tbuckley/cabot-search huggingface dataset:
On Counting Tandem Duplication Trees
Authors: J. Yang
Journal: Molecular Biology and Evolution (2004)

IntroductionLarge genomes are full of repeated DNA sequences.It was estimated that over half of the human DNA consistsof repeated sequences (Baltimore 2001; Eichler 2001;Leem et al. 2002). Tandem duplication is one of theimportant evolutionary mechanisms for producing re-peated DNA sequences, in which the copies that may ormay not contain genes are adjacent along the genome.Fitch (1977) ﬁrst observed that tandem duplicationhistories are much more constrained than speciationhistories and proposed to model them assuming thatunequal crossover is the biological mechanism from whichthey originate. The corresponding trees are now calledtandem duplication trees, the term tandem sometimesbeing omitted for the sake of conciseness. With more andmore genomic sequences becoming known, inferringtandem duplication history has again redrawn researchers’attention (Benson and Dong 1999; Tang, Waterman, andYooseph 2002; Elemento, Gascuel, and Lefranc 2002;Zhang et al. 2003).The aim of this article is, ﬁrst, to present a simplerecurrence formula for the number of rooted duplicationtrees based on the recurrence formula proved in Gascuel etal. (2003). We also give a simple non-counting proof ofthe fact that the number of rooted duplication trees forn segments is exactly twice the number of unrootedduplication trees for n segments. Notice that this fact wasproved based on a counting argument in Gascuel et al.(2003).Duplication Tree ModelAssume n sequence segments f1, 2, ..., ng wereformed from a locus by tandem duplication. Then, assumethat the locus had grown from a single copy througha series of tandem duplications. Each duplication replaceda stretch of DNA sequences containing several repeatswith two identical and adjacent copies of itself. If thestretch contains k repeats, the duplication is called a k-duplication.A rooted duplication tree M for tandemly repeatedsegments f1, 2, ..., ng is a rooted binary tree that containsblocks as shown in ﬁgure 1. A node in M representsa repeat. Obviously, the root represents the original copy atthe locus and leaves the given segments.A block in M represents a duplication event. Eachnon-leaf node appears in a unique block; no node is anancestor of another in a block. If the block corresponds toa k-duplication, it has k nodes u
Prolonged QTc Interval and High B-Type Natriuretic Peptide Levels Together Predict Mortality in Patients With Advanced Heart Failure
Authors: Bojan Vrtovec, Reynolds Delgado, Aly Zewail, Cynthia D. Thomas, Barbara M. Richartz, Branislav Radovancevic
Journal: Circulation (2003)

The role of QTc interval prolongation in heart failure remains poorly defined. To better understand it, we analyzed the QTc interval duration in patients with heart failure with high B-type natriuretic peptide (BNP) levels and analyzed the combined prognostic impact of prolonged QTc and elevated BNP.QTc intervals were measured in 241 patients with heart failure who had BNP levels >400 pg/mL. QT interval duration was determined by averaging 3 consecutive beats through leads II and V4 on a standard 12-lead ECG and corrected by using the Bazett formula. QTc intervals were prolonged (>440 ms) in 122 (51%) patients and normal in 119 (49%). The BNP levels in these 2 groups were not significantly different (786+/-321 pg/mL in the prolonged QTc group versus 733+/-274 pg/mL in the normal QTc group, P=0.13). During 6 months of follow-up, 46 patients died, 9 underwent transplantation, and 17 underwent left ventricular assist device implantation. The deaths were attributed to pump failure (n=24, 52%), sudden cardiac death (n=18, 39%), or noncardiac causes (n=4, 9%). Kaplan-Meier survival rates were 3 times higher in the normal QTc group than in the prolonged QTc group (P<0.0001). On multivariate analysis, prolonged QTc interval was an independent predictor of all-cause death (P=0.0001), cardiac death (P=0.0001), sudden cardiac death (P=0.004), and pump failure death (P=0.0006).Prolonged QTc interval is a strong, independent predictor of adverse outcome in patients with heart failure with BNP levels >400 pg/mL.
To wash or not to wash? That is the question
Authors: P McCrory
Journal: British Journal of Sports Medicine (2003)

