tbuckley/cabot-search huggingface dataset:
The order of sequence alignment can bias the selection of tree topology.
Authors: J A Lake
Journal: Molecular Biology and Evolution (1991)

Sequential pairwise alignment of multiple sequences is a widely used procedure (Kruskal 1983 ).It is useful and generally successful when sequences within a set differ by relatively few substitutions.Although it is well known that differential substitution rates can artifactually bias the assessment of tree topology (Felsenstein 1978), it is not generally known that the order in which sequences are aligned can bias tree selection.To test the effect of alignment order, the classical four-taxon test has been applied to the "tree of life" (Lake et al. 1984; Woese and Olsen 1986) by using alternative alignments and three reconstruction algorithms [maximum parsimony (Fitch 197 1)) transversion parsimony (Brown et al. 1982), and evolutionary parsimony (Lake 1987)].There is enormous interest in this tree because it relates all known organisms and because its topology is expected to provide insight into the evolution of modem organisms.Because the tree spans large evolutionary distances, its topology has been difficult to establish.By means of sequences from elongation factor Tu ( EF-Tu), the most conserved protein sequence known to span the tree of life, it is shown that specific alignment orders systematically favor alternative trees.In particular, if taxa A and B are pairwise aligned and if C and D are pairwise aligned, the resulting alignment of the EF-Tu sequences more often gives the tree that has A and B as topological neighbors and C and D as topological neighbors, regardless of the tree reconstruction algorithm used.Because all three reconstruction algorithms produced the same tree for any particular alignment, unequal rate effects appear to be secondary for EF-Tu sequences.This indicates that order-dependent alignment biases are distinct from unequal rate effects and that, for some data, they could be as important as unequal rate effects.Pairwise alignments of protein sequences were performed with the ALIGN program available in the Dayhoff package (Dayhoff et al. 1983 ).The penalty for a break was 6, and the mutation data matrix corresponded to 250 accepted point mutations with a bias of +2.These are reasonable values for the weights and correspond to those used in the examples in the description of the ALIGN program.[For an insightful discussion of alignment weights, see the paper by Fitch and Smith ( 1983); also see Waterman and Perlwitz ( 1984) .]EF-Tu sequences were aligned as protein sequences to obtain more robust alignments and were back-translated into nucleic acid sequences (e.g., phe was translated as UUY, leu as YUN, arg as NGN, and ser as NNN) so that the maximum-, transversion-, and evolutionary-parsimony methods could be compared by equivalent data.Only positions consisting of a single nucleotide (i.e., U, C, A, or G but not R, Y, or N) in each of the four sequences were scored.These uniquely defined replacement sites are presumed to correspond to the most conserved nucleotide positions.A multiple alignment of four sequences can be achieved by successively aligning 1.
Mechanocompatible Polymer‐Extracellular‐Matrix Composites for Vascular Tissue Engineering
Authors: Bin Jiang, Rachel Suen, Jiao‐Jing Wang, Zheng J. Zhang, Jason A. Wertheim, Guillermo A. Ameer
Journal: Advanced Healthcare Materials (2016)

Small‐diameter vascular grafts developed from vascular extracellular matrix (ECM) can potentially be used for bypass surgeries and other vascular reconstruction and repair procedures. The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical cross‐linking, which increases ECM mechanical stiffness compared to native arteries. Herein, the importance of maintaining ECM mechanocompatibility is demonstrated, and a mechanocompatible strategy to immobilize heparin onto the ECM via a biodegradable elastomer is described. Specifically, poly(1,8‐octamethylene citrate)‐ co ‐cysteine is hybridized to the ECM, forming a polymer‐ECM composite that allows for heparin immobilization via maleimide–thiol “click” chemistry. Heparinized composites reduce platelet adhesion by &gt;60% in vitro, without altering the elastic modulus of the ECM. In a rat abdominal aortic interposition model, intimal hyperplasia in heparinized mechanocompatible grafts is 65% lower when compared to ECM‐only control grafts at four weeks. In contrast, grafts that are heparinized with carbodiimide chemistry exhibit increased intimal hyperplasia (4.2‐fold) and increased macrophage infiltration (3.5‐fold) compared to ECM‐only control grafts. All grafts show similar, partial endothelial cell coverage and little to no ECM remodeling. Overall, a mechanocompatible strategy to improve ECM thromboresistance is described and the importance of ECM mechanical properties for proper in vivo graft performance is highlighted.
Impact of stenotrophomonas maltophilia in cystic fibrosis: A retrospective analysis
Authors: Elien Dewaele, Pieter Goeminne, Hans Scheers, Lieven Dupont, Paul Van den Brande
Journal: European Respiratory Journal (2011)

Introduction: Stenotrophomonas maltophilia (SM) has been isolated more frequently in cystic fibrosis patients (CF) the past few years but the real significance of its presence remains to be elucidated. We investigated the impact of a positive sputum culture with SM on lung disease morbidity in our CF population.

