tbuckley/cabot-search huggingface dataset:
Improving the Prediction of Preeclampsia
Authors: Ellen W. Seely, Caren G. Solomon
Journal: New England Journal of Medicine (2016)

Preeclampsia is a leading cause of maternal and neonatal death in the United States and worldwide,1 yet effective strategies are lacking for prevention and treatment. Since delivery remains the only "cure," preeclampsia is a major cause of iatrogenic prematurity.Although the pathogenesis of preeclampsia is not completely understood, altered levels of angiogenic factors appear to play a role.2 Elevated levels of soluble fms-like tyrosine kinase 1 (sFlt-1; an inhibitor of vascular endothelial growth factor), reduced levels of placental growth factor (PlGF), and an increased sFlt-1:PlGF ratio have been reported both in women with established preeclampsia and in women before the . . .
Chromosome 9p and Hereditary Cutaneous Malignant Melanoma
Authors: S. J. BALE, N. C. DRACOPOLI
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Chromosome 9p and Hereditary Cutaneous Malignant Melanoma Get access SHERRI J. BALE, SHERRI J. BALE Family Studies Section, Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer InstituteExecutive Plaza North, Rm. 439, National Institutes of Health, Bethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar NICHOLAS C. DRACOPOLI NICHOLAS C. DRACOPOLI Center for Cancer Research, Massachusetts Institute of TechnologyCambridge, MA Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 1, January 1989, Page 70, https://doi.org/10.1093/jnci/81.1.70 Published: 01 January 1989
SWOG/Intergroup 9623: A phase III comparison of intensive sequential chemotherapy to high dose chemotherapy and autologous hematopoietic progenitor cell support (AHPCS) for primary breast cancer in women with ≥4 involved axillary lymph nodes
Authors: S. I. Bearman, S. Green, J. Gralow, W. Barlow, C. Hudis, A. Wolff, J. Ingle, G. Hortobagyi, R. Livingston, S. Martino
Journal: Journal of Clinical Oncology (2005)

572 Background: This randomized trial compared intensive sequential chemotherapy using doxorubicin (ADR), paclitaxel (TAX), and cyclophosphamide (CTX) (Arm 1) versus induction chemotherapy with ADR + CTX followed by high dose chemotherapy and AHPCS (transplant) (Arm 2) with respect to disease-free survival (DFS), overall survival (OS), and toxicity. Methods: Patients with resected primary breast cancer with ≥ 4+ nodes were eligible. Arm 1 received 3 doses each of ADR (80 mg/m2), TAX (200 mg/m2), and CTX (3g/m2) given sequentially at 14-day intervals with filgrastim support. Arm 2 received induction ADR (80 mg/m2) + CTX (600 mg/m2) for 4 cycles at q3 week intervals followed by high dose chemotherapy (STAMP I or V) with AHPCS. The primary study outcome was DFS. The planned sample size was 1000 patients, sufficient for a 1-sided 0.025 level test to have 90% power to detect an Arm 1/Arm 2 hazard ratio (HR) of 1.45. Two interim analyses for both positive and negative results were planned at level 0.005. Log-rank and Cox models were used for DFS and OS analysis. Results: 539 eligible patients were enrolled between 7/96–2/01, when accrual was stopped due to poor recruitment. At the second interim analysis in 10/03 the estimated HR was significantly below 1.45 (p=0.001). The decision to report the current result was made. In the analysis of DFS there were 58 and 67 failures in the 271 and 265 patients on Arms 1 and 2, respectively. For OS, there were 36 and 43 deaths in Arms 1 and 2, respectively. The 99% CI for the HR is 0.53–1.32 for DFS and 0.46–1.48 for OS. 4 patients died due to treatment-related toxicity; 1 in Arm 1 and 3 in Arm 2. 59% of patients in Arm 1 experienced grade 4 hematologic toxicity; grade 4 non-hematologic toxicities were rare. In Arm 2, grade 4 hematologic toxicity was 92% during transplant; grade 4 non-hematologic toxicity was 10%. Discussion: Transplantation did not show superior DFS or OS compared to intensive sequential chemotherapy and actually had poorer outcomes. There is no evidence that adjuvant high dose chemotherapy with AHPCS provides better outcomes for women with ≥4 positive nodes. No significant financial relationships to disclose.
Abstract 3823: Platinum anti-cancer drugs attenuate T cell-mediated immune suppression through STAT6/PD-L2
Authors: W. Joost Lesterhuis, Cornelis J.A. Punt, Dagmar Eleveld-Trancikova, Bas J.H. Jansen, Gerty Schreibelt, Annemiek De Boer, Gosse J. Adema, Carl G. Figdor, I. Jolanda M. De Vries
Journal: Cancer Research (2010)

