tbuckley/cabot-search huggingface dataset:
Extensive epigenetic reprogramming during the life cycle of Marchantia polymorpha
Authors: Marc W. Schmid, Alejandro Giraldo-Fonseca, Moritz Rövekamp, Dmitry Smetanin, John L. Bowman, Ueli Grossniklaus
Journal: Genome biology (2018)

In plants, the existence and possible role of epigenetic reprogramming has been questioned because of the occurrence of stably inherited epialleles. Evidence suggests that epigenetic reprogramming does occur during land plant reproduction, but there is little consensus on the generality and extent of epigenetic reprogramming in plants. We studied DNA methylation dynamics during the life cycle of the liverwort Marchantia polymorpha. We isolated thalli and meristems from male and female gametophytes, archegonia, antherozoids, as well as sporophytes at early and late developmental stages, and compared their DNA methylation profiles.Of all cytosines tested for differential DNA methylation, 42% vary significantly in their methylation pattern throughout the life cycle. However, the differences are limited to few comparisons between specific stages of the life cycle and suggest four major epigenetic states specific to sporophytes, vegetative gametophytes, antherozoids, and archegonia. Further analyses indicated clear differences in the mechanisms underlying reprogramming in the gametophytic and sporophytic generations, which are paralleled by differences in the expression of genes involved in DNA methylation. Differentially methylated cytosines with a gain in methylation in antherozoids and archegonia are enriched in the CG and CHG contexts, as well as in gene bodies and gene flanking regions. In contrast, gain of DNA methylation during sporophyte development is mostly limited to the CHH context, LTR retrotransposons, DNA transposons, and repeats.We conclude that epigenetic reprogramming occurs at least twice during the life cycle of M. polymorpha and that the underlying mechanisms are likely different between the two events.
Characterization of Aeroallergens Sensitization And Atopy In The Pediatric Population Of Puerto Rico
Authors: Wilfredo Cosme-Blanco, Lorena Gonzalez-Sepulveda, Veronica Solivan-Vargas, Anardi Agosto-Mujica, Sona Rivas-Tumanyan, Sylvette Nazario
Journal: Journal of Allergy and Clinical Immunology (2018)
Combining Cep290 and Mkks ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis
Authors: Rivka A. Rachel, Helen L. May-Simera, Shobi Veleri, Norimoto Gotoh, Byung Yoon Choi, Carlos Murga-Zamalloa, Jeremy C. McIntyre, Jonah Marek, Irma Lopez, Alice N. Hackett, Jun Zhang, Matthew Brooks, Anneke I. den Hollander, Philip L. Beales, Tiansen Li, Samuel G. Jacobson, Raman Sood, Jeffrey R. Martens, Paul Liu, Thomas B. Friedman, Hemant Khanna, Robert K. Koenekoop, Matthew W. Kelley, Anand Swaroop
Journal: Journal of Clinical Investigation (2012)
Analysis of mitochondrial DNA mutations in epithelial ovarian tumors
Authors: Felix O. Aikhionbare, Sharifeh Mehrabi, K. Kumaresan, Edward Partridge
Journal: Cancer Research (2006)

