First Trimester Vaginal Microbiome as Pregnancy Outcome Predictor

• We have developed clinical definiKons of healthy and complicated pregnancies based on pathologies that will be used in future VaHMP studies. • Although one study7 found dysbioKc vagitypes in all three semesters of women who had PPROM, none of our PPROM subjects had a BVAB1 vagitype, and there were equal Gardnerella vaginalis vagitypes in both the controls and subjects who had PPROM (Fig. 2). • While there were more PPROM subjects with Lactobacillus iners vagitypes, this Lactobacillus is less protecKve as it can coexist with pathogenic anaerobic bacteria. • “Candidatus Mycoplasma girerdii”, Lactobacillus jensenii, and Ureaplasma were significantly associated with PPROM in the first trimester samples as well as in all samples collected (Fig. 3). “Candidatus Mycoplasma girerdii” is strongly linked with Trichomonas vaginalis and elicits a strong pro-inflammatory response8 which could explain the etiology of preterm delivery associated with trichomoniasis

Increased Trauma Activation Is Not Equally Beneficial For All Elderly Trauma Patients

Background Physiologic changes in the elderly lead to higher morbidity and mortality after injury. Increasing level of trauma activation has been proposed to improve geriatric outcomes; but, the increased cost to the patient and stress to the hospital system are significant downsides. The purpose of this study was to identify the age at which an increase in activation status is beneficial. Methods A retrospective review of trauma patients ≥ 70 years old from October 1, 2011, to October 1, 2016 was performed. On October 1, 2013, a policy change increased the activation criteria to the highest level for patients ≥ 70 years of age with a significant mechanism of injury. Patients who presented prior to (PRE) were compared to those after the change (POST). Data collected included age, injury severity score (ISS), length of stay (LOS), complications and mortality. Primary outcome was mortality and secondary outcome was LOS. Multivariable regressions controlled for age, ISS, injury mechanism, and number of complications. Results 4341 patients met inclusion criteria, 1919 in PRE and 2422 in POST. Mean age was 80.4 and 81 years in PRE and POST groups respectively (p=0.0155). Mean ISS values were 11.6 and 12.4 (p<0.0001) for the PRE and POST groups. POST had more level 1 activations (696 vs. 220, p<0.0001). After controlling for age, ISS, mechanism of injury, and number of complications, mortality was significantly reduced in the POST group ≥ age 77 years (OR 0.53, 95% CI: 0.3 - 0.87), (Figure 1). Hospital LOS was significantly reduced in the POST group ≥ age 78 (regression coefficient -0.55, 95% CI: -1.09, -0.01) (Figure 2). Conclusions This study suggests geriatric trauma patients ≥ 77 years benefit from the highest level of trauma activation with shorter LOS and lower mortality. A focused approach to increasing activation level for elderly patients may decrease patient cost. Level of Evidence Level III Type of Study Economic/Decisio

A checklist of the hawkmoths (Lepidoptera: Sphingidae) of the Cayman Islands: with implications for the pollination of the ghost orchid \u3ci\u3eDendrophylax fawcettii \u3c/i\u3eRolfe (Orchidaceae: Angraecinae) and consideration of bat predation

This checklist synthesises historic collections of Sphingidae (Lepidoptera) made during the summer months in the Cayman Islands in 1938 and 1975 with modern records drawn from a variety of sources. We report observations and collections made in all seasons of the year and provide natural history and larval food details. Four species, Phryxus caicus (Cramer) in all three islands, plus Isognathus rimosa (Grote), Enyo lugubris (Linnaeus), and Eumorpha satellitia (Linnaeus) in Grand Cayman only, are here reported as new records, for a total of 25 sphingid species occurring in the Cayman Islands. Seven species are new records for Grand Cayman, five are added for Little Cayman and two for Cayman Brac. Potential hawkmoth pollinators for the Cayman Islands endemic ghost orchid, Dendrophylax fawcettii Rolfe (Orchidaceae: Angraecinae) are reviewed and Cayman records of hawkmoths as prey of the big-eared bat Macrotus waterhousii minor Gundlach (Phyllostomidae) are discussed. The hawkmoths (Lepidoptera: Sphingidae) of the Cayman Islands are the only moths to have received more than passing treatment as a group in the published literature. The catalogue provided by Askew (1994) remains the most recent, and with one exception, is based only on collections made in the early rainy seasons of 1938 and 1975. The results of the Oxford University Biological Expedition to all three Cayman Islands, conducted between April and August 1938, were reported by Jordan (1940), and those of the Royal Society–Cayman Islands Government Expedition to Little Cayman in June–July 1975 by Askew (1980). These combined lists, to which Askew (1994) was able to add the 1911 specimen of Pachylia ficus (Linnaeus) from Grand Cayman deposited at the Natural History Museum, London by T.M. Savage English, resulted in a total of twenty-one species of Sphingidae reported from the Cayman Islands as of 1994. Since that time, insect collections have been established at the National Trust for the Cayman Islands, the Department of Environment and the Department of Agriculture. The authors have also made personal collections. Particularly since the advent of digital equipment, photographic images of hawkmoths made by resident and visiting naturalists have provided significant primary records and supplemental data. This checklist synthesises the historic collections and the modern records, reports occurrence for all months of the year, and provides natural history information where available. We assess the larval food plant availability, the affinities and permanence of the sphingid fauna of the islands