In my office, I have 12 general textbooks on sport medicine. I am not bragging about this but simply stating an easily verifiable fact. I had recently been reading a newspaper article that noted that the second biggest killer of children in the world is not malaria or tuberculosis, nor AIDS. It is diarrhoea. Over 2000 children die every single day throughout the world from this problem. The simplest solution to reducing this disease …
Apoptosis Resistance of MCF-7 Breast Carcinoma Cells to Ionizing Radiation Is Independent of p53 and Cell Cycle Control but Caused by the Lack of Caspase-3 and a Caffeine-Inhibitable Event
Authors: Frank Essmann, Ingo H. Engels, Gudrun Totzke, Klaus Schulze-Osthoff, Reiner U. Jänicke
Journal: Cancer Research (2004)

Abstract We have shown previously that ionizing radiation (IR) induces a persistent G2-M arrest but not cell death in MCF-7 breast carcinoma cells that harbor functional p53 but lack caspase-3. In the present study, we investigated the mechanisms of apoptosis resistance and the roles of p53, caspase-3, and cell cycle arrest in IR-induced apoptosis. The methylxanthine caffeine and the staurosporine analog UCN-01, which can inhibit ATM and Chk kinases, efficiently abrogated the IR-induced G2-M arrest and induced mitochondrial activation as judged by the loss of the mitochondrial membrane potential and the release of cytochrome c and Smac/Diablo. However, despite these proapoptotic alterations, cell death and activation of the initiator caspase-9 were not induced in MCF-7 cells but were interestingly only observed after reexpression of caspase-3. Sensitization to IR-induced apoptosis by caffeine or UCN-01 was abrogated neither by cycloheximide nor by pifithrin-α, an inhibitor of the transcriptional activity of p53. Furthermore, suppression of p53 by RNA interference could not prevent caffeine- and IR-induced mitochondrial alterations and apoptosis but resulted in an even more pronounced G2-M arrest. Collectively, our results clearly show that the resistance of MCF-7 cells to IR-induced apoptosis is caused by two independent events; one of them is a caffeine- or UCN-01–inhibitable event that does not depend on p53 or a release of the G2-M arrest. The second event is the loss of caspase-3 that surprisingly seems essential for a fully functional caspase-9 pathway, even despite the previous release of mitochondrial proapoptotic proteins.
Local glucocorticoid production in the mouse lung is induced by immune cell stimulation
Authors: N. Hostettler, P. Bianchi, C. Gennari‐Moser, D. Kassahn, K. Schoonjans, N. Corazza, T. Brunner
Journal: Allergy (2011)

To cite this article: Hostettler N, Bianchi P, Gennari‐Moser C, Kassahn D, Schoonjans K, Corazza N, Brunner T. Local glucocorticoid production in the mouse lung is induced by immune cell stimulation. Allergy 2012; 67 : 227–234. Abstract Background: Glucocorticoids (GC) are potent anti‐inflammatory and immunosuppressive steroid hormones, mainly produced by the adrenal glands. However, increasing evidence supports the idea of additional extra‐adrenal sources of bioactive GC. The lung epithelium is constantly exposed to a plethora of antigenic stimuli, and local GC synthesis could contribute to limit uncontrolled immune reactions and tissue damage. Methods: Expression of steroidogenic enzymes and GC synthesis in ex vivo organ cultures was studied in mouse lung tissue after in vivo stimulation of immune cells. Results: Mouse lung tissue was found to express steroidogenic enzymes required for the synthesis of corticosterone from cholesterol and to synthesize corticosterone in large quantities after immune cell activation by anti‐CD3 antibody, lipopolysaccharide, or TNFα. In marked contrast, ovalbumin‐induced allergic airway inflammation failed to promote lung GC synthesis. Although the lung expresses all steroidogenic enzymes necessary for de novo synthesis of corticosterone from cholesterol, functional data indicated that inactive serum‐derived dehydrocorticosterone is converted to active corticosterone by 11β‐hydroxysteroid dehydrogenase 1. Conclusion: Our results support the notion that local GC synthesis represents a novel immunoregulatory mechanism to limit uncontrolled immune responses in the lung and indicate that defective local steroidogenesis may contribute to the pathogenesis of allergic airway inflammation.
Inflammatory arthritis in children with osteochondrodysplasias
Authors: R. Scuccimarri
Journal: Annals of the Rheumatic Diseases (2000)

Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with these diseases commonly develop an early degenerative arthritis or osteoarthritis. Occasional observations of inflammatory arthritis have been made in this population but such observations are based on clinical grounds alone without confirmatory imaging studies. Four patients followed up in a paediatric rheumatology clinic with three different skeletal dysplasias, who had both clinical and radiological evidence of an inflammatory arthritis and coexistent degenerative arthritis, are described.
Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis: a 10-year longitudinal study from the EUSTAR database
Authors: Elina G Wirz, Veronika K Jaeger, Yannick Allanore, Gabriela Riemekasten, Eric Hachulla, Oliver Distler, Paolo Airò, Patricia E Carreira, Mohammed Tikly, Serena Vettori, Alexandra Balbir Gurman, Nemanja Damjanov, Ulf Müller-Ladner, Jörg Distler, Mangtao Li, Peter Häusermann, Ulrich A Walker
Journal: Annals of the Rheumatic Diseases (2015)

To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort.695 patients with SSc with a baseline visit within 1 year after RP onset were followed in the prospective multinational EUSTAR database. During the 10-year observation period, cumulative probabilities of cutaneous lesions were assessed with the Kaplan-Meier method. Cox proportional hazards regression analysis was used to evaluate risk factors.The median modified Rodnan skin score (mRSS) peaked 1 year after RP onset, and was 15 points. The 1-year probability to develop an mRSS ≥2 in at least one area of the arms and legs was 69% and 25%, respectively. Twenty-five per cent of patients developed diffuse cutaneous involvement in the first year after RP onset. This probability increased to 36% during the subsequent 2 years. Only 6% of patients developed diffuse cutaneous SSc thereafter. The probability to develop DUs increased to a maximum of 70% at the end of the 10-year observation. The main factors associated with diffuse cutaneous SSc were the presence of anti-RNA polymerase III autoantibodies, followed by antitopoisomerase autoantibodies and male sex. The main factor associated with incident DUs was the presence of antitopoisomerase autoantibodies.Early after RP onset, cutaneous manifestations exhibit rapid kinetics in SSc. This should be accounted for in clinical trials aiming to prevent skin worsening.
Hemodynamic Predictors of Mortality in Adults with Sickle Cell Disease
Authors: Alem Mehari, Shoaib Alam, Xin Tian, Michael J. Cuttica, Christopher F. Barnett, George Miles, Dihua Xu, Catherine Seamon, Patricia Adams-Graves, Oswaldo L. Castro, Caterina P. Minniti, Vandana Sachdev, James G. Taylor, Gregory J. Kato, Roberto F. Machado
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Background: Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality, but no prior studies have evaluated quantitative relationships of mortality to physiological measures of pre- and postcapillary PH.Objectives: To identify risk factors associated with mortality and to estimate the expected survival in a cohort of patients with SCD with PH documented by right heart catheterization.Methods: Nine-year follow-up data (median, 4.7 yr) from the National Institutes of Health SCD PH screening study are reported. A total of 529 adults with SCD were screened by echocardiography between 2001 and 2010 with no exclusion criteria. Hemodynamic data were collected from 84 patients. PH was defined as mean pulmonary artery pressure (PAP) ≥ 25 mm Hg. Survival rates were estimated by the Kaplan-Meier method, and mortality risk factors were analyzed by the Cox proportional hazards regression.Measurements and Main Results: Specific hemodynamic variables were independently related to mortality: mean PAP (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.05–2.45 per 10 mm Hg increase; P = 0.027), diastolic PAP (HR, 1.83; 95% CI, 1.09–3.08 per 10 mm Hg increase; P = 0.022), diastolic PAP − pulmonary capillary wedge pressure (HR, 2.19; 95% CI, 1.23–3.89 per 10 mm Hg increase; P = 0.008), transpulmonary gradient (HR, 1.78; 95% CI, 1.14–2.79 per 10 mm Hg increase; P = 0.011), and pulmonary vascular resistance (HR, 1.44; 95% CI, 1.09–1.89 per Wood unit increase; P = 0.009) as risk factors for mortality.Conclusions: Mortality in adults with SCD and PH is proportional to the physiological severity of precapillary PH, demonstrating its prognostic and clinical relevance despite anemia-induced high cardiac output and less severely elevated pulmonary vascular resistance.
The Atopic Status of Children Treated for Wheezing in Costa Rica: The Importance of Sensitization to Dust Mite
Authors: D. Murphy, M. Soto-Quiros, L. Avila, J. Hunt, T. Platts-Mills, H. Carper, S. Odio, A. O'Rourke, M. Davis, P. Heymann
Journal: Journal of Allergy and Clinical Immunology (2010)
Cell–Matrix Interactions in the Pathobiology of Calcific Aortic Valve Disease
Authors: Jan-Hung Chen, Craig A. Simmons
Journal: Circulation Research (2011)

