tbuckley/cabot-search huggingface dataset:
Predicting the need for colectomy in severe ulcerative colitis: a critical appraisal of clinical parameters and currently available biomarkers
Authors: S. Travis, J. Satsangi, M. Lemann
Journal: Gut (2010)

Acute severe ulcerative colitis is a potentially life-threatening condition. It is most readily identified by the criteria of Truelove and Witts,1 which have been adopted by international bodies: a patient who has a bloody stool frequency of six or more per day and tachycardia (>90 bpm, or temperature greater than 37.8°C, or anaemia (haemoglobin  30 mm/h).1–4 However, the response to intensive treatment with corticosteroids has remained unchanged for 50 years. In a systematic review of 32 trials of steroid therapy for acute severe colitis involving 1991 patients from 1974 to 2006, the overall response to intravenous hydrocortisone, methylprednisolone, or betamethasone was 67% (95% CI 65% to 69%), and 29% (95% CI 28% to 31%) came to colectomy.5 The only major difference from 1955 was that mortality was 1% (95% CI 0.7% to 1.6%) and not 7%. The colectomy rate did not change between 1974 and 2006.

The UK national inflammatory bowel disease audit in 2008 identified a mortality of 2.8% among 317 patients.6 Old age dominated death (11/16 who died were aged 80–89years), but the morbidity in young people has yet to be quantified. A nationwide linkage analysis in Scotland also strongly implicates age as the critical determinant of mortality in patients hospitalised for ulcerative colitis—the 3-year mortality in 245 patients aged 65 years and over was 39%, whereas none of 212 patients aged 30 years or less died (p<0.001).7 Co-morbidity was independently associated with mortality, but it remains unclear whether older people die from co-morbidity, complications of immunosuppression, delayed surgery, or surgery itself. The prime concern in managing acute severe colitis must be to reduce both morbidity and mortality.

We address two principal clinical dilemmas in managing acute severe colitis: how to identify at an early stage those who are likely …
Hypothalamic tanycytes: potential roles in the control of feeding and energy balance
Authors: Matei Bolborea, Nicholas Dale
Journal: Trends in Neurosciences (2013)

Tanycytes, glial-like cells that line the third ventricle, are emerging as components of the hypothalamic networks that control body weight and energy balance. They contact the cerebrospinal fluid (CSF) and send processes that come into close contact with neurons in the arcuate and ventromedial hypothalamic nuclei. Tanycytes are glucosensitive and are able to respond to transmitters associated with arousal and the drive to feed. At least some tanycytes are stem cells and, in the median eminence, may be stimulated by diet to generate new neurons. The quest is on to understand how tanycytes detect and respond to changes in energy balance and how they communicate with the rest of the nervous system to effect their functions.
De novo ChIP-seq analysis
Authors: Xin He, A. Ercument Cicek, Yuhao Wang, Marcel H. Schulz, Hai-Son Le, Ziv Bar-Joseph
Journal: Genome biology (2015)

Methods for the analysis of chromatin immunoprecipitation sequencing (ChIP-seq) data start by aligning the short reads to a reference genome. While often successful, they are not appropriate for cases where a reference genome is not available. Here we develop methods for de novo analysis of ChIP-seq data. Our methods combine de novo assembly with statistical tests enabling motif discovery without the use of a reference genome. We validate the performance of our method using human and mouse data. Analysis of fly data indicates that our method outperforms alignment based methods that utilize closely related species.
An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients
Authors: M.A. Vollebergh, E.H. Lips, P.M. Nederlof, L.F.A. Wessels, M.K. Schmidt, E.H. van Beers, S. Cornelissen, M. Holtkamp, F.E. Froklage, E.G.E. de Vries, J.G. Schrama, J. Wesseling, M.J. van de Vijver, H. van Tinteren, M. de Bruin, M. Hauptmann, S. Rodenhuis, S.C. Linn
Journal: Annals of Oncology (2010)

