bluuebunny/crossref_metadata_2025 huggingface dataset:
Historical and contemporary views on cholera transmission: are we repeating past discussions? Can lessons learned from cholera be applied to COVID‐19?
Authors: Jensen Peter Kjær Mackie , Grant Stephen Lawrence , Perner Mads Linnet , Hossain Zenat Zebin , Ferdous Jannatul , Sultana Rebeca , Almeida Sara , Phelps Matthew , Begum Anowara
Published: March 2021

Cholera, a devastating diarrheal disease that caused several global pandemics in the last centuries, may share some similarities with the new COVID‐19. Cholera has affected many populations in history and still remains a significant burden in developing countries. The main transmission route was thought to be predominantly through contaminated drinking water. However, revisiting the historical data collected during the Copenhagen 1853 cholera outbreak allowed us to re‐evaluate the role of drinking‐water transmission in a city‐wide outbreak and reconsider some critical transmission routes, which have been neglected since the time of John Snow. Recent empirical and cohort data from Bangladesh also strengthened the dynamic potentiality of other transmission routes (food, fomite, fish, flies) for transmitting cholera. Analyzing this particular nature of the cholera disease transmission, this paper will describe how the pattern of transmission routes are similar to COVID‐19 and how the method of revisiting old data can be used for further exploration of new and known diseases.
Corticosteroid delivery using oral mucosa equivalents for the treatment of inflammatory mucosal diseases
Authors: Said Zulfahmi , Murdoch Craig , Hansen Jens , Siim Madsen Lars , Colley Helen E.
Published: March 2021

Oral lichen planus (OLP) is an immune‐mediated disease of the oral mucosa with idiopathic aetiology. It is frequently treated with topical corticosteroids (applied as gels, mouthwashes, or sprays); however, the mucosal exposure times of topical corticosteroids are short because of removal by the constant flow of saliva and mechanical forces. In this study we used cell monolayers, as well as oral mucosal equivalents (OMEs) containing activated T‐cells, to examine corticosteroid potency and delivery of clobetasol‐17‐propionate from a novel electrospun mucoadhesive patch. The OMEs displayed tight junctions, desmosomes, hemidesmosomes, and an efficient permeability barrier. Following application of corticosteroids to cells cultured as monolayers, the degree of cytotoxicity measured correlated to the level of potency recognized for each corticosteroid; by contrast, OMEs were largely unaffected by corticosteroid treatment. Permeation of clobetasol‐17‐propionate into and through the OMEs was time‐ and dose‐dependent, regardless of whether this corticosteroid was delivered in liquid form or from a mucoadhesive patch, and both liquid‐ and patch‐delivered clobetasol‐17‐propionate significantly reduced the secretion of interleukin‐2 by activated T‐cells. This study confirms that OMEs are more suitable models than cell monolayers for evaluating toxicity and drug delivery. After topical exposure, clobetasol‐17‐propionate accumulated in OMEs at a higher level than betamethasone‐17‐valerate and hydrocortisone‐17‐valerate, and exerted its immunosuppressive actions following application via the patch delivery system, highlighting the efficacy of this mode of drug delivery to treat OLP.
Exertional heat illness in Thoroughbred racehorses – Pathophysiology, case definition and treatment rationale
Authors: Brownlow M. A. , Mizzi J. X.
Published: March 2021

The combination of extreme heat, humidity and strenuous exercise is potentially challenging to the thermoregulatory system of a Thoroughbred racehorse, and under certain circumstances can cause a condition called exertional heat illness (EHI). It is difficult to predict its occurrence in an individual animal due to the combination on race day of extrinsic and intrinsic risk factors. Education regarding EHI is essential to its prevention, and lack of understanding amongst those responsible for the horse’s care may in fact be the most important risk factor. The pathophysiology of EHI is similar across elite athletic species and is directly related to an elevation in core body temperature that exceeds the ‘critical thermal maximum’, causing widespread destruction of cells. It is not only the high core temperature but also its duration that will dictate outcome. Treatment strategies should decrease the hyperthermia to near normal levels within 30 min of onset, which will minimise adverse consequences. This review article outlines the pathophysiological changes as EHI progresses, and the case definition at each emergent level. Pharmacological treatment strategies and their rationale are presented. Aggressive cooling, however, is the key treatment and requires a technique which is both practical and effective in rapidly reducing core body temperature. The treatment paradigm is early detection, rapid assessment enabling prioritisation of individuals and aggressive cooling. Each stage is critically discussed.
The hospitable body at work—A research agenda
Authors: Zampoukos Kristina
Published: March 2021

This paper critically examines the hospitable body and how it is put to work, how certain bodies are selected and become associated with certain occupations and spaces of work, and how the hospitable body is produced, transformed, and commodified in accordance with prevailing modes of production. Drawing on examples primarily obtained from the Nordic countries, I review current research on hospitality workers, while also manifesting how employers portray and, at times, exploit the hospitable body. This is followed by a presentation of a research agenda for the continued study of the hospitable body at work, addressing the need for in‐depth, context‐sensitive studies on worker strategies to counteract harassment. I conclude by suggesting that the working body can be theorized as concurrently being relational and “in the making,” and as a bounded territory in need of protection against the hazards of flexible work regimes, stress, harassment, and precariousness.
Balloon cell melanoma: a systematic review
Authors: Wei Grace , Hennessy Kerry , Kevin Heard L. , Gaudi Sudeep , Mhaskar Rahul , Patel Rishi R. , Bennett Adam E.
Published: March 2021

