the earliest stages, challenging the notion that continuous morphogen gradients dictate mid-gestation cortical arealization6,10. Moreover, integrating single-nuclei RNA-sequencing and in situ whole transcriptomics revealed an early upregulation of synaptogenesis in V1-specific Layer 4 neurons, suggesting a role of synaptogenesis in this discrete border formation. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This work not only provides a valuable resource for the field, but also establishes a spatially resolved single-cell analysis paradigm that paves the way for a comprehensive developmental atlas of the human brain.

Impact of electron beam welding on the microstructure of PM2000 ODS steel

This work investigated the impact of electron beam (EB) welding, using various traverse speeds of the electron beam (1200–2200 mm/min), on the microstructure of PM2000 ODS steel which was characterized using analytical electron microscopy and microhardness. The different heat inputs during welding explored in this study (72–39 J/mm), related to the traverse speed used, correlated with small differences in the widths of the fusion zone. Only minor differences in local microstructures and hardness of the fusion zones were detected amongst the four butt welds produced. The fusion zone is characterized by large columnar grains in the ferritic matrix, together with a coarsened Y-Al-O particle distribution and a reduction in its particle number density as compared to the base material. There is also a sharp border between the fusion zone and base material, with the joint showing little evidence of a heat-affected zone. These changes in microstructure during welding led to a hardness reduction of ∼30 % in the fusion zone of the welds with respect to the base material.

Pseudosquamous Adenocarcinoma of the Lung: Clinicopathologic and Immunohistochemical Study of 10 Cases.

Pseudosquamous adenocarcinoma of the lung is an unusual morphologic variant of poorly differentiated non-small cell lung carcinoma that superficially resembles a squamous cell carcinoma. We have examined 10 cases of these tumors in 4 women and 6 men, aged 47 to 93 years. The tumors were all peripheral and measured from 1.5 to 5.5cm. All cases were characterized by solid nests of large polygonal tumor cells containing atypical nuclei with abundant cytoplasm and sharp cell borders, adopting a pavement-like architecture that simulated squamous cell carcinoma. Some cases demonstrated intracytoplasmic hyaline inclusions suggestive of keratinization. The nests of tumor cells often showed central comedo-like areas of necrosis. Intercellular bridges were not seen in any of the cases. The tumors often displayed marked clearing of the cytoplasm enhancing their epidermoid appearance. In 4 cases, the solid pseudosquamous areas were seen to merge with a focal lepidic adenocarcinoma component, and in 1 case, abortive microscopic foci of acinar differentiation were also noted within the tumor. One case showed focal sarcomatoid spindle cell areas. The tumor cells were negative for p40 and CK5/6 and labeled with TTF1 or Napsin-A, confirming an adenocarcinoma phenotype. Clinical follow-up information was available in 8 patients; 6 patients died of their tumors between 6 months to 11 years after diagnosis (mean: 3.1y). One patient died of complications related to surgery and one patient with a low-stage tumor died at 27 years from other causes. Solid pattern adenocarcinomas can be confused for squamous cell carcinoma and may require immunohistochemistry to determine their true phenotype.

ОСНОВНЫЕ И ДОПОЛНИТЕЛЬНЫЕ ПРИЗНАКИ В ОСНОВЕ ДИАГНОСТИКИ ДЕСКВАМАТИВНОГО ГИНГИВИТА ПРИ КРАСНОМ ПЛОСКОМ ЛИШАЕ СЛИЗИСТОЙ ОБОЛОЧКИ РТА