Abstract It has become evident that many immune inhibitory mechanisms in the tumor micro-environment prevent the development of effective T cell responses against the tumor cells in cancer patients. Therapeutic interventions aimed at blocking these pathways have been shown to result in enhanced anti-tumor immunity, but they lack direct cytotoxic effects. Cancer chemotherapeutic drugs have these direct cytotoxic anti-tumor effects and although for some anti-cancer drugs indirect activation of the immune system via induction of an immunogenic type of tumor cell death has been described, their effect on inhibitory pathways in anti-tumor immunity is unknown. We investigated the effect of a wide array of chemotherapeutics on dendritic cell (DC) function and on tumor cell immunogenicity. Using allogeneic and antigen-specific in vitro models, we found that when DCs were matured/activated in the presence of platinum-based chemotherapy, they showed strongly enhanced T cell stimulatory capacity. Programmed death receptor-ligand 2 (PD-L2) expression by DC was markedly reduced upon platinum exposure. The enhanced T cell stimulatory capacity by DC upon platinum exposure was abrogated in the presence of PD-L2 blocking antibodies. This was also observed when the regulator of PD-L2 expression, signal transducer and activator of transcription 6 (Stat6), was knocked down using siRNA. In addition, we found that STAT6 was dephosphorylated in tumor cells by platinum compounds, leading to marked downregulation of PD-L2, resulting in enhanced recognition by tumor-specific T cells. In line with these in vitro findings, we found enhanced Th1 cytokine secretion and T cell proliferative responses in cancer patients upon treatment with platinum-based chemotherapy, confirming the in vivo occurrence of platinum-induced immune deviation. Our findings show that treatment with platinum compounds not only results in enhanced T cell stimulation by DC, but at the same time enhances the sensitivity of the tumor for lysis by cytotoxic T cells. This novel double action of platinum compounds may initiate combinations with other immune stimulatory compounds to increase clinical efficacy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3823.
Surgeon is suspended because of concerns over eight "avoidable" deaths
Authors: C. Dyer
Journal: BMJ (2013)

A consultant liver and pancreatic surgeon has been suspended from duties by his employers for nearly a year, amid concerns about eight “avoidable” deaths among his patients.

David Paul Berry, who worked at the University Hospital of Wales in Cardiff, was suspended last January “following concerns about the outcomes for some liver patients whilst in his care,” Cardiff and Vale University Health Board said in a statement.

The health …
Treatment of Hepatic Failure with ex Vivo Pig-Liver Perfusion Followed by Liver Transplantation
Authors: Ravi S. Chari, Bradley H. Collins, John C. Magee, J. Michael DiMaio, Allan D. Kirk, Robert C. Harland, Richard L. McCann, Jeffrey L. Platt, William C. Meyers
Journal: New England Journal of Medicine (1994)

In 1990, more than 27,000 patients died of liver failure in the United States1. Perfusion through a liver from another person or a member of another species, such as a monkey, outside the body was used in the past to stabilize the condition of some patients with acute or subacute liver failure2–5. Few patients survived, however, and this approach was superseded by orthotopic liver transplantation6. Liver transplantation is associated with higher mortality for patients with fulminant hepatic failure than for patients with chronic liver disease, however. Patients with fulminant hepatic failure often have multiorgan failure and . . .
Two techniques for guide wire advancement along a tortuous pancreatic duct: the through-the-stent and flipped “U-wire” techniques
Authors: K. Mönkemüller, D. Popa, J. Ramesh, C. Wilcox
Journal: Endoscopy (2013)

