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Promoting male participation in maternal healthcare is essential for improved maternal health outcomes. This study explored existing strategies to promote male participation in maternal healthcare and assessed their implementation challenges within healthcare facilities in the Jaman North District in Ghana. A qualitative approach was implemented in April 2020. Interviews were administered to a stratified purposive sample of 18 respondents comprising six midwives and 12 male partners of postnatal mothers. All interviews were audio-recorded, transcribed, and manually analysed using thematic analysis. The findings revealed early service, male partner invitation, male partner incentivisation, public sensitization, and male informed education, as strategies to promote male participation in the district. The implementation of these strategies has been constrained by socio-cultural and health system factors, namely, perception of pregnancy as non-illness, perceived experiences gained by women during previous births, cultural stereotypes, unconducive environment of healthcare facilities, inappropriate timing of facility attendance and unexpected costs associated with male participation. Promoting male participation, therefore, requires dedicated policy attention to the existing socio-cultural and health system constraints. The Ghana Health Service and other stakeholders should consider both community-level and targeted sensitization on the benefits of male participation in maternal healthcare and a general improvement in maternal healthcare infrastructure.

Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer (BC),often diagnosed as early-onset and late-stage disease with worse prognosis due to lack of targeted therapeutic options. In the US, approximately 10% of BC diagnoses annually are TNBC, however, frequency of TNBC diagnoses are significantly higher among African American (AA) women, driving a 40% higher mortality rate among AA women compared to White/European American (EA) women. Work from our International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort has linked west African ancestry to frequency of TNBC diagnoses, where we reported increased TNBC disease among women of west African ancestry (AA and Ghanaian) compared EA or east African (Ethiopian) women. Quantification of west African ancestry across the ICSBCS cohort has revealed significantly higher percentage of west African ancestry among TNBC patients, and this significant result remained when only considering AA women with TNBC. We hypothesize that African ancestry-specific factors drive differences in TNBC tumor etiology, and in combination with external factors yield a unique TNBC tumor microenvironment (TME). Approaching this work with a genetic ancestry (versus self-reported race) focus allows us the opportunity to define these unique factors that will ultimately translate into targeted therapeutic opportunities for this underserved population. To address this persisting disparity, we have leveraged multiomics approaches to: (1) identify unique African ancestry-specific gene expression profiles and enrichments using transcriptomic approaches, and (2) determine mutational profiles and signatures enriched among women of African ancestry with TNBC with whole genome sequencing (WGS). Utilizing a TNBC transcriptomics cohort enriched with women of African ancestry (n = 26), including AA, Ghanaian and Ethiopian TNBC patients, we have identified an African ancestry-associated gene signature comprised of 613 genes. After quantifying genetic ancestry across our patient cohort, we performed gene linear regression analyses to identify this gene signature. We also performed self-reported race (SRR) comparative analyses for differences in gene expression across population groups, and report that African ancestry associated gene are largely distinct from genes associated with SRR. Our African ancestry-associated gene signature revealed significant enrichment in immune cell trafficking pathways, where predicted activation of immune cell migration was observed among women with higher proportion of African ancestry. Deconvolution of the bulk RNAseq data revealed increases in tumor associated leukocytes proportions among AA and Ghanaian women, specifically B- and T- cell populations. Two separate validation cohorts looking at immunohistochemistry and multiplexed geospatial analysis also showed significant increases in T-cell infiltration into TNBC tumors of African ancestry women. Leveraging sub-continental ancestry estimations across the cohort, we additionally identified over 2000 genes associated with 5 African sub-continental reference populations, where significant enrichment in terms related to immune response was also observed. We hypothesize that these African ancestry-associated genes (1) will show enrichment with local ancestry estimates at the gene loci, and (2) that ancestral informative markers (AIMs) or population-private single nucleotide polymorphisms (SNPs) are expression quantitative trait loci (eQTLs) driving the observed African ancestry-specific gene expression observed. Workflow development is underway to apply local ancestry estimation methods to RNAseq data, to determine these associations in a loci-specific manner. WGS analysis was also completed on a cohort of patients with TNBC (n = 51) and hormone receptor positive (HR+) BC (n =23). Both cohorts are primarily comprised of AA patients and include Ethiopian patients with HR+ BC (n = 4) and TNBC (n = 3), and Ghanaian patients with TNBC (n = 3). Analysis of top mutated genes revealed significantly high frequency of TP53 mutations in TNBC (82%) compared to HR+ cases (35%) (p = 0.0001), with primarily missense and nonsense mutations in the P53 DNA-binding domain. All TNBC African cases harbored TP53 mutation, where only 1 Ethiopian HR+ case had a TP53 missense mutation. We compared COSMIC mutational signatures between TP53 mutation carriers and non-carriers and report a significant increase in proportion of Signature 3 (p = 0.0298), associated with double-strand break repair, and Signature 8 (p = 0.0026), which is associated with BC but has an unknown etiology. Of note, Signature 3 is often associated with germline BRCA1/2 mutations, and work is underway to determine BRCA1/2 status across our cohort. We have also reported the rs2363956 germline variant of the ANKLE1 gene as a potential TNBC protective allele among AA women, where ANKLE1 is reported to play a role in DNA repair pathways. We observe a higher fraction of Signature 3 across among the minor allele of ANKLE1 rs2363956 GG genotype, and a similar, lower fraction of Signature 3 among heterozygotes (GT) and major allele (TT) genotypes. DNAH5 and DNAH9 missense mutations were also detected among TNBC cases (16% and 14%, respectively), and not among HR+ cases (0%) (p = 0.05, p = 0.09, respectively). Mutations in DNA5 have been associated with chemosensitivity in ovarian cancer patients, and mutations in both DNAH5 and DNAH9 genes have been associated with chemosensitivity among patients with gastric cancer. GATA3 mutations were found exclusively among HR+ cases (26%, p = 0.0005), and PIK3CA mutations were also found at a significantly higher frequency among HR+ cases (30%) compared to TNBC cases (8%) (p = 0.03). Leveraging the diversity of our robust ICSBCS cohort, we have begun to define ancestry-associated phenotypes that are present in the TNBC TME of women with African ancestry. Our transcriptomic analyses have highlighted that ancestry-specific gene signatures are distinct from SRR-associated signatures, and we are currently working to define specific drivers of these ancestry-associated genes. We also highlight an increased immune response associated with higher fractions of African ancestry, that may provide opportunities to adapt current therapeutic options, such as immunotherapy, to this patient population. Our WGS work also highlights differences in mutational processes and mutation signatures among African ancestry women with TNBC and nonTNBC disease. We report an increased burden of TP53 mutations is present among TNBC patients and is highly correlated to increased Signature 3, which is associated with BRCAness and DNA repair deficiency. Work is currently underway to determine germline BRCA1/2 status of this patient population, as BRCA1/2 status may also be predictive of immunotherapy response. Taken together, these African ancestry specific phenotypes characterized among patients with TNBC highlight prospective biomarker or therapeutic opportunities for these historically underserved populations. Citation Format: Rachel Martini, Max Chao, Timothy Chu, Ishmael Kyei, Ernest Adjei, Mahteme Bekele, Paula Ginter, Kofi Gyan, Olivier Elemento, Nicolas Robine, John Carpten, Lisa Newman, Melissa Davis. Multiomics in disparities research: Identifying African ancestry-specific mechanisms in the triple negative breast cancer tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr NG03.