Balloon cell melanoma (BCM) is a rare presentation of malignant melanoma characterized by large, foamy melanocytes lacking pigmentation. This is a comprehensive review of the clinical, dermoscopic, and histological features among BCM cases reported in the literature. A systematic review of all case reports and series published since 1970 was conducted via MEDLINE, Embase, and Web of Science, using "balloon cell melanoma" and synonymous search terms. Our systematic search identified 76 cases (49% male, 51% female) of BCM in the literature. The mean age at presentation was 57.81 years. Prior skin cancer, particularly melanoma (47%), accounted for 58% of pertinent medical history. Prominent clinical exam findings included raised (46%), ulcerated (73%) lesions larger than 1 cm (68%) in the lower extremities (35%). Median Breslow thickness of primary BCM cases was 2.5 mm. Hairpin vessels (75%) and structureless architecture (75%) were predominant on dermoscopy. Notable histopathology included large (47%), vacuolated (58%) cells with foamy cytoplasm (62%) and conspicuous nucleoli (27%). Positive S‐100 immunohistochemistry (73%) was most frequently employed to diagnose BCM. We observed 47% primary and 53% metastatic BCM cases. Of metastatic BCMs, balloon cells in the primary lesion were unknown in 48%, devoid in 33%, and present in 20% of cases. All metastases displayed predominant balloon cell morphology. BCM may represent an advanced phase in the progression of malignant melanoma. Improved awareness of BCM characteristics among clinicians may reduce the risk of misdiagnoses.
Associations between fruit juice and milk consumption and change in BMI in a large prospective cohort of U.S. adolescents and preadolescents
Authors: Sakaki Junichi R. , Li Jing , Gao Simiao , Ha Kyungho , Tamimi Rulla M. , Chavarro Jorge E. , Chen Ming‐Hui , Sun Qi , Hart Jaime E. , Chun Ock K.
Published: March 2021

Background

There are concerns that fruit juice and milk contribute to childhood obesity.

Objective

Determine the relationship between fruit juice and milk intakes and body mass index (BMI) change among preadolescents/adolescents.

Methods

Participants aged 9 to 16 years old from the Growing Up Today Study II completed surveys including validated food frequency questionnaires in 2004, 2006 and 2008. The contributions of one serving of juice or milk to total energy intake and 2‐year change in BMI were evaluated using multiple linear regression. Additional analyses were conducted with subgroups of juice (orange juice and other fruit juice) and milk (low fat and high fat). Missing values for BMI were imputed using a multiple imputation approach, after which data from 8173 participants and 13 717 2‐year interval observations were analysed.

Results

Baseline fruit juice consumption was inversely associated with BMI change in girls (β = −.102 kg/m2, SE = 0.038, P value = .008) but not boys after controlling for race, age, baseline BMI, and baseline and 2‐year changes in total energy intake and physical activity. Orange juice was inversely associated with BMI change among girls (β = −.137 kg/m2, SE = 0.053, P value = .010) while other fruit juice, low fat and high fat milk were not associated with BMI change.

Conclusion

Orange juice was inversely associated with 2‐year BMI change among preadolescent/adolescent girls but not boys and there were no significant associations with other juices or milk among either gender.
Connecting sleep, the neurocognitive memory system, and Bourdieu's habitus concept: Is sleep a generative force of the habitus?
Authors: Drews Henning Johannes
Published: March 2021

Bourdieu's habitus theory has been criticized for allegedly being static and deterministic. This is partly due to insufficiently elaborated microstructural aspects of the habitus. Previous works have tried to elaborate the habitus' individual side by drawing on neuropsychological and neuroscientific concepts including the neuropsychological memory system. Despite its relevance for several social processes, sleep has not been considered in this context. The present work investigates the interrelatedness of habitus, sleep, and the memory system with particular focus on the determinism and staticity critique. It shows that the neuropsychological memory system overlaps largely with implicit memory and sleep plays an important role in the formation of habitus‐relevant memory. Moreover, sleep enhances processes such as memory consolidation, reflexivity, associative creativity, and dream‐associated simulation of unknown situations which counter the determinism and staticity critique. The present article argues that habitus, memory, and sleep are closely related and memory and sleep represent operational micro‐structures of the habitus. Moreover, sleep‐related processes represent a generative force that renders the habitus more dynamic. Finally, strengths and weaknesses of the habitus‐memory‐sleep nexus are discussed and further lines of research are outlined.
Identification of Fungal Limonene-3-Hydroxylase for Biotechnological Menthol Production
Authors: Schempp Florence M. , Strobel Ingmar , Etschmann Maria M. W. , Bierwirth Elena , Panten Johannes , Schewe Hendrik , Schrader Jens , Buchhaupt Markus
Published: March 2021