BackgroundBreast cancer cells deficient for BRCA1 are hypersensitive to agents inducing DNA double-strand breaks (DSB), such as bifunctional alkylators and platinum agents. Earlier, we had developed a comparative genomic hybridisation (CGH) classifier based on BRCA1-mutated breast cancers. We hypothesised that this BRCA1-likeCGH classifier could also detect loss of function of BRCA1 due to other causes besides mutations and, consequently, might predict sensitivity to DSB-inducing agents.Patients and methodsWe evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup).ResultsWe observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-likeCGH tumours [41/230 = 18%, multivariate hazard ratio (HR) = 0.12, 95% confidence interval (CI) 0.04–0.43] compared with patients with non-BRCA1-likeCGH tumours (189/230 = 82%, HR = 0.78, 95% CI 0.50–1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-likeCGH tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12).ConclusionBRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.
Reversible Versus Irreversible EGFR Tyrosine-Kinase Inhibitors for Non-Small-Cell Lung Cancer (NSCLC): a Preclinical and Pharmacokinetic Comparison
Authors: B.M. Liederer, T. Friess, D. Shames, M. Wright, C.E.C.A. Hop
Journal: Annals of Oncology (2015)
Excretion of thromboxane A2 and prostacyclin metabolites before and after exercise testing in patients with and without signs of ischemic heart disease.
Authors: A Wennmalm, J Nowak, T Bjurö
Journal: Circulation (1990)

We addressed the hypothesis that platelets are not activated in association with effort-induced myocardial ischemia in stable coronary disease. Seventy-two patients undergoing a diagnostic bicycle exercise test were stratified according to the development of chest pain (yes/no, 33/39) and of exercise-induced ST-segment depression of at least 200 microV in the electrocardiogram (yes/no, 12/60). Noninvasive indexes of platelet activation and of platelet/vessel wall interaction (urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 [Tx-M] and prostacyclin [PGI-M], respectively) were analyzed in samples collected in the basal state and after the test. Basal Tx-M and PGI-M did not differ in patients with (236 +/- 35 and 131 +/- 22 pg/mg creatinine, respectively) and without (185 +/- 16 and 101 +/- 13 pg/mg creatinine, respectively) chest pain, or in those with (178 +/- 45 and 162 +/- 41 pg/mg, respectively) and without (216 +/- 22 and 104 +/- 11 pg/mg, respectively) ST-segment depression during the test. Patients without chest pain or without ST-segment depression moderately increased (p less than 0.05) their urinary Tx-M (by 21% and 13%, respectively) and PGI-M (by 28% and 23%, respectively) after exercise. No significant increases were observed in those developing chest pain or ST depression during exercise. These data indicate that effort-induced myocardial ischemia is not associated with an increase in platelet activation or platelet/vessel wall interaction in patients with stable coronary disease.
Escalated-Dose BEACOPP in the Treatment of Patients With Advanced-Stage Hodgkin's Lymphoma: 10 Years of Follow-Up of the GHSG HD9 Study
Authors: Andreas Engert, Volker Diehl, Jeremy Franklin, Andreas Lohri, Bernd Dörken, Wolf-Dieter Ludwig, Peter Koch, Mathias Hänel, Michael Pfreundschuh, Martin Wilhelm, Lorenz Trümper, Walter-Erich Aulitzky, Martin Bentz, Mathias Rummel, Orhan Sezer, Hans-Konrad Müller-Hermelink, Dirk Hasenclever, Markus Löffler
Journal: Journal of Clinical Oncology (2009)