The most characteristic manifestations of desquamative gingivitis are bright hyperemia, the appearance of blisters of various sizes on the free and attached gum and erosion. This type of lesion can occur in diseases such as lichen planus, pemphigus, systemic lupus erythematosus. Despite the manifesting clinical picture, difficulties arise at the clinical reception in diagnosing both the symptom itself and the underlying disease. All this increases the interest in studying the main and additional clinical signs of specific gum lesions in lichen planus of the oral mucosa. In this paper, the manifestations of the signs of desquamative gingivitis observed by us in various forms of lichen planus are presented in detail, the main and additional signs of specific gingival lesions are highlighted, which make it possible to increase the effectiveness of the primary diagnosis of specific gingival lesions in patients with diseases of the oral mucosa.
 Subject of the study. To systematize the main and additional signs of forms of desquamative gingivitis with lichen planus of the oral mucosa.
 Purpose of the study. Identify and describe the main and additional clinical signs of forms of desquamative gingivitis in the red lichen planus of the oral mucosa.
 Methodology. The analysis of complaints, anamnesis, results of clinical and laboratory examination methods was carried out, photographs of clinical manifestations on the mucous membrane and the red border of the lips of the main and additional signs of a specific lesion of the gum were studied in detail.
 Results. The conducted clinical study made it possible to identify and describe in detail the main (bright hyperemia with sharp borders, uneven nature of the lesion, the spread of the process to the gum in the area of missing teeth, etc.) and additional clinical manifestations (papules, blisters, hemorrhages, dryness, epithelial atrophy) of desquamative gingivitis in all forms of red lichen planus of the oral mucosa.
 Conclusions. Knowledge of the identified signs will increase the effectiveness of the primary diagnosis of specific gum lesions.

The Impact of Host Language Proficiency on Migrants’ Employment Outcomes

This paper estimates the economic gains from proficiency in the host country’s language on migrants’ employment outcomes by exploiting the exogenous placement of refugees to Swiss cantons and a sharp language border dividing German- and French-speaking regions. Using administrative data on African refugees who applied for Swiss asylum between 2008 and 2017, I compare French-speaking refugees assigned to the French-speaking region to French-speaking refugees assigned to the German-speaking region and adjust for common regional differences with outcomes from English-speaking African refugees. The results suggest that language proficiency more than doubles the employment level in the first five years after arrival. (JEL J15, J24, J31, J82, R23)

Dermatoscopic Patterns in Vitiligo.

Vitiligo is a chronic, acquired autoimmune pigmentary skin disease, most times it can be diagnosed clinically. Dermoscopy can confirm vitiligo in a non-invasive way. It is a diagnostic technique that visualizes sub-macroscopic morphological structures which correspond with specific histological structures. It detects subtle changes in the pigment pattern, evaluates vitiligo activity, attempts of re-pigmentation, leucotrichia, and differentiates it from other hypo pigmentary disorders. Most dermatoscopic clues used to assess vitiligo activity are found at the perifollicular level in the center and edge of the lesion. Perifollicular pigmentation is present in both active lesions and treated pigmented lesions with treatment. However, perifollicular depigmentation represents poor response, in treated lesions, and poor prognosis in untreated ones. The center of the lesion has reduced and/or absent pigment network, in active and stable lesions. If on dermoscopy the center of the lesion shows islands of pigment, erythema, or telangiectasias, re-pigmentation is suggested. At the periphery of the lesion, unstable vitiligo usually shows up as a diffuse border, trichrome pattern, micro-Koebner/comet tail phenomenon, satellite lesions, or a tapioca sago pattern. In stable lesions it is more frequent to find well defined or trichromic border. Pigmented lesions commonly present sharp borders and marginal or perilesional hyperpigmentation.

Observer- and radiomics model-based computed tomography classification of suppurative versus tuberculous lymphadenitis complicated with nodal necrosis of the neck in children.

