tbuckley/cabot-search huggingface dataset:
Inferring the Strength of Selection in Drosophila under Complex Demographic Models
Authors: J. Gonzalez, J. M. Macpherson, P. W. Messer, D. A. Petrov
Journal: Molecular Biology and Evolution (2008)

Transposable elements (TEs) constitute a substantial fraction of the genomes of many species, and it is thus important to understand their population dynamics. The strength of natural selection against TEs is a key parameter in understanding these dynamics. In principle, the strength of selection can be inferred from the frequencies of a sample of TEs. However, complicated demographic histories, such as found in Drosophila melanogaster, could lead to a substantial distortion of the TE frequency distribution compared with that expected for a panmictic, constant-sized population. The current methodology for the estimation of selection intensity acting against TEs does not take into account demographic history and might generate erroneous estimates especially for TE families under weak selection. Here, we develop a flexible maximum likelihood methodology that explicitly accounts both for demographic history and for the ascertainment biases of identifying TEs. We apply this method to the newly generated frequency data of the BS family of non-long terminal repeat retrotransposons in D. melanogaster in concert with two recent models of the demographic history of the species to infer the intensity of selection against this family. We find the estimate to differ substantially compared with a prior estimate that was made assuming a model of constant population size. Further, we find there to be relatively little information about selection intensity present in the derived non-African frequency data and that the ancestral African subpopulation is much more informative in this respect. These findings highlight the importance of accounting for demographic history and bear on study design for the inference of selection coefficients generally.
Precursor B Cell Receptor–Dependent B Cell Proliferation and Differentiation Does Not Require the Bone Marrow or Fetal Liver Environment
Authors: Antonius G. Rolink, Thomas Winkler, Fritz Melchers, Jan Andersson
Journal: The Journal of Experimental Medicine (2000)

The capacity of precursor B (pre-B) I cells from fetal liver and bone marrow to proliferate and differentiate into surface immunoglobulin–positive immature B cells in vitro was analyzed. Both fetal liver– and bone marrow–derived progenitors do so in a pre-B cell receptor (pre-BCR)–dependent manner in tissue culture medium alone, without addition of other cells or cytokines. Approximately 20% of the initial pre-B I cells enter more than one division. Analyses at the single-cell level show that ∼15% divide two to five times. Coculture of pre-B I cells with stromal cells did not enhance proliferation or differentiation, whereas the presence of interleukin 7, especially in combination with stromal cells, resulted mainly in the expansion of pre-B I cells and prevented their further differentiation. Thus, the environment of fetal liver or bone marrow is not required for the pre-BCR to exert its function, which is to select and expand cells that have undergone an inframe VH-DHJH rearrangement that produces a pre-BCR–compatible μH chain. It appears unlikely that a ligand for the pre-BCR drives this pre-B cell proliferation.
PRL-3 Down-regulates PTEN Expression and Signals through PI3K to Promote Epithelial-Mesenchymal Transition
Authors: Haihe Wang, Samantha Yiling Quah, Jing Ming Dong, Edward Manser, Jing Ping Tang, Qi Zeng
Journal: Cancer Research (2007)

