tbuckley/cabot-search huggingface dataset:
Variable Penetrance Is Linked with Monoallelic Gene Expression in Inherited GATA2-Mutated MDS/AML
Authors: Ahad Al Seraihi, Ana Rio-Machin, Kiran Tawana, Csaba Bödör, Shamzah Araf, James A Heward, Matthew Smith, Sameena Iqbal, Steven Best, Nicholas Lea, Donal McLornan, Alicia Ellison, Hemanth Tummala, Shirleny Romualdo Cardoso, Jamie D. Cavenagh, Tom Vulliamy, Inderjeet Dokal, Jude Fitzgibbon
Journal: Blood (2016)
Mono-ovulatory cycles: a key goal in profertility programmes
Authors: None ESHRE Capri Workshop Group
Journal: Human Reproduction Update (2003)

Mono‐ovulatory cycles for women are optimal because singleton pregnancies have a better outcome than multiples. Multiple births began to increase in the 1950s after the first appearance of effective ovulation induction for the treatment of anovulation. Since the 1980s when ovulation induction and IVF were more broadly applied to the treatment of unexplained and persistent infertility, there has been an unprecedented rise in multiple births. Strategies to achieve mono‐ovulation during treatment of anovulatory patients are distinct from those for the treatment of ovulating patients who have unexplained and persistent infertility. Anovulatory patients with hypogonadotrophic hypogonadism can be treated with exogenous pulsatile GnRH, which restores normal gonadotrophin secretion, ovulation rates and conception rates. The multiple pregnancy rate is not increased with GnRH treatment. In patients with normogonadotrophic anovulation, attention should be given to diet and exercise before any other interventions are considered. Pharmacological induction of ovulation can be achieved with antiestrogen, gonadotrophin or pulsatile GnRH treatment; antiestrogen is the first choice with gonadotrophin more widely used for clomiphene citrate (CC)‐resistant patients. Obesity and polycystic ovaries are common in this group, so that gonadotrophin and GnRH treatment are associated with lower responses compared with hypogonadotrophic hypogonadism, and higher multiple pregnancy rates. Low dosage protocols are being tested that may lower the multiple birth rates. The role of drugs enhancing sensitivity to insulin, e.g. metformin, remains undetermined. Laparoscopic ovarian diathermy achieves conception rates that are equivalent to gonadotrophin treatment, with fewer multiple births. Augmenting normal ovulation processes for couples with unexplained and persistent infertility is less effective. Pregnancy rates are statistically significantly higher with CC but the size of the increase is not clinically important. CC with intrauterine insemination is associated with a clinically important effect on conception. Achieving mono‐ovulation is more difficult in assisted reproductive technology cycles because success depends on maintaining the level of FSH above the threshold level longer than normal in order to increase the number of mature follicles. Milder stimulation for IVF and IVF in the untreated cycle show great potential, however, especially in view of the trend toward transfer of a single embryo in assisted reproductive treatment cycles.
Macrophage type 2 differentiation in a patient with laryngeal squamous cell carcinoma and metastatic prostate adenocarcinoma to the cervical lymph nodes
Authors: Michael C. Topf, Madalina Tuluc, Larry A. Harshyne, Adam Luginbuhl
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes. <h3>Case presentation</h3> We report a 59-year-old male with recurrent T4 squamous cell carcinoma (SCC) of the larynx with synchronous prostate adenocarcinoma confined to the prostate and regional pelvic lymph nodes, without metastatic disease. The patient underwent salvage total laryngectomy and bilateral neck dissection with final pathology revealing a recurrent moderately differentiated SCC involving the larynx as well as prostate cancer in draining level 4 cervical lymph nodes bilaterally. CD163 staining was performed on the primary tumor, a negative draining lymph node, and a level four lymph node with a focus of metastatic prostate cancer and compared to benign controls. The negative draining lymph node demonstrated a large CD163 population of cells as did the interface of the focus of prostate cancer and surrounding lymph node. CD163 levels were markedly increased in this patient compared to benign lymph node controls. The macrophage differentiation at the primary tumor in the larynx was strongly CD163 positive supporting an immune permissive environment for tumor growth and metastasis. <h3>Conclusion</h3> We describe a unique case of solitary metastatic prostate cancer to cervical lymph nodes in the setting of a laryngeal cancer. These observations suggest that SCC-derived factors drive a tumor-supportive environment in draining lymph nodes dominated by an overwhelming number of CD163+, M2 macrophages. Lymph nodes that are 'primed' by SCC differentiation to M2 phenotype may be at higher risk of harboring metastases.
Abstract 2298: Antibiotic use and breast cancer risk: results from the Sister Study
Authors: Sandra L. Deming-Halverson, M. Elizabeth Hodgson, Aimee D'Aloisio, David Shore, Dale Sandler
Journal: Cancer Research (2017)