(−)-Menthol is an important flavor and fragrance compound and furthermore has medicinal uses. To realize a two-step synthesis starting from renewable (+)-limonene, a regioselective limonene-3-hydroxylase enzyme is necessary. We identified enzymes from two different fungi which catalyze this hydroxylation reaction and represent an important module for the development of a biotechnological process for (−)-menthol production from renewable (+)-limonene.
Contributions of the Four Essential Entry Glycoproteins to HSV-1 Tropism and the Selection of Entry Routes
Authors: Hilterbrand Adam T. , Daly Raecliffe E. , Heldwein Ekaterina E.
Published: March 2021

Herpes simplex viruses (HSV-1 and HSV-2) contain up to 16 different proteins in their envelopes. Four of these, glycoproteins gB, gD, gH, and gL, are termed essential with regard to entry, whereas the rest are typically referred to as nonessential based on the entry phenotypes of the respective single genetic deletions.
Mathematical Modeling of Population Dynamics Based on Recurrent Equations: Results and Prospects. Part I
Authors: Frisman E. Ya. , Zhdanova O. L. , Kulakov M. P. , Neverova G. P. , Revutskaya O. L.
Published: March 2021

Approaches to modeling population dynamics using discrete-time models are described in this two-part review. The development of the scientific ideas of discrete time models, from the Malthus model to modern population models that take into account many factors affecting the structure and dynamics, is presented. The most important and interesting results of recurrent equation application to biological system analysis obtained by the authors are given. In the first part of this review, the population dynamic effects that result from density-dependent regulation of population, the age and sex structures, and the influence of external factors are considered.
A novel development indicator based on population-average height trajectories of children aged 0–5 years modelled using 145 surveys in 64 countries, 2000–2018
Authors: Ohuma Eric O , Bassani Diego G , Qamar Huma , Yang Seungmi , Roth Daniel E
Published: March 2021

Introduction

Children’s growth status is an important measure commonly used as a proxy indicator of advancements in a country’s health, human capital and economic development. We aimed to assess the feasibility of using Super-Imposition by Translation And Rotation (SITAR) models for summarising population-based cross-sectional height-by-age data of children under 5 years across 64 countries.

Methods

Using 145 publicly available Demographic and Health Surveys of children under 5 years across 64 low-income and middle-income countries from 2000 to 2018, we created a multicountry pseudo-longitudinal dataset of children’s heights.

Results

SITAR models including two parameters (size and intensity) explained 81% of the between-survey variation in mean boys’ height and 80% in mean girls’ height. Size parameters for boys and girls (relative to the WHO child growth standards) were distributed non-normally around a mean of −5.2 cm for boys (range: −7.9 cm to −1.6 cm) and −4.9 cm for girls (range: −7.7 cm to −1.2 cm). Boys exhibited 10% slower linear growth compared with the WHO (range: 19.7% slower to 1.6% faster) and girls 11% slower linear growth compared with the WHO (range: 21.4% slower to 1.0% faster). Variation in the SITAR size parameter was ≥90% explained by the combination of average length within the first 60 days of birth (as a proxy for fetal growth) and intensity, regardless of sex, with much greater contribution by postnatal intensity (r≥0.89 between size and intensity).

Conclusions

SITAR models with two random effects can be used to model child linear growth using multicountry pseudo-longitudinal data, and thereby provide a feasible alternative approach to summarising early childhood height trajectories based on survey data. The SITAR intensity parameter may be a novel indicator for specifically tracking progress in the determinants of postnatal growth in low-income and middle-income countries.
IDH-Based Radiogenomic Characterization of Glioma Using Local Ternary Pattern Descriptor Integrated with Radiographic Features and Random Forest Classifier
Authors: Gore Sonal , Jagtap Jayant
Published: March 2021

Mutations in family of Isocitrate Dehydrogenase (IDH) gene occur early in oncogenesis, especially with glioma brain tumor. Molecular diagnostic of glioma using machine learning has grabbed attention to some extent from last couple of years. The development of molecular-level predictive approach carries great potential in radiogenomic field. But more focused efforts need to be put to develop such approaches. This study aims to develop an integrative genomic diagnostic method to assess the significant utility of textures combined with other radiographic and clinical features for IDH classification of glioma into IDH mutant and IDH wild type. Random forest classifier is used for classification of combined set of clinical features and radiographic features extracted from axial T2-weighted Magnetic Resonance Imaging (MRI) images of low- and high-grade glioma. Such radiogenomic analysis is performed on The Cancer Genome Atlas (TCGA) data of 74 patients of IDH mutant and 104 patients of IDH wild type. Texture features are extracted using uniform, rotation invariant Local Ternary Pattern (LTP) method. Other features such as shape, first-order statistics, image contrast-based, clinical data like age, histologic grade are combined with LTP features for IDH discrimination. Proposed random forest-assisted model achieved an accuracy of 85.89% with multivariate analysis of integrated set of feature descriptors using Glioblastoma and Low-Grade Glioma dataset available with The Cancer Imaging Archive (TCIA). Such an integrated feature analysis using LTP textures and other descriptors can effectively predict molecular class of glioma as IDH mutant and wild type.
Fractional DP-chromatic number of planar graphs of large girth
Authors: Wu Jianglin
Published: March 2021