Abstract PRL-3 is a metastasis-associated phosphatase. We and others have shown that its overexpression increases cell motility and invasiveness. These phenotypic changes are reminiscent of the epithelial-mesenchymal transition (EMT) that occurs during embryonic development and oncogenesis. The EMT is a complex process that converts epithelia into migratory mesenchymal cells. We here attempt to unravel the underlying mechanistic basis of these phenomena. HeLa cells transiently expressing EGFP-PRL-3 (HeLa-PRL-3) exhibit reduced levels of paxillin. Similarly, Chinese hamster ovary cells stably expressing myc-PRL-3 (CHO-PRL-3) also show marked reductions in paxillin, phosphorylated paxillin-Tyr31, and vinculin at focal adhesion complexes and notable reductions in the levels of RhoA-GTP, Rac1-GTP, and filamentous-actin filaments. DLD-1 human colorectal cancer cells engineered to express EGFP-PRL-3 (DLD-1-PRL-3) underwent changes consistent with EMT. In these cells, PRL-3 activates Akt and inactivates glycogen synthase kinase-3β as assessed by phosphospecific antibodies. PRL-3 up-regulates mesenchymal markers fibronectin and Snail and down-regulates epithelial markers E-cadherin, γ-catenin (plakoglobin), and integrin β3, which are major effectors in the EMT pathway. The changes in these EMT characteristics brought about by PRL-3 can be abrogated by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, implying that PRL-3 acts upstream of PI3K and could play an initiating role to trigger the EMT switch during cancer metastasis. In addition, PRL-3 can down-regulate phosphatase and tensin homologue deleted on chromosome 10, which is an important antagonist of PI3K, further reinforcing PI3K/Akt function in PRL-3–triggered EMT. Catalytically inactive PRL-3 (C104S) was impaired in the above PRL-3–mediated events, indicating that these properties require phosphatase activity. Targeting PRL-3 may thus be a useful strategy to impede cancer cell invasion and metastasis. [Cancer Res 2007;67(7):2922–6]
Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial
Authors: M.A. Judson, R.P. Baughman, U. Costabel, S. Flavin, K.H. Lo, M.S. Kavuru, Marjolein Drent, D.A. Culver, G.S. Davis, C.M. Fogarty, G.W. Hunninghake, A.S. Teirstein, M. Mandel, D. McNally, L. Tanoue, L. Newman, Y. Wasfi, H. Patrick, M.D. Rossman, G. Raghu, O. Sharma, D. Wilkes, H. Yeager, J.F. Donahue, M. Kaye, N. Sweiss, N. Vetter, M. Thomeer, M. Brutsche, L. Nicod, D. Valeyre, P. Chanez, C. Albera, Jan Grutters, Henk Hoogsteden, J. Muller-Quernheim, R. Bonnet, F. Kanniess
Journal: European Respiratory Journal (2008)

The aim of the present study was to investigate the efficacy of infliximab for the treatment of extrapulmonary sarcoidosis. A prospective, randomised, double-blind, placebo-controlled trial was conducted, with infliximab at 3 and 5 mg·kg −1 body weight administered over 24 weeks. Extrapulmonary organ severity was determined by a novel severity tool (extrapulmonary physician organ severity tool; ePOST) with an adjustment for the number of organs involved (ePOSTadj). In total, 138 patients enrolled in the trial of infliximab versus placebo for the treatment of chronic corticosteroid-dependent pulmonary sarcoidosis. The baseline severity of extrapulmonary organ involvement, as measured by ePOST, was similar across treatment groups. After 24 weeks of drug-therapy study, the change from baseline to week 24 in ePOST was greater for the combined infliximab group compared with the placebo group. After adjustment for the number of extrapulmonary organs involved, the improvement in ePOSTadj observed in the combined infliximab group was also greater than that observed in placebo-treated patients, after 24 weeks of therapy. The improvements in ePOST and ePOSTadj were not maintained during a subsequent 24-week washout period. Infliximab may be beneficial compared with placebo in the treatment of extrapulmonary sarcoidosis in patients already receiving corticosteroids, as assessed by the severity tool described in the present study.
Serological markers for melanoma
Authors: L. Brochez, J-M. Naeyaert
Journal: British Journal of Dermatology (2000)

Journal Article Serological markers for melanoma Get access L. Brochez, L. Brochez Fund for Scientific Research Flanders, Egmontstraat 5, B‐1000 Brussels, BelgiumDepartment of Dermatology, University Hospital Gent, De Pintelaan 185, B‐9000 Gent, Belgium Search for other works by this author on: Oxford Academic Google Scholar J‐M. Naeyaert J‐M. Naeyaert Department of Dermatology, University Hospital Gent, De Pintelaan 185, B‐9000 Gent, Belgium Jean‐Marie Naeyaert. E‐mail: JeanMarie.Naeyaert@.rug.ac.be Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 2, 1 August 2000, Pages 256–268, https://doi.org/10.1046/j.1365-2133.2000.03649.x Published: 01 August 2000
Antibodies to interleukin 2. Effects on immune responses in vitro and in vivo.
Authors: A Granelli-Piperno, L Andrus, E Reich
Journal: The Journal of Experimental Medicine (1984)