Long non-coding RNA LCAL62 / LINC00261 is associated with lung adenocarcinoma prognosis

Background: More than half of non-small cell lung cancer (NSCLC) patients present with metastatic disease at initial diagnosis with an estimated five-year survival rate of ~5%. Despite advances in understanding primary lung cancer oncogenesis metastatic disease remains poorly characterized. Recent studies demonstrate important roles of long non-coding RNAs (lncRNAs) in tumor physiology and as prognostic markers. Therefore, we present the first transcriptome analysis to identify lncRNAs altered in metastatic lung adenocarcinoma leading to the discovery and characterization of the lncRNA Patients and methods: RNA-Seq, microarray, nanoString expression, and clinical data from 1,116 LUAD patients across six independent cohorts and 83 LUAD cell lines were used to discover and evaluate the survival association of metastasis associated lncRNAs. Coexpression and gene set enrichment analyses were used to establish gene regulatory networks and implicate metastasis associated lncRNAs in specific biological processes. Results: Our integrative analysis discovered Conclusion: We discovered tha

Pan-cancer analysis reveals recurrent BCAR4 gene fusions across solid tumors

UNLABELLED: Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient to induce an oncogenic phenotype. We show that the minimum common region to all gene fusions harbors an open reading frame that is necessary to drive proliferation. IMPLICATIONS: BCAR4 gene fusions represent an underappreciated class of gene fusions that may have biological and clinical implications across solid tumors

LINC00355 regulates p27 KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer

Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p2

DANSR: A tool for the detection of annotated and novel small RNAs

Existing small noncoding RNA analysis tools are optimized for processing short sequencing reads (17-35 nucleotides) to monitor microRNA expression. However, these strategies under-represent many biologically relevant classes of small noncoding RNAs in the 36-200 nucleotides length range (tRNAs, snoRNAs, etc.). To address this, we developed DANSR, a tool for the detection of annotated and novel small RNAs using sequencing reads with variable lengths (ranging from 17-200 nt). While DANSR is broadly applicable to any small RNA dataset, we applied it to a cohort of matched normal, primary, and distant metastatic colorectal cancer specimens to demonstrate its ability to quantify annotated small RNAs, discover novel genes, and calculate differential expression. DANSR is available as an open source tool

Multi-institutional analysis shows that low PCAT-14 expression associates with poor outcomes in prostate cancer

AbstractBackgroundLong noncoding RNAs (lncRNAs) are an emerging class of relatively underexplored oncogenic molecules with biological and clinical significance. Current inadequacies for stratifying patients with aggressive disease presents a strong rationale to systematically identify lncRNAs as clinical predictors in localized prostate cancer.ObjectiveTo identify RNA biomarkers associated with aggressive prostate cancer.Design, setting, and participantsRadical prostatectomy microarray and clinical data was obtained from 910 patients in three published institutional cohorts: Mayo Clinic I (N=545, median follow-up 13.8 yr), Mayo Clinic II (N=235, median follow-up 6.7 yr), and Thomas Jefferson University (N=130, median follow-up 9.6 yr).Outcome measurements and statistical analysisThe primary clinical endpoint was distant metastasis-free survival. Secondary endpoints include prostate cancer-specific survival and overall survival. Univariate and multivariate Cox regression were used to evaluate the association of lncRNA expression and these endpoints.Results and limitationsAn integrative analysis revealed Prostate Cancer Associated Transcript-14 (PCAT-14) as the most prevalent lncRNA that is aberrantly expressed in prostate cancer patients. Down-regulation of PCAT-14 expression significantly associated with Gleason score and a greater probability of metastatic progression, overall survival, and prostate cancer-specific mortality across multiple independent datasets and ethnicities. Low PCAT-14 expression was implicated with genes involved in biological processes promoting aggressive disease. In-vitro analysis confirmed that low PCAT-14 expression increased migration while overexpressing PCAT-14 reduced cellular growth, migration, and invasion.ConclusionsWe discovered that androgen-regulated PCAT-14 is overexpressed in prostate cancer, suppresses invasive phenotypes, and lower expression is significantly prognostic for multiple clinical endpoints supporting its significance for predicting metastatic disease that could be used to improve patient management.Patient summaryWe discovered that aberrant prostate cancer associated transcript-14 expression during prostate cancer progression is prevalent across cancer patients. Prostate cancer associated transcript-14 is also prognostic for metastatic disease and survival highlighting its importance for stratifying patients that could benefit from treatment intensification