The hallmarks of calcific aortic valve disease (CAVD) are the significant changes that occur in the organization, composition, and mechanical properties of the extracellular matrix (ECM), ultimately resulting in stiffened stenotic leaflets that obstruct flow and compromise cardiac function. Increasing evidence suggests that ECM maladaptations are not simply a result of valve cell dysfunction; they also contribute to CAVD progression by altering cellular and molecular signaling. In this review, we summarize the ECM changes that occur in CAVD. We also discuss examples of how the ECM influences cellular processes by signaling through adhesion receptors (matricellular signaling), by regulating the presentation and availability of growth factors and cytokines to cells (matricrine signaling), and by transducing externally applied forces and resisting cell-generated tractional forces (mechanical signaling) to regulate a wide range of pathological processes, including differentiation, fibrosis, calcification, and angiogenesis. Finally, we suggest areas for future research that should lead to new insights into bidirectional cell-ECM interactions in the aortic valve, their contributions to homeostasis and pathobiology, and possible targets to slow or prevent the progression of CAVD.
High-Dose Therapy for Patients With Primary Multifocal and Early Relapsed Ewing’s Tumors: Results of Two Consecutive Regimens Assessing the Role of Total-Body Irradiation
Authors: S. Burdach, A. Meyer-Bahlburg, H.J. Laws, R. Haase, B. van Kaik, B. Metzner, A. Wawer, R. Finke, U. Göbel, J. Haerting, H. Pape, H. Gadner, J. Dunst, H. Juergens
Journal: Journal of Clinical Oncology (2003)

Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity.Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation.The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME.TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.
Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposals for a revised grading system and consensus management guidelines
Authors: J. Bernier, E.G. Russi, B. Homey, M.C. Merlano, R. Mesía, F. Peyrade, W. Budach
Journal: Annals of Oncology (2011)
Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients
Authors: H. Cortes-Funes, C. Gomez, R. Rosell, P. Valero, C. Garcia-Giron, A. Velasco, A. Izquierdo, P. Diz, C. Camps, D. Castellanos, V. Alberola, F. Cardenal, J.L. Gonzalez-Larriba, J.M. Vieitez, I. Maeztu, J.J. Sanchez, C. Queralt, C. Mayo, P. Mendez, T. Moran, M. Taron
Journal: Annals of Oncology (2005)
Genomic and Protein Expression Profiling Identifies CDK6 As Novel Independent Prognostic Marker in Medulloblastoma
Authors: Frank Mendrzyk, Bernhard Radlwimmer, Stefan Joos, Felix Kokocinski, Axel Benner, Daniel E. Stange, Kai Neben, Heike Fiegler, Nigel P. Carter, Guido Reifenberger, Andrey Korshunov, Peter Lichter
Journal: Journal of Clinical Oncology (2005)

