"Nobody Will Tell You. You've Got to Ask!": An Examination of Patient-Provider Communication Needs and Preferences among Black and White Women with Early-Stage Breast Cancer.

Patient-provider communication is a critical component of healthcare and is associated with treatment quality and outcomes for women with breast cancer. This qualitative study examines similarities and differences in patient perspectives of communication needs between Black and White breast cancer survivors. We conducted four focus groups (N = 28) involving women with early-stage breast cancer on adjuvant endocrine therapy (AET), stratified by race and length of time on AET (< 6 months and >6 months). Each group was moderated by a race-concordant moderator and analyzed by emergent themes. Participants expressed common patient-provider communication needs, namely increased sensitivity from oncologists during the initial cancer diagnosis, personalized information to facilitate treatment decisions, emotional support during the transition from active treatment to maintenance, and rapid provider responses to mobile app-based queries. Communication differences by race also emerged. Black women were less likely than White women to describe having their informational needs met. White women praised longstanding relationships with providers, while Black women shared personal stories of disempowered interactions and noted the importance of patient advocates. White women more often reported privacy concerns about technology use. Unlike White women, Black women reported willingness to discuss sensitive topics, both online and offline, but believed those discussions made their providers feel uncomfortable. Early-stage breast cancer patients on AET, regardless of race, have similar needs for patient-centered communication with their oncologists. However, Black women were more likely to report experiencing poorer communication with providers than White women, which may be improved by technology and advocates.

A qualitative exploration of race-based differences in social support needs of diverse women with breast cancer on adjuvant therapy.

OBJECTIVE: Social support is a critical component of breast cancer care and is associated with clinical and quality of life outcomes. Significant health disparities exist between Black and White women with breast cancer. Our study used qualitative methods to explore the social support needs of Black and White women with hormone receptor-positive breast cancer on adjuvant endocrine therapy (AET). METHODS: We conducted four focus group (FG) interviews (N = 28), stratified by race (ie, Black and White) and time on AET. FGs were audiotaped, transcribed, and analyzed according to conventions of thematic analysis. RESULTS: Participants noted the importance of having their informational and emotional social support needs met by friends and family members. White participants reported support provided by others with breast cancer was crucial; Black women did not discuss other survivors as part of their networks. Notably, both White and Black participants used the FG environment to provide experiential social support to each other. CONCLUSIONS: White participants noted that having other breast cancer survivors in their support network was essential for meeting their social support needs. However, Black participants did not reference other breast cancer survivors as part of their networks. Cancer centers should consider reviewing patients' access to experiential support and facilitate opportunities to connect women in the adjuvant phase.

THRIVE study protocol: a randomized controlled trial evaluating a web-based app and tailored messages to improve adherence to adjuvant endocrine therapy among women with breast cancer.

BACKGROUND: Long-term use of adjuvant endocrine therapy (AET) among women with early-stage, hormone receptor-positive breast cancer significantly reduces the risk of hospitalizations, cancer recurrence, and mortality. AET is associated with adverse symptoms that often result in poor adherence. A web-enabled app offers a novel way to communicate and manage symptoms for women on AET. In a region with significant racial disparities in breast cancer outcomes, our study tests the impact of a web-enabled app that collects and transmits patient-reported symptoms to healthcare teams to facilitate timely and responsive symptom management on medication adherence. METHODS: In this randomized controlled trial, we randomize 300 patients initiating AET to one of three arms: 1) an "App" group (n = 100) that receives weekly reminders to use the THRIVE study app; 2) an "App+Feedback" group (n = 100) that receives weekly reminders and tailored feedback based on their use of the app; or 3) a "Usual Care" group (n = 100) that receives usual care only. Participants are stratified by race: 50% White and 50% Black. The duration of the intervention is six months following enrollment, and outcomes are assessed at 12-months. The primary outcome is adherence, which is captured using an electronic monitoring pillbox. Secondary outcomes include symptom burden, quality of life, self-efficacy for managing symptoms, and healthcare costs. We also evaluate the impact of the intervention on racial disparities in adherence. Data are derived from three sources: electronic health record data to capture treatment changes, healthcare utilization, and health outcomes; self-report survey data related to adherence, symptom burden, and quality of life; and an electronic medication monitoring device that captures adherence. DISCUSSION: A successful web-enabled intervention could be disseminated across systems, conditions, and populations. By evaluating the impact of this intervention on a comprehensive set of measures, including AET adherence, patient outcomes, and costs, our study will provide valuable and actionable results for providers, policy makers, and insurers who strive to achieve the "Triple Aim" - reduce costs while improving health outcomes and the patient care experience. TRIAL REGISTRATION: NCT03592771. Prospectively registered on July 19, 2018.