Methods: Patients from the CF database were reviewed for presence of SM. Lung function and BMI data were analyzed at 1 y before, at acquisition, at 6 months, 1 and 2 y after acquisition. We compared data between three groups: patients intermittently colonized with SM (IC), chronically colonized (CC) patients and a control group (CG) of CF patients that never acquired SM in their sputum and were matched for gender, age, Pseudomonas status and pancreas insufficiency.

Results: Median age was 18 y (IQR 12–25). FEV1% was significantly different between three groups, with lower values in the CC and IC 6 months (p=0.013) before and at time of SM acquisition (p=0.0003). There was no significant difference in lung function evolution between three groups (FEV1% p=0.34, FVC% p=0.24, PEF% p=0.33), but a trend was seen for BMI evolution (p=0.06) with worse BMI over time in the IC (p=0.04) and CC (p=0.06). There was significant increase in # hospitalizations and number of IV courses with antibiotic use after acquisition of SM with highest increase in CC (p=0.04).

Conclusion: CF patients with positive sputum culture with SM had worse lung function not only at time of acquisition but also in preceding months. Acquisition of SM was not associated with accelerated FEV1 decline but BMI decreased in patients with SM and exacerbation rate and number of IV antibiotic courses increased after acquisition of SM.
Abstract 42: Association of Optimism with Cardiovascular Health: Results From the Hispanic Community Health Study/Study (HCHS/SOL) of Latinos Sociocultural Ancillary Study
Authors: Rosalba Hernandez, Hector Gonzalez, Wassim Tarraf, Mercedes Carnethon, Frank J Penedo, Linda Gallo, William Arguelles, Christina Buelna, Sonia Davis, Franklyn Gonzalez, Carmen R Isasi, Jessica L McCurley, John M Ruiz, Martha Daviglus
Journal: Circulation (2016)

Introduction: There is mounting evidence linking positive psychological functioning to restorative health processes and favorable medical outcomes. However, very little is known about the relationship between optimism--an indicator of psychological functioning--and the American Heart Association ( AHA ) defined concept of cardiovascular health ( CVH ), particularly in Hispanics/Latinos of diverse backgrounds. Hypothesis: Persons with greater optimism will have more favorable CVH profiles. Methods: We analyzed data from adults ages 18-75 that participated in the Hispanic Community Health Study/Study of Latinos ( HCHS/SOL ) Sociocultural Ancillary Study in 2010-11. Optimism was assessed using the Life-Orientation Test-Revised, with scores ranging from 6-24 and higher scores indicative of greater levels of optimism. AHA classification standards were used to derive a composite CVH score with subsequent grouping into categorizes of poor (0-7 points), intermediate (8-11 points), and ideal (12-14 points). Metrics considered when calculating the overall CVH score included diet, body mass index, physical activity, cholesterol, blood pressure, fasting glucose, and smoking status. Multinomial logistic regression was used to examine associations of optimism with ideal and intermediate CVH (poor CVH—ref. group), after adjusting for socio-demographic factors and depressive symptoms. Results: Among 4,960 participants with complete data, 9.2% were categorized as having ideal CVH. In multivariable-adjusted models, participants with moderate levels of optimism were more likely to have intermediate [OR = 1.37: 95%CI = 1.08, 1.74] and ideal [OR = 1.61: 95%CI = 1.04, 2.48] CVH when compared to the least optimistic group ( Table 1 ). Conclusions: The current study offers preliminary evidence for an association between optimism and CVH in a large heterogeneous group of Hispanic/Latino adults. Future studies should explore the concept of optimistic bias and whether exaggerated levels of optimism are detrimental to health.
Factors influencing performance of MRI in newly diagnosed breast cancer patients
Authors: C. Lehman, C. Gatsonis, C. Kuhl, E. Hendrick, E. Pisano, L. Hanna, S. Peacock, S. Smazal, D. Maki, M. Schnall
Journal: Journal of Clinical Oncology (2007)