Medulloblastoma is the most common malignant brain tumor in children. Despite multimodal aggressive treatment, nearly half of the patients die as a result of this tumor. Identification of molecular markers for prognosis and development of novel pathogenesis-based therapies depends crucially on a better understanding of medulloblastoma pathomechanisms.We performed genome-wide analysis of DNA copy number imbalances in 47 medulloblastomas using comparative genomic hybridization to large insert DNA microarrays (matrix-CGH). The expression of selected candidate genes identified by matrix-CGH was analyzed immunohistochemically on tissue microarrays representing medulloblastomas from 189 clinically well-documented patients. To identify novel prognostic markers, genomic findings and protein expression data were correlated to patient survival.Matrix-CGH analysis revealed frequent DNA copy number alterations of several novel candidate regions. Among these, gains at 17q23.2-qter (P < .01) and losses at 17p13.1 to 17p13.3 (P = .04) were significantly correlated to poor prognosis. Within 17q23.2-qter and 7q21.2, two of the most frequently gained chromosomal regions, confined amplicons were identified that contained the PPM1D and CDK6 genes, respectively. Immunohistochemistry revealed strong expression of PPM1D in 148 (88%) of 168 and CDK6 in 50 (30%) of 169 medulloblastomas. Overexpression of CDK6 correlated significantly with poor prognosis (P < .01) and represented an independent prognostic marker of overall survival on multivariate analysis (P = .02).We identified CDK6 as a novel molecular marker that can be determined by immunohistochemistry on routinely processed tissue specimens and may facilitate the prognostic assessment of medulloblastoma patients. Furthermore, increased protein-levels of PPM1D and CDK6 may link the TP53 and RB1 tumor suppressor pathways to medulloblastoma pathomechanisms.
Survival of HIV-infected patients in the intensive care unit in the era of highly active antiretroviral therapy
Authors: S J Dickson, S Batson, A J Copas, S G Edwards, M Singer, R F Miller
Journal: Thorax (2007)

<h3>Background:</h3> Several studies have described improved outcomes for HIV-infected patients admitted to the intensive care unit (ICU) since the introduction of highly active antiretroviral therapy (HAART). A study was undertaken to examine the outcome from the ICU for HIV-infected patients and to identify prognostic factors. <h3>Methods:</h3> A retrospective study of HIV-infected adults admitted to a university affiliated hospital ICU between January 1999 and December 2005 was performed. Information was collected on patient demographics, receipt of HAART (no patient began HAART on the ICU), reason for ICU admission and hospital course. Outcomes were survival to ICU discharge and to hospital discharge. <h3>Results:</h3> 102 patients had 113 admissions to the ICU; HIV infection was newly diagnosed in 31 patients. Survival (first episode ICU discharge and hospital discharge) was 77% and 68%, respectively, compared with 74% and 65% for general medical patients. ICU and hospital survival was 78% and 67% in those receiving HAART, and 75% and 66% in those who were not. In univariate analysis, factors associated with survival were: haemoglobin (OR = 1.25, 95% CI 1.03 to 1.51, for an increase of 1 g/dl), CD4 count (OR = 1.59, 95% CI 0.98 to 2.58, for a 10-fold increase in cells/µl), APACHE II score (OR = 0.51, 95% CI 0.29 to 0.90, for a 10 unit increase) and mechanical ventilation (OR = 0.29, 95% CI 0.10 to 0.83). <h3>Conclusions:</h3> The outcome for HIV-infected patients admitted to the ICU was good and was comparable to that in general medical patients. More than a quarter of patients had newly diagnosed HIV infection. Patients receiving HAART did not have a better outcome.
AN INQUIRY INTO THE CAUSES OF INFANTILE FACIAL ECZEMA, AND THE RELATION OF BESNIER'S PRURIGO TO THIS CONDITION
Authors: GODFREY W. BAMBEK
Journal: British Journal of Dermatology (1931)

Journal Article AN INQUIRY INTO THE CAUSES OF INFANTILE FACIAL ECZEMA, AND THE RELATION OF BESNIER'S PRURIGO TO THIS CONDITION Get access GODFREY W. BAMBEK, B.A., M.D., M.R.C.P. GODFREY W. BAMBEK, B.A., M.D., M.R.C.P. Skin Department, Hospital for Sick Children, Great Ormond Street Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 43, Issue 6, 1 June 1931, Pages 279–297, https://doi.org/10.1111/j.1365-2133.1931.tb09504.x Published: 01 June 1931