Growing evidence highlights an association between an imbalance in the composition and abundance of bacteria in the breast tissue (referred as microbial dysbiosis) and breast cancer in women. However, studies on the breast tissue microbiome have not been conducted in non-Hispanic Black (NHB) women. We investigated normal and breast cancer tissue microbiota from NHB and non-Hispanic White (NHW) women to identify distinct microbial signatures by race, stage, or tumor subtype. Using 16S rRNA gene sequencing, we observed that phylum Proteobacteria was most abundant in normal (n = 8), normal adjacent to tumor (normal pairs, n = 11), and breast tumors from NHB and NHW women (n = 64), with fewer Firmicutes, Bacteroidetes, and Actinobacteria. Breast tissues from NHB women had a higher abundance of genus Ralstonia compared to NHW tumors, which could explain a portion of the breast cancer racial disparities. Analysis of tumor subtype revealed enrichment of family Streptococcaceae in TNBC. A higher abundance of genus Bosea (phylum Proteobacteria) increased with stage. This is the first study to identify racial differences in the breast tissue microbiota between NHB and NHW women. Further studies on the breast cancer microbiome are necessary to help us understand risk, underlying mechanisms, and identify potential microbial targets.

Obesity is a chronic condition resulting from a long-term pattern of poor diet and lifestyle. Long-term consumption of high-fat diet (HFD) leads to persistent activation and leptin resistance in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH). Here, for the first time, we demonstrate acute effects of HFD on AgRP neuronal excitability and highlight a critical role for diet composition. In parallel with our earlier finding in obese, long-term HFD mice, we found that even brief HFD feeding results in persistent activation of ARH AgRP neurons. However, unlike long-term HFD-fed mice, AgRP neurons from short-term HFD-fed mice were still leptin-sensitive, indicating that the development of leptin-insensitivity is not a prerequisite for the increased firing rate of AgRP neurons. To distinguish between diet composition, caloric intake, and body weight, we compared acute and long-term effects of HFD and CD in pair-fed mice on AgRP neuronal spiking. HFD consumption in pair-fed mice resulted in a significant increase in AgRP neuronal spiking despite controls for weight gain and caloric intake. Taken together, our results suggest that diet composition may be more important than either calorie intake or body weight for electrically remodeling arcuate AgRP/NPY neurons.

Desilylation of the 2-phosphinophosphinine 2-PPh 2-3-Me-6-SiMe 3-PC 5 H 2 with HCl gave 2-PPh 2-3-Me-PC 5 H 3 , demonstrating the late-stage modification of this bidentate heterocyclic ligand. Group 6 metal carbonyl complexes of these ligands showed κ 2-binding and very small bite-angles of 65.1-68.3°, and also demonstrated that the donor properties of 2phosphinophosphinines can be tuned readily by the presence of the SiMe 3 group which gives a more π-accepting phosphinine ligand. The properties of 2-phosphinophosphinines were compared to bidentate diphosphorus ligands computationally, contextualizing them in the Ligand Knowledge Base for bidentate P,P donor ligands (LKB-PP) and were found to occupy an area of ligand space adjacent to Ar 2 PN(R)NAr 2 ligands that have been successfully used in ethylene oligomerization reactions, but with well-separated properties in the second principal component. Testing 2-phosphinophosphinines in Cr-catalyzed ethylene oligomerization reactions showed key differences to standard PNP ligands in that a high proportion of alkyl-and alkenyl-cyclopentanes were formed. This demonstrates that the different donor properties of 2-phosphinophosphinines influence the reactivity of the key 7-membered metallacycle postulated in the metallacyclic reaction mechanism, generating products from isomerization and subsequent ethylene insertion. Alkyl-and alkenyl-cyclopentanes represent new products for the key industrial feedstock ethylene, with the alkenes having potential as new monomers, comonomers or additives for plastics. Computational evaluation of ligand properties and the resulting property maps can play a role in suggesting future ligand developments to change the selectivity of this industriallyrelevant system in the pursuit of new products generated from ethylene.

Summary Sickle cell disease ( SCD ) affects over 2 million people worldwide with high morbidity and mortality in underdeveloped countries. Therapeutic interventions aimed at reactivating fetal haemoglobin (HbF) is an effective approach for improving survival and ameliorating the clinical severity of SCD . A class of agents that inhibit DNA methyltransferase ( DNMT ) activity show promise as HbF inducers because off‐target effects are not observed at low concentrations. However, these compounds are rapidly degraded by cytidine deaminase when taken by oral administration, creating a critical barrier to clinical development for SCD . We previously demonstrated that micro RNA 29B ( MIR 29B ) inhibits de novo DNMT synthesis, therefore, the goal of our study was to determine if MIR 29 mediates HbF induction. Overexpression of MIR 29B in human KU 812 cells and primary erythroid progenitors significantly increased the percentage of HbF positive cells, while decreasing the expression of DNMT 3A and the HBG repressor MYB . Furthermore, HBG promoter methylation levels decreased significantly following MIR 29B overexpression in human erythroid progenitors. We subsequently, observed higher MIR 29B expression in SCD patients with higher HbF levels compared to those with low HbF. Our findings provide evidence for the ability of MIR 29B to induce HbF and supports further investigation to expand treatment options for SCD .

