tbuckley/cabot-search huggingface dataset:
Sulodexide for the Prevention of Recurrent Venous Thromboembolism
Authors: Giuseppe M. Andreozzi, Angelo A. Bignamini, Giovanni Davì, Gualtiero Palareti, Jiří Matuška, Martin Holý, Katarzyna Pawlaczyk-Gabriel, Andrej Džupina, German Y. Sokurenko, Yury P. Didenko, Laurentia D. Andrei, Gianfranco Lessiani, Adriana Visonà
Journal: Circulation (2015)

Patients with a first episode of unprovoked venous thromboembolism have a high risk of recurrence after discontinuation of anticoagulant therapy. Extending anticoagulation reduces the risk of recurrence but is associated with increased bleeding. Sulodexide, a glycosaminoglycan, exerts antithrombotic and profibrinolytic actions with a low bleeding risk when administered orally, but its benefit for preventing recurrent venous thromboembolism is not well known.In this multicenter, double-blind study, 615 patients with first-ever unprovoked venous thromboembolism who had completed 3 to 12 months of oral anticoagulant treatment were randomly assigned to sulodexide 500 lipasemic units twice daily or placebo for 2 years, in addition to elastic stockings. The primary efficacy outcome was recurrence of venous thromboembolism. Major or clinically relevant bleeding was the primary safety outcome. Venous thromboembolism recurred in 15 of the 307 patients who received sulodexide and in 30 of the 308 patients who received placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.27-0.92; P=0.02). The analysis in which lost to follow-up was assigned to failure yielded a risk ratio among treated versus control subjects of 0.54 (95% confidence interval, 0.35-0.85; P=0.009). No major bleeding episodes occurred; 2 patients in each treatment group had a clinically relevant bleeding episode. Adverse events were similar in the 2 groups.Sulodexide given after discontinuation of anticoagulant treatment reduced the risk of recurrence in patients with unprovoked venous thromboembolism, with no apparent increase of bleeding risk.URL: https://www.clinicaltrialsregister.eu/. Identifier: EudraCT number 2009-016923-77.
Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs
Authors: Jenny Chen, Alexander A. Shishkin, Xiaopeng Zhu, Sabah Kadri, Itay Maza, Mitchell Guttman, Jacob H. Hanna, Aviv Regev, Manuel Garber
Journal: Genome biology (2016)

Recent advances in transcriptome sequencing have enabled the discovery of thousands of long non-coding RNAs (lncRNAs) across many species. Though several lncRNAs have been shown to play important roles in diverse biological processes, the functions and mechanisms of most lncRNAs remain unknown. Two significant obstacles lie between transcriptome sequencing and functional characterization of lncRNAs: identifying truly non-coding genes from de novo reconstructed transcriptomes, and prioritizing the hundreds of resulting putative lncRNAs for downstream experimental interrogation.We present slncky, a lncRNA discovery tool that produces a high-quality set of lncRNAs from RNA-sequencing data and further uses evolutionary constraint to prioritize lncRNAs that are likely to be functionally important. Our automated filtering pipeline is comparable to manual curation efforts and more sensitive than previously published computational approaches. Furthermore, we developed a sensitive alignment pipeline for aligning lncRNA loci and propose new evolutionary metrics relevant for analyzing sequence and transcript evolution. Our analysis reveals that evolutionary selection acts in several distinct patterns, and uncovers two notable classes of intergenic lncRNAs: one showing strong purifying selection on RNA sequence and another where constraint is restricted to the regulation but not the sequence of the transcript.Our results highlight that lncRNAs are not a homogenous class of molecules but rather a mixture of multiple functional classes with distinct biological mechanism and/or roles. Our novel comparative methods for lncRNAs reveals 233 constrained lncRNAs out of tens of thousands of currently annotated transcripts, which we make available through the slncky Evolution Browser.
Hyaluronidase 1 is a vital mediator of brain metastasis in melanoma.
Authors: Deirdre O'Sullivan, Melissa O'Neal, Brunnhilde Felding-Habermann
Journal: Cancer Research (2008)

