DOT1L complex suppresses transcription from enhancer elements and ectopic RNAi in .

Methylation of histone H3 on lysine 79 (H3K79) by DOT1L is associated with actively transcribed genes. Earlier, we described that DOT-1.1, the homolog of mammalian DOT1L, cooperates with the chromatin-binding protein ZFP-1 (AF10 homolog) to negatively modulate transcription of highly and widely expressed target genes.

Learning from history: Lord Brain and Hashimoto's encephalopathy.

We present two historic cases of severe encephalopathy associated with antithyroid antibodies. The first was published by Lord Brain of Eynsham, and the second was from our department's archives. Although both cases are from archival sources, they continue to inform current clinical care.

Number of Circulating CD 73-Expressing Lymphocytes Correlates With Survival After Cardiac Arrest.

Background Patients resuscitated from cardiac arrest ( CA ) have highly variable neurological, circulatory, and systemic ischemia-reperfusion injuries. After the initial hypoxic-ischemic insult, a cascade of immune and inflammatory responses develops and is often fatal. The role of the immune response in pathophysiological characteristics and recovery is not well understood.

Do treatment effects of a web-based cognitive behavioral therapy for insomnia intervention differ for users with and without pain interference? A secondary data analysis.

Cognitive-behavioral therapy for insomnia (CBT-I) shows treatment benefits among individuals with pain interference; however, effects of Internet-delivered CBT-I for this population are unknown. This secondary analysis used randomized clinical trial data from adults assigned to Internet-delivered CBT-I to compare changes in sleep by pre-intervention pain interference. Participants (N = 151) completed the Insomnia Severity Index (ISI) and sleep diaries [sleep onset latency (SOL); wake after sleep onset (WASO)] at baseline, post-assessment, 6- and 12-month follow-ups.

Integrating Oral Health: Physician Assistant Education in 2017.

Purpose: This study describes the inclusion of oral health in physician assistant (PA) education programs in 2017. A 2014 study found that 78% of responding programs (n = 98 of 125) had integrated this content into their curriculum. The current study represents a partnership between the National Interprofessional Initiative on Oral Health, the Center for Integration of Primary Care and Oral Health, and the PA Leadership Initiative in Oral Health.

Neurological Pupil Index and Pupillary Light Reflex by Pupillometry Predict Outcome Early After Cardiac Arrest.

Background: The absence of the pupillary light reflex (PLR) 3 days after cardiac arrest predicts poor outcome, but quantitative PLR assessment with pupillometry early after recovery of spontaneous circulation (ROSC) and throughout targeted temperature management (TTM) has rarely been evaluated.

Methods: Fifty-five adult patients treated with TTM with available pupillometry data from the NeurOptics NPi-200 were studied. Discharge outcome was classified good if the cerebral performance category score was 1-2, poor if 3-5.

MIReAD, a minimum information standard for reporting arthropod abundance data.

Arthropods play a dominant role in natural and human-modified terrestrial ecosystem dynamics. Spatially-explicit arthropod population time-series data are crucial for statistical or mathematical models of these dynamics and assessment of their veterinary, medical, agricultural, and ecological impacts. Such data have been collected world-wide for over a century, but remain scattered and largely inaccessible.

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.

Objectives: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.

Methods: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease.

Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial.

Background: Iron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial.

Methods: We did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA.

Critical questions in ovarian cancer research and treatment: Report of an American Association for Cancer Research Special Conference.

Substantial progress has been made in understanding ovarian cancer at the molecular and cellular level. Significant improvement in 5-year survival has been achieved through cytoreductive surgery, combination platinum-based chemotherapy, and more effective treatment of recurrent cancer, and there are now more than 280,000 ovarian cancer survivors in the United States. Despite these advances, long-term survival in late-stage disease has improved little over the last 4 decades.

Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples.

Background: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage.

Methods: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study.

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.

Background: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain.

Methods: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks.

Improving neurodevelopmental outcomes in children with congenital heart disease: protocol for a randomised controlled trial of working memory training.

Introduction: Executive function (EF) impairments are among the most prevalent neurodevelopmental morbidities in youth with congenital heart disease (CHD). To date, no studies have investigated the efficacy of cognitive interventions to improve EF outcomes in children with CHD.

Methods And Analysis: This is a single-centre, single-blinded, two-arm randomised controlled trial to test the efficacy of Cogmed Working Memory Training (Cogmed) versus standard of care in children with CHD after open-heart surgery in infancy.

How effective is LENA in detecting speech vocalizations and language produced by children and adolescents with ASD in different contexts?