Introduction Breast cancer is the most common cause of cancer related deaths in women worldwide; however, significant disparities are evident in the epidemiology of breast cancer subtypes and clinical outcomes of different racial/ethnic groups. African Americans are 40% more likely to die from breast cancer—a disparity that is partially explained by genetic predisposition to early onset breast cancer and triple negative breast cancer (TNBC), an aggressive subtype linked to West African ancestry and associated with BRCA-1 germline mutations. Pathogenic BRCA mutations significantly alter breast cancer treatment, informing alternate screening, chemoprevention, prophylactic resections and use of PARB inhibitors; however, AAs have higher prevalence of BRCA variants of uncertain significance (VUS) secondary to underrepresentation of African ancestry in the reference genome. The aim of this study is therefore to further characterize BRCA mutations and BRCA VUS in breast cancer patients with African ancestry. Methods RNA Sequencing platforms were used to determine somatic mutation profiles from primary tumor samples of over 70 breast cancer patients from Ethiopia and Ghana, by identifying single nucleotide polymorphisms (SNPs) in BRCA 1 and 2. Each sequence variant was evaluated for consequence on the gene, previously reported clinical significance, and allele frequency by self-reported race in comparison to global allele frequencies. Results BRCA1: 10 BRCA1 SNPs were identified: Missense: Rs1799966, rs16942, rs16941, rs799917, rs4986850, rs1799950; synonymous: rs1060915, rs16940, rs1799949; variant of 3'UTR: rs3092995. Rs1799966, rs16942, rs16941 and rs1799950 cause deleterious missense mutations, and have been reported as uncertain clinical significance. No SNPs were previously reported pathogenic, 6 had uncertain significance, and 4 were classified as either benign or likely benign. Allele frequency of Rs799917 was high among Ethiopian, Ghanaian, and 1KG African subgroups. BRCA2: 13 BRCA2 SNPs were identified: Missense: rs766173, rs144848, rs1799944, rs169547; synonymous: rs1801439, rs1801499, rs1801406, rs543304, rs206075, rs1799955, rs9590940; downstream/missense: rs1801426; variant of 5'Prime UTR: rs1799943. Rs766173 caused a deleterious missense mutation, with conflicting interpretations of pathogenicity. No SNPs were previously reported pathogenic, 4 had uncertain significance, and 8 were either benign or likely benign. No SNPs had high allele frequency in African ancestry. Conclusions The BRCA-1 SNP Rs799917 has a high allele frequency rate among Ethiopian, Ghanaian, and 1KG African ancestry, suggesting this mutation is potentially unique to African ancestry. Further investigation with RNA seq or whole genome sequencing in larger cohorts is warranted. Citation Format: Solange Bayard, Rachel Martini, Yalei Chen, Brittany Jenkins, Isra Elhussin, Esther Cheng, Syed Hoda, Paula Ginter, Jeffrey Hanover, Rozina Zeidan, Joseph Oppong, Kofi Gyan, Clayton Yates, Rick Kittles, Engida Abebe, Ishmael Kyei, Frances Aitpillah, Michael Adinky, Lisa Newman, Melissa Davis. BRCA sequence variants in breast cancer patients with African ancestry [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-139.

