tbuckley/cabot-search huggingface dataset:
Late Ebola virus relapse causing meningoencephalitis: a case report
Authors: Michael Jacobs, Alison Rodger, David J Bell, Sanjay Bhagani, Ian Cropley, Ana Filipe, Robert J Gifford, Susan Hopkins, Joseph Hughes, Farrah Jabeen, Ingolfur Johannessen, Drosos Karageorgopoulos, Angie Lackenby, Rebecca Lester, Rebecca S N Liu, Alisdair MacConnachie, Tabitha Mahungu, Daniel Martin, Neal Marshall, Stephen Mepham, Richard Orton, Massimo Palmarini, Monika Patel, Colin Perry, S Erica Peters, Duncan Porter, David Ritchie, Neil D Ritchie, R Andrew Seaton, Vattipally B Sreenu, Kate Templeton, Simon Warren, Gavin S Wilkie, Maria Zambon, Robin Gopal, Emma C Thomson
Journal: The Lancet (2016)

There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2).A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach.On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus.Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern.Royal Free London NHS Foundation Trust.
A community outbreak of Legionnaires’ disease in South Wales, August–September 2010
Authors: M Keramarou, M R Evans, Collective for the South Wales Legionnaires’ D
Journal: Eurosurveillance (2010)

During August and September 2010, an outbreak comprising 22 cases of Legionnaires' disease was identified by the public health service in Wales. The cases are distributed over a wide geographical area in South East Wales. There are two space-time clusters centred on the upper Rhymney Valley and the lower Cynon Valley respectively. Epidemiological investigations are compatible with cooling towers in each location as the potential source, but environmental inspections were satisfactory and microbiological investigations are inconclusive.
Functional and Molecular Impact Of Dp1-Dependent Alternate Splicing In Multiple Myeloma
Authors: Mariateresa Fulciniti, Manoj Bashin, Mehmet Kemal Samur, Rajya Bandi, Parantu K Shah, Antonia Cagnetta, Cheng Li, Florence Magrangeas, Stephane Minvielle, Herve Avet-Loiseau, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2013)
Sexual behavior of homeless mentally ill men at risk for HIV
Authors: E Susser, E Valencia, M Miller, W Y Tsai, H Meyer-Bahlburg, S Conover
Journal: American Journal of Psychiatry (1995)

The authors investigated sexual behaviors related to HIV transmission among homeless mentally ill men in a New York City shelter. A previous study of a similar population found HIV prevalence to be 19%.In standardized interviews with 122 men, data on sexual behaviors for the previous 6 months were collected. The frequency and nature of sexual episodes that may facilitate HIV transmission were examined. In addition, sexual risk behaviors among broadly defined diagnostic groups were compared.Of the 122 men, 65 (53%) had sex, 56 with women and 20 with men (11 who had sex with both women and men are counted in each group). The sexually active men, in most cases, had only occasional sex (once per month or less). The majority of sexually active men--29 (52%) of those who had sex with women and 12 (60%) of those who had sex with men--had sex without a condom and with nonmonogamous partners. Comorbid cocaine abuse or dependence was significantly associated with high-risk sexual behaviors.The majority of these men had sex occasionally or not at all. Nonetheless, because many of them had unprotected sex with nonmonogamous partners, the few sexual episodes may have carried an appreciable risk of HIV transmission. Moreover, men with a comorbid cocaine dependence may represent a group with an especially high risk for sexual HIV transmission. The authors propose that in this population, preventive interventions could modify the nature, if not the frequency, of sexual episodes.
Seventh International Meeting of the European Laboratory Working Group on Diphtheria - Vienna, June 2002
Authors: C Kelly, A Efstratiou
Journal: Eurosurveillance (2003)