Purpose The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up had indicated improved tumor control with BEACOPP escalated. Since the long-term safety and efficacy of this regimen has been debated, we report the 10-year follow-up. Patients and Methods Patients received one of three chemotherapy regimens: eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); eight cycles of BEACOPP baseline; or eight cycles of BEACOPP escalated. Results Median follow-up was 111 months. At 10 years, freedom from treatment failure (FFTF) was 64%, 70%, and 82% with OS rates of 75%, 80%, and 86% for patients treated with COPP/ABVD (arm A), BEACOPP baseline (arm B), and BEACOPP escalated (arm C), respectively (P &lt; .001). BEACOPP escalated was significantly better than BEACOPP baseline in terms of FFTF (P &lt; .0001) and OS (P = .0053). A total of 74 second malignancies (6.2%) were documented, including acute myeloid leukemia (0.4%, 1.5%, and 3.0%), non-Hodgkin's lymphoma (2.7%, 1.7%, and 1.0%), and solid tumors (2.7%, 3.4%, and 1.9%). The corresponding overall secondary malignancy rates were 5.7%, 6.6%, and 6.0%, respectively. Conclusion The 10-year follow-up of the HD9 trial demonstrates a stabilized significant improvement in long-term FFTF and OS for BEACOPP escalated in advanced-stage HL. These results challenge ABVD as standard of care for this patient population.
Sir James Crichton-Browne (1840-1938): pioneer neurologist and scientific drop-out
Authors: E H Jellinek
Journal: Journal of the Royal Society of Medicine (2005)

In an era when surgery was hazardous, psychiatry custodial, and medicine at best pastoral, James Crichton Browne in his ten years as director of the West Riding Lunatic Asylum at Wakefield initiated a scientific approach to the brain and its diseases and later gave it a voice by co-founding Brain, the first journal of what would now be called the neurosciences.

Crichton-Browne has been the subject of a long and fully referenced study by the historian Michael Neve and the psychiatrist Trevor Turner,1 including his life as alienist, as Lord Chancellor's Visitor in Lunacy, and as prolific activist on social, medical and literary matters. But they are brief on his research efforts at the Asylum at Wakefield between his 26th and 37th years, and then his co-founding of Brain which furthered the schism of neurology from psychiatry.

He was born at Edinburgh into a cultured professional setting, and was given his second name Crichton to mark the munificence of his godmother, Mrs Elizabeth Crichton, who had given £100 000 to found an asylum at Dumfries in 1839. After visiting James' father, WAF Browne, at the asylum at Montrose, the oldest Scottish asylum, where he had published What asylums were, are, and ought to be in 1838, she had installed him as the first superintendent of the new Crichton Royal Institution at Dumfries in the following year.2

The young James read medicine at Edinburgh where he worshipped Thomas Laycock (1812-1876), the professor of medicine who had previously had John Hughlings Jackson as apprentice at York.
A single intravenous injection of oncolytic picornavirus SVV-001 eliminates medulloblastomas in primary tumor-based orthotopic xenograft mouse models
Authors: L. Yu, P. A. Baxter, X. Zhao, Z. Liu, L. Wadhwa, Y. Zhang, J. M. Su, X. Tan, J. Yang, A. Adesina, L. Perlaky, M. Hurwitz, N. Idamakanti, S. R. Police, P. L. Hallenbeck, S. M. Blaney, M. Chintagumpala, R. L. Hurwitz, X.-N. Li
Journal: Neuro-Oncology (2010)

Difficulties of drug delivery across the blood–brain barrier (BBB) and failure to eliminate cancer stem cells (CSCs) are believed to be the major causes of tumor recurrences in children with medulloblastoma (MB). Seneca Valley virus-001 (SVV-001) is a naturally occurring oncolytic picornavirus that can be systemically administered. Here, we report its antitumor activities against MB cells in a panel of 10 primary tumor-based orthotopic xenograft mouse models. We found that SVV-001 killed the primary cultured xenograft cells, infected and replicated in tumor cells expressing CSC surface marker CD133, and eliminated tumor cells capable of forming neurospheres in vitro in 5 of the 10 xenograft models. We confirmed that SVV-001 could pass through BBB in vivo. A single i.v. injection of SVV-001 in 2 anaplastic MB models led to widespread infection of the preformed intracerebellar (ICb) xenografts, resulting in significant increase in survival (2.2–5.9-fold) in both models and complete elimination of ICb xenografts in 8 of the 10 long-term survivors. Mechanistically, we showed that the intracellular replication of SVV-001 is mediated through a subverted autophagy that is different from the bona fide autophagic process induced by rapamycin. Our data suggest that SVV-001 is well suited for MB treatment. This work expands the current views in the oncolytic therapy field regarding the utility of oncolytic viruses in simultaneous targeting of stem and nonstem tumor cells.
Ovarian hyperstimulation syndrome: classifications and critical analysis of preventive measures
Authors: M.A. Aboulghar
Journal: Human Reproduction Update (2003)