Antibodies to highly purified mouse interleukin 2 (IL-2) were raised in rabbits; a 1:500 dilution of antiserum completely blocked the in vitro mitogenic effect of 10(-9) M IL-2. The antisera functioned effectively to immunoprecipitate biosynthetically labeled IL-2 and the purified immunoglobulins were useful in the construction of affinity columns for the adsorption and one-step immunopurification of IL-2. The antibodies were apparently specific for IL-2 among the lymphokines, they did not block the biological effects of IL-1, IL-3, gamma-IFN, B cell stimulating factor(s), and cytotoxic T cell differentiation factor(s). When anti-IL-2 was added to the in vitro reactions, it blocked mixed leukocyte reactions (MLR) and associated lymphocyte proliferation, the in vitro generation of cytotoxic T cells, and antibody formation as assessed by erythrocyte-specific plaque-forming cells (PFC). When injected into mice, anti-IL-2 antibodies also reduced the formation of cytotoxic lymphocytes in response to allogeneic cells, suggesting that endogenous IL-2 participates in such reactions in vivo. Taken together, the results indicate that these IL-2 antibodies will be useful adjuncts in the analysis of immune response both in vivo and in vitro.
NERVOUS AND MENTAL SYMPTOMS IN A CASE OF ADDISON'S DISEASE
Authors: J. G. P. Phillips
Journal: BMJ (1912)

MIDA AJOUN I 7C5 21 92.NI some.facial-twitcliing ensued, and in a ihinute or so sie w-ould .beall right once more.Formerlv she had- complained of a "singing in the ears."This vanished, and her trouble was always a "hot feeling at the top of the head."Marked irregularity of the pulse was noted before several of t4ese minor attacks, and the jugular puLlse was often found -to be exactly double that of the radial.The blood pressure fell to 195 mm.Hg.She was treated with stryclhnine and belladonna in small doses, anld also by liq.trinitrin in 1-minim doses tllree times a day.This wvas gradually raised to 3 minims.Slhe continued in this condition till September 20th, wvhen Sir William Osler and Dr. Gibson saw
Relationship between duration of brain death and hemodynamic (in)stability on progressive dysfunction and increased immunologic activation of donor kidneys
Authors: Joost A.B. van Der Hoeven, Grietje Molema, Gert J. Ter Horst, Reni L. Freund, Janneke Wiersema, Reinout van Schilfgaarde, Henri G.D. Leuvenink, Rutger J. Ploeg
Journal: Kidney International (2003)
ERCP and sphincterotomy after Billroth II gastrectomy.
Authors: A Forbes, P B Cotton
Journal: Gut (1984)

Endoscopic retrograde cholangiopancreatography (ERCP) procedures are more difficult in patients who have undergone partial gastrectomy with Billroth II anastomosis. Results improve with experience; we have achieved full diagnostic information in only 52% of 63 attempts, but ultimately in 60% of the 53 patients concerned. Therapeutic endeavours were more successful with useful results in eight of 10 patients during the last two years. Alternative diagnostic and therapeutic techniques should be used wherever possible in these patients.
First-In-Human Phase I Study of Lurbinectedin (PM01183) in Patients with Advanced Solid Tumors
Authors: María Elena Elez, Josep Tabernero, David Geary, Teresa Macarulla, S. Peter Kang, Carmen Kahatt, Arturo Soto-Matos Pita, Carlos Fernandez Teruel, Mariano Siguero, Martin Cullell-Young, Sergio Szyldergemajn, Mark J. Ratain
Journal: Clinical Cancer Research (2014)

Lurbinectedin (PM01183) binds covalently to DNA and has broad activity against tumor cell lines. This first-in-human phase I study evaluated dose-limiting toxicities (DLT) and defined a phase II recommended dose for PM01183 as a 1-hour intravenous infusion every three weeks (q3wk).Thirty-one patients with advanced solid tumors received escalating doses of PM01183 following an accelerated titration design.PM01183 was safely escalated over 200-fold, from 0.02 to 5.0 mg/m(2). Dose doubling was utilized, requiring 15 patients and nine dose levels to identify DLT. The recommended dose was 4.0 mg/m(2), with one of 15 patients having DLT (grade 4 thrombocytopenia). Clearance was independent of body surface area; thus, a flat dose of 7.0 mg was used during expansion. Myelosuppression, mostly grade 4 neutropenia, occurred in 40% of patients but was transient and manageable, and none was febrile. All other toxicity was mild and fatigue, nausea and vomiting were the most common at the recommended dose. Pharmacokinetic parameters showed high interindividual variation, though linearity was observed. At or above the recommended dose, the myelosuppressive effect was significantly associated with the area under the concentration-time curve from time zero to infinity (white blood cells, P = 0.0007; absolute neutrophil count, P = 0.016). A partial response was observed in one patient with pancreatic adenocarcinoma at the recommended dose.A flat dose of 7.0 mg is the recommended dose for PM01183 as a 1-hour infusion q3wk. This dose is tolerated and active. Severe neutropenia occurred at this dose, although it was transient and with no clinical consequences in this study.
The use of controlled reperfusion strategies in cardiac surgery to minimize ischaemia/reperfusion damage
Authors: F. Beyersdorf
Journal: Cardiovascular Research (2009)