The Seventh International Meeting of the European Laboratory Working Group on Diphtheria (ELWGD) was held in Vienna, Austria in June 2002 and brought together the microbiologists and epidemiologists responsible for diphtheria in many countries throughout the world. The ELWGD was formed in 1993 in response to the epidemics of diphtheria in Russia and the Newly Independent States (NIS) of the former Soviet Union (1,2). These epidemics, and others elsewhere, highlighted the importance of strengthening and maintaining both epidemiological surveillance and reliable laboratory screening. Since December 2001, these areas have been progressed and strengthened by European Commission (EC) funding to undertake a feasibility study for diphtheria surveillance amongst European Union (EU) member states and accession countries, and to establish a definitive and official European diphtheria surveillance network called DIPNET (EC DG SANCO Agreement No. S12.324473 (2001 CVG4-012)). This was the first international meeting of the ELWGD to be organised and funded under the auspice of the DIPNET (European Diphtheria Surveillance Network).
Favorable Outcome Of Hematopoietic Stem Cell Transplantation Using a Targeted Once-Daily IV Busulfan Fludarabine Etoposide Regimen In Pediatric and Infant ALL Patients
Authors: Hyoung Jin Kang, Ji Won Lee, Sung jin Kim, Seung Hwan Lee, Kyung-Sang Yu, Nam Hee Kim, Mi Kyoung Jang, Hyery Kim, Sang Hoon Song, Kyung Duk Park, Hee Young Shin, In-Jin Jang, Hyo Seop Ahn
Journal: Blood (2013)
Quantitative Studies on the Multiplication of Neoplastic Cells <italic>in Vivo</italic>. IV. Influence of Doubled Chromosome Number on Growth Rate and Final Population Size<xref ref-type="fn" rid="FN1">2</xref>
Authors: Theodore S. Hauschka, Sarah T. Grinnell, László Révész, George Klein
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Quantitative Studies on the Multiplication of Neoplastic Cells in Vivo. IV. Influence of Doubled Chromosome Number on Growth Rate and Final Population Size Get access Theodore S. Hauschka, Theodore S. Hauschka Roswell Park Memorial Institute, Buffalo, New York, and Wallenberg Laboratory, Institute for Cell Research and Genetics, Karolinska Institutet, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Sarah T. Grinnell, Sarah T. Grinnell Roswell Park Memorial Institute, Buffalo, New York, and Wallenberg Laboratory, Institute for Cell Research and Genetics, Karolinska Institutet, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar László Révész, László Révész Roswell Park Memorial Institute, Buffalo, New York, and Wallenberg Laboratory, Institute for Cell Research and Genetics, Karolinska Institutet, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar George Klein George Klein Roswell Park Memorial Institute, Buffalo, New York, and Wallenberg Laboratory, Institute for Cell Research and Genetics, Karolinska Institutet, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 1, July 1957, Pages 13–31, https://doi.org/10.1093/jnci/19.1.13 Published: 01 July 1957 Article history Received: 04 March 1957 Published: 01 July 1957
Abstract PR14: Potent knock down of lncRNAs in vitro and in vivo with antisense LNA™ GapmeRs
Authors: Johnathan Lai, Asli Ozen, Peter Mouritzen, Niels Tolstrup, Niels Montano Frandsen
Journal: Cancer Research (2016)