This paper proves that for any integer [Formula: see text], every planar graph [Formula: see text] of girth at least [Formula: see text] has fractional DP-chromatic number at most [Formula: see text].
NONLINEAR ARDL APPROACH AND PPP: EVIDENCE FROM 82 COUNTRIES
Authors: ARIZE AUGUSTINE C. , BAHMANI-OSKOOEE MOHSEN
Published: March 2021

Since the introduction of asymmetric cointegration and error-correction modeling, old theories have been getting a renewed attention, and purchasing power parity theory (PPP) is no exception. In this paper, we revisit the PPP by applying this relatively new technique. When we applied the symmetric cointegration test of Pesaran et al. [ Pesaran, MH, Y Shin and RJ Smith ( 2001 ). Bounds testing approaches to the analysis of level relationships. Journal of Applied Econometrics, 16(3), 289–326], we found cointegration between the nominal exchange rate and relative prices in 22 out of 82 countries. However, application of the asymmetric cointegration method of Shin et al. [ Shin, Y, B Yu and M Greenwood-Nimmo ( 2014 ). Modelling asymmetric cointegration and dynamic multipliers in a nonlinear ARDL framework. In R. Sickels and W. Horrace (eds.), Festschrift in Honor of Peter Schmidt: Econometric Methods and Applications, pp. 281–314. New York: Springer] increased the number to 51 out of 82 countries. Nonlinear adjustment of relative prices was said to be the main contributing factor.
A theoretical foundation for games of complete/incomplete contracts
Authors: Ma Chenghu , Wong Wing-Keung
Published: March 2021

This paper provides a theoretical foundation for complete/incomplete contracts to extend game theory for multi-agent interactions. We explain why rational agents may agree to sign incomplete contracts even though signing a complete contract incurs no cost. Some arguments claim that an incomplete contract creates strategic uncertainty. Under common assumptions of rationality, an incomplete contract can be the final solution if the agents’ attitudes toward uncertainty are not neutral. Assuming that agents can form coalitions by participating in the game and they are uncertainty averse, we develop equilibrium solutions for complete/incomplete contracts in an extensive game of multi-agent interactions.
Assessment of Noise Levels of Equipment Used in the Practical Dental Teaching Activities
Authors: Amine Meriem , Aljalil Zineb , Redwane Asmaa , Delfag Ikram , Lahby Imane , Bennani Anas
Published: March 2021

Introduction. Practical activities in dentistry are characterized by a high noise level that can have adverse effects on the hearing health of professors, students, and teaching staff. The objective of our study was to make an assessment of the noise level during the practical fixed prosthodontics activities in the Faculty of Dentistry of Casablanca. Materials and Methods. We conducted a descriptive cross-sectional study to measure the noise level in the practical room of fixed prosthodontics. The measurements were obtained during 4 sessions over a duration of 2 hours and 30 minutes, each with the use of a SdB + sound level meter at 4 different locations. Results. The results showed the following: an average value of 69.35 dB (A) for the first practical session (south), an average value of 71.07 dB (A) for the 2nd practical session (east), an average value of 70.36 dB (A) for the 3rd practical session (west), and an average value of 72.06 dB (A) for the 4th practical session (center of the room). Discussion and Conclusion. The results obtained are similar to the results found in previous studies in other countries. These results are below the thresholds of the legislation and international standards. However, we have recorded punctual peaks that exceed the recommended level, requiring the introduction of the means of prevention and the measures of safety against the noise as well at the level of the practical activity classroom and the realization of more in-depth studies concerning the evaluation of the daily exposure of the professors, students, and teaching staff to noise.
Abstract IA005: Immune escape during breast tumor progression
Authors: Polyak Kornelia
Published: March 2021

The drivers of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. We have analyzed genetic, gene expression, epigenetic profiles of cells composing the tumor and identified cell type-specific changes during tumor progression. Importantly, while we could not detect progression stage- stage-specific alterations in tumor epithelial cells, myoepithelial cells and cells composing the microenvironment showed consistent differences between DCIS and IDC. Overall, there is a general decline in intratumor activated GZMB+CD8+ T cells accompanied by changes in innate immune cells that promote tumor outgrowth. We demonstrate that these progression stage-specific alterations are also present in a rat model of breast cancer and that combined targeting of multiple components of the tumor ecosystem increases the efficacy of anti-cancer therapies. Our data highlight the role of microenvironmental, especially immune-related changes in driving breast tumor progression.

