Molecular features of androgen-receptor low, estrogen receptor-negative breast cancers in the Carolina breast cancer study

Purpose: Androgen receptor (AR) expression is absent in 40–90% of estrogen receptor (ER)-negative breast cancers. The prognostic value of AR in ER-negative patients and therapeutic targets for patients absent in AR remains poorly explored. Methods: We used an RNA-based multigene classifier to identify AR-low and AR-high ER-negative participants in the Carolina Breast Cancer Study (CBCS; N = 669) and The Cancer Genome Atlas (TCGA; N = 237). We compared AR-defined subgroups by demographics, tumor characteristics, and established molecular signatures [PAM50 risk of recurrence (ROR), homologous recombination deficiency (HRD), and immune response]. Results: AR-low tumors were more prevalent among younger (RFD = + 10%, 95% CI = 4% to 16%) participants in CBCS and were associated with HER2 negativity (RFD = − 35%, 95% CI = − 44% to − 26%), higher grade (RFD = + 17%, 95% CI = 8% to 26%), and higher risk of recurrence scores (RFD = + 22%, 95% CI = 16.1% to 28%), with similar results in TCGA. The AR-low subgroup was strongly associated with HRD in CBCS (RFD = + 33.3%, 95% CI = 23.8% to 43.2%) and TCGA (RFD = + 41.5%, 95% CI = 34.0% to 48.6%). In CBCS, AR-low tumors had high adaptive immune marker expression. Conclusion: Multigene, RNA-based low AR expression is associated with aggressive disease characteristics as well as DNA repair defects and immune phenotypes, suggesting plausible precision therapies for AR-low, ER-negative patients

Intraoperative ultrasound-guided iodine-125 seed implantation for unresectable pancreatic carcinoma

<p>Abstract</p> <p>Background</p> <p>To assess the feasibility and efficacy of using ¹²⁵I seed implantation under intraoperative ultrasound guidance for unresectable pancreatic carcinoma.</p> <p>Methods</p> <p>Fourteen patients with pancreatic carcinoma that underwent laparotomy and considered unresectable were included in this study. Nine patients were pathologically diagnosed with Stage II disease, five patients with Stage III disease. Fourteen patients were treated with ¹²⁵I seed implantation guided by intraoperative ultrasound and received D₉₀of ¹²⁵I seeds ranging from 60 to 140 Gy with a median of 120 Gy. Five patients received an additional 35–50 Gy from external beam radiotherapy after seed implantation and six patients received 2–6 cycles of chemotherapy.</p> <p>Results</p> <p>87.5% (7/8) of patients received partial to complete pain relief. The response rate of tumor was 78.6%, One-, two-and three-year survival rates were 33.9% and 16.9%, 7.8%, with local control of disease achieved in 78.6% (11/14), and the median survival was 10 months (95% CI: 7.7–12.3).</p> <p>Conclusion</p> <p>There were no deaths related to ¹²⁵I seed implant. In this preliminary investigation, ¹²⁵I seed implant provided excellent palliation of pain relief, local control and prolong the survival of patients with stage II and III disease to some extent.</p

A high-quality bonobo genome refines the analysis of hominid evolution

The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation1,2. Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps are closed, including the resolution of about half of the segmental duplications and almost all of the full-length mobile elements. We compare the bonobo genome to those of other great apes1,3,4,5 and identify more than 5,569 fixed structural variants that specifically distinguish the bonobo and chimpanzee lineages. We focus on genes that have been lost, changed in structure or expanded in the last few million years of bonobo evolution. We produce a high-resolution map of incomplete lineage sorting and estimate that around 5.1% of the human genome is genetically closer to chimpanzee or bonobo and that more than 36.5% of the genome shows incomplete lineage sorting if we consider a deeper phylogeny including gorilla and orangutan. We also show that 26% of the segments of incomplete lineage sorting between human and chimpanzee or human and bonobo are non-randomly distributed and that genes within these clustered segments show significant excess of amino acid replacement compared to the rest of the genome

Spotlight on tavaborole for the treatment of onychomycosis

Sphoorthi Jinna, Justin Finch Department of Dermatology, University of Connecticut School of&nbsp;Medicine, Farmington, CT, USA Abstract: Onychomycosis is a fungal nail plate infection that has been increasing in prevalence. A variety of oral and topical anti-fungal agents are currently available but their use is limited by their adverse effect profile, drug&ndash;drug interactions, and limited efficacy. Therefore, there is a great need for newer anti-fungal agents. Tavaborole is one of these newer agents and was approved by the US Food and Drug Administration in July 2014 for the topical treatment of mild to moderate toenail onychomycosis. Tavaborole is a novel, boron-based anti-fungal agent with greater nail plate penetration than its predecessors, due to its smaller molecular weight. It has proven through several Phase II and III trials that it can be a safe and effective topical agent for the treatment of mild to moderate toenail onychomycosis without the need for debridement. In this paper, we review the landscape of topical and systemic treatment of onychomycosis, with particular attention to the pharmacokinetics, safety, and efficacy of topical tavaborole. Keywords: tavaborole, boron-based antifungals, oxaboroles, onychomycosi

Ignored: A Practical Theology Inquiry of Korean-Speaking Young Adults in a Transnational Congregational Context

This dissertation focuses on an overlooked population in the study of Korean American Christianity—Korean-speaking young adults in immigrant churches. Considering that almost all of the literature about the emerging generation in Korean churches in the U.S. exclusively attend to the English speaking generation, this research project raises the question of “How should the Korean immigrant church as a community understand and serve Korean speaking young adults?” In light of this central research question, this study seeks to bring awareness to the hidden younger generation of Korean-speaking young adults, and to suggest a discernment process for Korean immigrant churches in the U.S. to engage in more faithful practices. The opening two chapters lay the methodological groundwork. With an overarching methodology of practical theology and a qualitative research method, chapter 1 provides a detailed account of the research methodology, including how this study’s field research was conducted. Chapter 2 surveys and evaluates the current understanding of this consistently ignored population from the existing literature. Chapter 3 expounds upon the results from data collected through a survey of 404 Korean-speaking young adults and 40 in-depth interviews with Korean American pastors. Throughout the discussion of the research findings, this study addresses Korean-speaking young adults’ intersectional struggles (as emerging adults and ethnic minorities), their experiences of loneliness, their transnational perspectives, and their relationships with their church communities. Based on these findings, chapter 4 proposes an ecclesiology for Korean immigrants and their young people in a transnational context, in conversation with contemporary migration theology. This constructive ecclesiology recommends that the Korean immigrant church as a community should embody these features: people finding their identity and dignity based on the imago dei, beyond national origin or migration status; people experiencing belonging and formation together within the framework of an adoptive family of siblings; and people participating in and contributing to God’s ongoing redemptive work from a missional church perspective. Finally, chapter 5 suggests some pragmatic ways to move forward. This chapter articulates four necessary transformations for Korean immigrant churches to process and pursue as a community, moving: from a fragmented church structure to an intergenerationally connected community; from a knowledge-based and unidirectional teaching discipleship program to spiritual formation in an adoptive family of siblings; from hierarchical leadership to missional church leadership; and from a self-conceived identity as a traditional immigrant church to a transnational church. This study finishes by proposing Appreciative Inquiry as a simple but helpful way to begin actualizing these changes