African American women are substantially underrepresented in breast cancer genetic research studies and clinical trials, yet they are more likely to die from breast cancer. Lack of trust in the medical community is a major barrier preventing the successful recruitment of African Americans into research studies. When considering the city of Memphis, TN, where the percentage of African Americans is significantly higher than the national average and it has a high rate of breast cancer mortality inequities among African American women, we evaluated the feasibility of utilizing a community-based participatory (CBPR) approach for recruiting African American women into a breast cancer genetic study, called the Sistas Taking A Stand for Breast Cancer Research (STAR) study. From June 2016 and December 2017, African American women age 18 and above were recruited to provide a 2 mL saliva specimen and complete a health questionnaire. A total of 364 African American women provided a saliva sample and completed the health questionnaire. Greater than 85% agreed to be contacted for future studies. Educational workshops on the importance of participating in cancer genetic research studies, followed by question and answer sessions, were most successful in recruitment. Overall, the participants expressed a strong interest and a willingness to participate in the STAR study. Our findings highlight the importance of implementing a CBPR approach that provides an educational component detailing the importance of participating in cancer genetic research studies and that includes prominent community advocates to build trust within the community.

Background. The fourth-year of the Bachelor of Dental Surgery (BDS) degree is considered the most stressful in the curriculum. Cognitive reappraisal is a self-applied method of stress management where an individual recognises his/her physiological responses to stress as a positive phenomenon helping him/her rise to the challenge, rather than a negative one in response to a threat situation. Aim. To investigate whether teaching fourth-year dental students to apply cognitive reappraisal reduces their perceived levels of stress. Methods. A survey was emailed to all fourth-year dental students, inviting them to respond to a 20-item questionnaire adapted from the Dental Environmental Stress (DES) Survey. Respondents were randomly assigned to reappraisal intervention/experimental (EXP) and control intervention (CON) groups, and each group was asked to watch an educational video. The EXP group video educated respondents on how to apply cognitive reappraisal in stressful situations, and the CON group video described generic methods of stress management. A follow-up survey was conducted after 3 weeks. Results. The respondent rate was 47.6%. Change scores were calculated by subtracting the follow-up DES scores from baseline DES scores. The average change score for the experimental group was +3.1, indicating a decrease in average perceived stress levels. Conversely, the average change score for the CON group was −1.06, indicating an increase in average perceived stress levels. However, this difference did not reach a statistical significance. Conclusion. EXP group has shown to have positive effects on stress management, and its effects on BDS students demonstrate promise.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that is non-responsive to hormonal therapies and disproportionately impact women of African ancestry. We previously showed that TN breast tumors have a distinct microbial signature that differs from less aggressive breast tumor subtypes and normal breast tissues. However, it is unknown whether these differences in breast tumor microbiota may be driven by alterations in microbial metabolites, leading to potentially protective or pathogenic consequences. The goal of this global metabolomic profiling study was to investigate alterations in microbial metabolism pathways in normal and breast tumor tissues, including TNBC, of non-Hispanic black (NHB) and non-Hispanic white (NHW) women. In this study, we profiled the microbiome (16S rRNA) from breast tumor tissues and analyzed 984 metabolites from a total of 51 NHB and NHW women. Breast tumor tissues were collected from 15 patients with TNBC, 12 patients with less aggressive luminal A-type (Luminal) breast cancer, and 24 healthy controls for comparison using UHPLC-tandem mass spectrometry. Principal component analysis and hierarchical clustering of the global metabolomic profiling data revealed separation between metabolic signatures of normal and breast tumor tissues. Random forest analysis revealed a unique biochemical signature associated with elevated lipid metabolites and lower levels of microbial-derived metabolites important in controlling inflammation and immune responses in breast tumor tissues. Significant relationships between the breast microbiome and the metabolome, particularly lipid metabolism, were observed in TNBC tissues. Further investigations to determine whether alterations in sphingolipid, phospholipid, ceramide, amino acid, and energy metabolism pathways modulate Fusobacterium and Tenericutes abundance and composition to alter host metabolism in TNBC are necessary to help us understand the risk and underlying mechanisms and to identify potential microbial-based targets.

Non-Hispanic black (NHB) women are more likely to be diagnosed and die from triple negative breast cancer (TNBC) than non-Hispanic white (NHW) women. We previously showed that TNBC tissues display a distinct microbial signature. Obesity which contributes to chronic low-grade inflammation and gut microbial dysbiosis further exacerbates TNBC outcomes for NHB women. However, it is unclear the extent to which microbial differences in breast tumor tissues may be driven by alterations in microbial metabolites as a result of obesity status. Therefore, the aim of this global metabolomic profiling study was to investigate alterations in microbial metabolism pathways in breast tissues of NHB and NHW obese women (avg. BMI = 35.7) relative to non-obese women (avg. BMI = 23.4) with and without TNBC. In this study, we analyzed 984 metabolites derived from a total of 51 NHB and NHW women, including 15 patients with TNBC, 12 patients with less aggressive Luminal A-type breast cancer, and 24 healthy controls for comparison using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to identify microbial metabolites and metabolomic signatures that differ by breast tumor subtype and obesity status. We detected 501 significantly increased metabolites and 33 significantly decreased metabolites in TNBC patients compared to controls. Principal component analysis and hierarchical clustering of the global metabolite profiling data revealed separation between the metabolic signatures of normal and breast tumor tissue. Random forest analysis revealed a unique biochemical signature associated with elevated L-Tryptophan (Trp) and Kynurenine (Kyn) metabolites and lower levels of microbial-derived metabolites critical for controlling inflammation and immune response in obese individuals and those with TNBC. TCGA analysis further revealed that expression of key Trp enzymes was significantly associated with worse survival outcomes in TNBC patients compared to other breast tumor subtypes. Our findings highlight a potential role for Trp metabolism through the Kyn pathway in obesity and TNBC risk. Further investigations into the Kyn metabolomic pathway may prove to be a novel therapeutic target for TNBC. Citation Format: Alana Smith, Qingqing Gu, Ernestine Kubi Amos-Abanyie, Elizabeth Tolley, Lu Lu, Beverly Lyn-Cook, Athena Starlard-Davenport. Tryptophan metabolism is associated with obesity and triple negative breast cancer risk in black and white women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3022.