Activation domains for controlling plant gene expression using designed transcription factors.

Targeted gene regulation via designed transcription factors has great potential for precise phenotypic modification and acceleration of novel crop trait development. To this end, designed transcriptional activators have been constructed by fusing transcriptional activation domains to DNA-binding proteins. In this study, a transcriptional activator from the herpes simplex virus, VP16, was used to identify plant regulatory proteins. Transcriptional activation domains were identified from each protein and fused with zinc finger DNA-binding proteins (ZFPs) to generate designed transcriptional activators. In addition, specific sequences within each transcriptional activation domain were modified to mimic the VP16 contact motif that interacts directly with RNA polymerase II core transcription factors. To evaluate these designed transcriptional activators, test systems were built in yeast and tobacco comprising reporter genes driven by promoters containing ZFP-binding sites upstream of the transcriptional start site. In yeast, transcriptional domains from the plant proteins ERF2 and PTI4 activated MEL1 reporter gene expression to levels similar to VP16 and the modified sequences displayed even greater levels of activation. Following stable transformation of the tobacco reporter system with transcriptional activators derived from ERF2, GUS reporter gene transcript accumulation was equal to or greater than those derived from VP16. Moreover, a modified ERF2 domain displayed significantly enhanced transcriptional activation compared with VP16 and with the unmodified ERF2 sequence. These results demonstrate that plant sequences capable of facilitating transcriptional activation can be found and, when fused to DNA-binding proteins, can enhance gene expression.

Trait stacking via targeted genome editing.

Modern agriculture demands crops carrying multiple traits. The current paradigm of randomly integrating and sorting independently segregating transgenes creates severe downstream breeding challenges. A versatile, generally applicable solution is hereby provided: the combination of high-efficiency targeted genome editing driven by engineered zinc finger nucleases (ZFNs) with modular 'trait landing pads' (TLPs) that allow 'mix-and-match', on-demand transgene integration and trait stacking in crop plants. We illustrate the utility of nuclease-driven TLP technology by applying it to the stacking of herbicide resistance traits. We first integrated into the maize genome an herbicide resistance gene, pat, flanked with a TLP (ZFN target sites and sequences homologous to incoming DNA) using WHISKERS™-mediated transformation of embryogenic suspension cultures. We established a method for targeted transgene integration based on microparticle bombardment of immature embryos and used it to deliver a second trait precisely into the TLP via cotransformation with a donor DNA containing a second herbicide resistance gene, aad1, flanked by sequences homologous to the integrated TLP along with a corresponding ZFN expression construct. Remarkably, up to 5% of the embryo-derived transgenic events integrated the aad1 transgene precisely at the TLP, that is, directly adjacent to the pat transgene. Importantly and consistent with the juxtaposition achieved via nuclease-driven TLP technology, both herbicide resistance traits cosegregated in subsequent generations, thereby demonstrating linkage of the two independently transformed transgenes. Because ZFN-mediated targeted transgene integration is becoming applicable across an increasing number of crop species, this work exemplifies a simple, facile and rapid approach to trait stacking.

Silent suffering: the impact of sexual health challenges on patient-clinician communication and adherence to adjuvant endocrine therapy among Black women with early-stage breast cancer.

PURPOSE: Adjuvant endocrine therapy (AET) increases sexual health challenges for women with early-stage breast cancer. Black women are more likely than women of other racial/ethnic groups to report adverse symptoms and least likely to initiate and maintain AET. Little is known about how sexual health challenges influence patient-clinician communication and treatment adherence. This study explores facilitators of and barriers to patient-clinician communication about sexual health and how those factors might affect AET adherence among Black women with early-stage breast cancer. METHODS: We conducted 32 semi-structured, in-depth interviews among Black women with early-stage breast cancer in the U.S. Mid-South region. Participants completed an online questionnaire prior to interviews. Data were analyzed using thematic analysis. RESULTS: Participants' median age was 59 (range 40-78 years, SD = 9.0). Adverse sexual symptoms hindered participants' AET adherence. Facilitators of patient-clinician communication about sexual health included female clinicians and peer support. Barriers included perceptions of male oncologists' disinterest in Black women's sexual health, perceptions of male oncologists' biased beliefs about sexual activity among older Black women, cultural norms of sexual silence among Southern Black women, and medical mistrust. CONCLUSIONS: Adverse sexual symptoms and poor patient-clinician communication about sexual health contribute to lower AET adherence among Black women with early-stage breast cancer. New interventions using peer support models and female clinicians trained to discuss sexual health could ameliorate communication barriers and improve treatment adherence. IMPLICATIONS FOR CANCER SURVIVORS: Black women with early-stage breast cancer in the U.S. Mid-South may require additional resources to address sociocultural and psychosocial implications of cancer survivorship to enable candid discussions with oncologists.