Ischaemia and reperfusion occur during almost every cardiac operation, and one of the key elements to achieve a successful operation is to counteract the detrimental effects of induced ischaemia and reperfusion during the operation. The cardiac surgeon is in a unique position to protect the heart before ischaemia is induced and to avoid further damage during the reperfusion period. The surgeon can alter the composition of the reperfusate and the conditions of reperfusion so that the ischaemia/reperfusion injury is minimal, even after very complex procedures that require long aortic cross-clamp periods. This in turn allows him to perform a near-perfect surgical repair of the underlying disease without the pressure of time. The vast knowledge gained in this field over the years has led to application in other organs, such as the limbs (acute limb ischaemia), lungs (lung transplantation), kidney and liver (kidney and liver transplantation), and more recently even for the brain [acute cerebral artery occlusion (stroke)] and the whole body (cardiopulmonary resuscitation). Further improvements in reperfusion strategies will allow salvage of tissue and even whole body after ischaemic periods thought previously to be irreversibly damaged.
Electrophysiological study of isolated perfused human collecting ducts: Ion dependency of the transepithelial potential difference.
Authors: H R Jacobson, J B Gross, S Kawamura, J D Waters, J P Kokko
Journal: Journal of Clinical Investigation (1976)

Cortical and outer medullary collecting duct segments were dissected from human kidneys and perfused in vitro. The transepithelial potential difference was measured and found to be lumen positive +6.8 +/- 0.6 mV (n= 20). This lumen-positive potential difference was inhibited by ouabain and furosemide but not by acetazolamide. Replacement of chloride in bath and perfusion fluids caused a reversible decrease of the potential difference to near zero. We conclude from these studies: (a) the lumen-positive potential difference is dependent upon the presence of chloride ion suggesting the existence of an active electrogenic chloride reabsorptive process in the human collecting duct and (b) it is possible to examine human renal physiology directly using in vitro microperfusion of tubule segments.
Spontaneous regression of hepatocellular carcinoma.
Authors: R C Ayres, D A Robertson, K C Dewbury, G H Millward-Sadler, C L Smith
Journal: Gut (1990)

A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment.
Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies
Authors: Yukiya Yamamoto, Hitoshi Kiyoi, Yasuyuki Nakano, Ritsuro Suzuki, Yoshihisa Kodera, Shuichi Miyawaki, Norio Asou, Kazutaka Kuriyama, Fumiharu Yagasaki, Chihiro Shimazaki, Hideki Akiyama, Kenji Saito, Miki Nishimura, Toshiko Motoji, Katsuji Shinagawa, Akihiro Takeshita, Hidehiko Saito, Ryuzo Ueda, Ryuzo Ohno, Tomoki Naoe
Journal: Blood (2001)
Hematocrit Levels and Hospitalization Risks in Hemodialysis Patients
Authors: HONG XIA, JIM EBBEN, JENNIE Z. MA, ALLAN J. COLLINS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The association between hematocrit level and future hospitalization risks in hemodialysis patients has not been fully investigated on a national level. A total of 71,717 prevalent Medicare hemodialysis patients who survived a 6-mo entry period from July 1 through December 31, 1993 were studied, and their risk of hospitalizations was evaluated the next year. Five hematocrit groups were defined from Medicare recombinant human erythropoietin-treated patients: &lt;27%, 27 to &lt;30%, 30 to &lt;33%, 33 to &lt;36%, and ≥36%. A Cox regression model was used to investigate the association between hematocrit level and the risk of first hospitalization, and the Andersen-Gill regression model evaluated multiple hospitalizations during the next year, adjusting for patient comorbidity and severity of disease. Compared with the baseline group of 30 to &lt;33%, patients with hematocrit levels &lt;30% had a 14 to 30% increased risk of hospitalization without disease severity adjustment ( p = 0.0001) and a 7 to 18% increased risk with disease severity adjustment ( p = 0.0001). Patients in the 33 to &lt;36% group had the lowest risk at 0.93 and 0.88 ( p = 0.0001), with and without adjustment for disease severity. It is concluded that patients with hematocrits of &lt;30% have an increased risk of future hospitalization, with hematocrit levels between 33 and 36% having the lowest associated risks.
What dose of 5-aminosalicylic acid (mesalazine) in ulcerative colitis?
Authors: S A RILEY
Journal: Gut (1998)