4500  Mutations of mitochondrial DNA (mtDNA) have been implicated in a variety of pathological conditions including cancer. Mitochondria generate Reactive oxygen Species (ROS) that accumulate with age which damage mtDNA as well as nuclear DNA and eventually promoting carcinogenesis. To gain a better understanding of the critical role of mtDNA mutations in epithelial ovarian tumors progression, we have assessed the mtDNA mutations in clinical stages (I-IV and including borderline, and cystadenofibromas) of three histopathologically confirmed epithelial ovarian tumor subtype tissues; serous, mucinous and endometrioid. High-resolution restriction analyses and PCR-based sequencing were employed to identify mitochondrial mutations in this study. The entire mitochondrial genome of each sample was PCR amplified using 9 overlapping primer sets. The primer boundaries of these PCR products define haploblocks for subsequent analyses. Sixty-seven tissue samples were used in the study that included various stages of serous, mucinous, and endometrioid ovarian tumor subtypes. For comparison purposes, samples from the general population (n=119) for which mtDNA was amplified using lymphocytes as a surrogate tissue were used in sequences alignment with our study samples. Results from restriction analyses identified a number of band shifts indicating site gains or losses that predicted sequence changes in the ND2, COII, ND5 and D-loop of mitochondrial gene regions. Sequencing revealed 310 mtDNA mutations, of which 47 of 310 (15%) have previously been reported and 263 of 310 (85%) were identified as novel mutations. Most of these mutations were in D-loop, COI COII and ND1 regions and we observed a high frequency of these mutations in stages III and IV. A T8890A transition was detected in all our borderline and stage I samples of serous tumor subtype. The results suggest that mtDNA mutations play a potential role as modifying risk factors in the epithelial ovarian tumoriogenesis.
Longitudinal Evaluation of Renal Function in Multiple Myeloma
Authors: Marlies Antlanger, Thomas Reiter, Eleonore Pablik, Christoph Minichsdorfer, Edit Porpaczy, Susanne Rasoul-Rockenschaub, Heinz Gisslinger, Hermine Agis, Maria-Theresa Krauth
Journal: Blood (2017)
Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis
Authors: J. Fernandez, J. Acevedo, R. Wiest, T. Gustot, A. Amoros, J. Martínez, F. Saliba, R. Jalan, T. Welzel, M. Pavesi, P. Gines, V. Arroyo
Journal: Journal of Hepatology (2017)
Severe Cytokine Release Syndrome Is a Fatal Complication after PBSC, but Not after BM Haploidentical Transplantation with Post-Transplant Cyclophosphamide
Authors: Jacopo Mariotti, Daniela Taurino, Stefania Bramanti, Barbara Sarina, Lucio Morabito, Carmelo Carlo-Stella, Armando Santoro, Luca Castagna
Journal: Blood (2017)
Are leprosy case numbers reliable?
Authors: Claudio Guedes Salgado, Josafá Gonçalves Barreto, Moisés Batista da Silva, Isabela Maria Bernardes Goulart, Jaison Antônio Barreto, Nesio Fernandes de Medeiros Junior, José Augusto Nery, Marco Andrey Cipriani Frade, John Stewart Spencer
Journal: The Lancet Infectious Diseases (2018)
Redactions in protocols for drug trials: what industry sponsors concealed
Authors: Mikkel Marquardsen, Michelle Ogden, Peter C. Gøtzsche
Journal: Journal of the Royal Society of Medicine (2018)

Objective To describe the redactions in contemporary protocols for industry-sponsored randomised drug trials with patient relevant outcomes and to evaluate whether there was a legitimate rationale for the redactions. Design Cohort study. Under the Freedom of Information Act, we requested access to trial protocols approved by a research ethics committee in Denmark from October 2012 to March 2013. We received 17 consecutive protocols, which had been redacted before we got them, and nine protocols without redactions. In five additional cases, the companies refused to let the committees give us access, and in three other cases, documents were missing. Participants Not applicable. Setting Not applicable. Main outcome measure Amount and nature of redactions in 22 predefined key protocol variables. Results The redactions were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials: data analysis, handling of missing data, detection and analysis of adverse events, definition of the outcomes, interim analyses and premature termination of the study, sponsor’s access to incoming data while the study is running, ownership to the data and investigators’ publication rights. The parts of the text that were redacted differed widely, both between companies and within the same company. Conclusions We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.
18F-FDG PET/CT Detected Delayed Endoleak in an Aortoiliac Endovascular Aneurysm Repair
Authors: Byung Jin Kim, Kevin M. Bradley, Manil Subesinghe
Journal: Clinical Nuclear Medicine (2018)

Abstract We present a case of a type Ia endoleak detected using 18 F-FDG PET/CT 10 years after an abdominal aortoiliac endovascular aneurysm repair in an 83-year-old man. The 18 F-FDG PET/CT scan was performed to evaluate a solitary pulmonary nodule but, in addition, demonstrated unexpected blood pool activity outside the stent graft and within the abdominal aortic aneurysm sac, indicating an endoleak; no FDG activity should be present within the aneurysm sac after stent graft placement. A subsequent CT angiogram confirmed the endoleak. This case illustrates the value of PET/CT in unexpectedly demonstrating this serious, late complication of endovascular aneurysm repair.
R-CHOP, radioimmunotherapy, and maintenance rituximab in untreated follicular lymphoma (SWOG S0801): a single-arm, phase 2, multicentre study
Authors: Paul M Barr, Hongli Li, W Richard Burack, Michael LeBlanc, Sonali M Smith, Ajay K Gopal, Justin D Floyd, Daniel O Persky, Oliver W Press, Richard I Fisher, Jonathan W Friedberg
Journal: The Lancet Haematology (2018)
To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis: a position paper of ESGBOR, the ESCMID study group for Lyme borreliosis
Authors: R.B. Dessau, A.P. van Dam, V. Fingerle, J. Gray, J.W. Hovius, K.-P. Hunfeld, B. Jaulhac, O. Kahl, W. Kristoferitsch, P.-E. Lindgren, M. Markowicz, S. Mavin, K. Ornstein, T. Rupprecht, G. Stanek, F. Strle
Journal: Clinical Microbiology and Infection (2017)
Time for a change: is idiopathic pulmonary fibrosis still idiopathic and only fibrotic?
Authors: Paul J Wolters, Timothy S Blackwell, Oliver Eickelberg, James E Loyd, Naftali Kaminski, Gisli Jenkins, Toby M Maher, Maria Molina-Molina, Paul W Noble, Ganesh Raghu, Luca Richeldi, Marvin I Schwarz, Moises Selman, Wim A Wuyts, David A Schwartz
Journal: The Lancet Respiratory Medicine (2018)
A Neglected Epidemic
Authors: Barry R. Bloom
Journal: New England Journal of Medicine (2018)