Targeted insertion of large DNA sequences by homology-directed repair or non-homologous end joining in engineered tobacco BY-2 cells using designed zinc finger nucleases.

Targeted integration of recombinant DNA fragments into plant genomes by DNA double-strand break (DSB) repair mechanisms has become a powerful tool for precision engineering of crops. However, many targeting platforms require the screening of many transgenic events to identify a low number of targeted events among many more random insertion events. We developed an engineered transgene integration platform (ETIP) that uses incomplete marker genes at the insertion site to enable rapid phenotypic screening and recovery of targeted events upon functional reconstitution of the marker genes. The two marker genes, encoding neomycin phosphotransferase II (nptII) and Discosoma sp. red fluorescent protein (DsRed) enable event selection on kanamycin-containing selective medium and subsequent screening for red fluorescent clones. The ETIP design allows targeted integration of donor DNA molecules either by homology-directed repair (HDR) or non-homologous end joining (NHEJ)-mediated mechanisms. Targeted donor DNA integration is facilitated by zinc finger nucleases (ZFN). The ETIP cassette was introduced into Nicotiana tabacum BY-2 suspension cells to generate target cell lines containing a single copy locus of the transgene construct. The utility of the ETIP platform has been demonstrated by targeting DNA constructs containing up to 25-kb payload. The success rate for clean targeted DNA integration was up to 21% for HDR and up to 41% for NHEJ based on the total number of calli analyzed by next-generation sequencing (NGS). The rapid generation of targeted events with large DNA constructs expands the utility of the nuclease-mediated gene addition platform both for academia and the commercial sector.

Sistas Taking a Stand for Breast Cancer Research (STAR) Study: A Community-Based Participatory Genetic Research Study to Enhance Participation and Breast Cancer Equity among African American Women in Memphis, TN.

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.

RpaA regulates the accumulation of monomeric photosystem I and PsbA under high light conditions in Synechocystis sp. PCC 6803.

The response regulator RpaA was examined by targeted mutagenesis under high light conditions in Synechocystis sp. PCC 6803. A significant reduction in chlorophyll fluorescence from photosystem I at 77 K was observed in the RpaA mutant cells under high light conditions. Interestingly, the chlorophyll fluorescence emission from the photosystem I trimers at 77 K are similar to that of the wild type, while the chlorophyll fluorescence from the photosystem I monomers was at a much lower level in the mutant than in the wild type under high light conditions. The RpaA inactivation resulted in a dramatic reduction in the monomeric photosystem I and the D1 protein but not the CP47 content. However, there is no significant difference in the transcript levels of psaA or psbA or other genes examined, most of which are involved in photosynthesis, pigment biosynthesis, or stress responses. Under high light conditions, the growth of the mutant was affected, and both the chlorophyll content and the whole-chain oxygen evolution capability of the mutant were found to be significantly lower than those of the wild type, respectively. We propose that RpaA regulates the accumulation of the monomeric photosystem I and the D1 protein under high light conditions. This is the first report demonstrating that inactivation of a stress response regulator has specifically reduced the monomeric photosystem I. It suggests that PS I monomers and PS I trimers can be regulated independently for acclimation of cells to high light stress.

Targeted transgene integration in plant cells using designed zinc finger nucleases.

Targeted transgene integration in plants remains a significant technical challenge for both basic and applied research. Here it is reported that designed zinc finger nucleases (ZFNs) can drive site-directed DNA integration into transgenic and native gene loci. A dimer of designed 4-finger ZFNs enabled intra-chromosomal reconstitution of a disabled gfp reporter gene and site-specific transgene integration into chromosomal reporter loci following co-transformation of tobacco cell cultures with a donor construct comprised of sequences necessary to complement a non-functional pat herbicide resistance gene. In addition, a yeast-based assay was used to identify ZFNs capable of cleaving a native endochitinase gene. Agrobacterium delivery of a Ti plasmid harboring both the ZFNs and a donor DNA construct comprising a pat herbicide resistance gene cassette flanked by short stretches of homology to the endochitinase locus yielded up to 10% targeted, homology-directed transgene integration precisely into the ZFN cleavage site. Given that ZFNs can be designed to recognize a wide range of target sequences, these data point toward a novel approach for targeted gene addition, replacement and trait stacking in plants.