<h3>Abstract</h3> With the exponential development and exploitation of social media sites and platforms such as facebook, twitter and instagram, a diversity type of news are reached to the users,resulting in a major influence on human health and safety.Spreading misinformation and disinformation during the Covid-19 pandemic has become increasingly significant. Although it is usually not a criminal act, it can cause serious endangerment to public health. Such infodemic movement is often lead to advance geopolitical interests by the states, to achieve some sort of profit by some opportunists and individuals or discredit official sources. Hence,it has become crucial to automate the detection of fake news in order to shield people from any harmful repercussions. In this paper, the importance of semantics in Covid-19 fake news detection is highlighted based on a convolutional neural network classifier and a hashmap color-based technique. The experiments are performed with CoAID(Covid-19 heAlthcare mIsinformation Dataset),and the results prove that the loss of semantics yields to a poor performance of the classifier. This implicates additional constraints to the training images,with focus on creating a CNN-based color hashmap classifier that includes anterior and posterior neighbors.
Clinical Characteristics and Outcome of Infective Endocarditis Involving Implantable Cardiac Devices
Authors: Eugene Athan, Vivian H Chu, Pierre Tattevin, Christine Selton-Suty, Phillip Jones, Christoph Naber, José M Miró, Salvador Ninot, Nuria Fernández-Hidalgo, Emanuele Durante-Mangoni, Denis Spelman, Bruno Hoen, Tatjana Lejko-Zupanc, Enrico Cecchi, Franck Thuny, Margaret M Hannan, Paul Pappas, Margaret Henry, Vance G Fowler, Anna Lisa Crowley, Andrew Wang
Journal: JAMA (2012)

Infection of implantable cardiac devices is an emerging disease with significant morbidity, mortality, and health care costs.To describe the clinical characteristics and outcome of cardiac device infective endocarditis (CDIE) with attention to its health care association and to evaluate the association between device removal during index hospitalization and outcome.Prospective cohort study using data from the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), conducted June 2000 through August 2006 in 61 centers in 28 countries. Patients were hospitalized adults with definite endocarditis as defined by modified Duke endocarditis criteria.In-hospital and 1-year mortality.CDIE was diagnosed in 177 (6.4% [95% CI, 5.5%-7.4%]) of a total cohort of 2760 patients with definite infective endocarditis. The clinical profile of CDIE included advanced patient age (median, 71.2 years [interquartile range, 59.8-77.6]); causation by staphylococci (62 [35.0% {95% CI, 28.0%-42.5%}] Staphylococcus aureus and 56 [31.6% {95% CI, 24.9%-39.0%}] coagulase-negative staphylococci); and a high prevalence of health care-associated infection (81 [45.8% {95% CI, 38.3%-53.4%}]). There was coexisting valve involvement in 66 (37.3% [95% CI, 30.2%-44.9%]) patients, predominantly tricuspid valve infection (43/177 [24.3%]), with associated higher mortality. In-hospital and 1-year mortality rates were 14.7% (26/177 [95% CI, 9.8%-20.8%]) and 23.2% (41/177 [95% CI, 17.2%-30.1%]), respectively. Proportional hazards regression analysis showed a survival benefit at 1 year for device removal during the initial hospitalization (28/141 patients [19.9%] who underwent device removal during the index hospitalization had died at 1 year, vs 13/34 [38.2%] who did not undergo device removal; hazard ratio, 0.42 [95% CI, 0.22-0.82]).Among patients with CDIE, the rate of concomitant valve infection is high, as is mortality, particularly if there is valve involvement. Early device removal is associated with improved survival at 1 year.
An Address on Plymouth as a Health-Resort; Together with some Remarks on the Contagious Diseases Act
Authors: P. Swain
Journal: BMJ (1887)

When Dr. Sanger is as accomplished in the use of the microscope as Dallinger, he will probably find in the contents of these tubes the' still smaller beasts which, by repeated buttings against the fragmeuts of dead tissue, prepare the food on which the bacteria live.;The bac-