The Lantern Vol. 2, No. 3, June 1934

• Looking Backward and Forward • Hahd on de Nerves • My Lavender Lady • The Perpetual Borrower • Into the Depths • The Best There Is • I Wonder • A Day Out of a German Boy\u27s Life • Book Review: Work of Art • Fear • Early Summer (A Sketch)https://digitalcommons.ursinus.edu/lantern/1003/thumbnail.jp

The Lantern Vol. 2, No. 2, March 1934

• Fulfillment Through Expression • Ole Man Ennis • Nos Illusions by Philippe Vallee • A Celtic May Day Festival • Dew Drops • Baker Street Fiction • March Winds • Winter Sunset • Book Review: No Second Spring • A Thought • The Cask of Amontillado • Illustrationhttps://digitalcommons.ursinus.edu/lantern/1002/thumbnail.jp

The Lantern Vol. 1, No. 1, May 1933

• Remember: Translation of Rappelle-toi by Alfred de Musset • Lighting the Lantern • Footfalls • To a Lovely Lady • The Sons of Martha • Strategy • Lumine Lunae • Poetry in Retrospect • Nirvana • A Domestic Episode • At Night • Haman and Hitler • This is What He Said • Bookocracy • Four Loves • Cities and Personalitieshttps://digitalcommons.ursinus.edu/lantern/1000/thumbnail.jp

The Lantern Vol. 2, No. 1, December 1933

• Petition • Keep it Burning! • Jes\u27 Before Christmas • Noel: Translation from Theophile Gautier • A Young Jew Meets Jesus • Book Review: Little Man, What Now? • Book Review: Thunder and Dawn • Continuity • La Veille de Noel (Reflexions d\u27un Provincial) • Noel Sceptique par Jules LaFargue • Horizon • Winter Night • Linoleum Cutshttps://digitalcommons.ursinus.edu/lantern/1001/thumbnail.jp

CATMoS: Collaborative Acute Toxicity Modeling Suite.

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495

African-Americans Have a Higher Propensity for Death from COVID-19: Rationale and Causation

The purpose of this article is to provide an understanding about the mechanisms that contribute to the proliferation of COVID-19 morbidity and mortality among high-risk populations, and especially African-Americans. African-Americans are succumbing to novel SARS-CoV-2 (COVID-19) at an alarming rate. Current data indicate that while African-Americans represent less than 13.4% of the United States\u27 population, they account for one-third of more than 4.77 million persons with verified COVID-19 infections. Currently, more than 50,258 African-Americans have succumbed to the disease. African-Americans are disproportionately impacted by COVID-19 to an extent unobserved in other racial/ethnic subgroups. In addition, this article describes the physiological event inflammation-mediation storming (cytokine storming). Social determinants of health such as income, education, and employment are hypothesized to impact cogent health care delivery for African-Americans. Included in this article are data on clinical outcomes that highlight the role of pre-existing (health disparities) conditions like diabetes, hypertension, cardiovascular disease, obesity, and lung disease, as barriers to optimal outcomes among African-Americans who are hospitalized with COVID-19. Also explored in this article is causation for vascular complications. A further aim of this article is to provide insight into cause and effect rationales for COVID-19 and health disparities, from both biosocial and health inequality perspectives. Linkages between these selected health disparities and COVID-19 are examined to determine possible deteriorating effects of COVID-19. Finally, techniques are offered to render culturally competent care to African-Americans diagnosed with COVID-19 who present concomitantly with health disparities

Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer

Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs