From Poe to South Park: The Influence and Development of Lovecraft’s ‘Cosmic Horror’ in American Culture

H.P. Lovecraft’s ‘Cosmic Horror’ has been a staple of horror and gothic fiction, and therefore American culture, for more than 80 years. In this paper, I examine the development of the genre of horror, starting with Edgar Allen Poe’s influence, and trace its development up to contemporary popular American culture exemplified by the TV show South Park. While Lovecraft’s material has always been drawing from the same concept of the fear of the unknown and human powerlessness in the face of greater forces, the context, sources and reasons for this powerlessness have constantly changed over the decades. In this paper I offer an examination of where this idea of ‘Cosmic Horror’ originally came from, how Lovecraft developed it further and, ultimately, how American culture has adapted the source material to fit a contemporary context. By contrasting Lovecraft’s early works with Poe’s, I shed light on the beginnings of the sub-genre before taking a look at the height of ‘Cosmic Horror’ in Lovecraft’s most famous texts of the Cthulhu myth and ultimately look at a trilogy of South Park episodes to put all of this into a modern American perspective. By doing so, I reveal how Lovecraft’s tales and the underlying philosophy have always been an important part of American culture and how they continue to be relevant even today

Dynamic optical coherence tomography. a non-invasive imaging tool for the distinction of nevi and melanomas

Along with the rising melanoma incidence in recent decades and bad prognoses resulting from late diagnoses, distinguishing between benign and malignant melanocytic lesions has become essential. Unclear cases may require the aid of non-invasive imaging to reduce unnecessary biopsies. This multicentric, case-control study evaluated the potential of dynamic optical coherence tomography (D-OCT) to identify distinguishing microvascular features in nevi. A total of 167 nevi, including dysplastic ones, on 130 participants of all ages and sexes were examined by D-OCT and dermoscopy with a histological reference. Three blinded analyzers evaluated the lesions. Then, we compared the features to those in 159 melanomas of a prior D-OCT study and determined if a differential diagnosis was possible. We identified specific microvascular features in nevi and a differential diagnosis of melanomas and nevi was achieved with excellent predictive values. We conclude that D-OCT overcomes OCT´s inability to distinguish melanocytic lesions based on its focus on microvascularization. To determine if an addition to the gold standard of a clinical-dermoscopic examination improves the diagnosis of unclear lesions, further studies, including a larger sample of dysplastic nevi and artificial intelligence, should be conducted

Dynamic optical coherence tomography: a non-invasive imaging tool for the distinction of nevi and melanomas

Along with the rising melanoma incidence in recent decades and bad prognoses resulting from late diagnoses, distinguishing between benign and malignant melanocytic lesions has become essential. Unclear cases may require the aid of non-invasive imaging to reduce unnecessary biopsies. This multicentric, case-control study evaluated the potential of dynamic optical coherence tomography (D-OCT) to identify distinguishing microvascular features in nevi. A total of 167 nevi, including dysplastic ones, on 130 participants of all ages and sexes were examined by D-OCT and dermoscopy with a histological reference. Three blinded analyzers evaluated the lesions. Then, we compared the features to those in 159 melanomas of a prior D-OCT study and determined if a differential diagnosis was possible. We identified specific microvascular features in nevi and a differential diagnosis of melanomas and nevi was achieved with excellent predictive values. We conclude that D-OCT overcomes OCT´s inability to distinguish melanocytic lesions based on its focus on microvascularization. To determine if an addition to the gold standard of a clinical-dermoscopic examination improves the diagnosis of unclear lesions, further studies, including a larger sample of dysplastic nevi and artificial intelligence, should be conducted

Line-field confocal optical coherence tomography: a new tool for the differentiation between nevi and melanomas?

