tbuckley/cabot-search huggingface dataset:
A Genetic Study of Human Breast Cancer&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: David E. Anderson, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1972)

Two groups of pedigrees were compared, one pertaining to cancer patients with family histories of neoplasms other than those of the breast (controls), and the other to breast cancer patients with family histories of breast cancer. First-degree relatives of breast cancer patients, excluding the affected relatives who led to ascertainment of these patients, manifested a twofold to threefold higher breast cancer frequency than control relatives, a type of finding observed in past studies. The risks increased from 1.8–3.1 for relatives of patients with premenopausal diagnoses compared with control relatives, but no increase in risk was observed for relatives of patients with postmenopausal diagnosis. When the disease in the patient was bilateral, the risk for their relatives was fivefold in excess of controls, and if both premenopausal and bilateral, the risk was ninefold. The risks for relatives of patients with unilateral disease, whether premenopausal or postmenopausal, ranged from 1.2–1.8, only slightly higher than control values. Relatives of bilateral patients manifested a ninefold higher risk of bilateral cancer itself than did relatives of unilateral patients. These results suggest that genetic factors are more important in patients with early onset of multiple disease than in patients with late onset of a single tumor. Moreover, the well-known twofold to threefold risks generally cited for relatives of breast cancer patients may not always apply, and may well be much too low, particularly if the disease is familial, premenopausal, and involves multiple tumor foci.
Treatment of children with asthma
Authors: N. Speight
Journal: BMJ (1995)

EDITOR,--In their excellent and comprehensive account of treating asthmatic children John Rees and John Price rightly emphasise the importance of “partnership in management” and “self management plans,” including “an agreed action plan of what to do…if the child has an acute asthma attack.”1 However, in the subsequent part of the article dealing with acute severe asthma, the principle of partnership with parents …
Similar clinical features in follicular lymphomas with and without breaks in the BCL2 locus
Authors: E Leich, E Hoster, M Wartenberg, M Unterhalt, R Siebert, K Koch, W Klapper, M Engelhard, B Puppe, H Horn, A M Staiger, C Stuhlmann-Laeisz, H W Bernd, A C Feller, M Hummel, D Lenze, H Stein, S Hartmann, M L Hansmann, P Möller, W Hiddemann, M Dreyling, G Ott, A Rosenwald
Journal: Leukemia (2015)
Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials
Authors: Jane Wardle, Christian von Wagner, Ines Kralj-Hans, Stephen P Halloran, Samuel G Smith, Lesley M McGregor, Gemma Vart, Rosemary Howe, Julia Snowball, Graham Handley, Richard F Logan, Sandra Rainbow, Steve Smith, Mary C Thomas, Nicholas Counsell, Steve Morris, Stephen W Duffy, Allan Hackshaw, Sue Moss, Wendy Atkin, Rosalind Raine
Journal: The Lancet (2015)

Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening.
Government consults on charging overseas visitors for emergency care
Authors: Gareth Iacobucci
Journal: BMJ (2015)

Migrants and overseas visitors from outside the European Union are to be charged for using emergency departments, ambulances, and some general practice services in England under new plans tabled by the UK government.

A Department of Health (DH) consultation published on 7 December 20151 proposes to extend the range of services that non-EU patients must pay for beyond those set out in the current regulations, which apply only to secondary care treatment in hospitals.

Under the new proposals non-EU patients would be required to pay for primary care services such as phlebotomy, physiotherapy, eye care, and dentistry, as well as for ambulance services and attendance at emergency departments. Standard GP consultations would remain free.

