Ankfn1-mutant vestibular defects require loss of both ancestral and derived paralogs for penetrance in zebrafish.

How and to what degree gene duplication events create regulatory innovation, redundancy, or neofunctionalization remain important questions in animal evolution and comparative genetics. Ankfn1 genes are single copy in most invertebrates, partially duplicated in jawed vertebrates, and only the derived copy retained in most mammals. Null mutations in the single mouse homolog have vestibular and neurological abnormalities.

ZNF423 patient variants, truncations, and in-frame deletions in mice define an allele-dependent range of midline brain abnormalities.

Interpreting rare variants remains a challenge in personal genomics, especially for disorders with several causal genes and for genes that cause multiple disorders. ZNF423 encodes a transcriptional regulatory protein that intersects several developmental pathways. ZNF423 has been implicated in rare neurodevelopmental disorders, consistent with midline brain defects in Zfp423-mutant mice, but pathogenic potential of most patient variants remains uncertain.

Does Surgical Teaching Take Time? Resident Participation in Minimally Invasive Hysterectomy for Endometrial Cancer.

Study Objective: To determine the association between resident involvement and operative time for minimally invasive surgery (MIS) for endometrial cancer.

Design: A retrospective cohort study (Canadian Task Force classification II-2).

Setting: An integrated health care system in Northern California.

Fertility preservation and survival among young women with early ovarian cancer living in US counties with gynecologic oncologist services.

Objective: To examine the association between living in a county with gynecologic oncologist provision, the performance of fertility sparing surgery, and survival among young women with early epithelial ovarian cancer.

Methods: The present retrospective cohort study was based on the SEER 18 dataset of the US National Cancer Institute. Women younger than 45 years with early stage epithelial ovarian cancer diagnosed between 2000 and 2012 were included.

Urinary diversions: A time to enrich surgical training?

Objective: To assess the potential exposure to complex urologic procedures, specifically urinary diversion, during a gynecologic oncology fellowship.

Methods: We queried the University HealthSystem Consortium (UHC) database to determine the total number of urinary diversions performed from October 2008 to August 2012. This data was used to estimate the mean number of urinary diversions performed each year.

Barriers prevent patient access to personalized therapies identified by molecular tumor profiling of gynecologic malignancies.

Objective: This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies.

Methods: We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations.

Patient and physician factors associated with participation in cervical and uterine cancer trials: an NRG/GOG247 study.

Purpose: The aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials.

Methods: Prospective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial.

Novel synthetic toll-like receptor 4/MD2 ligands attenuate sterile inflammation.

Toll-like receptor (TLR) stimulation has been implicated as a major contributor to chronic inflammation. Among these receptors, TLR4 has been described as a key regulator of endogenous inflammation and has been proposed as a therapeutic target. Previously, we discovered by high-throughput screening a group of substituted pyrimido[5,4-b]indoles that activated a nuclear factor-κB reporter in THP-1 human monocytic cells.

Bariatric surgery decreases the risk of uterine malignancy.

Objective: To describe the risk of uterine malignancy among women who have had weight loss surgery.

Methods: We performed a retrospective cohort study among inpatient admissions of women 18years, or older, registered in the University HealthSystem Consortium (UHC) dataset. The rate of uterine malignancy per hospital admission was calculated.

Regional variation in surgical assessment of lymph nodes for staging among women with early-stage epithelial ovarian cancer.

Objective: To investigate geographical and socioeconomic variations in performance of lymph node dissection for the evaluation of patients with early-stage epithelial ovarian cancer.

Methods: A population-based, retrospective cohort study was conducted using data from the National Cancer Institute's SEER Program for 15 geographic registries and county-level measures. Women with early-stage epithelial ovarian cancer registered between 2000 and 2008 with known lymph node assessment status were studied.

Innate immune protection against infectious diseases by pulmonary administration of a phospholipid-conjugated TLR7 ligand.

Pulmonary administration of Toll-like receptor (TLR) ligands protects hosts from inhaled pathogens. However, systemic side effects induced by TLR stimulation limit clinical development. Here, a small-molecule TLR7 ligand conjugated with phospholipid, 1V270 (also designated TMX201), was tested for innate immune activation and its ability to prevent pulmonary infection in mice.

The influence of time perspective on cervical cancer screening among Latinas in the United States.

To develop effective interventions to increase cervical cancer screening among Latinas, we should understand the role of cultural factors, such as time perspective, in the decision to be screened. We examined the relation between present time orientation, future time orientation, and self-reported cervical cancer screening among Latinas. A group of 206 Latinas completed a survey measuring factors associated with screening.

Excess risk of Clostridium difficile infection in ovarian cancer is related to exposure to broad-spectrum antibiotics.