Computed tomography (CT) can be used for the early detection of lymphadenitis. Radiomics is able to identify a large amount of hidden information from images. However, few CT-based radiomics studies on cervical lymphadenitis in children have been published. This study aimed to investigate the role of visual CT analysis and CT radiomics in differentiating cervical suppurative node necrosis from tuberculous node necrosis in pediatric patients. A total of 101 patients with cervical suppurative lymphadenitis (n=52) or cervical tuberculous lymphadenitis (n=49) were included. Clinical data and CT images were retrieved for analysis. For visual observation, 11 major CT features were identified for univariate and multivariate analyses. For radiomics analysis, image segmentation, feature value extraction, and dimension reduction, feature selection and the construction of radiomics-based models were performed through the RadCloud platform. For the visual observation, significant differences were found between the two groups, including the short diameter of the largest necrotic lymph node (P=0.03), sharp border of the node (P=0.02), fusion of nodes (P=0.02), regular silhouette of the necrotic area (P=0.001), multilocular necrotic area (P=0.02), node calcification (P=0.004), and enhancement degree of the nodal nonnecrotic area (P=0.01). No feature was found to be an independent predictor for suppurative or tuberculous lymphadenitis (P>0.05 for all features). Concerning the radiomics analysis, after feature value extraction and dimension reduction, nine related features were selected. The support vector machine classifier achieved high diagnostic performance in distinguishing suppurative from tuberculous lymphadenitis. The area under the curve, accuracy, sensitivity, and specificity of the support vector machine model test set were 0.89 (95% confidence interval: 0.72-1.00), 0.88, 0.78, and 0.90, respectively. Compared to observer-based CT image analyses, radiomics model-based CT image analyses exhibit better performance in the differential diagnosis of cervical suppurative and tuberculous lymphadenitis complicated with nodal necrosis in children.

Using CT Radiomics and Machine Learning to Distinguish Radiotherapy vs. Immune Checkpoint Inhibitor-Induced Pneumonitis in Non-Small Cell Lung Cancer Patients

Both radiotherapy (RT) and immune checkpoint inhibitors (ICIs) may induce pneumonitis which is difficult to distinguish clinically. We tested the utility of computed tomography (CT) in identifying the cause of pneumonitis in patients with non-small cell lung cancer (NSCLC) who received RT, ICIs and RT combined with ICIs (RT+ICIs). In this study, we analyzed the clinical characteristics and CT morphology of 130 NSCLC patients who developed pneumonitis after receipt of ICIs only (n = 50), thoracic RT only (n = 50) (ICIs only + RT only, the training cohort, n = 100), and RT+ICIs (the test cohort, n = 30). CT radiomics features were extracted using 3D-Slicer software and selected using LASSO regression for training a random forest (RF) classifier and a linear discriminant analysis (LDA) classifier to discern pneumonitis etiology. Patients who received RT or ICIs only were defined as the training cohort since the cause of their pneumonitis was readily identifiable. Patients who received RT+ICIs were defined as the test cohort and the cause of their pneumonitis were determined by clinicians as the ground truth. In the study, the median time from the initiation of treatment to pneumonitis was 1.9 months in RT+ICIs patients, which was shorter than 2.5 months in RT only and 2.7 months in ICIs only patients. In addition, the patients in RT+ICIs group have more high grade (grade 3-4) pneumonitis compared to patients in ICIs only or RT only group (p<0.05). Pneumonitis after the combined therapy was not a simple superposition mode of RP and CIP, resulting in the distinct characteristics of both RT and ICIs-related pneumonitis. (1) Some cases resembled RP with sharp borders in the ipsilateral lung and others resembled the bilateral distribution of typical CIP, while some patients exhibit an intermediate morphology; (2) Some pneumonitis occurred in the areas of low and medium doses of radiation rather than the high-dose radiation areas similar to RP; (3) Some pneumonitis was initially limited to the ipsilateral lung that had received radiation and then developed in bilateral lungs. The RF classifier showed favorable discrimination between CIP and RP with an area under the receiver operating curve (AUC) of 0.859 (95% CI: 0.7884-0.9292) in the training cohort and 0.851 (95% CI: 0.6998-1) in the test cohort. The simplified LDA classifier consisting of 7 LASSO-selected features achieved an AUC of 0.881 (95% CI: 0.815-0.947) in the training cohort and 0.842 (95% CI: 0.686-0.997) in the test cohort. RT and ICIs-related pneumonitis exhibit distinct clinical characteristics and morphologic features on CT. CT radiomics-based classifiers could provide a noninvasive method to identify the predominant etiology in NSCLC patients who developed pneumonitis after thoracic RT and ICIs.