SIMPLE SUMMARY: Typical benign nevi and advanced melanomas can be easily discriminated, but there are still some melanocytic lesions where even experts are not sure about the correct diagnosis and degree of malignity. The high penetration depth of optical coherence tomography (OCT) allows an assessment of tumor thickness of the lesion precisely, but without cellular resolution the differentiation of melanocytic lesions remains difficult. On the other hand, reflectance confocal microscopy (RCM) allows for very good morphological identification of either a nevus or a melanoma, but cannot show the infiltration depth of the lesion because of its low penetration depth. Since the new device of line-field confocal optical coherence tomography (LC-OCT) technically closes the gap between these other two devices, in this study, we wanted to examine if it is possible to differentiate between nevi and melanomas with LC-OCT, and which criteria are the most important for it. ABSTRACT: Until now, the clinical differentiation between a nevus and a melanoma is still challenging in some cases. Line-field confocal optical coherence tomography (LC-OCT) is a new tool with the aim to change that. The aim of the study was to evaluate LC-OCT for the discrimination between nevi and melanomas. A total of 84 melanocytic lesions were examined with LC-OCT and 36 were also imaged with RCM. The observers recorded the diagnoses, and the presence or absence of the 18 most common imaging parameters for melanocytic lesions, nevi, and melanomas in the LC-OCT images. Their confidence in diagnosis and the image quality of LC-OCT and RCM were evaluated. The most useful criteria, the sensitivity and specificity of LC-OCT vs. RCM vs. histology, to differentiate a (dysplastic) nevus from a melanoma were analyzed. Good image quality correlated with better diagnostic performance (Spearman correlation: 0.4). LC-OCT had a 93% sensitivity and 100% specificity compared to RCM (93% sensitivity, 95% specificity) for diagnosing a melanoma (vs. all types of nevi). No difference in performance between RCM and LC-OCT was observed (McNemar’s p value = 1). Both devices falsely diagnosed dysplastic nevi as non-dysplastic (43% sensitivity for dysplastic nevus diagnosis). The most significant criteria for diagnosing a melanoma with LC-OCT were irregular honeycombed patterns (92% occurrence rate; 31.7 odds ratio (OR)), the presence of pagetoid spread (89% occurrence rate; 23.6 OR) and the absence of dermal nests (23% occurrence rate, 0.02 OR). In conclusion LC-OCT is useful for the discrimination between melanomas and nevi

Transitioning to molecular diagnostics in pediatric high-grade glioma: Experiences with the 2016 WHO classification of CNS tumors

BACKGROUND: Pediatric neuro-oncology was profoundly changed in the wake of the 2016 revision of the WHO Classification of Tumors of the Central Nervous System. Practitioners were challenged to quickly adapt to a system of tumor classification redefined by molecular diagnostics. METHODS: We designed a 22-question survey studying the impact of the revised WHO classification on pediatric high-grade glioma. The survey collected basic demographics, general attitudes, issues encountered, and opinions on pediatric subtypes. Participant answers were analyzed along socioeconomic lines utilizing the human development index (HDI) of the United Nations and membership in the group of seven (G7) world economic forum. RESULTS: Four hundred and sixty-five participants from 53 countries were included, 187 pediatric neurooncologists (40%), 160 neuropathologists (34%), and 118 other experts (26%). When asked about pediatric high-grade glioma entities, participants from very high development countries preferred treating a patient based on genetic findings. Participants from high and medium development countries indicated using traditional histology and tumor location as mainstays for therapeutic decisions. Non-G7 countries tended to regard the introduction of molecularly characterized tumor entities as a problem for daily routine due to lack of resources. CONCLUSIONS: Our findings demonstrate an overall greater reliance and favorability to molecular diagnostics among very high development countries. A disparity in resources and access to molecular diagnostics has left some centers unable to classify pediatric high-grade glioma per the WHO classification. The forthcoming edition should strain to abate disparities in molecular diagnostic availability and work toward universal adaptation

Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: results from the HIT-MED database