Abstract Background: Regular antibiotic use is hypothesized to influence breast cancer risk by a number of mechanisms including disruption of intestinal microflora which plays a role in the conversion of food-based phytochemicals into bioactive substances suggested to be protective against cancer, and by influences on the immune system and inflammatory response. Previous results have been mixed, and given the sparse and conflicting data in epidemiologic literature, we analyzed the association between regular antibiotic use and breast cancer risk, overall and by different classes of antibiotics. Methods: Regular antibiotic use, as characterized by class type and number, duration, and indication for use, was evaluated for its association with breast cancer risk among participants of the NIEHS Sister Study, a prospective cohort of 50,884 US women aged 35-74 without breast cancer who have had a sister diagnosed with breast cancer. Results: 5,312 (10.4%) of women in the Sister Study reported ever having regular antibiotic use (at least 3 times per week for 3 months in a row or longer) with a median duration of 1.50 years (0.25 – 53.8). 34% of regular uses reported use greater than 2 years. Skin conditions including acne and rosacea were the most common indications for use (6.02%). The hazard ratio (HR) was 1.10 (0.99-1.27) for ever regular antibiotic use and 1.40 (1.16-1.69) for greater than 2 years of regular use. Results are suggestive of an increased risk among regular users who have only ever used one class rather than more than one class of antibiotics. Adjusted hazard ratios were 1.40 (0.99-1.99) for tetracyclines only, 1.45 (0.95-2.20) for penicillins only, 1.42 (0.94-2.15) for macrolides alone. However, there does not appear to be an association between ever regular use of more than one class of antibiotics and breast cancer. Furthermore, there was no association between indications for ever regular use and breast cancer risk, among all women reporting regular use of antibiotics, regardless of class. Conclusion: Overall, there is a suggestion that ever regular use of a single class of antibiotics, but not use of more than one class, may be associated with increased breast cancer risk. However, given that most individuals reported only a single episode of regular antibiotic use for a duration of less than 2 years; further exploration is warranted to rule out effects of underlying indication for use or explore other possible class specific-confounders. Citation Format: Sandra L. Deming-Halverson, M. Elizabeth Hodgson, Aimee D'Aloisio, David Shore, Dale Sandler. Antibiotic use and breast cancer risk: results from the Sister Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2298. doi:10.1158/1538-7445.AM2017-2298
PTH-010 Intubation failure during gastroscopy – incidence, predictors and follow-up findings
Authors: J Li, K Siau, NC Fisher, S Ishaq
Journal: Endoscopy (2017)

<h3>Introduction</h3> Intubation failure (IF) occurs when a trained endoscopist is unable to progress via the oropharynx and into the upper oesophagus. The incidence is unknown, but estimated at 1.8%.<sup>[1]</sup> There have been no studies exploring IF and follow-up findings. We aimed to assess the incidence, causes and predictors of IF, and follow-up findings. <h3>Method</h3> We retrospectively identified all gastroscopies performed at a district general hospital between August 2010–2016, and reviewed cases with IF. Procedural data were collected, and patients allocated into groups based on 'failure to tolerate' (e.g. pulling out scope, anxiety) or 'failure to progress'. Barium, computed tomography (CT), and repeat gastroscopy findings were reviewed to assess for structural causes of IF. Statistical analyses were made using Pearson's chi<sup>2</sup>. <h3>Results</h3> The incidence of IF was 0.95% (248/26130). 238 patients were identified, with a mean age of 63.2 (SD 16.1), with 'failure to progress' in 41 and 'failure to tolerate' in 197. Subsequent investigations included barium radiology (59.7%, n=142), CT (21%, n=50), repeat gastroscopy (29.4%, n=70) and no further investigations (19.7%, n=47). Structural pharyngeal abnormalities were detected in 41 (28.9%), comprising of cricopharyngeal hypertrophy (CPH) [49%], Zenker's diverticulum (ZD) [14.6%], pharyngeal web (12.2%), ZD with CPH (9.8%), cervical spondylosis (7.3%) and other (7.3%). Endoscopist status was a predictor of IF (OR for medical vs. non-medical endoscopist 0.7, 95% CI: 0.5–0.9, p=0.007). Within the IF cohort, predictors of structural causes on barium radiology included: dysphagia (OR 5.5, 95% CI: 2.5–11.8, p&lt;0.001), failure to progress (OR 5.2, 95% CI: 2.3–12.0, p&lt;0.001) and age ≥65 (OR 4.0, 95% CI: 1.8–8.9, p&lt;0.001). Repeat gastroscopy was successful in 63/70 (2 using nasendoscope) after increasing midazolam dosage (mean increase=1.5 mg, 95% CI: 1.0–2.0 mg, p&lt;0.001). Diagnostic yield for barium radiology, CT and repeat gastroscopy were 69.0%, 54.0% and 64.3% respectively. The concordance of endoscopic indication and pathology on further investigation for IF was 110/192 (57.3%). In patients undergoing barium radiology and repeat gastroscopy, the false negative rate for endoscopy was 17/30 (56.7%), consisting of pharyngeal pathology (n=9), dysmotility (n=4) and significant reflux (n=4). <h3>Conclusion</h3> We present novel data regarding IF, and report an incidence of ≈1%. Patients should be investigated further owing to high risk of underlying pathology, particularly if associated with age ≥65, dysphagia, and failure of endoscopic progression. Barium radiology is comparable to repeat gastroscopy in terms of diagnostic yield, and may be more helpful in evaluating pharyngeal and functional pathology. <h3>Reference</h3> . Ponchon T, GIE, April2000;51(4):AB275. <h3>Disclosure of Interest</h3> None Declared
Abstract 15542: Toll-like Receptor 7 Mediates Extracellular RNA-induced Cytokine Production in Cardiomyocytes
Authors: Yan Feng, Jiayan Cai, Lin Zou, Dan Li, Wei Chao
Journal: Circulation (2014)