A 52-year-old man with a history of renal transplantation, immunosuppression, and valvular heart disease developed severe acute pancreatitis with a pancreatic pseudocyst. Endoscopic retrograde cholangiopancreatography (ERCP) performed 6 weeks previously had revealed a large pancreatic duct leak requiring the placement of a plastic stent.
THE LATE SODIUM CURRENT INHIBITOR ELECLAZINE SUPPRESSES ATRIAL PREMATURE BEATS AND ATRIAL FIBRILLATION IN AN INTACT PORCINE MODEL
Authors: Henrique Fuller, Fernanda Justo, Bruce Nearing, Sridharan Rajamani, Luiz Belardinelli, Richard Verrier
Journal: Journal of the American College of Cardiology (2016)
Resurgence of malaria after discontinuation of indoor residual spraying of insecticide in a previously high transmission intensity area of Uganda
Authors: Saned Raouf, Arthur Mpimbaza, Ruth Kigozi, Asadu Sserwanga, Grant Dorsey
Journal: The Lancet Global Health (2016)

Background In 2009, Uganda implemented a programme of indoor residual spraying of insecticide (IRS) in ten districts in the Northern Region with historically high malaria transmission intensity. This programme was successful in reducing the burden of malaria; however, in May, 2014, IRS was discontinued, to be replaced by universal distribution of long-lasting insecticide-treated bednets. The aim of this study was to assess changes in malaria morbidity during and after IRS discontinuation in one district in Uganda.
GE-37 * INTEGRATED GENOMIC ANALYSIS OF LOW GRADE GLIOMA AND GLIOBLASTOMA REVEALS MOLECULAR STRATIFICATION BY IDH STATUS ACROSS GRADES AND HISTOLOGIES
Authors: R. Verhaak, A. Iavarone
Journal: Neuro-Oncology (2014)