The aim of this review was to summarize previously published classifications for ovarian hyperstimulation syndrome (OHSS), as well as to analyse the available methods for preventing OHSS. Withholding hCG and cycle cancellation--once the main methods of preventing OHSS--are now seldom used. There is a growing body of evidence to support the use of coasting to prevent OHSS, without cycle cancellation. However, most studies on coasting are retrospective, and well-designed prospective randomized studies are lacking. There is no current consensus as to how coasting should be carried out. A serum estradiol level of 3000 pg/ml is generally considered optimum for administration of hCG. It appears that intravenous albumin or hydroxyethyl starch at the time of oocyte retrieval is beneficial in preventing OHSS, but does not offer complete protection. There is insufficient evidence to support routine cryopreservation of all embryos for the later transfer of frozen-thawed embryos in high-risk patients. Several uncontrolled studies have reported the protective effect of GnRH agonist to trigger ovulation in preventing OHSS, though the method is applicable solely for gonadotrophin-only or GnRH antagonist cycles. A single dose of recombinant LH to trigger ovulation significantly reduced OHSS as compared with hCG. The possible role of GnRH antagonist protocols in reducing the incidence of OHSS is debatable. The above measures to prevent OHSS were successful in reducing the incidence of the syndrome, but complete prevention is not as yet possible.
Quality of Life After Transhiatal Compared With Extended Transthoracic Resection for Adenocarcinoma of the Esophagus
Authors: A.G.E.M. de Boer, J.J.B. van Lanschot, J.W. van Sandick, J.B.F. Hulscher, P.F.M. Stalmeier, J.C.J.M. de Haes, H.W. Tilanus, H. Obertop, M.A.G. Sprangers
Journal: Journal of Clinical Oncology (2004)

To assess 3 years of quality of life in patients with esophageal cancer in a randomized trial comparing limited transhiatal resection with extended transthoracic resection.Quality-of-life questionnaires were sent at baseline and at 5 weeks; 3, 6, 9, and 12 months; and 1.5, 2, 2.5, and 3 years after surgery. Physical and psychological symptoms, activity level, and global quality of life were assessed with the disease-specific Rotterdam Symptom Checklist. Generic quality of life was measured with the Medical Outcomes Study Short Form-20.A total of 199 patients participated. Physical symptoms and activity level declined after the operation and gradually returned toward baseline within the first year (P < .01). Psychological well-being consistently improved after baseline (P < .01), whereas global quality of life showed a small initial decline followed by continuous gradual improvement (P < .01). Quality of life stabilized in the second and third year. Three months after the operation, patients in the transhiatal esophagectomy group (n = 96) reported fewer physical symptoms (P = .01) and better activity levels (P < .01) than patients in the transthoracic group (n = 103), but no differences were found at any other measurement point. For psychological symptoms and global quality of life, no differences were found at any follow-up measurement. A similar pattern was found for generic quality of life.No lasting differences in quality of life of patients who underwent either transhiatal or transthoracic resection were found. Compared with baseline, quality of life declined after the operation but was restored within a year in both groups.
Decline in mortality, AIDS, and hospital admissions in perinatally HIV-1 infected children in the United Kingdom and Ireland
Authors: D M Gibb
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To describe changes in demographic factors, disease progression, hospital admissions, and use of antiretroviral therapy in children with HIV. <b>Design</b> Active surveillance through the national study of HIV in pregnancy and childhood (NSHPC) and additional data from a subset of children in the collaborative HIV paediatric study (CHIPS). <b>Setting</b> United Kingdom and Ireland. <b>Participants</b> 944 children with perinatally acquired HIV-1 under clinical care. <b>Main outcome measures</b> Changes over time in progression to AIDS and death, hospital admission rates, and use of antiretroviral therapy. <b>Results</b> 944 children with perinatally acquired HIV were reported in the United Kingdom and Ireland by October 2002; 628 (67%) were black African, 205 (22%) were aged ≥ 10 years at last follow up, 193 (20%) are known to have died. The proportion of children presenting who were born abroad increased from 20% in 1994-5 to 60% during 2000-2. Mortality was stable before 1997 at 9.3 per 100 child years at risk but fell to 2.0 in 2001-2 (trend P &lt; 0.001). Progression to AIDS also declined (P &lt; 0.001). From 1997 onwards the proportion of children on three or four drug antiretroviral therapy increased. Hospital admission rates declined by 80%, but with more children in follow up the absolute number of admissions fell by only 26%. <b>Conclusion</b> In children with HIV infection, mortality, AIDS, and hospital admission rates have declined substantially since the introduction of three or four drug antiretroviral therapy in 1997. As infected children in the United Kingdom and Ireland are living longer, there is an increasing need to address their medical, social, and psychological needs as they enter adolescence and adult life.
Total and Specific Nasal IgE to Dermatophagoides Pteronyssinus in Patients with Persistent Rhinitis
Authors: C. Rondon, S. Lopez, R. R-Pena, J.J. Romero, T.D. Fernandez, C. Antunez, I. Dona, M.S. Fuentes, J.L. Rodriguez-Bada, M. Blanca
Journal: Journal of Allergy and Clinical Immunology (2006)
Stem Cell Approaches for the Treatment of Renal Failure
Authors: James C. Brodie, H. David Humes
Journal: Pharmacological Reviews (2005)