The consultation also proposes tightening the eligibility …
A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG‐ACRIN cancer research group (E1908)
Authors: Clive S. Zent, Xin Victoria Wang, Rhett P. Ketterling, Curtis A. Hanson, Edward N. Libby, Jacqueline C. Barrientos, Timothy G. Call, Julie E. Chang, Jane J. Liu, Alejandro R. Calvo, Hillard M. Lazarus, Jacob M. Rowe, Selina M. Luger, Mark R. Litzow, Martin S. Tallman
Journal: American Journal of Hematology (2015)

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti‐CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (≥ 65 years) patients (median age 76 years, n = 31) with treatment naïve progressive CLL. Patients received 8‐12 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg/m 2 weekly)( n = 16) or low dose (20 mg/m 2 3x week)( n = 15) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression‐free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti‐CD20 mAb therapy as a potentially more effective use of anti‐CD20 mAb in the treatment of CLL. Am. J. Hematol. 91:308–312, 2016. © 2015 Wiley Periodicals, Inc.
Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation
Authors: Daniel Goldstein, Alan J. Moskowitz, Annetine C. Gelijns, Gorav Ailawadi, Michael K. Parides, Louis P. Perrault, Judy W. Hung, Pierre Voisine, Francois Dagenais, A. Marc Gillinov, Vinod Thourani, Michael Argenziano, James S. Gammie, Michael Mack, Philippe Demers, Pavan Atluri, Eric A. Rose, Karen O’Sullivan, Deborah L. Williams, Emilia Bagiella, Robert E. Michler, Richard D. Weisel, Marissa A. Miller, Nancy L. Geller, Wendy C. Taddei-Peters, Peter K. Smith, Ellen Moquete, Jessica R. Overbey, Irving L. Kron, Patrick T. O’Gara, Michael A. Acker
Journal: New England Journal of Medicine (2015)

In a randomized trial comparing mitral-valve repair with mitral-valve replacement in patients with severe ischemic mitral regurgitation, we found no significant difference in the left ventricular end-systolic volume index (LVESVI), survival, or adverse events at 1 year after surgery. However, patients in the repair group had significantly more recurrences of moderate or severe mitral regurgitation. We now report the 2-year outcomes of this trial.We randomly assigned 251 patients to mitral-valve repair or replacement. Patients were followed for 2 years, and clinical and echocardiographic outcomes were assessed.Among surviving patients, the mean (±SD) 2-year LVESVI was 52.6±27.7 ml per square meter of body-surface area with mitral-valve repair and 60.6±39.0 ml per square meter with mitral-valve replacement (mean changes from baseline, -9.0 ml per square meter and -6.5 ml per square meter, respectively). Two-year mortality was 19.0% in the repair group and 23.2% in the replacement group (hazard ratio in the repair group, 0.79; 95% confidence interval, 0.46 to 1.35; P=0.39). The rank-based assessment of LVESVI at 2 years (incorporating deaths) showed no significant between-group difference (z score=-1.32, P=0.19). The rate of recurrence of moderate or severe mitral regurgitation over 2 years was higher in the repair group than in the replacement group (58.8% vs. 3.8%, P<0.001). There were no significant between-group differences in rates of serious adverse events and overall readmissions, but patients in the repair group had more serious adverse events related to heart failure (P=0.05) and cardiovascular readmissions (P=0.01). On the Minnesota Living with Heart Failure questionnaire, there was a trend toward greater improvement in the replacement group (P=0.07).In patients undergoing mitral-valve repair or replacement for severe ischemic mitral regurgitation, we observed no significant between-group difference in left ventricular reverse remodeling or survival at 2 years. Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure-related adverse events and cardiovascular admissions. (Funded by the National Institutes of Health and Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00807040.).
Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis
Authors: Yanxiong Gan, Shichao Zheng, Jan P.A. Baak, Silei Zhao, Yongfeng Zheng, Nini Luo, Wan Liao, Chaomei Fu
Journal: Acta Pharmaceutica Sinica B (2015)

Curcumin, the medically active component from Curcuma longa (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein–protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation.
99mTc-Macroaggregated Albumin SPECT/CT Perfusion Imaging of Omental Extrahepatic Vascularization
Authors: Ba D. Nguyen, Ming Yang, Michael C. Roarke
Journal: Clinical Nuclear Medicine (2015)