Abstract Exiqon develops strategies for the optimal design of single stranded LNA™-enhanced antisense oligonucleotides (ASOs, also known as LNA™ GapmeRs) that catalyze RNaseH dependent degradation of target mRNAs and long non-coding RNAs (lncRNA). We have developed an empirically derived design algorithm to provide ASOs that achieve potent target knockdown with a high hit-rate. We describe the latest improvements to the design algorithm, including the incorporation of alignments to both spliced and unspliced transcriptomes in the Ensembl database, to provide maximal target specificity. Many lncRNAs are nuclear retained or have long residence time in the nucleus. This makes them hard to target by RNAi based methods. However since RNaseH is almost exclusively present in the nucleus nuclear RNAs are expected to be particularly sensitive LNA™ GapmeR targets. We have tested LNA™ GapmeRs to knockdown multiple different RNA targets in vitro – including mRNA and lncRNA targets residing in either cytoplasmic or nuclear compartments. Our results demonstrate that all of these targets were equally efficiently silenced irrespective of the type of RNA target and its subcellular localization. We also report highly efficient and long lasting knockdown of a nuclear retained lncRNA in a broad range of tissues in mice subjected to systemic adminstration of a LNA™ GapmeR. LNA GapmeRs are therefore excellent tools for lncRNA loss of function analysis in vitro and in vivo and provide an excellent platform for therapeutic targeting of lncRNA. Risk of hybridization based off-target activity with gapmers has traditionally been considered to be low. However in a recent publication1 it was shown that unless properly designed antisense off-target activity with gapmers can be quite significant. Surprisingly, particularly sensitive off-targets were frequently localized in introns of primary transcripts causing significant reduction of the amount of mature spliced mRNAs. Since RNaseH is confined to the nucleus we therefore speculated that the true target of gapmers might be unspliced primary transcripts in the nucleus rather than the spliced mature transcripts that are exported to the cytoplasm. We present data showing that intron targeting LNA GapmeRs often provide highly potent knockdown of the mature spliced RNA. These results have profound implications on therapeutic gapmer design. 1. Kamola PJ, Nucl. Acids Res. 2015, pii: gkv857 This abstract is also presented as Poster B45. Citation Format: Johnathan Lai, Asli Ozen, Peter Mouritzen, Niels Tolstrup, Niels Montano Frandsen. Potent knock down of lncRNAs in vitro and in vivo with antisense LNA™ GapmeRs. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr PR14.
Hyperserotonemia and platelet serotonin uptake and release in schizophrenia and affective disorders
Authors: S M Stahl, D J Woo, I N Mefford, P A Berger, R D Ciaranello
Journal: American Journal of Psychiatry (1983)

The authors found that platelet serotonin concentrations were significantly elevated in patients with chronic schizophrenia and in patients with bipolar major depressive disorder. High-affinity serotonin uptake was significantly reduced only in patients with bipolar major depressive disorder. Thrombin-induced release of serotonin from platelets in any patient group was not different from that of normal control subjects. Platelet serotonin storage in chronic schizophrenic patients was also not different from that in normal control subjects. These platelet findings could not be explained by age, sex, or medication variables. The authors suggest that the pharmacodynamics of platelet serotonin may be different in chronic schizophrenia than in bipolar major depressive disorder.
Abstract A11: Identification of the premalignant cell of origin in human glioblastoma multiforme
Authors: Siddhartha S. Mitra, Sharareh Gholamin, Rahul Sinha, Rachel M. Morganti, Irving Weissman, Samuel H. Cheshier
Journal: Cancer Research (2015)

Abstract One of the major difficulties in identifying the cell of origin for glioblastoma is the complex cellular composition of this disease. It is now hypothesized that the different subtypes of high-grade glioma may have different cell of origin and in mouse models it has been shown that the cell of origin resides within the progenitor populations. To identify the human cell of origin we delineated the stages of CNS stem cell differentiation in fetal and adult human brain. After a functional high throughput screen, we identified a panel of four antibodies (i.e CD15, Notch1, EGFR, and CD90) that in various combinations can separate long-term self-renewing multi-potent neural stem cells (NSCs) from multi-potent progenitors with limited self-renewal capacity (NPC) from non-neoplastic human fetal and adult Brain (sub-ventricular zone). FACS sorted cells were analyzed for single cell lineage multi-potentiality, lineage bias and self-renewal to trace and characterize their lineage relationships. In surgical human glioblastoma samples, however we observed in-vivo tumor initiating and in-vitro tumorsphere-forming frequency was predominant in the progenitor cells and not in the neural stem cells. Interestingly we did observe a small frequency of NSC cells forming distinct lesions in the brain, which on further analysis showed the presence of both the NSC and NPC, whereas the tumor initiating enriched population did not show the presence of the NSC but only tumor initiating NPCs. Taken together our data suggests the presence of “normal” or pre-malignant stem cells in glioblastoma, RNAseq and targeted sequencing of known mutations identified the genomic events which can distinguish these pre-malignant neural stem cells from the tumor initiating cancer stem cells. These pre-malignant cells could comprise a cellular reservoir that may need to be targeted to prevent tumor relapse. Citation Format: Siddhartha S. Mitra, Sharareh Gholamin, Rahul Sinha, Rachel M. Morganti, Irving Weissman, Samuel H. Cheshier. Identification of the premalignant cell of origin in human glioblastoma multiforme. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A11.
Incongruence between Clinicians' Assessment and Self-Reported Functioning Is Related to Psychopathology among Patients Diagnosed with Gastrointestinal Disorders
Authors: Amanda Rodriguez-Urrutia, Francisco Jose Eiroa-Orosa, Anna Accarino, Carolina Malagelada, Fernando Azpiroz
Journal: Psychotherapy and Psychosomatics (2016)