TCGA has performed comprehensive molecular characterization of glioblastoma (GBM) and diffuse low grade glioma (LGG), which suggested heterogeneity in clinical diagnosis: GBM with isocitrate dehydrogenase (IDH) gene mutations corresponded with a hypermethylator/G-CIMP phenotype and relatively favorable outcome, while IDH-wildtype LGG were associated with GBM-like genomic and methylation features and poor survival. By integrating the GBM and LGG datasets, the TCGA LGG-GBM working group aims to classify them in a clinically relevant manner and to shed light on potential targets for therapy. Unsupervised clustering of 289 LGG and 398 GBM using methylation profiles resulted into six major groups, mainly driven by IDH status and age. G-CIMP/IDH mutant GBM clustered with IDH mutant LGGs and IDHwt LGG grouped with IDHwt GBM. Some but not all LGG with 1p/19q co-deletion, a hallmark of oligodendroglioma, clustered separate from other LGGs and associated with less favorable outcome, suggesting clinical value of methylation based patient stratification. IDH-wildtype LGG and GBM clustered into a classical-mesenchymal class and a proneural-mesenchymal subtype, the latter with normal-like methylation features. Unsupervised transcriptome clustering of 282 LGGs and 152 GBMs was again driven by IDH status, followed by strong associations with mutations in TP53/ATRX. Supervised comparison of IDH wildtype LGG and GBM suggested upregulation of oxidative phosphorylation gene sets in GBM which may provide an intriguing possibility of pathogenetic differences between histologically different but genomically similar gliomas. We evaluated the distribution of genomic alterations in glioma disease pathways and found that G-CIMP GBM uniquely associated with abnormalities in the MYC pathway, revealing a possible explanation for the aggressive behavior of IDH-mutant GBM relative to IDH-mutant LGG. In this first of its kind study, we improve our understanding of gliomagenesis by identifying shared and subtype-unique disease pathways and provide new modalities towards integrated classification of diffuse low and high grade glioma.
P1164 THE DISEASE BURDEN OF CHRONIC HEPATITIS C VIRUS (HCV) INFECTION IN EGYPT: FUTURE IMPACT OF VARYING TREATMENT STRATEGIES
Authors: I. Waked, W. Doss, M. El-Sayed, C. Estes, H. Razavi, G. Shiha, A. Yosry, G. Esmat
Journal: Journal of Hepatology (2014)
S112 The natural history of wheeze from birth to adult life: a cohort study
Authors: M. L. Burr, F. D. J. Dunstan, S. Hand, K. P. Jones, S. Rolf
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Wheeze is a common symptom at all ages. Its natural history from birth to adulthood was studied in a birth cohort of individuals at high risk of atopic illness. The objective was to ascertain factors associated with wheeze at different ages, distinguishing between wheeze that occurred at successive time points (persistent wheeze) and wheeze newly occurring (incident wheeze). <h3>Methods</h3> 497 infants were selected antenatally as having a first-degree relative with a history of asthma, hay fever or eczema. During their first year and at 7 years the children were examined, symptoms were recorded, skin prick tests performed and serum IgE measured. At 15 and 23 years further questionnaires were completed and (at 23) blood and skin tests performed. <h3>Results</h3> Information was obtained on 483 individuals at 1 year, 453 at seven, 363 at 15 and 304 at 23. The prevalence of wheeze was fairly constant over time (around 30%), remission being balanced by incidence over each interval. Wheeze at 1 year predicted wheeze at ages seven and 15, and at seven it predicted wheeze at 15 and 23, but it was associated with different factors at different times and according to whether it was persistent or incident. In infancy it was related to non-atopic factors such as infection, maternal smoking and breastfeeding (protective). Persistent wheeze to age 15 was related to respiratory infections in infancy and to atopy. Incident wheeze from one to 7 years was strongly associated with atopy, while late-onset wheeze was related to rhino conjunctivitis, smoking and (marginally) body mass. <h3>Conclusions</h3> Advances in the understanding and prevention of wheeze may be assisted by directing attention to maternal smoking, breastfeeding and respiratory infections in infancy, atopy in childhood, rhino conjunctivitis in adolescence, and smoking and perhaps obesity in adult life.
Abstract 3222: Telomerase expression is upregulated in response to severe oxidative stress
Authors: Wallace Sharif, DeMario Butts, Jamelle Brown
Journal: Cancer Research (2010)

Abstract Telomerase is aberrantly expressed in 90% of all cancers, and is well characterized for its ability to extend the ends of chromosomes, the telomere. Although telomerase expression is predominantly associated with its ability to extend telomeres, there have been recent findings that suggest that telomerase has multiple cellular functions independent of its catalytic ability, and some of those functions help promote cell survival in response to severe oxidative stress. To date, telomerase expression as been implicated in aiding a cell's response to double strand breaks in DNA, mitochondria dysfunction, inhibition of apoptosis, and the promotion of cell proliferation. The protein component of telomerase, TERT, is also thought to specifically enhance cell viability in response to the hypoxic microenvironment of a tumor. These protective roles of TERT could be vital in promoting cell survival during severe hypoxia. Telomerase expression is upregulated by the kinase Akt, which is in turn induced by the neuregulin/ErbB signaling pathway. Neuregulin is a glycoprotein that is necessary for smooth muscle and neuronal development. Neuregulin activates the ErbB tyrosine kinase family, which promotes cell survival, proliferation, and differentiation. Recently, neuregulin has been shown to be upregulated in response to severe hypoxia, and may reduce the inflammation response to oxidative stress. The mechanism of neuregulin protection is unclear, though microarray data shows that neuregulin expression decreases the expression of several pro-inflammatory cytokines. We hypothesize that neuregulin can regulate the expression of telomerase during severe oxidative stress, and that telomerase expression promotes cell survival during hypoxia. Inducing oxidative stress and hypoxia in differentiated rat neuroblastoma cells caused significant increases in telomerase expression. The addition of physiologic levels of neuregulin was able to induce telomerase expression, indicating that telomerase activation could play an important role in the cellular response to oxidative stress. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3222.
Cancer-Prevention Diet Wins Praise on Navy Destroyer
Authors: P. Dakutis
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Cancer-Prevention Diet Wins Praise on Navy Destroyer Get access Peter Dakutis Peter Dakutis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 5, 4 March 1992, Pages 297–298, https://doi.org/10.1093/jnci/84.5.297 Published: 04 March 1992
M37 Does The Tuberculin Skin Test Increase The Detection Of Tb Infection When Screening Hiv Positive Patients? Three Years' Experience In A District General Hospital
Authors: A. Bennett, J. Ashby, M. Curtiss, N. Pal, T. Wambaa, S. Menzies
Journal: Thorax (2014)