Citation Format: Kornelia Polyak. Immune escape during breast tumor progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA005.
Abstract IA012: Engineering precision cancer immunotherapy
Authors: DuPage Michel
Published: March 2021

The treatment of cancer has been revolutionized by the development of immune-based therapies designed to boost the number and function of cytotoxic T cells that kill tumor cells. However, it is already apparent that this strategy alone will not benefit all patients, as the majority of cancers generate a highly immunosuppressive tumor microenvironment (TME) that shuts down even the most potent T cells. Furthermore, as a consequence of ramping up the immune system, these immune stimulating drugs instigate significant autoimmune toxicity. We aim to develop a radical new strategy to circumvent both challenges by identifying immunosuppressive regulatory mechanisms unique to cancerous tissues, thereby uncovering pathways active only in tumors that can be targeted to generate precision cancer immunotherapies that preserve immune tolerance in healthy tissues. The focus will be on Regulatory T cells (Tregs), a subset of immunosuppressive CD4+T cells that lie at the fulcrum of immunity, directing cells of the immune system to go or stop. In cancer, Tregsinfiltrate tumors and dampen anti-tumor immune responses, but Tregs also play an essential role in preventing autoimmunity. This proposal will test the hypothesis that human cancers generate an immunosuppressive TME by enforcing a unique epigenetic program in intratumoral Tregsthat, if identified, could provide new targets to selectively modulate tumor-infiltrating Tregsand limit autoimmunity. To do this, the research will employ genetically engineered mouse (GEM) cancers, an accurate and flexible platform to test the full complement of factors that make up the TME of human cancers, combined with sophisticated genetic tools to track Treg entry and activity in the TME. Our investigations thus far have led us to the investigation of Ezh2 activity, a H3K27 methyltransferase, in defining Treg behavior selectively in the TME.

Citation Format: Michel DuPage. Engineering precision cancer immunotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA012.
Abstract IA020: Mechanics, multinucleation, and EMT
Authors: Nelson Celeste M.
Published: March 2021

Multinucleation is found in more than one third of tumors and is linked to increased tolerance for mutation, resistance to chemotherapy, and invasive potential. The integrity of the genome depends on proper execution of the cell cycle, which can be altered through mechanotransduction pathways as the tumor microenvironment stiffens during tumorigenesis. We recently found that inducers of epithelial-mesenchymal transition (EMT), including transforming growth factor-beta (TGFbeta), also promote multinucleation in stiff microenvironments through Snail-dependent expression of the filament-forming protein septin-6, resulting in midbody persistence, abscission failure, and multinucleation. Consistently, we observed elevated expression of Snail and septin-6 as well as multinucleation in a human patient sample of metaplastic carcinoma of the breast, a rare classification characterized by deposition of collagen fibers and active EMT. In contrast, a soft microenvironment protected mammary epithelial cells from becoming multinucleated by preventing Snail-induced upregulation of septin-6. I will describe data suggesting that tissue stiffening during tumorigenesis synergizes with oncogenic signaling to promote genomic abnormalities that drive cancer progression.

Citation Format: Celeste M. Nelson. Mechanics, multinucleation, and EMT [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA020.
Abstract LT003: Endothelin-1 drives invadopodia and cross-talk with submesothelial matrix invasion cell through ILK
Authors: Masi Ilenia , Caprara Valentina , Spadaro Francesca , Chellini Lidia , Sestito Rosanna , Zancla Andrea , Rainer Alberto , Bagnato Anna , Rosanò Laura
Published: March 2021

During the metastatic progression, invading cells might achieve degradation and invasion into the extracellular matrix (ECM) using invadopodia, actin-based protrusions. Several growth factors, among other stimuli, might induce invadopodia, generating signaling cues implicated from the initial steps of anchoring and protein recruitment to the final steps of matrix degradation or structure dissembling. In this context, the endothelin A receptor (ETAR) a drives invadopodia in serous ovarian cancer (SOC) cells through the scaffolding function of β-arrestin1 (β-arr1), although the coordinated signaling network is not fully explored. Growing evidence demonstrated that integrins and associated proteins, such as integrin-linked kinase (ILK), operate in the same subcellular compartments to control invadopodium maturation and ECM degradation. Since endothelin-1 (ET-1) through ETAR regulated by ILK, in this study whether ET-1/β-arr1-driven ILK signaling could provide additional mean to enhance invadopodium activity in ovarian cancer progression. We found that β-arr1 functions as a linker for ILK/βPIX (Pax-interacting exchange factor beta) complex, required for activation of Rac3 GTPase, emerging at a crossroad between adhesion and proteolytic signaling, resulting to be overexpressed in tumour compared normal ovarian tissues. Rac3 operates the phosphorylation of PAK1 and cofilin, and regulates invadopodia-dependent ECM degradation and invasion. Moreover, ETAR/ILK/Rac3-dependent signaling supports the communication of SOC cells with mesothelial cells, favouring adhesion and transmigration to. In vivo, ambrisentan, an ETAR antagonist, inhibits the adhesion of HG-SOC cells to intraperitoneal organs, and their spreading, associated with a reduction of invadopodia markers. Finally, high ETAR/ILK expression positively correlates with poor prognosis, representing SOC prognostic factors. Our findings uncover a paradigm indicating where ET-1R/β-arr1/ILK pathway integrates adhesive and proteolytic signaling to invadopodia-mediated ECM degradation, favouring cancer-stroma interactions and SOC metastatic behaviour.