In a previous exploratory study we observed no relevant differences in psychopathology, personality, and functioning between inpatients diagnosed with gastrointestinal motor disorders (GMDs) or functional gastrointestinal disorders (FGDs) [1]. However, we observed higher levels of incongruence between clinician-assessed performance status and patients’ self-reported levels of functioning among patients diagnosed with FGDs. Likewise, research in other medical conditions has shown incongruences between self-reported and clinician-reported or objective measures [2]. Furthermore, in a study on chronic depression, the authors found that discrepancies between patients’ and physicians’ assessments of medical comorbidities were related to higher levels of depressive symptomatology [3]. In this line, the aim of this study was to explore whether the inconsistencies between clinician-assessed and patient self-reported levels of functioning could be related to psychopathology among patients admitted for evaluation of gastrointestinal motility.
An Evaluation of Modern Pressure Recording Systems
Authors: DONALD L. FRY, FRANK W. NOBLE, ALEXANDER J. MALLOS
Journal: Circulation Research (1957)

An evaluation of the stability and accuracy of modern physiologic pressure measuring systems is reported with a brief review of some of the problems of catheter pressure recording. Evaluation of stability consisted of measuring the drift of the baseline and of the calibration factors of the gage and amplifier combination with time and temperature change. Evaluation of the accuracy of these pressure measuring systems consisted of determining their static accuracy, their dynamic accuracy, and the pressure errors introduced by catheter accelerations and bending.
Abstract IA02: Genome regulation by long noncoding RNAs
Authors: Howard Y. Chang
Journal: Cancer Research (2016)

Abstract The discovery of extensive transcription of long noncoding RNAs (lncRNAs) provide an important new perspective on the centrality of RNA in gene regulation. I will discuss genome-scale strategies to discover and characterize lncRNAs. Genome-wide mapping of RNA secondary structures, termed the structurome, provides important clues to potential functions of regulatory RNAs. An emerging theme from multiple model systems is that lncRNAs form extensive networks of ribonucleoprotein (RNP) complexes with numerous chromatin regulators, and target these enzymatic activities to appropriate locations in the genome. Consistent with this notion, long noncoding RNAs can function as modular scaffolds to specify higher order organization in RNP complexes and in chromatin states. The importance of these modes of regulation is underscored by the newly recognized roles of long RNAs in developmental patterning and cancer. Citation Format: Howard Y. Chang. Genome regulation by long noncoding RNAs. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr IA02.
Abstract MS1-2: Targeting CDK 4/6 in breast cancer
Authors: R Finn
Journal: Cancer Research (2016)