3672  Melanoma has a high propensity to metastasize to the CNS and patients with brain metastases have a poor prognosis. The difficulty of treating these patients is exacerbated by the tendency of melanoma to produce multiple tumors throughout the brain by intracranial metastasis from the initial brain lesion.  Both tumor growth within the brain and the seeding of additional lesions requires degradation and remodeling of the brain extracellular matrix. The composition of the brain’s unique extracellular matrix is incompletely understood but its structural organization is based on long strands of very high molecular weight hyaluronic acid decorated with a variety of aggregated proteins and proteoglycans which form networks of crosslinked fibers.  Using the human melanoma cell line, MDA MB 435, we found that variant sub-lines derived from lung, bone and brain metastases from orthotopically implanted cells in SCID mice, share a significant upregulation of the hyaluronic acid degrading enzyme, hyaluronidase 1 (Hyal1). Hyaluronic acid zymography showed that the parental 435 cell line expresses barely detectable amounts of Hyal1 and the level of enzyme secreted by cells cultured from the experimental primary tumors at the site of orthotopic implantation is also very low. The striking metastasis-associated up-regulation of Hyal1 suggested that this enzyme might be a central mediator of the metastatic process in melanoma.  Our laboratory is especially interested in developing a molecular profile of the events underlying survival and dissemination of tumor cells in the brain. In this study, brain-metastatic variants of luciferase-tagged MDA MB 435 cells (435/Brain) were established in tissue culture and used to examine the role of Hyal1 during tumor growth in the brains of SCID mice. We generated a panel of stable knockdowns of Hyal1 in 435/Brain cells using shRNA in a lentiviral vector. Knockdown of Hyal1 was confirmed by PCR, hyaluronic acid zymography and by analysis of HA digestion products by agarose gel electrophoresis. A control shRNA sequence which has no homology to known human gene sequences was used as a baseline comparison in all experiments.  In vivo imaging of luciferase tagged 435/Brain cells was used to visualize growth and metastasis of control and Hyal1 knockdowns after stereotactically guided implantation in the brain striatum of SCID mice. Control and knockdown cells formed tumors at the site of implantation. However, Hyal 1 knockdown strongly diminished the capacity of the cells to migrate from the initial tumor location, in contrast to control cells which rapidly seeded metastases in multiple locations in the brains and spines of the injected animals.  These data imply that tumor-derived Hyal1, an enzyme which has been shown to be important in the metastatic spread of several tumor types, can also degrade the form of hyaluronic acid found in the brain extracellular matrix and mediate intra-cranial migration of cancer cells.
Progesterone and Synthetic Progestin Controversies
Authors: V. Craig Jordan, Philipp Y. Maximov, Ping Fan
Journal: JAMA Oncology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract 842: Two new loci and gene sets related to sex determination and cancer progression are associated with susceptibility to testicular germ cell tumor
Authors: Tom Grotmol, Wenche Kristiansen, Robert Karlsson, Trine B. Rounge, Thomas Whitington, Bettina K. Andreassen, Patrik KE Magnusson, Hans-Olov Adami, Clare Turnbull, Trine B. Haugen, Fredrik Wiklund
Journal: Cancer Research (2015)