Citation Format: Ilenia Masi, Valentina Caprara, Francesca Spadaro, Lidia Chellini, Rosanna Sestito, Andrea Zancla, Alberto Rainer, Anna Bagnato, Laura Rosanò. Endothelin-1 drives invadopodia and cross-talk with submesothelial matrix invasion cell through ILK [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr LT003.
Abstract PO005: Hepatic stellate cells suppress NK cell sustained breast cancer dormancy
Authors: Correia Ana Luisa
Published: March 2021

The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment. These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a singular therapeutic window to prevent metastatic disease, a comprehensive understanding of the distribution, composition and dynamics of dormant DTC reservoirs is imperative. Here we reveal tissue-specific microenvironments that restrain or concede progression of breast cancer in the liver, a frequent site of metastasis and most times associated with patients’ cause of death. Using mouse models, we show that the dormant milieu features a selective accumulation of natural killer (NK) cells. Preserving the NK cell pool with adjuvant interleukin-15-based immunotherapy prevents hepatic metastases and prolongs survival. Exit from dormancy follows a dramatic contraction of the NK cell compartment, and concurrent accumulation of activated stellate cells. Our data identify the interplay between NK cells and activated stellate cells as a master switch of cancer dormancy, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing DTC outgrowth and metastasis.

Citation Format: Ana Luisa Correia. Hepatic stellate cells suppress NK cell sustained breast cancer dormancy [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO005.
Abstract PO007: Role of PI3K pathway in reprogramming the tumor niche of angiosarcoma
Authors: Wenthe Sophia , Schulte Ashley J. , Angelos Mathew G. , Kaufman Dan S. , Modiano Jaime F. , Kim Jong Hyuk
Published: March 2021

Angiosarcoma (AS) is a highly aggressive, rare soft-tissue sarcoma that forms malignant blood vessels. Approximately half of patients have metastatic or unresectable disease with a median overall survival of less than 6 months, and tumor-related mortality is high. Inflamed tissue is frequently seen in angiosarcomas, and immune cells are key components that contribute to the landscape of the tumor microenvironment. Hemangiosarcoma (HSA) occurs commonly in companion dogs, and it shares clinical and morphological features with human AS. Recurrent mutations in TP53 and genes involved in PI3K pathway such as PIK3CA, and PIK3R1 were observed in both human AS and canine HSA, and the mutational landscape was associated with distinct molecular tumor subtypes; in particular, differing immunophenotypes. Recently, we have shown that human AS and canine HSA establish convergent transcriptional programs driven by angiogenic fusion genes and TP53 mutation. However, these vascular tumors are genomically complex, and molecular mechanisms that establish the tumor microenvironment are incompletely known. In this study, we analyzed RNA-seq transcriptomic data generated from human AS tissues (n=13) and canine HSA tissues (n=76) and HSA cell lines (n=11). The data showed that the tumors of both species enriched gene signatures associated with maintenance of hematopoietic stem cells. Then, we found that canine HSA cells supported expansion and differentiation of human CD34+ umbilical cord blood cells using long-term culture-initiating cell and colony-forming unit assays. We also developed xenograft models of canine HSA that facilitate myelopoiesis and macrophage infiltration in the tumor tissue. Our data showed that gene signatures of monocytes and naïve macrophages were detectable in canine HSA cells. In human ASs, macrophage-associated genes, in particular M2 macrophage signatures were significantly enriched, compared to normal tissues. Collectively, our data suggest that human AS and canine HSA have cell-autonomous capacity to govern hematopoietic progenitors and immune cells, potentially establishing the tumor immune niche. We engineered HSA cells to induce homozygous H1047R mutations in PIK3CA gene using CRISPR-Cas9 system. Our ongoing work is to determine if regulating PI3K pathway in the tumor cells contributes to the molecular programs that create the tumor niche of the vascular malignancy.

Citation Format: Sophia Wenthe, Ashley J. Schulte, Mathew G. Angelos, Dan S. Kaufman, Jaime F. Modiano, Jong Hyuk Kim. Role of PI3K pathway in reprogramming the tumor niche of angiosarcoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO007.
Inorganic Nitrite Supplementation Improves Endothelial Function With Aging
Authors: Rossman Matthew J. , Gioscia-Ryan Rachel A. , Santos-Parker Jessica R. , Ziemba Brian P. , Lubieniecki Kara L. , Johnson Lawrence C. , Poliektov Natalie E. , Bispham Nina Z. , Woodward Kayla A. , Nagy Erzsebet E. , Bryan Nathan S. , Reisz Julie A. , D’Alessandro Angelo , Chonchol Michel , Sindler Amy L. , Seals Douglas R.
Published: March 2021