<h3>Background</h3> HIV infection is the strongest single risk factor for the development of active tuberculosis (TB) in individuals with latent TB infection (LTBI).<sup>1</sup> NICE guidelines recommend screening HIV-positive patients for LTBI with an Interferon Gamma Release Assay (IGRA), plus a Tuberculin Skin Test (TST) in patients with a CD4 count &lt;200 cells/mm<sup>3</sup> if IGRA negative. <h3>Method</h3> We began screening HIV-positive patients for LTBI in July 2011; this prospective study reports our 3 year data. Patients had an IGRA (T-SPOT. TB<sup>®</sup>), and a TST was performed in those with a negative result and a CD4 count &lt;200 cells/mm<sup>3</sup>. <h3>Results</h3> 116 HIV-positive patients were screened (Table 1): <h3>CD4 Count ≥200 Group</h3> Of 88 patients, 4 (5%) had a history of previous TB infection and were excluded. 70/84 (83%) had a negative IGRA, 9/84 (11%) had a positive IGRA (3 had active TB and 6 LTBI) and 5/84 (6%) had inconclusive IGRA results. Of these, 4/5 had a repeat IGRA (2 positive, 1 negative, 1 awaited) and 1 was lost to follow up. <h3>CD4 Count &lt;200 Group</h3> Of 28 patients, 1 (4%) had a history of previous TB infection and was excluded. 24/27 (89%) had a negative IGRA and were referred to TB clinic for a TST. Of these, 18/24 (75%) had a negative TST, 3/24 (12.5%) did not attend and 3/24 (12.5%) are awaiting appointments. 2/27 (7%) had a positive IGRA and were treated for LTBI. One (4%) had an inconclusive IGRA result but did not attend follow up. <h3>Conclusions</h3> Screening for TB in HIV is worthwhile, with a 12% detection rate in our cohort. Performing a TST did not detect any additional cases of TB infection in the CD4 &lt;200 group. Performing this test is time-consuming, costly and inconvenient, and we suggest that screening should be with an IGRA alone. The detection rate of TB infection was lower in those with more advanced immunocompromise, which raises concern about the sensitivity of the screening tests. <h3>References</h3> Treatment of latent tuberculosis infection in HIV infected persons. Akolo C, Adetifa I <i>et al</i>. Cochrane Database of Systematic Reviews 2010, Issue 1
Enhanced Subclinical Coagulation Activation During Diabetic Ketoacidosis
Authors: Yahya Büyükaşik, Naciye ş İleri, İbrahim C Haznedaroğlu, Selma Karaahmetoğlu, Osman Müftüoğlu, şErafettin Kirazll, Semra Dündar
Journal: Diabetes Care (1998)
Costs and benefits in hunter-gatherer punishment
Authors: Christopher Boehm
Journal: Behavioral and Brain Sciences (2012)

Abstract Hunter-gatherer punishment involves costs and benefits to individuals and groups, but the costs do not necessarily fit with the assumptions made in models that consider punishment to be altruistic – which brings in the free-rider problem and the problem of second-order free-riders. In this commentary, I present foragers' capital punishment patterns ethnographically, in the interest of establishing whether such punishment is likely to be costly; and I suggest that in many cases abstentions from punishment that might be taken as defections by free-riders are actually caused by social-structural considerations rather than being an effect of free-rider genes. This presentation of data supplements the ethnographic analysis provided by Guala.