Purpose Breast cancer, the most common cancer worldwide, is the leading cause of cancer mortality in Ghanaian women. Previous studies find Ghanaian women are diagnosed at a younger age and at more advanced stages (III and IV), and have tumors with characteristics similar to African American women. We sought to remedy gaps in knowledge about breast cancer survival in Ghana and its relation to demographic and biologic factors of the tumors at diagnosis to assist in cancer control and registration planning. Methods Individuals with a breast cancer diagnosis who sought care at Komfo Anokye Teaching Hospital from 2009 to 2014 were identified via medical records. Follow-up telephone interviews were held to assess survival. Kaplan-Meier plots and Cox proportional hazards models assessed survival associated with clinical and demographic characteristics. Results A total of 223 patients completed follow-up and were analyzed. The median survival was 3.8 years. Approximately 50% of patients were diagnosed with grade 3 tumors, which significantly increased the risk of recurrence or death (hazard ratio [HR] for grade 2 versus 1, 2.98; 95% CI, 1.26 to 7.02; HR grade 3 v 1, 2.56; 95% CI, 1.08 to 6.07; P = .04). No other variables were significantly associated with survival. Conclusion Higher tumor grade was significantly associated with shorter survival, indicating impact of aggressive biology at diagnosis on higher risk of cancer spread and recurrence. Contrary to prevailing notions, telephone numbers were not reliable for follow-up. Collecting additional contact information will likely contribute to improvements in patient care and tracking. A region-wide population-based active registry is important to implement cancer control programs and improve survival in sub-Saharan Africa.

This study analyzes a survey conducted at a gathering of clinicians who specialize in breast cancer in sub-Saharan Africa to better understand what they need from international collaborators.

The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa.Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression.The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. For the entire group, 44 % were AR-positive and 45 % were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared with ER/PR-negative tumors (87 vs. 26 %; p0.0001), but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45 % were ALDH1-positive and 24 % were AR-positive. ALDH1 positivity was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019).We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.

Women with African ancestry in western, sub-Saharan Africa and in the United States represent a population subset facing an increased risk of being diagnosed with biologically aggressive phenotypes of breast cancer that are negative for the estrogen receptor, the progesterone receptor, and the HER2/neu marker. These tumors are commonly referred to as triple-negative breast cancer. Disparities in breast cancer incidence and outcome related to racial or ethnic identity motivated the establishment of the International Breast Registry, on the basis of partnerships between the Komfo Anokye Teaching Hospital in Kumasi, Ghana, the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan, and the Henry Ford Health System in Detroit, Michigan. This research collaborative has featured educational training programs as well as scientific investigations related to the comparative biology of breast cancer in Ghanaian African, African American, and white/European American patients. Currently, the International Breast Registry has expanded to include African American patients throughout the United States by partnering with the Sisters Network (a national African American breast cancer survivors’ organization) and additional sites in Ghana (representing West Africa) as well as Ethiopia (representing East Africa). Its activities are now coordinated through the Henry Ford Health System International Center for the Study of Breast Cancer Subtypes. Herein, we review the history and results of this international program at its 10-year anniversary.