Abstract Genome-wide association (GWA) studies have reported 19 distinct susceptibility loci for testicular germ cell tumor (TGCT). The aim of the present study was to identify additional loci and gene sets associated with susceptibility to TGCT. A GWA study for TGCT was performed by genotyping 610,240 single nucleotide polymorphisms (SNPs) in 1,326 cases and 6,687 controls from Sweden and Norway. We put forward 34 SNPs from 17 novel regions and 11 SNPs previously reported, for replication in 710 case-parent triads and 289 cases and 290 controls. Predefined biological pathways and processes, in addition to a custom-built sex determination gene set, were subject to enrichment analyses using Meta-Analysis Gene Set Enrichment of Variant Associations (M) and Improved Gene Set Enrichment Analysis for Genome-wide Association Study (I). In the combined meta-analysis, we observed genome-wide significant association for rs7501939 on chromosome 17q12 (OR = 1.29, 95% CI = 1.19-1.40, P = 1.1 × 10-9) and rs2195987 on chromosome 19p12 (OR = 1.31, 95% CI: 1.19-1.45, P = 3.2 × 10-8). The marker rs7501939 on chromosome 17q12 is located in an intron of the HNF1B gene, encoding a member of the homeodomain-containing superfamily of transcription factors. The sex determination gene set (FDRM &amp;lt; 0.001, FDRI &amp;lt; 0.001) and pathways related to NF-κB, glycerophospholipid and ether lipid metabolism, as well as cancer and apoptosis, was associated with TGCT (FDR &amp;lt; 0.1). In addition to revealing two new TGCT susceptibility loci, our results support the notion that genes governing normal germ cell development in utero are implicated in the development of TGCT. Citation Format: Tom Grotmol, Wenche Kristiansen, Robert Karlsson, Trine B. Rounge, Thomas Whitington, Bettina K. Andreassen, Patrik KE Magnusson, Hans-Olov Adami, Clare Turnbull, Trine B. Haugen, Fredrik Wiklund. Two new loci and gene sets related to sex determination and cancer progression are associated with susceptibility to testicular germ cell tumor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 842. doi:10.1158/1538-7445.AM2015-842
The presentation and management of complex female genital malformations
Authors: Pedro Acién, Maribel Acién
Journal: Human Reproduction Update (2015)

BACKGROUNDCommon uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis.
Tandem autotransplantation for the treatment of metastatic breast cancer.
Authors: E R Broun, R Sridhara, G W Sledge, D Loesch, P H Kneebone, M Hanna, R Hromas, K Cornetta, L H Einhorn
Journal: Journal of Clinical Oncology (1995)

PURPOSE To investigate the tolerability and impact on progression-free and overall survival of two consecutive cycles of high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) in patients with previously untreated metastatic breast cancer. PATIENTS AND METHODS Twenty-eight patients received conventional-dose induction therapy (ITx) followed by a planned two cycles of HDC with ABMT. Median age was 45 years (range, 34 to 60 years). Sites of disease were bone (seven patients), visceral (three), soft tissue (11), multiple (six), and CNS (one). The ITx regimens of cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, fluorouracil, prednisone, and tamoxifen (CAMFTP) (three patients); fluorouracil, doxorubicin, and cyclophosphamide (FAC; 11 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; four patients); or doxorubicin or mitoxantrone/cyclophosphamide (10 patients) were given to maximum response (three to five cycles). HDC was cyclophosphamide 6 g/m2, carboplatin 2 g/m2, and etoposide 625 mg/m2 with ABMT. RESULTS Of 28 patients, 24 received two (86%) cycles of HDC. Four received only one cycle due to persistent toxicity from course 1 (one patient), no response to course 1 (two), and death on course 1 (one). Grade 3 to 4 nonhematologic toxicities included mucositis (in one or both cycles in 21 of 28 patients; 75%), diarrhea, nausea, and vomiting. Reversible peripheral neuropathy was seen in 15 of 28 patients and was severe in one. Documented infections were seen in 19 of 52 cycles. There was one transplant-related death. Six patients were converted from partial remission (PR) to complete remission (CR) with HDC; two of 24 patients (8%) were converted from PR to CR with the second cycle of HDC. Progression-free survival rate is nine of 28 patients (32%) with median follow-up of 23 months (range, 13 to 36+ months). Eighteen of 28 patients (64%) have progressed at 1 to 17 months from ABMT. CONCLUSION Two cycles of HDC with ABMT was well tolerated with a high response rate in patients with metastatic breast cancer. The importance of the second cycle of HDC in this population is unclear.
Risk Factors for Recurrence and Metastasis After Breast-Conserving Therapy for Ductal Carcinoma-In-Situ: Analysis of European Organization for Research and Treatment of Cancer Trial 10853
Authors: Nina Bijker, Johannes L. Peterse, Luc Duchateau, Jean-Pierre Julien, Ian S. Fentiman, Christian Duval, Silvana Di Palma, Joëlle Simony-Lafontaine, Isabelle de Mascarel, Marc J. van de Vijver
Journal: Journal of Clinical Oncology (2001)