Imagine a global epidemic with more than 10 million new cases and 1.7 million deaths in a single year, far greater than the 28,600 cases and 11,315 deaths that were caused by Ebola virus disease in West Africa in 2014 and 2015. In addition, this imagined epidemic affects every country and kills about 25% of patients with HIV/AIDS in Africa. And think about a half million patients with the disease who are resistant to treatment, who represent a threat to communities and to health care providers. One does not need a great imagination to recognize that this is the current . . .
The size, morphology, site, and access score predicts critical outcomes of endoscopic mucosal resection in the colon
Authors: Mayenaaz Sidhu, David Tate, Lobke Desomer, Gregor Brown, Luke Hourigan, Eric Lee, Alan Moss, Spiro Raftopoulos, Rajvinder Singh, Stephen Williams, Simon Zanati, Nicholas Burgess, Michael Bourke
Journal: Endoscopy (2018)

Abstract Background The SMSA (size, morphology, site, access) polyp scoring system is a method of stratifying the difficulty of polypectomy through assessment of four domains. The aim of this study was to evaluate the ability of SMSA to predict critical outcomes of endoscopic mucosal resection (EMR). Methods We retrospectively applied SMSA to a prospectively collected multicenter database of large colonic laterally spreading lesions (LSLs) ≥ 20 mm referred for EMR. Standard inject-and-resect EMR procedures were performed. The primary end points were correlation of SMSA level with technical success, adverse events, and endoscopic recurrence. Results 2675 lesions in 2675 patients (52.6 % male) underwent EMR. Failed single-session EMR occurred in 124 LSLs (4.6 %) and was predicted by the SMSA score (P &lt; 0.001). Intraprocedural and clinically significant postendoscopic bleeding was significantly less common for SMSA 2 LSLs (odds ratio [OR] 0.36, P &lt; 0.001 and OR 0.23, P &lt; 0.01) and SMSA 3 LSLs (OR 0.41, P &lt; 0.001 and OR 0.60, P = 0.05) compared with SMSA 4 lesions. Similarly, endoscopic recurrence at first surveillance was less likely among SMSA 2 (OR 0.19, P &lt; 0.001) and SMSA 3 (OR 0.33, P &lt; 0.001) lesions compared with SMSA 4 lesions. This also extended to second surveillance among SMSA 4 LSLs. Conclusion SMSA is a simple, readily applicable, clinical score that identifies a subgroup of patients who are at increased risk of failed EMR, adverse events, and adenoma recurrence at surveillance colonoscopy. This information may be useful for improving informed consent, planning endoscopy lists, and developing quality control measures for practitioners of EMR, with potential implications for EMR benchmarking and training.
Abstract 15332: A Novel Mouse Model of Left Ventricular Noncompaction: Iroquois Homeobox Genes 3 and 4 Are Required for Ventricular Compaction
Authors: Wei Fan Liu, Kyoung-Han Kim, Rong Mo, Yu-qing Zhou, Matthijs van Eede, Benoit Bruneau, Mark Henkelman, Chi-chung Hui
Journal: Circulation (2016)

Left ventricular noncompaction (LVNC) is a primary congenital cardiomyopathy characterized by prominent trabeculations and intra-trabecular recesses in the ventricular wall. This disease is suggest...
History of the Treatment of Female Sexual Dysfunction(s)
Authors: Peggy J. Kleinplatz
Journal: Annual Review of Clinical Psychology (2018)