The authors present a case of omental perfusion by an extrahepatic branch of the right hepatic artery depicted during pre-embolization planning with 99mTc-macroaggregated albumin SPECT/CT imaging. This omental scintigraphic finding corresponds to an extrahepatic branch of the right hepatic artery demonstrated by selective angiography and related CT angiography. The authors would like to add the omentum to the previously reported sites of extrahepatic vascularization encountered during the hepatic pre-embolization imaging.
Abstract 4484: BTP-114: An albumin binding cisplatin prodrug with improved and sustained tumor growth inhibition
Authors: Benoit Moreau, Rossitza Alargova, Adam Brockman, Kerry Whalen, Jamie Quinn, Kristan Meetze, Patrick Bazinet, Michelle DuPont, Beata Krawiec, Kristina Kriksciukaite, Charles Lemelin, Patrick LimSoo, Haley Oller, Mike Ramstack, Danielle Rockwood, Rajesh Shinde, Sukhjeet Singh, Brian White, Tsun AuYeung, Craig Dunbar, Mark Bilodeau, Richard Wooster
Journal: Cancer Research (2015)

Abstract Platinum drugs have proven to be effective in treating cancer, for example &amp;gt;90% of men with testicular cancer are cured with a platinum therapeutic. Platinum drugs are also widely used for the adjuvant treatment of common cancers such as those of the lung, colon and ovary. However for the majority of tumor types the clinical response rates for platinum therapies are low, for example the 1 year survival rate for lung cancer patients treated with platinum therapeutics is ∼30%. The key limitations of the existing platinum therapies are the dose limiting toxicities that restrict dose and/or duration of therapy and the absence of personalization that targets the drugs to the patients most likely to benefit. To address these issues we have designed a novel prodrug of cisplatin, BTP-114. On infusion into the blood a maleimide group on BTP-114 covalently attaches to serum albumin. This prolongs the circulation of BTP-114 in plasma and alters the biodistribution of the compound. Importantly the dose of platinum can be increased and the amount of platinum that accumulated in xenograft tumor tissue and the amount of platinum bound to tumor DNA are both increased relative to cisplatin. An elevation of DNA damage in tumor cells in vivo is observed with BTP-114. Together the properties of BTP-114 result in pronounced and sustained tumor growth inhibition compared to cisplatin. In parallel to the discovery of BTP-114 we have explored potential biomarkers to predict which tumors are most likely to respond. These data will be presented towards developing BTP-114 as a personalized platinum medicine for cancer patients. BM and RA contributed equally to this work. Citation Format: Benoit Moreau, Rossitza Alargova, Adam Brockman, Kerry Whalen, Jamie Quinn, Kristan Meetze, Patrick Bazinet, Michelle DuPont, Beata Krawiec, Kristina Kriksciukaite, Charles Lemelin, Patrick LimSoo, Haley Oller, Mike Ramstack, Danielle Rockwood, Rajesh Shinde, Sukhjeet Singh, Brian White, Tsun AuYeung, Craig Dunbar, Mark Bilodeau, Richard Wooster. BTP-114: An albumin binding cisplatin prodrug with improved and sustained tumor growth inhibition. [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 4484. doi:10.1158/1538-7445.AM2015-4484
Evidence that a lipolytic enzyme—hematopoietic-specific phospholipase C-β2—promotes mobilization of hematopoietic stem cells by decreasing their lipid raft-mediated bone marrow retention and increasing the promobilizing effects of granulocytes
Authors: M Adamiak, A Poniewierska-Baran, S Borkowska, G Schneider, A Abdelbaset-Ismail, M Suszynska, A Abdel-Latif, M Kucia, J Ratajczak, M Z Ratajczak
Journal: Leukemia (2015)

Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α4β1-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an important role in mobilizing HSPCs into the peripheral blood (PB) by (i) inducing degranulation of BM-residing granulocytes and (ii) promoting their egress from the BM into the PB so that they permeabilize the endothelial barrier for subsequent egress of HSPCs. We report here that hematopoietic cell-specific phospholipase C-β2 (PLC-β2) has a crucial role in pharmacological mobilization of HSPCs. On the one hand, when released during degranulation of granulocytes, it digests GPI-A, thereby disrupting membrane lipid rafts and impairing retention of HSPCs in BM niches. On the other hand, it is an intracellular enzyme required for degranulation of granulocytes and their egress from BM. In support of this dual role, we demonstrate that PLC-β2-knockout mice are poor mobilizers and provide, for the first time, evidence for the involvement of this lipolytic enzyme in the mobilization of HSPCs.
Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles
Authors: Andrew D. A. C. Smith, Kate Tilling, Scott M. Nelson, Debbie A. Lawlor
Journal: JAMA (2015)