In view of the increasing number of patients treated with breast-conserving treatment (BCT) for ductal carcinoma-in-situ (DCIS), risk factors for recurrence and metastasis should be identified.Clinical and pathologic characteristics from patients with DCIS in the European Organization for Research and Treatment of Cancer trial 10853 (excision with or without radiotherapy) were related to the risk of recurrence. Pathologic features were derived from a central review of 863 of the 1,010 randomized cases (85%). The median follow-up was 5.4 years.Factors associated with an increased risk of local recurrence in the multivariate analysis were young age (< or = 40 years) (hazard ratio, 2.14; P =.02), symptomatic detection of DCIS (hazard ratio, 1.80; P =.008), growth pattern (solid and cribriform) (hazard ratios, 2.67 and 2.69, respectively; P =.012), involved margins (hazard ratio, 2.07; P =.0008), and treatment by local excision alone (hazard ratio, 1.74; P =.009). The risk of invasive recurrence was not related to the histologic type of DCIS (P =.63), but the risk of distant metastasis was significantly higher in poorly differentiated DCIS compared with well-differentiated DCIS (hazard ratio, 6.57; P =.01).Patients with poorly differentiated DCIS have a high risk of distant metastasis after invasive local recurrence. Margin status is the most important factor in the success of BCT for DCIS; additionally, young age and symptomatic detection of DCIS have negative prognostic value.
Molecular Differences in Major and Minor Allergens From US Grass Species Support the Association of Several Pollens for Specific Immunotherapy
Authors: Thierry Batard, Henri Chabre, Véronique Baron-Bodo, Emmanuel Nony, Aurélie Lautrette, Marie-Noëlle Couret, Pierrick Lemoine, Nathalie Berjont, Maud Hrabina, Karine Jain, Philippe Moingeon
Journal: Journal of Allergy and Clinical Immunology (2013)
TREATMENT OF PULMONARY EMBOLISM
Authors: J Hirsh
Journal: Annual Review of Medicine (1987)

Most clinically important pulmonary emboli are associated with thrombosis of the proximal deep veins of the leg. Anticoagulant therapy is highly successful in reducing death and recurrence from pulmonary embolism and is the treatment of choice in the majority of these patients. Thrombolytic therapy is usually reserved for selected patients with clinically serious or massive pulmonary embolism. Vena caval interruption is limited to patients who have an absolute contraindication to anticoagulant therapy or who develop recurrent pulmonary embolism despite adequate anticoagulant therapy. Pulmonary embolectomy has a high mortality and should therefore be restricted to the most desperate cases.
Erratum. Glycemic Variability Is Associated With Reduced Cardiac Autonomic Modulation in Women With Type 2 Diabetes. Diabetes Care 2015;38:682–688
Authors: Jesper Fleischer, Simon Lebech Cichosz, Pernille Hoeyem, Esben Laugesen, Per Loegstrup Poulsen, Jens Sandahl Christiansen, Lise Tarnow, Troels Krarup Hansen
Journal: Diabetes Care (2015)
Development and Results of a Multiple Myeloma Specific Custom 77-Gene Mutation Panel for Clinical Targeted Sequencing
Authors: K. Martin Kortuem, A. Keith Stewart, Laura Ann Bruins, Gregory Ahmann, George Vasmatzis, S. Vincent Rajkumar, Shaji Kumar, Angela Dispenzieri, Martha Q Lacy, Morie A Gertz, Rafael Fonseca, Mia Champion, P. Leif Bergsagel, Esteban Braggio
Journal: Blood (2014)
HIV pre-exposure prophylaxis could help 1.2 million in US
Authors: Michael McCarthy
Journal: BMJ (2015)

More than 1.2 million people in the United States are at high enough risk for HIV infection to be candidates for daily oral pre-exposure prophylaxis (PrEP) but most are not receiving the treatment, officials at the US Centers for Disease Control and Prevention (CDC) said on 24 November.