This article reviews the history of the treatment of women's sexual problems from the Victorian era to the twenty-first century. The contextual nature of determining what constitutes female sexual psychopathology is highlighted. Conceptions of normal sexuality are subject to cultural vagaries, making it difficult to identify female sexual dysfunctions. A survey of the inclusion, removal, and collapsing of women's sexual diagnoses in the Diagnostic and Statistical Manual of Mental Disorders from 1952 to 2013 illuminates the biases in the various editions. Masters and Johnson's models of sexual response and dysfunction paved the way for the diagnosis and treatment of women's sexual dysfunctions. Their sex therapy paradigm is described. Conceptions of and treatments for anorgasmia, arousal difficulties, vaginismus, dyspareunia, and low desire are reviewed. The medicalization of human sexuality and the splintering of sex therapy are discussed, along with current trends and new directions in sexual health care for women.
Overexpression of c-Src enhances HER2/Neu/ErbB2 and HER3/ErbB3 heterocomplex formation and its function
Authors: Tsuyoshi Miyake, Rumey C. Ishizawar, Sarah J. Parsons
Journal: Cancer Research (2006)

1456  Overexpression of HER2/Neu/ErbB2 is known as an indicator of poor prognosis in breast cancer. This suggests that the HER2 signaling pathway has a crucial role to play in a subset of breast cancers. Elevated activity of c-Src has been detected in >70% of breast cancer cases. Since c-Src and HER family members are frequently overexpressed together in human breast cancer and the HER2/HER3 heterocomplex exhibits the greatest oncogenic potential in model systems, we examined the role of c-Src in the HER2/HER3 signal transduction pathway. We found in both a murine fibroblast model and in human breast cancer cells that c-Src activity enhances heterocomplex formation of HER2 and HER3. The amount of heterocomplex found in cells is reduced by treatment with PP2, a c-Src kinase inhibitor, or overexpression of a kinase-inactive form of c-Src. PP2 treatment also reduces the amount of PI-3 kinase p85 subunit binding to the HER2/HER3 heterocomplex and phosphorylation of the Y861 residue of Focal adhesion kinase(FAK). Furthermore, cellular motility and anchorage-independent growth promoted by HER2/HER3 heterocomplex are dependent upon c-Src activity. These results suggest a mechanism whereby c-Src enhances HER2/HER3 heterocomplex which through PI-3 kinase and FAK, regulates cellular motility and/or anchorage-independent growth.
Glecaprevir/pibrentasvir for hepatitis C virus genotype 3 patients with cirrhosis and/or prior treatment experience: A partially randomized phase 3 clinical trial
Authors: David Wyles, Fred Poordad, Stanley Wang, Laurent Alric, Franco Felizarta, Paul Y. Kwo, Benedict Maliakkal, Kosh Agarwal, Tarek Hassanein, Frank Weilert, Samuel S. Lee, Jens Kort, Sandra S. Lovell, Ran Liu, Chih‐Wei Lin, Tami Pilot‐Matias, Preethi Krishnan, Federico J. Mensa
Journal: Hepatology (2017)

This study assessed the efficacy and safety of ribavirin‐free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options. SURVEYOR‐II, Part 3 was a partially randomized, open‐label, multicenter, phase 3 study. Treatment‐experienced (prior interferon or pegylated interferon ± ribavirin or sofosbuvir plus ribavirin ± pegylated interferon therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily. Treatment‐naive or treatment‐experienced patients with compensated cirrhosis were treated with G/P for 12 or 16 weeks, respectively. The primary efficacy endpoint was the percentage of patients with sustained virologic response at posttreatment week 12 (SVR12). Safety was evaluated throughout the study. There were 131 patients enrolled and treated. Among treatment‐experienced patients without cirrhosis, SVR12 was achieved by 91% (20/22; 95% confidence interval [CI], 72‐97) and 95% (21/22; 95% CI, 78‐99) of patients treated with G/P for 12 or 16 weeks, respectively. Among those with cirrhosis, SVR12 was achieved by 98% (39/40; 95% CI, 87‐99) of treatment‐naive patients treated for 12 weeks and 96% (45/47; 95% CI, 86‐99) of patients with prior treatment experience treated for 16 weeks. No adverse events led to discontinuation of study drug, and no serious adverse events were related to study drug. Conclusion : Patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis achieved high SVR12 rates following 12 or 16 weeks of treatment with G/P. The regimen was well tolerated. (H epatology 2018;67:514‐523).
A phase I, open-label study of GSK2816126, an enhancer of zeste homolog 2 (EZH2) inhibitor, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), other non-Hodgkin’s lymphomas (NHL), multiple myeloma (MM) and solid tumor.
Authors: Timothy Anthony Yap, Peter W. M. Johnson, Jane Winter, John Leonard, Lisa Giulino-Roth, Thierry Horner, Kristen Radswillas, Jennifer Carver, Arindam Dhar
Journal: Journal of Clinical Oncology (2016)