To determine the efficacy of inorganic nitrite supplementation on endothelial function in humans and mechanisms of action, we performed (1) a randomized, placebo-controlled, parallel-group clinical trial with sodium nitrite (80 mg/day, 12 weeks) in older adults (N=49, 68±1 year) and (2) reverse-translation experiments in young (6 months) and old (27 months) c57BL/6 mice. In the clinical trial, sodium nitrite increased plasma nitrite (
P
<0.05) and was well tolerated. Brachial artery flow-mediated dilation (endothelial function) was increased 28% versus baseline after nitrite supplementation (
P
<0.05) but unchanged with placebo. Nitrotyrosine, a marker of oxidative stress, was reduced by 45% versus baseline in biopsied endothelial cells after nitrite, but not placebo, treatment. Plasma from nitrite-treated, but not placebo-treated, subjects decreased whole-cell (CellROX) and mitochondria-specific (MitoSOX) reactive oxygen species in cultured human umbilical vein endothelial cells (
P
<0.05). Old mice (old [27 months] control, n=9) had ≈30% lower ex vivo carotid artery endothelium-dependent dilation (EDD) versus young mice (young [6 months] control, n=9) due to reduced NO bioavailability (
P
<0.05). Nitrite supplementation (drinking water, 50 mg/L, 8 weeks) restored EDD and NO bioavailability in old mice (n=10) to (6 months) control. Mitochondrial reactive oxygen species suppression of EDD was present in old control (increased EDD with a mitochondrial-targeted antioxidant,
P
<0.05) but not in young control or old mice supplemented with sodium nitrite. A mitochondrial reactive oxygen species inducer (rotenone) further impaired EDD in old control (
P
<0.05); young control and old mice supplemented with sodium nitrite were protected. Markers of mitochondrial health were greater in aorta of old mice supplemented with sodium nitrite versus old control (
P
<0.05). Inorganic nitrite supplementation improves endothelial function with aging by increasing NO, decreasing mitochondrial reactive oxygen species/oxidative stress, and increasing mitochondrial stress resistance.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02393742.
Novelties in Malagasy Euphorbia (Euphorbiaceae)
Authors: HAEVERMANS THOMAS , HETTERSCHEID WILBERT L. A.
Published: March 2021

In this paper we clarify the identity and natural distribution of Euphorbia milii by defining an epitype for it, and elevate to specific rank infraspecific names published under E. milii and provide detailed synonymy for taxa reinstated at the specific rank such as Euphorbia splendens, Euphorbia bevilaniensis, Euphorbia hislopii. We publish novelties such as E. cylindroclada, Euphorbia imperatae (including Euphorbia milii forma lutea), Euphorbia pachyspina, Euphorbia tananarivae, and Euphorbia werneri.We also investigate the taxonomy and nomenclature of other Malagasy succulent Euphorbia and identify new synonyms for Euphorbia beharensis, Euphorbia berevoensis, Euphorbia delphinensis, Euphorbia mangokyensis, Euphorbia paulianii, and Euphorbia bosseri. We publish at a new rank E. begardii (basionym E. primulifolia var. begardii), E. crassicaulis (basionym E. francoisii var. crassicaulis, with a new synonym E. decaryi var. crassicaulis), and Euphorbia hardyi (basionym E. platyclada var. hardyi). We also clarify the typification of E. isalensis. lectotypify Euphorbia leandriana and, clarify its circumscription, with E. horombensis as a new synonym of this name.
Teleconnections Governing the Interannual Variability of Great Plains Low-Level Jets in May
Authors: Agrawal Shubhi , Ferguson Craig R. , Bosart Lance , Burrows D. Alex
Published: March 2021

A spectral analysis of Great Plains 850-hPa meridional winds (V850) from ECMWF’s coupled climate reanalysis of 1901–2010 (CERA-20C) reveals that their warm season (April–September) interannual variability peaks in May with 2–6-yr periodicity, suggestive of an underlying teleconnection influence on low-level jets (LLJs). Using an objective, dynamical jet classification framework based on 500-hPa wave activity, we pursue a large-scale teleconnection hypothesis separately for LLJs that are uncoupled (LLJUC) and coupled (LLJC) to the upper-level jet stream. Differentiating between jet types enables isolation of their respective sources of variability. In the U.S. south-central plains (SCP), May LLJCs account for nearly 1.6 times more precipitation and 1.5 times greater V850 compared to LLJUCs. Composite analyses of May 250-hPa geopotential height (Z250) conditioned on LLJC and LLJUC frequencies highlight a distinct planetary-scale Rossby wave pattern with wavenumber 5, indicative of an underlying circumglobal teleconnection (CGT). An index of May CGT is found to be significantly correlated with both LLJC (r = 0.62) and LLJUC (r = −0.48) frequencies. Additionally, a significant correlation is found between May LLJUC frequency and NAO (r = 0.33). Further analyses expose decadal-scale variations in the CGT–LLJC and CGT–LLJUC teleconnections that are linked to the PDO. Dynamically, these large-scale teleconnections impact LLJ class frequency and intensity via upper-level geopotential anomalies over the western United States that modulate near-surface geopotential and temperature gradients across the SCP.
Questions for Conversational Preaching
Authors: Voelz Richard W.
Published: March 2021

This essay considers the role of questions within sermons, in dialogue, with efforts to develop an ethos of conversational preaching. Questions reveal much about who preachers are, how they relate to listeners, and how they envision the homiletical situation. And in so doing, they continue to highlight the relationship between theology and rhetoric in preaching.
Multiple Group Comparisons of the Fixed and Random Effects From the Generalized Linear Mixed Model
Authors: Kasper Daniel , Schulz-Heidorf Katrin , Schwippert Knut
Published: March 2021