Abstract For decades, cyclin-dependent kianses (CDKs) have been known to be critical regulators of cell cycle progression leading to the Nobel Prize in 2001 for their identification and characterization. Subsequently, alteration in these and associated proteins have been implicated in cancer. In breast cancer, they have been associated with various molecular subtypes, prognosis, and response to therapy. The concept of blocking CDKs has been around for some time but only recently have they seen clinical success. First generation CDK inhibitors did not demonstrate significant clinical activity and had unacceptable toxicity. In addition to having an appropriate compound, as with other molecular targeted agents, identification of a patient population most likely to benefit is critical to successful clinical development. Palbociclib (PD-0332991, Pfizer) is a first-in-class CDK 4/6 specific inhibitor. Pre-clinical studies identified that ER+ breast cancer models were most sensitive to growth inhibition with palbociclib and identified a synergistic interaction in inhibiting proliferation in combination with anti-estrogens (Finn et al 2009). These data served as a hypotheses for the Phase II Paloma-1/ TRIO 18 study of palbociclib +letrozole vs letrozole alone (Finn et al Lancet Oncolog 2015). Results of this study demonstrated a significant improvement in PFS with the combination and served as the basis for the expedited approval of palbociclib +letrozole as first line therapy for advanced post-menopausal ER+ breast cancer. Most common toxicities were neutropenia, leukopenia and fatigue. Subsequently, a consistent benefit was seen in combination with fulvestrant in more advanced settings (Turner et al NEJM 2015) with a similar toxicity profile. Currently there are several other CDK 4/6 inhibitors in development in breast cancer and other malignancies including abemaciclib (LY2835219, EliLilly) and ribociclib (LEE011, Novartis). In the presentation we will review the rationale for CDK 4/6 inhibition in breast cancer as well as clinical efficacy and toxicity data and the ongoing development of this new class of agent in breast cancer. Citation Format: Finn R. Targeting CDK 4/6 in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr MS1-2.
Abstract 2535: The Adverse Long-Term Impact of Renal Impairment on Patients undergoing Percutaneous Coronary Intervention in the DES Era
Authors: Clare Appleby, Joan Ivanov, Karen Mackie, Shahar Lavi, Doug Ing, Chris Overgaard, Peter Seidelin, Vlad Dzavik
Journal: Circulation (2008)

Renal impairment (RI) is known to be associated with poor in-hospital outcomes following percutaneous coronary intervention (PCI) but its effect on outcomes beyond one year, particularly in the drug eluting stent (DES) era has not been reported. We undertook an observational study to determine the long-term impact of renal impairment on patients undergoing PCI at a large, tertiary cardiac referral centre. Baseline creatinine was available for 11,969 of the 15,012 consecutive patients undergoing PCI at our institution between April 2000 and Sept 2007. Patients were stratified into those with or without at least moderate RI, defined as a creatinine clearance &lt;60ml/min (CKD class ≤ 3). In-hospital mortality and morbidity were calculated for each cohort. Follow up data was obtained through linkage to a provincial registry. Kaplan-Meier analysis was performed and Cox multiple regression analysis was used to identify independent predictors of late mortality and MACE (major adverse cardiovascular events), and to examine the association between DES use and late outcomes in the presence or absence of RI. Of the 11,953 patients with available long-term follow-up, 3070 had RI (25.7%). In hospital mortality and MACE were significantly increased in those patients (3.34% vs 0.44%, p&lt;0.001, and 5.73% vs 2.2%, p&lt;0.001, respectively). At 7 year follow-up, survival and MACE-free survival were both reduced (64.5 ± 1.4% vs 89.4 ± 0.5%, p&lt;0.001, and 44.0 ± 1.4% vs 63.4 ± 0.8%, p&lt;0.001). RI was identified as an independent predictor of both late mortality and cardiovascular events (HR 2.2, p&lt;0.0001 and HR 1.4, p&lt;0.0001) but DES use was associated with a significant risk reduction for these events (HR 0.7, p&lt;0.0001). In patients with RI, DES use, rather than bare metal stents, was associated with a reduction in mortality (HR 0.83, CI 0.66 –1.0, p=0.1) and reduced subsequent CABG (HR 0.46, CI 0.22– 0.97, p=0.041) but had no effect on repeat PCI (p=0.63). In a large registry of “all-comers” for PCI, RI was an independent predictor of adverse late outcomes at 7 year follow-up. DES use however was associated with improved long-term outcomes in this high risk cohort.