The Role of CT-Based Radiomics Nomogram in Differential Diagnosis of Immune Checkpoint Inhibitor-Related Pneumonitis from Radiation Pneumonitis for Patients with ESCC

The combination of immunotherapy and chemoradiotherapy has widely used for patients with esophageal squamous cell carcinoma (ESCC) and induced treatment-related adverse effects, particularly immune checkpoint inhibitor-related pneumonitis (CIP) and radiation pneumonitis (RP). The aim of this study is to differentiate between CIP and RP by the CT radiomics and clinical or radiological parameters. A total of 76 ESCC patients with pneumonitis were enrolled in this retrospective study and divided into training dataset (n = 53) and validation dataset (n = 23). A total of 837 radiomics features were extracted from regions of interest (ROIs) based on the lung parenchyma window of CT images. A radiomics signature was constructed on the basis of the predictive features by the least absolute shrinkage and selection operator (LASSO). A logistic regression was applied to develop radiomics nomogram. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were applied to evaluate the performance of pneumonitis etiology identification. No significant difference was detected between training dataset and validation dataset. The radiomics signature which was made up of four radiomics features shown a favorable performance on differentiating between CIP and RP with the α-binormal-based and empirical AUC = 0.831 and 0.843. Patients with RP had a close relationship with location (p = 0.003) and shape of lesions (p = 0.002). The nomogram that combined with radiomics signature and clinical factors improved the classifying performance on discrimination in the training dataset (AUCαbin = 0.963 and AUCemp = 0.964). The results were verified in the validation dataset with AUC = 0.967 and 0.964. CT-based radiomics features have potential values for differentiating between patients with CIP and RP. Addition of bilateral changes and sharp border produced superior model performance on classifying, which could be a useful method to improve related clinical decision-making.

Evaluation of Micro-Needling Followed by Tranexamic Acid Cream versus Micro-Needling Followed by Tranexamic Acid Solution in Treatment of Melasma: A Comparative Split Face Study

Abstract Background Melasma is a common pigmentary disorder clinically characterized by symmetric light brown to bluish-gray macules and patches with irregular, sharp borders that affect cutaneous areas, particularly the face and neck. It is commonly identified in women of reproductive ages and more commonly described in darker-skinned patients with Fitzpatrick skin types IV to VI residing in high-intensity ultraviolet radiation worldwide. It causes significant cosmetic disfigurement, psychosocial stress, and embarrassment, affecting patients’ quality of life. Objectives To evaluate the efficacy and safety of microneedling followed by tranexamic acid (TXA) cream application versus microneedling followed by tranexamic acid solution in the treatment of facial melasma. Patients and Methods This prospective split-face comparative study included thirty female patients with different types of melasma, their ages ranged from 25 to 40 years. They were recruited from the Dermatology outpatient clinic of Ain Shams University Hospitals. All patients have been treated with TXA for 3 sessions; one session every month (the right side of the face was treated by microneedling followed by TXA 5 % cream while the left side of the face was treated by microneedling followed by TXA solution 5%). Additionally, the right side of the face was treated with TXA 5% cream, and the left side applied with placebo cream twice daily for 3 months. Assessment was done by Hemi Melasma Area and Severity Index score (Hemi -MASI), patients’ satisfaction score, clinical digital photography, dermoscopic examination and area percentage of melanin concentration assessed by histopathological examination. Results Our findings showed significant improvement in different types of melasma regarding Hemi MASI score, patients’ satisfaction score, and area percentage of melanin concentration assessed by histopathological examination by Fontana-Masson stain (FM) one month after 3rd treatment session in both sides of the face. However, a minor melasma recurrence was observed two months after 3rd treatment session on both sides of the face. Meanwhile, no significant difference was observed in the treatment response of microneedling followed by TXA cream versus microneedling followed by TXA solution one month after 1st and 2nd sessions regarding Hemi MASI score, while a significant difference was observed one month after the 3rd session. Conclusion Topical TXA appears to be a promising therapeutic option in the treatment of melasma without serious adverse effects. Topical TXA cream, which was applied twice daily by the patient combined with microneedling sessions with TXA cream, has better results in comparison with microneedling sessions with TXA solution with placebo cream.