The LENA system was designed and validated to provide information about the language environment in children 0 to 4 years of age and its use has been expanded to populations with a number of communication profiles. Its utility in children 5 years of age and older is not yet known. The present study used acoustic data from two samples of children with autism spectrum disorders (ASD) to evaluate the reliability of LENA automated analyses for detecting speech utterances in older, school age children, and adolescents with ASD, in clinic and home environments.

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease.

Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein () locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C.

Cells Lacking the Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival.

Small cell lung cancer (SCLC) accounts for 15% of lung cancers and is almost always linked to inactivating and mutations. SCLC frequently responds, albeit briefly, to chemotherapy. The canonical function of the gene product RB1 is to repress the E2F transcription factor family.

Catastrophic High School and Collegiate Cheerleading Injuries in the United States: An Examination of the 2006-2007 Basket Toss Rule Change.

Background:: Cheerleading is a specialized athletic activity that can lead to catastrophic injuries. Cheerleading rules are in place to maximize safety of participants. The purpose of this study was to describe catastrophic cheerleading injuries among high school and collegiate-level participants in the United States and to explore whether the 2006-2007 basket toss rule change was effective at reducing the number of catastrophic injuries.

Interpretation of time-to-event outcomes in randomized trials: an online randomized experiment.

Background: Multiple features in the presentation of randomized controlled trial (RCT) results are known to influence comprehension and interpretation. We aimed to compare interpretation of cancer RCTs with time-to-event outcomes when the reported treatment effect measure is the hazard ratio (HR), difference in restricted mean survival times (RMSTD), or both (HR+RMSTD). We also assessed the prevalence of misinterpretation of the HR.

Design analysis indicates Potential overestimation of treatment effects in randomized controlled trials supporting Food and Drug Administration cancer drug approvals.

Objective: Statistical significance drives interpretation of randomized controlled trials (RCTs). We examined the type S error risk-claiming a new drug is falsely beneficial-and exaggeration ratio-how estimated effects differ from true effects-to re-emphasize direction and magnitude of treatment effects.

Study Design And Setting: We systematically reviewed RCTs supporting Food and Drug Administration (FDA) approval of cancer drugs between 2007 and 2016.

Making Meaning After the Death of a Child.

Two bereaved mothers recount how they made meaning after the deaths of their children, recounting how opportunities to tell their stories in medical settings enabled them to construct narratives that promoted resilience and a sense of control. Pediatric palliative care can be conceived as opening space for patients and guardians to tell their stories outside of the specifics of illness, so medical teams can work to accommodate families' values and goals, thereby initiating the process of meaning making. Viewing videos of parent stories enables medical trainees to enhance their communications skills, empathy, and compassion.

Caregiving Status and Health of Heterosexual, Sexual Minority, and Transgender Adults: Results From Select U.S. Regions in the Behavioral Risk Factor Surveillance System 2015 and 2016.

Background And Objectives: Insufficient research attention has been paid to the diversity of informal caregivers, including sexual and gender minority caregivers. This study examined health effects of caregiving separately from sexual orientation or gender identity status, while stratifying by gender among cisgender adults. We hypothesized that compared with heterosexual cisgender noncaregivers, heterosexual caregivers and lesbian/gay/bisexual (LGB), and transgender (T) noncaregivers would report poorer health outcomes (i.

Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer.

Background: Understanding the integrated immunogenomic landscape of advanced prostate cancer (APC) could impact stratified treatment selection.

Methods: Defective mismatch repair (dMMR) status was determined by either loss of mismatch repair protein expression on IHC or microsatellite instability (MSI) by PCR in 127 APC biopsies from 124 patients (Royal Marsden [RMH] cohort); MSI by targeted panel next-generation sequencing (MSINGS) was then evaluated in the same cohort and in 254 APC samples from the Stand Up To Cancer/Prostate Cancer Foundation (SU2C/PCF). Whole exome sequencing (WES) data from this latter cohort were analyzed for pathogenic MMR gene variants, mutational load, and mutational signatures.

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Description of the Spectrum of Choroidal Involvement in 245 Patients with Tubercular Uveitis.

: To contribute a global description of the spectrum of choroidal involvement in tubercular uveitis (TBU).: Retrospective cohort study of TBU patients with choroidal involvement from 25 centers between January 2004 and December 2014. Medical records of patients with a minimum follow-up of 1 year were reviewed.

High-dimensional immune phenotyping and transcriptional analyses reveal robust recovery of viable human immune and epithelial cells from frozen gastrointestinal tissue.

Simultaneous analyses of peripheral and mucosal immune compartments can yield insight into the pathogenesis of mucosal-associated diseases. Although methods to preserve peripheral immune cells are well established, studies involving mucosal immune cells have been hampered by lack of simple storage techniques. We provide a cryopreservation protocol allowing for storage of gastrointestinal (GI) tissue with preservation of viability and functionality of both immune and epithelial cells.