De Soto’s First Headquarters in Florida

Knowing that Hernando de Soto, his expedition, and the places he visited will probably be matters of discussion for years and years, I have not recently ventured any further contributions regarding them. However, challenge of one of my conclusions, the probable site of the Indian town of Ucita where De Soto established his first North American headquarters, has recently been made in a scientifically motivated paper (“The Terra Ceia Site, Manatee County, Florida.” No. 3 of the Publications of the Florida Anthropological Society, by Ripley P. Bullen), and this calls for some comments

De Soto and Terra Cei

In connection with my work as chairman of the De Soto Expedition Commission between 1935 and 1938 I made a study of the documentary and geographical evidence regarding the location of the point where De Soto landed on the Florida coast in 1539 and the position of his first headquarters. While I was assisted to some extent by other members of the Commission, the conclusions reached were more particularly mine and I assume all responsibility for them. They were originally stated in a paper printed in “The Florida Historical Quarterly” (vol. XVI, no. 3; Jan. 1938) and were incorporated later in the “Final Report of the United States De Soto Expedition Commission” (Washington, 1939). The point where the greater part of the Spanish army was landed was believed to be Shaws Point, and the native town where he established his headquarters apparently at the Indian site on Terra Ceia Island

CKS1 inhibition depletes leukemic stem cells and protects healthy hematopoietic stem cells in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive hematological disorder comprising a hierarchy of quiescent leukemic stem cells (LSCs) and proliferating blasts with limited self-renewal ability. AML has a dismal prognosis, with extremely low 2-year survival rates in the poorest cytogenetic risk patients, primarily due to the failure of intensive chemotherapy protocols to deplete LSCs and toxicity of therapy toward healthy hematopoietic cells. We studied the role of cyclin-dependent kinase regulatory subunit 1 (CKS1)-dependent protein degradation in primary human AML and healthy hematopoiesis xenograft models in vivo. Using a small-molecule inhibitor (CKS1i), we demonstrate a dual role for CKS1-dependent protein degradation in reducing patient-derived AML blasts in vivo and, importantly, depleting LSCs, whereas inhibition of CKS1 has the opposite effect on normal hematopoiesis, protecting normal hematopoietic stem cells from chemotherapeutic toxicity. Proteomic analysis of responses to CKS1i in our patient-derived xenograft mouse model demonstrate that inhibition of CKS1 in AML leads to hyper-activation of RAC1 and accumulation of lethal reactive oxygen species, whereas healthy hematopoietic cells enter quiescence in response to CKS1i, protecting hematopoietic stem cells. Together, these findings demonstrate that CKS1-dependent proteostasis is a key vulnerability in malignant stem cell biology.Peer reviewe

Follicle Stimulating Hormone and Anti-Müllerian Hormone per Oocyte in Predicting in vitro Fertilization Pregnancy in High Responders: A Cohort Study

Background: Follicle stimulating hormone (FSH) and Anti-Müllerian hormone (AMH) are utilized to differentiate between good and poor response to controlled ovarian hyperstimulation. Their respective roles in defining functional ovarian reserve remain, however, to be elucidated. To better understand those we investigated AMH and FSH per oocyte retrieved (AMHo and FSHo). Methodology/Principal Findings: Three-hundred and ninety-six women, undergoing first in vitro fertilization cycles, were retrospectively evaluated. Women with oocyte yields.75 th percentile for their age group were identified as high responders. In a series of logistic regression analyses, AMHo and FSHo levels were then evaluated as predictive factors for pregnancy potential in high responders. Patients presented with a mean age of 38.065.0 years, mean baseline FSH of 11.868.7 mIU/mL and mean AMH of 1.662.1 ng/mL. Those 88 women, who qualified as high responders, showed mean FSH of 9.766.5 mIU/mL, AMH of 3.163.1 ng/mL and oocyte yields of 15.867.1. Baseline FSH and AMH did not predict pregnancy in high responders. However, a statistically significant association between FSHo and pregnancy was observed in high responders, both after univariate regression (p = 0.02) and when adjusted for age, percentage of usable embryos, and number of embryos transferred (p = 0.03). Rate of useable embryos also significantly affected pregnancy outcome independently of FSHo (p = 0.01). AMHo was also associated with clinical pregnancy chances in high responders (p = 0.03

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Author Correction: Scalable and robust SARS-CoV-2 testing in an academic center.

An amendment to this paper has been published and can be accessed via a link at the top of the paper