TALL CELL VARIANT PAPILLARY THYROID CARCINOMA IN A PEDIATRICPATIENT: A CASE REPORT AND REVIEW OF THE LITERATURE

Paediatric thyroid cancer is uncommon and classical papillary carcinoma is the most represented histological type. Variant high cell papillary carcinoma (VHCPC) is an extremely rare entity in the paediatric age group, aggressive and a marker of poor prognosis, as well as poor survival. The presence and percentage of a minority high cell contingent should be mentioned in the histopathological report. We report the case of a 9-year-old female patient with no previous history of cancer who presented with a 5 cm long left cervical nodule. Macroscopic examination showed the presence of several poorly bounded, fleshy, homogeneous beige coloured, non-encapsulated nodules. On microscopic examination, the tumour showed a papillary, focally solid architecture. The tumour cells were 2-3 times taller than they were wide, with abundant eosinophilic cytoplasm, sharp borders, and oval nuclei, with incisions and numerous intranuclear pseudo inclusions. The tumour protruded beyond the thyroid capsule and came into contact with the surgical borders, with the presence of vascular emboli. Our work aims to highlight the anatomopathological and diagnostic particularities of this sub-variant of papillary carcinoma.

Current State and Prospects for Development of Head Lighting for Vehicles. Part 2. Advanced Designs for Vehicle Headlights

As it has been shown in part 1 of this paper, modern head lighting, due to objective design flaws, does not always meet the requirements of existing international standards, which means a decrease in road safety. To eliminate the previously Multibeam type. These types of headlights are currently either undergoing the stage of production tests or are used in extremely limited batches of vehicles in terms of the number of produced units. According with the results of this analysis, recommendations have been formulated for the design of advanced head lighting. The main of these recommendations is the use of single high-power LEDs with total internal reflection reflectors, which will provide a sharp cut-off border with efficient use of the source light flux. To increase the resistance of the headlight to temperature rise, it is proposed to use LEDs or other economical light sources together with phosphor parts. It is shown that adaptability is a useful but optional property of vehicle headlights, since it leads to complicate the design, and this is not always justified. The advantages of the headlight, created taking into account the above recommendations, are described, the main of which are the simplification of its design, reduction in weight and improvement of the thermal parameters of the product.

158 Controlling Glioblastoma Invasion In Vivo With CD97

INTRODUCTION: Increased levels of adhesion G Protein-Coupled Receptor (GPCR) CD97 have been detected in multiple metastatic cancers. Glioblastoma (GBM), a Grade-IV Glioma, also overexpress this receptor, and its levels positively correlate with more aggressive GBM invasion. METHODS: CD97 consists of two distinct domains: the large extracellular fragment interacting with ECM and other cell surface receptors and the GPCR core that activates heterotrimeric G Proteins G12/13. To investigate the mechanism of action of CD97, we generated a CD97 knockdown (shCD97) and overexpression (CD97-WT) constructs. Additionally, we generated two functional mutants: a constitutively active mutant lacking the N-Terminus (dNTF) and dominant-negative mutant (H436A) that cannot activate G-Proteins downstream. Glioma Stem Cells (GSC) were transduced by control and CD97 lentiviral constructs and implanted into mouse brains. Once tumors formed the brains were harvested, sliced, and immunostained to evaluate invasion and proliferation. Comparing mutants to control, dunnett’s multiple comparisons test was used for statistical analysis. RESULTS: Similar to CD97-WT, we found that both dNTF and H436A, increase tumor volume (p &lt; 0.05). In contrast, the shCD97 mutant decreased tumor size (p &lt; 0.05). Interestingly, only dNTF significantly increased tumor cell proliferation (p &lt; 0.005), yet CD97-WT and H436A affected proliferation of non-tumor cells in the tumor bulk, indicating that this process requires the N-Terminus Fragment. In addition, over-expression of CD97-WT dramatically increases tumor invasion along myelinated fibers of corpus collosum, and tumor spread in the brain tissue (p &lt; 0.05). Yet, the H436A mutant produced large, compact, and non-invasive tumors with sharp borders (p &lt; 0.05) indicating that cell migration requires activation of G12/13. Surprisingly, immunostaining revealed that CD97 knockdown cells displayed invasive phenotype. CONCLUSIONS: Our results demonstrate the dual role CD97 plays in GBM invasion and proliferation, alluding to the molecular mechanisms that can potentially be targeted in GBM treatment.

Is Geography Destiny? A Deleuzoguattarian Reading of The Little Black Fish

Samad Behrangi, who is known as one of the most significant revolutionary writers of modern literature in Iran, wrote The Little Black Fish in 1968. It is a world-famous children’s story that has been translated into many languages. The story is considered to be a political allegory that traces the adventures of a little black fish that seeks liberty. The fish decides to leave his homeland in order to find an alternative geography that will bestow him freedom. However, the act of migration from a tiny pool to a vast sea is not an easy task. The fish faces many hardships, including his family’s resistance and the various difficulties on his way. Samad Behrangi’s story profoundly shows the road to freedom is full of obstacles. In this perspective, it is possible to argue that the fish’s desire to reach the sea is a symbolic endeavor to create a new perception of a place that allows him to decentralize the sharp borders of his constructed identity. The journey provides the fish with an opportunity to interact with external milieus and to reinforce certain aspects of his life that help him to build a multidimensional identity. The fish does not fall into the stable and the assigned categories of individuality, but rather he is a multiple and always-in-process character. Within this framework, the fish’s journey aligns with Deleuze and Guattari’s concept of the “becoming” process. Behrangi shows how the fish breaks away from the normative codes of his society and transforms into a boundless and free individual. Deleuze and Guattari maintain that the multiplicity of becoming is always “dwelling within us” (1980, p.240). Therefore, as we see in the character of the fish, the process of becoming is a continual transformation, and it creates a permanent desire for change.

ANGI-07. THE DUAL ROLE CD97 PLAYS IN GLIOBLASTOMA INVASION AND PROLIFERATION

Abstract INTRODUCTION Increased levels of adhesion G Protein-Coupled Receptor(GPCR) CD97 have been detected in multiple metastatic cancers. Glioblastoma(GBM), also overexpress this receptor, and its levels positively correlate with more aggressive GBM invasion. Here, using primary human GBM cells we investigated the effects of CD97 knockdown and overexpression in-vitro and in-vivo. METHODS CD97 consists of two distinct domains: the large extracellular fragment interacting with ECM and other cell surface receptors and the GPCR core that activates heterotrimeric G Proteins G12/13. To investigate the mechanism of action of CD97, we generated a CD97 knockdown (shCD97) and overexpression (CD97-WT) constructs. Additionally, we generated two functional mutants: a constitutively active mutant lacking the N-Terminus (dNTF) and dominant-negative mutant (H436A) that cannot activate G-Proteins downstream. Glioma Stem Cells(GSC) were transduced by control and CD97 lentiviral constructs and implanted into mouse brains. Once tumors formed the brains were harvested, sliced, and immunostained to evaluate invasion and proliferation. Comparing mutants to control, dunnett’s multiple comparisons test was used for statistical analysis. RESULTS Similar to CD97-WT, we found that both dNTF and H436A, increase tumor volume(p&amp;lt; 0.05). In contrast, the shCD97 mutant decreased tumor size(p&amp;lt; 0.05). Interestingly, only dNTF significantly increased tumor cell proliferation(p&amp;lt; 0.005), yet CD97-WT and H436A affected proliferation of non-tumor cells in the tumor bulk, indicating that this process requires the N-Terminus Fragment. In addition, over-expression of CD97-WT dramatically increases tumor invasion along myelinated fibers of corpus collosum, and tumor spread in the brain tissue(p&amp;lt; 0.05). Yet, the H436A mutant produced large, compact, and non-invasive tumors with sharp borders(p&amp;lt; 0.05) indicating that cell migration requires activation of G12/13. Surprisingly, immunostaining revealed that CD97 knockdown cells displayed invasive phenotype. CONCLUSIONS Our results demonstrate the dual role CD97 plays in GBM invasion and proliferation, alluding to the molecular mechanisms that can potentially be targeted in GBM treatment.