<h3>Importance</h3> The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. <h3>Objective</h3> To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. <h3>Design, Setting, and Participants</h3> Prospective study of 156 947 UK women who received 257 398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. <h3>Exposures</h3> In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. <h3>Main Outcomes and Measures</h3> Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. <h3>Results</h3> Among the 156 947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257 398 cycles was 4 years (interquartile range, 2-6; range, &lt;1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner–related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. <h3>Conclusions and Relevance</h3> Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.
SIGMAR1 Regulates Membrane Electrical Activity in Response to Extracellular Matrix Stimulation to Drive Cancer Cell Invasiveness
Authors: David Crottès, Raphael Rapetti-Mauss, Francisca Alcaraz-Perez, Mélanie Tichet, Giuseppina Gariano, Sonia Martial, Hélène Guizouarn, Bernard Pellissier, Agnès Loubat, Alexandra Popa, Agnès Paquet, Marco Presta, Sophie Tartare-Deckert, Maria Luisa Cayuela, Patrick Martin, Franck Borgese, Olivier Soriani
Journal: Cancer Research (2015)

The sigma 1 receptor (Sig1R) is a stress-activated chaperone that regulates ion channels and is associated with pathologic conditions, such as stroke, neurodegenerative diseases, and addiction. Aberrant expression levels of ion channels and Sig1R have been detected in tumors and cancer cells, such as myeloid leukemia and colorectal cancer, but the link between ion channel regulation and Sig1R overexpression during malignancy has not been established. In this study, we found that Sig1R dynamically controls the membrane expression of the human voltage-dependent K(+) channel human ether-à-go-go-related gene (hERG) in myeloid leukemia and colorectal cancer cell lines. Sig1R promoted the formation of hERG/β1-integrin signaling complexes upon extracellular matrix stimulation, triggering the activation of the PI3K/AKT pathway. Consequently, the presence of Sig1R in cancer cells increased motility and VEGF secretion. In vivo, Sig1R expression enhanced the aggressiveness of tumor cells by potentiating invasion and angiogenesis, leading to poor survival. Collectively, our findings highlight a novel function for Sig1R in mediating cross-talk between cancer cells and their microenvironment, thus driving oncogenesis by shaping cellular electrical activity in response to extracellular signals. Given the involvement of ion channels in promoting several hallmarks of cancer, our study also offers a potential strategy to therapeutically target ion channel function through Sig1R inhibition.
Phase I/II study of ADXS11-001 or MEDI4736 immunotherapies alone and in combination, in patients with recurrent/metastatic cervical or human papillomavirus (HPV)-positive head and neck cancer
Authors: Ezra EW Cohen, Kathleen N Moore, Brian M Slomovitz, Christine H Chung, Matthew L Anderson, Shannon R Morris, David Mauro, Barbara Burtness
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Approaches that target key HPV genes critical for cancer growth and metastasis may improve survival for individuals diagnosed with carcinomas of the uterine cervix or head and neck. ADXS11-001 is a live attenuated Listeria monocytogenes (Lm) -listeriolysin O (LLO) immunotherapy
Southern Medical Students’ Views on Medicaid Expansion
Authors: Esme B. Cullen, Karen E. Hauer, Leo Eisenstein, Christy K. Boscardin, Steven A. Schroeder
Journal: JAMA Internal Medicine (2015)

Joshua J. Fenton, MD, MPH; Richard L. Kravitz, MD, MSPH; Anthony Jerant, MD; Debora A. Paterniti, PhD; Heejung Bang, PhD; Donna Williams, MD; Ronald M. Epstein, MD; Peter Franks, MD