There is limited understanding of the influence of multiple characteristics of food vending on students’ preferences for vended food. This study assessed students’ preferences and willingness to pay (WTP) for various characteristics of food vending service. A Discrete Choice Experiment (DCE) was administered to 585 students of the Wa Campus of the University for Development Studies, Ghana. The respondents were selected through multi-stage sampling. Data was collected using a structured experimental survey questionnaire. Six attributes (and attribute levels) were identified from a qualitative study and used to design the DCE: Food taste (natural vs. spicy), environmental sanitation (good vs. poor), vendor’s personal hygiene (good vs. poor), customer relations (good vs. poor), vendors’ location (far from vs. near to students) and price ((1US$=GH¢4.5) per plate (GH¢3, 6, 9 and 12). Nested logit modelling of the data showed that the highest preference and marginal WTP values were associated with good environmental sanitation, good personal hygiene, natural taste of food, good customer relation, and proximity of vendor, in that order. The study concludes that health consciousness is a major factor that attracts students to vended food. Food vendors should, therefore, improve upon the sanitation of their environments and their personal hygiene to attract and retain customers. Keywords: Food Vending Characteristics, Student Preferences, Willingness to Pay, Discrete Choice Experiment, Nested Logit Model

Most antiviral treatment options target the invading pathogen and unavoidably encounter loss of efficacy as the pathogen mutates to overcome replication restrictions. A good strategy for circumventing drug resistance, or for pathogens without treatment options, is to target host cell proteins that are utilized by viruses during infection. The small molecule WP1130 is a selective deubiquitinase inhibitor shown previously to successfully reduce replication of noroviruses and some other RNA viruses. In this study, we screened a library of 31 small molecule derivatives of WP1130 to identify compounds that retained the broad-spectrum antiviral activity of the parent compound in vitro but exhibited improved drug-like properties, particularly increased aqueous solubility. Seventeen compounds significantly reduced murine norovirus infection in murine macrophage RAW 264.7 cells, with four causing decreases in viral titers that were similar or slightly better than WP1130 (1.9 to 2.6 log scale). Antiviral activity was observed following pre-treatment and up to 1 hour postinfection in RAW 264.7 cells as well as in primary bone marrow-derived macrophages. Treatment of the human norovirus replicon system cell line with the same four compounds also decreased levels of Norwalk virus RNA. No significant cytotoxicity was observed at the working concentration of 5 µM for all compounds tested. In addition, the WP1130 derivatives maintained their broad-spectrum antiviral activity against other RNA viruses, Sindbis virus, LaCrosse virus, encephalomyocarditis virus, and Tulane virus. Thus, altering structural characteristics of WP1130 can maintain effective broad-spectrum antiviral activity while increasing aqueous solubility.

Maternal mortality remains a huge problem in the developing world, especially in Sub-Saharan Africa.1 According to the World Health Organization, efforts intended to decrease maternal deaths need to recognize and address unsafe abortions as a significant contributor to the high rates of maternal mortality found in developing countries.2,3 In Africa, where abortions are highly restricted, 680 women die per 100,000 abortions, compared with 0.2-1.2 women per 100,000 in developed countries, where most abortions are legal.4.

Background The ability of many countries to achieve national health goals such as the Millennium Development Goals remains hindered by inadequate and poorly distributed health personnel, including doctors. The distribution of doctors in Ghana is highly skewed, with a majority serving in two major metropolitan areas (Accra and Kumasi), and inadequate numbers in remote and rural districts. Recent policies increasing health worker salaries have reduced migration of doctors out of Ghana, but made little difference to distribution within the country. This qualitative study was undertaken to understand how practicing doctors and medical leaders in Ghana describe the key factors reducing recruitment and retention of health professionals into remote areas, and to document their proposed policy solutions. Methods In-depth interviews were carried out with 84 doctors and medical leaders, including 17 regional medical directors and deputy directors from across Ghana, and 67 doctors currently practicing in 3 regions (Greater Accra, Brong Ahafo, and Upper West); these 3 regions were chosen to represent progressively more remote distances from the capital of Accra. Results and discussion All participants felt that rural postings must have special career or monetary incentives given the loss of locum (i.e. moonlighting income), the higher workload, and professional isolation of remote assignments. Career 'death' and prolonged rural appointments were a common fear, and proposed policy solutions focused considerably on career incentives, such as guaranteed promotion or a study opportunity after some fixed term of service in a remote or hardship area. There was considerable stress placed on the need for rural doctors to have periodic contact with mentors through rural rotation of specialists, or remote learning centers, and reliable terms of appointment with fixed end-points. Also raised, but given less emphasis, were concerns about the adequacy of clinical equipment in remote facilities, and remote accommodations. Conclusions In-depth discussions with doctors suggest that while salary is important, it is career development priorities that are keeping doctors in urban centers. Short-term service in rural areas would be more appealing if it were linked to special mentoring and/or training, and led to career advancement.