Purpose: The purpose of the study was to determine if a diagnosis of ovarian cancer is independently associated with an increased risk of Clostridium difficile infection (CDI).

Methods: The University HealthSystem Consortium database was queried to perform a retrospective cohort study of women with and without ovarian cancer who were diagnosed with CDI. Inpatients undergoing total hysterectomy from 2008 to 2012 were studied.

Health promotion via deaf-friendly ministries.

Deaf community members face many barriers to accessing health information. This paper discusses the feasibility of creating a nationwide network of Deaf-friendly ministries to help disseminate cancer information in American Sign Language (ASL) to the Deaf community. Deaf-friendly ministries (N = 403), identified through Internet searches and one-on-one referrals, were sent up to three mailed invitations to join the network.

Prognosis following the use of complementary and alternative medicine in women diagnosed with breast cancer.

Objective: The purpose of this study was to assess whether CAM use affected breast cancer prognosis in those who did not receive systemic therapy.

Design: Secondary data analysis of baseline/survey data from the Women's Healthy Eating and Living (WHEL) study. 2562 breast cancer survivors participating in the study completed baseline assessments and a CAM use questionnaire.

Understanding the limits of large datasets.

Many health professionals use large datasets to answer behavioral, translational, or clinical questions. Understanding the impact of missing data in large databases, such as disease registries, can avoid erroneous interpretations of these data. Using the California Cancer Registry, the authors selected seven common cancers, seven sociodemographic and clinical variables, and the top three reporting sources, as examples of the type of data that would be deemed critical to most studies.

Changing demographics of cervical cancer in the United States (1973-2008).

Objective: To describe changes in the cervical cancer population.

Methods: The SEER database 9 registries from 1973 to 2008 were queried to perform a retrospective cohort study of women with invasive cervical cancer. Estimated annual percent change (EAPC) in incidence rates and 95% confidence intervals (CI) over the entire study period were compared according to age, stage, race, and cell type (squamous [SCC] and adenocarcinoma [ACA]).

Cardiovascular disease is the leading cause of death among endometrial cancer patients.

Objective: To evaluate the causes of death among women with endometrial cancer.

Methods: SEER registries from 1973-1988 were queried to perform a retrospective cohort study of women with invasive epithelial endometrial cancer. Causes of death were compared according to grade and stage.

A multigroup confirmatory factor analysis of the Patient Health Questionnaire-9 among English- and Spanish-speaking Latinas.

Depression is a significant problem for ethnic minorities that remains understudied partly due to a lack of strong measures with established psychometric properties. One screening tool, the Patient Health Questionnaire-9 (PHQ-9), which was developed for use in primary care has also gained popularity in research settings. The reliability and validity of the PHQ-9 has been well established among predominantly Caucasian samples, in addition to many minority groups.

Targeting granzyme B to tumor cells using a yoked human chorionic gonadotropin.

Purpose: Luteinizing hormone receptor (LHR) is found in abundance on human ovarian, breast, endometrial and prostate carcinomas but at only low levels on non-gonadal tissues. To selectively kill LHR-expressing tumors, granzyme B (GrB) was linked to a protein in which both chains of human chorionic gonadotropin were yoked together (YCG).

Methods: GrB-YCG was expressed and secreted from insect Sf9 cells.

Challenges associated with the targeted delivery of gelonin to claudin-expressing cancer cells with the use of activatable cell penetrating peptides to enhance potency.

Background: Treatment of tumors with macromolecular toxins directed to cytoplasmic targets requires selective endocytosis followed by release of intact toxin from the endosomal/lysosomal compartment. The latter step remains a particular challenge. Claudins 3 and 4 are tight junction proteins that are over-expressed in many types of tumors.

Superficial siderosis of the central nervous system due to bilateral jugular vein thrombosis.

Objective: To describe a novel cause of meningeal siderosis due to intermittent subarachnoid bleeding caused by chronic bilateral jugular vein thrombosis.

Design: Case report and review of literature.

Patient: A 51-year-old man with a distant history of cervical injury who presented with transient aphasia in the setting of progressive cognitive decline.

Measurement error of dietary self-report in intervention trials.

Dietary intervention trials aim to change dietary patterns of individuals. Participating in such trials could impact dietary self-report in divergent ways: Dietary counseling and training on portion-size estimation could improve self-report accuracy; participant burden could increase systematic error. Such intervention-associated biases could complicate interpretation of trial results.

Increasing Asian American women's research participation: the Asian grocery store-based cancer education program.

Background: Research study participants with diverse characteristics produce the most generalizable outcomes, but recruiting heterogeneous samples is difficult.

Methods: This pilot study tests whether Asian women (N=1079) with diverse language proficiencies, who were personally recruited to one study by a linguistically and culturally aligned recruiter, would enroll in another study with a single mailed invitation in English.

Results: The 134 participants in the second study represented 17.