Background Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims to evaluate the prognostic impact of molecular typing on pediatric spinal cord ependymomas. Methods Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database (German brain tumor registry for children, adolescents, and adults with medulloblastoma, ependymoma, pineoblastoma, and CNS-primitive neuroectodermal tumors) between 1992 and 2022 were included. Forty-seven tumors were analyzed by DNA methylation array profiling. In 6 cases, HOXB13 and MYCN proteins were detected as surrogate markers for specific methylation classes. Ten patients had NF2-related schwannomatosis. Results With a median follow-up time of 4.9 years, 5- and 10-year overall survival (OS) were 100% and 86%, while 5- and 10-year progression-free survival (PFS) were 65% and 54%. Myxopapillary ependymoma (SP-MPE, n = 32, 63%) was the most common molecular type followed by spinal ependymoma (SP-EPN, n = 17, 33%) and MYCN-amplified ependymoma (n = 2, 4%). One case could not be molecularly classified, and one was reclassified as anaplastic pilocytic astrocytoma. 5-year PFS did not significantly differ between SP-MPE and SP-EPN (65% vs. 78%, P = .64). MYCN-amplification was associated with early relapses (<2.3 years) in both cases and death in one patient. Patients with SP-MPE subtype B (n = 9) showed a non-significant trend for better 5 years-PFS compared to subtype A (n = 18; 86% vs. 56%, P = .15). The extent of resection and WHO tumor grades significantly influenced PFS in a uni- and multivariate analysis. Conclusions Molecular typing of pediatric spinal ependymomas aids in identifying very high-risk MYCN-amplified ependymomas. Further insights into the molecular heterogeneity of spinal ependymomas are needed for future clinical decision-making

Pediatric high-grade gliomas and the WHO CNS Tumor Classification - Perspectives of pediatric neuro-oncologists and neuropathologists in light of recent updates

Background: The WHO Classification of Tumors of the Central Nervous System has undergone major restructuring. Molecularly defined diagnostic criteria were introduced in 2016 (revised 4th edition) and expanded in 2021 (5th edition) to incorporate further essential diagnostic molecular parameters. We investigated potential differences between specialists in perception of these molecularly defined subtypes for pediatric high-grade gliomas (pedHGG). Methods: We designed a 22-question survey studying the impact of the revised 4th edition of the WHO classification on pedHGG. Data were collected and statistically analyzed to examine the spectrum of viewpoints and possible differences between neuro-oncologists and neuropathologists. Results: 465 participants from 53 countries were included; 187 pediatric neuro-oncologists (40%), 160 neuropathologists (34%), and 118 additional experts (26%). Neuro-oncologists reported issues with the introduction of molecularly defined tumor types, as well as the abolishment or renaming of established tumor entities, while neuropathologists did not to the same extent. Both groups indicated less relevant or insufficient diagnostic definitions were available in 2016. Reported issues were classified and assessed in the 2021 WHO classification and a substantial improvement was perceived. However, issues of high clinical relevance remain to be addressed, including the definition of clinical phenotypes for diffuse intrinsic pontine glioma and gliomatosis cerebri. Conclusions: Within the WHO classification of pediatric brain tumors, such as pedHGG, rapid changes in molecular characterization have been introduced. This study highlights the ongoing need for cross talk between pathologist and oncologist to advance the classification of pedHGG subtypes and ensure biological relevance and clinical impact

General support of physical exercise programs in pediatric oncology but differences in perception by childhood cancer care professionals at European and North-African/Arab centers

Purpose: To explore the perception of physical exercise programs for pediatric oncology patients among childhood cancer care professionals. We also aimed at comparing such perceptions between cultures. Healthcare professionals’ endorsement may be essential for initiating and promoting such programs. Methods: An anonymous survey was designed and administered voluntarily to childhood cancer care professionals (including pediatric oncologists, nurses, and physiotherapists) in European, North-African and Arab pediatric oncology centers. Results: Five-hundred-and twenty-eight professionals from 14 sites answered the survey. Most respondents considered physical exercise programs as a suitable therapeutic approach for pediatric cancer patients with a potential positive contribution to survival (81%), wellbeing (82%), quality of life (80%), and self-esteem (75%). 91% of respondents would also support the future introduction of physical exercise programs into standard pediatric oncological care. There was a comparatively higher appreciation of physical exercise programs among European centers compared to North-African / Arab centers. Conclusion: We registered a broad acceptance of physical exercise programs among all European and North-African / Arab childhood cancer care professionals. The positive perception was independent of any pre-existing experience with such programs and seems therefore representative. This finding may encourage the further promotion of physical exercise programs in pediatric oncology