In this article, we extend Liao’s test for across-group comparisons of the fixed effects from the generalized linear model to the fixed and random effects of the generalized linear mixed model (GLMM). Using as our basis the Wald statistic, we developed an asymptotic test statistic for across-group comparisons of these effects. The test can be applied when the fixed and random effects are multivariate normally distributed, and it works well for any link function and conditional distribution of the dependent variable of the GLMM. We also derived the asymptotic properties of this test, and because power information does not exist for either our new test statistic or Liao’s test, we implemented a power study to demonstrate the superiority of these tests over the alternatively proposed F test. Using an example, we show the application of the test and then discuss its possible restrictions with respect to the distribution of the random effects.
A Qualitative Exploration of Jezebel Stereotype Endorsement and Sexual Behaviors Among Black College Women
Authors: Leath Seanna , Jerald Morgan C. , Perkins Tiani , Jones Martinque K.
Published: March 2021

Researchers suggest that the Jezebel stereotype exerts a significant influence on Black women’s sexual decision making. The current qualitative study drew upon narrative data from individual, semistructured interviews with 50 Black women (ages 18-24 years) to explore how the Jezebel stereotype influenced their sexual beliefs and behaviors. Using consensual qualitative research methods, the following four themes emerged from the data: (a) how the Jezebel plays a role in their sexual exploration, (b) how the Jezebel contributes to sexual violence against Black women, (c) how the Jezebel is a hypersexual media representation of Black women’s sexuality, and (d) how the Jezebel is a negative sexual stereotype within family contexts. Our findings contextualize the enduring role of the Jezebel stereotype as a sexual script for Black women, as we found that many participants chose to adapt their clothing choices or sexual behaviors in light of their awareness and endorsement of the stereotype. The authors discuss the implications of study findings for Black women and girls’ sexual socialization and deconstructing deficit-based ideologies of Black women’s sexuality.
The Impact of Cross-border Labor Mobility on Real Estate Price Trends: A Natural Experiment
Authors: Dumeignil Camille
Published: March 2021

This article evaluate how cross-border labor mobility affects real estate price trends. To overcome the endogeneity of mobility choice, a natural experiment is used: The implementation of the “Agreement on the Free Movement of Persons” (AFMP) between the European Union (EU) and Switzerland, on 1 June 2007. This policy change the eligibility criteria for obtaining a cross-border permit by removing residence restrictions and creates a natural experiment for a difference-in-differences analysis. Based on French administrative data, results show that cross-border labor mobility does not affect house price trends in French border regions. However, the implementation of the AFMP has had a positive impact on the evolution of apartment prices in both the short term (six months) and the medium term (three years). In addition, the evolution of apartment prices shows sensitivity to distance from the border and to the housing quality segment.
Let’s See That Again: Using Instructional Videos to Support Asynchronous Mathematical Problem Solving Instruction for Students With Autism Spectrum Disorder
Authors: Cox Sarah K. , Root Jenny R. , Gilley Deidre
Published: March 2021

The Pandemic has required teachers to find ways to provide high-quality instruction in a virtual format. Video-based instruction (VBI) is a version of technology-aided instruction that has been effectively used in classrooms to improve mathematical outcomes for students with disabilities. This manuscript describes how a special education teacher can utilized VBI through free online platforms (i.e., SeeSaw, Loom) to implement a mathematical problem solving instructional strategy (modified schema-based instruction; MSBI) for students with autism spectrum disorder (ASD) while at home. MSBI utilizing VBI has successfully been used by teachers and researchers to improve additive and multiplicative problem solving skills for students with ASD. This manuscript describes how special education teachers can support students and their caregivers by providing high-quality problem solving instruction in a virtual environment.
Determination of Dynamic Modulus Master Curve of Damaged Asphalt Pavements for Mechanistic–Empirical Pavement Rehabilitation Design
Authors: Zeng Zhe “Alan” , Lee Kangjin “Caleb” , Kim Youngsoo Richard
Published: March 2021

For pavement rehabilitation design, the current mechanistic–empirical (ME) pavement design guide provides three levels of analysis methodology to determine dynamic modulus master curves for existing asphalt pavements. First, the ME pavement design guide recommends that Witczak’s predictive equation is employed to obtain the “undamaged” modulus master curve. Depending on the chosen level of analysis, either a falling weight deflectometer test (Level 1) or a condition survey (Levels 2 and 3) is conducted to determine the damage factor(s). The damage factor is used to shift the undamaged master curve downward to match the field conditions and obtain the “damaged” master curve. In this study, two pavement structures in North Carolina Highway 96 were selected to evaluate the accuracy of the ME pavement design guide using its three levels of analysis. Because this roadway is a multilayer full-depth pavement, the extracted field cores were divided into a top layer, bottom layer, and total core for investigative and comparative purposes. Accordingly, both laboratory measurements and pavement ME predictions of the dynamic modulus values were conducted separately. Results show that the predicted undamaged master curves are always higher than the measured master curves and Levels 1, 2, and 3 can each lead to significantly different damaged master curves. Considering both efficiency and accuracy for transportation agency practice, the Level 1 method is recommended, and if the existing pavement is a multilayered asphalt pavement, a total core extracted from all the layers is recommended to generate the input properties for Witczak’s predictive equation.