INTRODUCTION:  We have recently reported that extracellular RNA (exRNA) released from injured cardiomyocytes induces cytokine production and may contribute to myocardial ischemia/reperfusion (I/R) injury. However, the signaling mechanism by which exRNA exhibits its pro-inflammatory effect in cardiomyocytes is unknown.   HYPOTHESIS:  We hypothesize that exRNA induces inflammation through Toll-like receptors signaling.   METHODS:  Mouse myocardial I/R model: WT mice were subjected to Sham procedure or coronary occlusion for 45 min followed by reperfusion. exRNA extraction and quantitation: exRNA in culture media or mouse sera was extracted using Trizol LS and quantified using Quant-iT RNA assay kit. ELISA: MIP-2 in culture media was measured by ELISA.   RESULTS:  Twenty-four hours after hypoxia/serum-deprivation, RNA concentration in cardiomyocyte culture medium rose from 12 ng/ml to approx. 600 ng/ml. Freeze/thaw caused even greater RNA release (approx. 1500 ng/ml). In vivo, serum RNA level was increased from 183 ± 34 to 344 ± 68 ng/ml 24 hours after I/R. Moreover, in the presence of lipofectamine, purified exRNA induced MIP-2 production in a dose-dependent manner. exRNA-induced MIP-2 production was completely inhibited by RNase and Benzonase, but not DNase. The effect of the nucleases appeared specific as they had no effect on Pam3 (a TLR2 ligand)-induced MIP-2 production. Finally, exRNA-induced MIP-2 production in cardiomyocytes was partially (approx. 25%) and significantly inhibited by a specific TLR7 inhibitor (In), which completely blocked MIP-2 production induced by R837 (a TLR7 ligand). In contrast, TLR9-In had no effect on the exRNA-induced cytokines production. Similarly, TLR7-In, but not TLR9-In or TLR3 deletion, partially decreased exRNA-promoted MIP-2 production in macrophages.   CONCLUSIONS:  These data demonstrate that 1) RNA is released from hypoxic cardiomyocytes in vitro and ischemic myocardium in vivo; 2) exRNA-induced MIP-2 production is partially through TLR7, but not TLR9 or TLR3.
Recent Advances in Mitochondrial Aminoacyl-tRNA Synthetases and Disease
Authors: Marie Sissler, Ligia Elena González-Serrano, Eric Westhof
Journal: Trends in Molecular Medicine (2017)

Dysfunctions in mitochondria - the powerhouses of the cell - lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue. With newer information available, we propose that the pleiotropy and tissue-specificity of mt-aaRS-associated diseases result from the molecular integration of mitochondrial translation events within the cell; namely, through specific crosstalk between the cellular program and the energy demands of the cell. We place particular focus on neuronal cells.
Tackling submission and publication bias
Authors: Rainer Spiegel, Petra Opic, Saskia Semmlack, Sarah Tschudin-Sutter, Raoul Sutter
Journal: BMJ (2017)

Evoniuk and colleagues analysed whether submission and publication bias are based on study outcome.1 They retrospectively reviewed 1064 drug research studies sponsored by GlaxoSmithKline over six years and did not find evidence for either bias.1 This finding is different from previous studies and discussions.234 Has the acceptance of studies reporting “negative” results truly improved in the scientific community, so that submission or publication bias is no longer relevant? No, for at least three reasons.