Currently, the CDC recommends the combination of two antiretroviral drugs, tenofovir disoproxil fumarate and emtricitabine, taken in a single pill daily to prevent HIV in people at high risk for the infection. This combination, marketed in the US as Truvada, was approved for PrEP …
Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products
Authors: Cunlin Wang, David J. Graham, Robert C. Kane, Diqiong Xie, Michael Wernecke, Mark Levenson, Thomas E. MaCurdy, Monica Houstoun, Qin Ryan, Sarah Wong, Katrina Mott, Ting-Chang Sheu, Susan Limb, Chris Worrall, Jeffrey A. Kelman, Marsha E. Reichman
Journal: JAMA (2015)

<h3>Importance</h3> All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established. <h3>Objective</h3> To compare the risk of anaphylaxis among marketed IV iron products. <h3>Design, Setting, and Participants</h3> Retrospective new user cohort study of IV iron recipients (n = 688 183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013. <h3>Exposures</h3> Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data. <h3>Main Outcomes and Measures</h3> Anaphylaxis was identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups. <h3>Results</h3> A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100 000 persons for iron dextran (95% CI, 57.8-78.7 per 100 000) and 24 per 100 000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100 000) , with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3;<i>P</i> &lt; .001). At first exposure, when compared with iron sucrose, the adjusted OR of anaphylaxis for iron dextran was 3.6 (95% CI, 2.4-5.4); for iron gluconate, 2.0 (95% CI 1.2, 3.5); and for ferumoxytol, 2.2 (95% CI, 1.1-4.3). The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100 000 persons, 95% CI, 70.5- 93.1) and lowest with iron sucrose (21 per 100 000 persons, 95% CI, 15.3- 26.4). <h3>Conclusions and Relevance</h3> Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.
S-Nitrosylation of Calcium-Handling Proteins in Cardiac Adrenergic Signaling and Hypertrophy
Authors: Tomoya Irie, Patrick Y. Sips, Shinichi Kai, Kotaro Kida, Kohei Ikeda, Shuichi Hirai, Kasra Moazzami, Pawina Jiramongkolchai, Donald B. Bloch, Paschalis-Thomas Doulias, Antonis A. Armoundas, Masao Kaneki, Harry Ischiropoulos, Evangelia Kranias, Kenneth D. Bloch, Jonathan S. Stamler, Fumito Ichinose
Journal: Circulation Research (2015)

Rationale: The regulation of calcium (Ca 2+ ) homeostasis by β-adrenergic receptor (βAR) activation provides the essential underpinnings of sympathetic regulation of myocardial function, as well as a basis for understanding molecular events that result in hypertrophic signaling and heart failure. Sympathetic stimulation of the βAR not only induces protein phosphorylation but also activates nitric oxide–dependent signaling, which modulates cardiac contractility. Nonetheless, the role of nitric oxide in βAR-dependent regulation of Ca 2+ handling has not yet been explicated fully. Objective: To elucidate the role of protein S-nitrosylation, a major transducer of nitric oxide bioactivity, on βAR-dependent alterations in cardiomyocyte Ca 2+ handling and hypertrophy. Methods and Results: Using transgenic mice to titrate the levels of protein S-nitrosylation, we uncovered major roles for protein S-nitrosylation, in general, and for phospholamban and cardiac troponin C S-nitrosylation, in particular, in βAR-dependent regulation of Ca 2+ homeostasis. Notably, S-nitrosylation of phospholamban consequent upon βAR stimulation is necessary for the inhibitory pentamerization of phospholamban, which activates sarcoplasmic reticulum Ca 2+ -ATPase and increases cytosolic Ca 2+ transients. Coincident S-nitrosylation of cardiac troponin C decreases myocardial sensitivity to Ca 2+ . During chronic adrenergic stimulation, global reductions in cellular S-nitrosylation mitigate hypertrophic signaling resulting from Ca 2+ overload. Conclusions: S-Nitrosylation operates in concert with phosphorylation to regulate many cardiac Ca 2+ -handling proteins, including phospholamban and cardiac troponin C, thereby playing an essential and previously unrecognized role in cardiac Ca 2+ homeostasis. Manipulation of the S-nitrosylation level may prove therapeutic in heart failure.