An Extremely Rare Case of Renal Collision Tumor Comprised of Hyperpigmented Microcystic Chromophobe Renal Cell Carcinoma and Papillary Renal Cell Carcinoma

Abstract Introduction/Objective Renal collision tumors are rare lesions defined as the coexistence of two adjacent but histologically distinct tumors with sharp borders forming a single lesion. A combination of chromophobe renal cell carcinoma (ChRCC) and papillary renal cell carcinoma (RCC) is extremely rare. Here we report a collision tumor of hyperpigmented microcystic ChRCC, an uncommon variant of ChRCC, and papillary RCC. To our knowledge, it is the first reported case of this particular combination. Methods/Case Report A 70-year-old male with aortic stenosis presented with dyspnea and renal insufficiency. A renal mass was discovered incidentally. MRI characterized the left renal mass as 7.2 cm and bilobed. Radical nephrectomy was performed. Grossly, the tumor was located in the upper pole and consisted of two distinct components separated by fibrous tissue: a 5.4 cm black/orange mottled tumor and an adjacent 5.0 cm yellow lobulated tumor. Histologically, the larger tumor displayed a microcystic and solid pattern comprised of large cells with pale cytoplasm, hyperchromatic wrinkled nuclei, perinuclear halos, prominent cell membranes, and extensive intracellular and extracellular brown-black pigment, consistent with hyperpigmented microcystic ChRCC. The adjacent tumor showed diagnostic features of papillary RCC including papillae with fibrovascular cores lined by columnar cells with low nuclear grade, abundant macrophages, and foci of psammomatous calcifications. The hyperpigmented microcystic ChRCC was positive for CD117 and negative for Melan-A. Papillary RCC was strongly positive for Cytokeratin7 and Vimentin. Results (if a Case Study enter NA) N/A Conclusion Meticulous examination of the histologic features, aided by immunohistochemistry, can generate an accurate diagnosis of collision tumor and direct to the appropriate treatment choice.

Natural history of pulmonary coccidioidomycosis: Further examination of the VA-Armed Forces Database.

There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis (CM), including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955 to 1958, followed through 1966, who did not receive antifungal therapy. Patients were grouped by predominant pulmonary finding on chest radiographs. The all-cause mortality was low for all patients (4.6%). Cavities had a median size of 3-3.9cm (IQR: 2-2.9-4-4.9cm), with heterogeneous wall thickness and no fluid level, while nodules had a median size of 1-1.19cm (Interquartile range [IQR] 1-1.9-2-2.9cm) and sharp borders. The majority of cavities were chronic (85.6%), and just under half were found incidentally. Median complement fixation titers in both the nodular and cavitary groups were negative, with higher titers in the cavitary group overall. This retrospective cohort study of non-disseminated coccidioidomycosis, the largest to date, sheds light on the natural history, serologic markers, and radiologic characteristics of this understudied disease. These findings have implications for the evaluation and management of CM.