Firstly, Evoniuk and colleagues analysed only …
HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells
Authors: Christian Körner, Camille R. Simoneau, Philipp Schommers, Mitchell Granoff, Maja Ziegler, Angelique Hölzemer, Sebastian Lunemann, Janet Chukwukelu, Björn Corleis, Vivek Naranbhai, Douglas S. Kwon, Eileen P. Scully, Stephanie Jost, Frank Kirchhoff, Mary Carrington, Marcus Altfeld
Journal: Cell Host & Microbe (2017)
Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study
Authors: Catherine Orrell, Debbie P Hagins, Elena Belonosova, Norma Porteiro, Sharon Walmsley, Vicenç Falcó, Choy Y Man, Alicia Aylott, Ann M Buchanan, Brian Wynne, Cindy Vavro, Michael Aboud, Kimberly Y Smith, Pedro Enrique Cahn, Lidia Isabel Cassetti, Norma Porteiro Barreira, Jonathan Benjamin Angel, Alexandra de Pokomandy, Marianne Harris, Anita R. Rachlis, Sharon L. Walmsley, Clotilde Allavena, Oliver Bouchaud, Caroline Gatey, Agathe Rami, Salvatore Casari, Giovanni Di Perri, Adriano Lazzarin, Franco Maggiolo, Giovanni Penco, Tiziana Quirino, Giuliano Rizzardini, Jaime-Federico Andrade-Villanueva, Juan G. Sierra-Madero, Teresa Branco, Rosario Serrao, Eugenio JR. Teofilo, Ivan Melendez-Rivera, Lizette Santiago, Carmen D. Zorrilla, Elena Belonosova, Oksana E. Chernova, Vadim Pokrovsky, Aza Gasanovna Rakhmanova, Olga Tsybakova, Eugene Voronin, Catherine Orrell, Tasneem Vally, Livhuwani ML. Farisani, Boitumelo Lucrecia Sebopa, Carlos Aguado Barros, Alfredo Cano Sánchez, Manuel Castaño, Vicens Falcó Ferrer, Juan J. González García, Jose Hernandez-Quero, Eugenia Negredo Puigmal, María Jesús Pérez Elías, Daniel Podzamczer Palter, Joaquin Sogorb Portilla, Pompeyo Viciana Fernández, Weerawat Manosuthi, Kiat Ruxrungtham, David H. Dockrell, Phillip E. Hay, Margaret A. Johnson, Nicola E. Mackie, Chloe M. Orkin, Steve Taylor, Laveeza Bhatti, Indira Brar, Robert Owen Brennan, Jerry L. Cade, Beata Casanas, Kathleen Casey, Douglas Cunningham, Edwin DeJesus, Craig Dietz, Robin Henry Dretler, Joseph J. Eron, Franco Antoni B. Felizarta, Kenneth H. Fife, Debbie P. Hagins, Margaret Hoffman-Terry, Mamta Jain, Marc Alexander Johnson, Clifford A. Kinder, Princy N. Kumar, Stanley T. Lewis, Cheryl Kay McDonald, Armando D. Meza, Karam C. Mounzer, Cheryl L. Newman, Olayemi O. Osiyemi, Ronald Poblete, Rachel M. Presti, Moti Ramgopal, Joel Rosenstock, Rafik Samuel, Uriel Sebastian Sandkovsky, Alyssa So Young Shon, Daniel J. Skiest, Louis M. Sloan, Catherine B. Small, Pablo Tebas, Cornelius N. Van Dam
Journal: The Lancet HIV (2017)
Preparation and Application of Cell Membrane-Camouflaged Nanoparticles for Cancer Therapy
Authors: Yihui Zhai, Jinghan Su, Wei Ran, Pengcheng Zhang, Qi Yin, Zhiwen Zhang, Haijun Yu, Yaping Li
Journal: Theranostics (2017)