TPS2595 Background: EZH2 is the methyltransferase component of the polycomb repressive complex 2 that represses transcription of target genes via trimethylation of histone H3 at lysine 27 (H3K27me3). These targeted genes are involved in fundamental cellular processes, e.g., development and cell differentiation. EZH2 is deregulated (via mutation or overexpression) in many cancers; increased expression correlates with more aggressive tumor progression and poor prognosis. GSK2816126, a selective and potent inhibitor of wild-type (WT) and mutant EZH2, can decrease H3K27me3 levels in vitro and has demonstrated antiproliferative activity in several cell lines derived from EZH2 WT/mutant cancers. Methods: This is a Phase I, open-label, first-time-in-human, 2-part study. Part 1 is a dose-escalation phase to determine the safety, tolerability and recommended Phase 2 dose (RP2D) of GSK2816126 in patients ( ≥ 18 years) with relapsed/refractory DLBCL, tFL, other NHL, MM and solid tumors (all with ECOG PS of 0/1). An accelerated dose titration will be employed with one patient/dose level until the occurrence of a ≥ Grade 2 drug-related toxicity or dose-limiting toxicity; thereafter patients will be enrolled in a standard 3+3 design. A patient will receive a starting dose of 50mg GSK2816126 IV twice-weekly, and dose escalation will continue until an RP2D/MTD/MFD is determined. In Part 2, the clinical activity of GSK2816126 (objective response rate) will be evaluated in expansion cohorts of patients with MM, and with WT/mutant EZH2 germinal center B-cell–like DLBCL and tFL. Enrollment can be stopped early for futility. Additional study objectives include analysis of pharmacokinetics of GSK2816126 after single/repeat dosing, evaluation of the relationship between GSK2816126 exposure and safety/efficacy/pharmacodynamic parameters, durability of response and progression-free survival. Recruitment is ongoing across four centers (USA and UK); 40 patients will be enrolled in Part 1 (currently 16 enrolled) and 129 in Part 2. Clinical trial information: NCT02082977.
Short Sleep Duration Among Middle School and High School Students — United States, 2015
Authors: Anne G. Wheaton, Sherry Everett Jones, Adina C. Cooper, Janet B. Croft
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Insufficient sleep among children and adolescents is associated with increased risk for obesity, diabetes, injuries, poor mental health, attention and behavior problems, and poor academic performance (1-4). The American Academy of Sleep Medicine has recommended that, for optimal health, children aged 6-12 years should regularly sleep 9-12 hours per 24 hours and teens aged 13-18 years should sleep 8-10 hours per 24 hours (1). CDC analyzed data from the 2015 national, state, and large urban school district Youth Risk Behavior Surveys (YRBSs) to determine the prevalence of short sleep duration (<9 hours for children aged 6-12 years and <8 hours for teens aged 13-18 years) on school nights among middle school and high school students in the United States. In nine states that conducted the middle school YRBS and included a question about sleep duration in their questionnaire, the prevalence of short sleep duration among middle school students was 57.8%, with state-level estimates ranging from 50.2% (New Mexico) to 64.7% (Kentucky). The prevalence of short sleep duration among high school students in the national YRBS was 72.7%. State-level estimates of short sleep duration for the 30 states that conducted the high school YRBS and included a question about sleep duration in their questionnaire ranged from 61.8% (South Dakota) to 82.5% (West Virginia). The large percentage of middle school and high school students who do not get enough sleep on school nights suggests a need for promoting sleep health in schools and at home and delaying school start times to permit students adequate time for sleep.
Enhanced action control as a prior function of episodic memory
Authors: Philipp Rau, George Botterill
Journal: Behavioral and Brain Sciences (2018)

Abstract Improved control of agency is likely to be a prior and more important function of episodic memory than the epistemic-communicative role pinpointed by Mahr &amp; Csibra (M&amp;C). Taking the memory trace upon which scenario construction is based to be a stored internal model produced in past perceptual processing promises to provide a better account of autonoetic character than metarepresentational embedding.
Misconceptions about adaptive function
Authors: Jonathan Redshaw, Thomas Suddendorf
Journal: Behavioral and Brain Sciences (2018)

Abstract Mahr &amp; Csibra (M&amp;C) fail to make the important distinction between why a trait originally evolved, why it was maintained over time, and what its current utility is. Here we point out that episodic memory may have originally evolved as a by-product of a general metarepresentational capacity, and that it may have current functions beyond the communicative domain.
Interleukin-10 Directly Inhibits CD8+ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity
Authors: Logan K. Smith, Giselle M. Boukhaled, Stephanie A. Condotta, Sabrina Mazouz, Jenna J. Guthmiller, Rahul Vijay, Noah S. Butler, Julie Bruneau, Naglaa H. Shoukry, Connie M. Krawczyk, Martin J. Richer
Journal: Immunity (2018)