The inadequacy of current treatment modalities and insufficiency of donor organs for cadaveric transplantation have driven a search for improved methods of dealing with renal failure. The rising concept of cell-based therapeutics has provided a framework around which new approaches are being generated, and its combination with advances in stem cell research stands to bring both fields to clinical fruition. This budding partnership is presently in its very early stages, but an examination of the cell-based therapies currently under development clearly shows the magnitude of the role that stem cells will ultimately play. The issue over reports of unexpected plasticity in adult stem cell differentiation remains a focus of debate, and evidence for bone marrow-derived stem cell contributions to renal repair has been challenged. The search for adult renal stem cells, which could have a considerable impact on much of the work discussed here, appears to be narrowing. The use of embryonic tissue in research continues to provide valuable insights but will be the subject of intense societal scrutiny and debate before it reaches the stage of clinical application. Embryonic stem (ES) cells, with their ability to generate all, or nearly all, of the cell types in the adult body and a possible source of cells genetically identical to the donor, hold great promise but face ethical and political hurdles for human use. Immunoisolation of heterologous cells by encapsulation creates opportunities for their safe use as a component of implanted or ex vivo devices.
Targeting Sarcoplasmic Reticulum Ca <sup>2+</sup> Uptake to Improve Heart Failure
Authors: Karin R. Sipido, Peter Vangheluwe
Journal: Circulation Research (2010)

][3] The causality is more difficult to prove at this late time point. 4et, the observed reduction in the Ca 2ϩ available for myofilament activation and reduced Ca 2ϩ reuptake in the sarcoplasmic reticulum (SR) are obvious targets to improve myocyte contraction and relaxation and, thus, cardiac pump function.Early pharmacotherapy mimicked adrenergic stimulation, the physiological boost of contraction and relaxation, by raising cAMP.Although this worked well, and still does, for acute treatment, the long-term results showed an increase in mortality.Alternative therapy to enhance myofilament sensitivity seems a safer alternative. 5,6any animal models have been designed to reproduce heart failure in humans allowing study of myocyte remodeling at different stages of disease.The most extensively studied are genetic predisposition (the cardiomyopathic hamster), pressure overload (hypertensive models, aortic banding), myocardial infarction (MI), and tachycardia pacing (in dog or rabbit).Except for genetic model, obvious discrepancies with human disease are the fast time course of the disease and the relative lack of complexity, as, for example, the absence of atherosclerosis in most models of MI.Nevertheless these models have been very useful to demonstrate that very often in vivo cardiac dysfunction paralleled changes in Ca 2ϩ handling, suggesting causality.