Cancer is one of the leading causes of death worldwide. Many treatments have been developed so far, although effective, suffer from severe side effects due to low selectivity. Nanoparticles can improve the therapeutic index of their delivered drugs by specifically transporting them to tumors. However, their exogenous nature usually leads to fast clearance by mononuclear phagocytic system. Recently, cell membrane-camouflaged nanoparticles have been investigated for cancer therapy, taking advantages of excellent biocompatibility and versatile functionality of cell membranes. In this review, we summarized source materials and procedures that have been used for constructing and characterizing biomimetic nanoparticles with a focus on their application in cancer therapy.
The Peripheral Cannabinoid Receptor CB2 and CD40 Are Novel Biological Markers That Predict Outcome in Diffuse Large B-Cell Lymphoma of Elderly Patients.
Authors: Nazik Rayman, King H. Lam, Dries A.H Mulder, Ronnie B. van der Holt, Jeanette Doorduijn, Bob Lowenberg, Pieter Sonneveld, Ruud H.R Delwel
Journal: Blood (2004)
Abstract 202: Insulin Resistance as an Independent Predictor of Atherosclerosis Burden in Nondiabetic Patients with Acute Myocardial Infarction
Authors: Wassef Karrowni, Yan Li, Philip G Jones, Donna M Buchanan, Ramzi El Accaoui, Sharon Cresci, Mouin Abdallah, David E Lanfear, Thomas M Maddox, Darren K McGuire, John A Spertus, Phillip A Horwitz
Journal: Circulation Research (2012)

Introduction: Experimental evidence suggests that insulin resistance (IR) is a major risk factor for accelerated atherosclerosis through indirect effects on systemic risk factors and direct effects on insulin signaling in vascular endothelium and plaque macrophages. Hypothesis: IR in persons without diabetes mellitus is associated with multi-vessel coronary artery disease (CAD) in acute myocardial infarction (AMI) patients. Methods: We examined 1111 non-diabetic AMI patients (HbA1c ≤ 6.5) enrolled in the multicenter TRIUMPH (years 2004-2008) registry. IR was estimated using the homeostasis model assessment of IR (HOMA-IR: fasting insulin (mU/l) x fasting blood glucose (mmol/l)]/22.5). The primary outcome was the extent of angiographic atherosclerosis (≤1-vessel vs. multi-vessel disease). Modified Poisson regression models were used to examine the association between IR and multi-vessel CAD. Results: Subjects were divided into quartiles based on HOMA-IR values (quartile 1: male &lt;=1.35, female &lt;=1.26; quartile 4: male &gt;4.00, female &gt;3.64). After adjusting for age, sex, hypertension, smoking, family history of CAD, LDL, HDL, and body mass index (BMI), IR was independently associated with multi-vessel CAD (Figure). As compared to the lowest quartile of IR, the highest quartile had more multi-vessel CAD [RR (95% CI)- 1.35 (1.11-1.64)]. Conclusion: In a large cohort of non-diabetic AMI patients, IR was associated with more advanced, multi-vessel CAD, independent of lipid levels and other components of the metabolic syndrome. This association is consistent with established experimental evidence and supports IR as a potential target for preventing atherosclerosis.
A reappraisal of the benefit‐risk profile of hydroxyurea in polycythemia vera: A propensity‐matched study
Authors: Tiziano Barbui, Alessandro Maria Vannucchi, Guido Finazzi, Maria Chiara Finazzi, Arianna Masciulli, Alessandra Carobbio, Arianna Ghirardi, Gianni Tognoni
Journal: American Journal of Hematology (2017)

The use of hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has been criticized because no solid demonstration that this drug prevents thrombosis or prolongs survival has been so far produced. Here we present the outcomes of a large cohort of patients with PV included in the European Collaborative Low-dose Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow-up, had received only phlebotomy (PHL) or HU to maintain the hematocrit level < 45%. To assure comparability, we conducted a propensity score matching analysis. The two groups (PHL n = 342 and HU n = 681) were well balanced for the parameters included in the propensity score (overall balance: χ2 = 2.44, P = 0.964). Over a comparable period of follow-up (PHL = 29.9 vs. HU = 34.7 months), we documented an advantage of HU over PHL consistently significant with respect to the incidence of fatal/non-fatal cardiovascular (CV) events (5.8 vs. 3.0 per 100 person-years in PHL vs. HU group, P = 0.002) and myelofibrosis transformation that was only experienced by patients of PHL group. Evolution to acute leukemia was registered in three patients (two in PHL and one in HU group). The excess of mortality and total CV events in the PHL patients was restricted to the high-risk group, and, compared with HU cases, was significant higher in the PHL patients who failed to reach the hematocrit target < 0.45% (P = 0.000). In conclusion, this analysis provides reliable and qualified estimates of the therapeutic profile of HU and PHL treatments for future experimental studies and for the management of PV in clinical practice.