604 Background: There is wide variation in the use of breast MRI to screen the contralateral breast in patients recently diagnosed with unilateral breast cancer. Some centers routinely scan all patients with a recent diagnosis of breast cancer while others restrict breast MRI to patients with dense breast tissue, patients who are pre-menopausal, or patients with infiltrating lobular carcinoma. This international study evaluated performance measures of MRI by mammographic density, menopausal status and type of index cancer. Methods: 969 women from 21 sites with a recent diagnosis of unilateral breast cancer and a negative mammogram and CBE of the contralateral breast underwent breast MRI. Presence of breast cancer in the contralateral breast was determined by cancer positive breast biopsy within 12 months after study entry. Performance measures of breast MRI (cancer yield, sensitivity, specificity, negative predictive value, positive predictive value, biopsy rate) were compared between participant subsets defined by mammographic density (fatty vs dense), menopausal status (pre/peri menopausal vs post menopausal) and type of index cancer (invasive vs in situ and lobular vs non-lobular). Results: Performance measures of breast MRI were not influenced by breast density or index cancer histology. Cancer yield of MRI in dense breast women was 3% in both fatty and dense breasted women. Although cancer yield and sensitivity of MRI did not vary based on menopausal status, specificity was significantly higher among post-menopausal women in comparison to pre- or peri-menopausal women (p-value=0.002) as was positive biopsy rate (p-value 0.009). Conclusions: Performance of MRI in screening the contralateral breast in the newly diagnosed breast cancer patient is not influenced by breast density or index cancer histology. Specificity and positive biopsy rate are higher in post-menopausal women, which may be related to hormonal influences on breast tissue enhancement. [Table: see text]
TCTAP A-028 Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Non-ST-Elevation Acute Coronary Syndrome: Analysis of Pooled Data from the BEST, PRECOMBAT and SYNTAX Trials
Authors: Mineok Chang, Cheol Whan Lee, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Seong-Wook Park, Patrick W. Serruys, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2016)
Treatment of Acute Uremia by Peritoneal Lavage
Authors: Robert W. Buckley, Roger A. Scholten
Journal: New England Journal of Medicine (1947)

THE treatment of uremia has long been directed toward symptomatic relief, healing of the underlying renal lesion and, in acute and presumably temporary cases, maintenance of life long enough to allow the kidneys to reassume their essential functions. It is toward the last objective that attempts have been made by numerous workers to supply a temporary "substitute" for the kidneys, which would maintain excretion of uremic metabolites, whose retention is fatal to the organism. In a review of the chemical changes known to occur in uremia, Harrison and Mason1 stressed the importance of increased blood and tissue concentrations of urea, . . .
Nova et Vetera
Authors: C HASTINGS
Journal: BMJ (1960)

Exeter, with which Torquay is closely linked medically, has much that will interest members of the British Medical Association visiting Torquay for the Annual Meeting.Like other ancient cathedral cities it was in former days an important administrative metropolis.Its association with Drake and Raleigh will be well enough known, but as a medical centre it goes back at least to the twelfth century, when the first hospital was established for much the same reasons as those of St. Bartholomew's and St. ThoInas's in London and that of the Holy Cross at Winchester-to care for pilgrims and lepers.This hospital of St. Mary Magdalene later became an almshouse.Exeter had several other hospital foundations, some for the care of the aged, some for orphans.The latter became schools, one of which, the Blue Maidens Hospital (now developed into The modern Maynard Girls' School), has a special link with Torbay.On November 5, 1688, Prince William of Orange landed at Brixham with 15,000 troops of very assorted nationalities.His first major stopping-place en route for London, and the overthrow of James II, was at Exeter, which he entered on November 9.The weather was the worst that Devon can offer, and in wet seasons, John Haddy James, 1788-1869.such as the recent winter of 1959-60, it can be really terrible.
Endocardial Pacemaking and Insertion of a Permanent Internal Cardiac Pacemaker
Authors: Donald S. Abelson, Philip Samet, George Rand, John Moraca
Journal: New England Journal of Medicine (1961)

SEVERAL methods have been developed in the past decade for the management of patients with repeated episodes of cardiac asystole or ventricular rates too slow to permit adequate perfusion of vital organs. Drug therapy has often proved disappointing. Recent emphasis has centered on various mechanical means of controlling the ventricular rate. Zoll and his co-workers1 have pioneered in the latter approach, employing external cardiac pacemakers that require relatively high voltage and current density. Skin burns have resulted from prolonged use — that is, for more than twenty-four hours. Severe pain has also been a problem. Weirich, Gott and Lillehei2 treated . . .
Rituximab followed by localized radiation therapy in limited stage indolent non-Hodgkin’s lymphoma: Preliminary results of a pilot study
Authors: U. Ricardi, A. R. Filippi, A. Cuttica, D. Caracciolo, M. Zanni, M. Bazzan, R. Freilone, P. Franco, M. Boccadoro, C. Tarella
Journal: Journal of Clinical Oncology (2005)

6696 Background: The most common approach for limited-stage low-grade non-Hodgkin’s lymphoma (NHL) is localized radiotherapy (L-RT). However, some studies have reported prolonged disease-free survival if chemotherapy (CT) is combined with RT. Nevertheless, there is some concern about the use of cytotoxic drugs in this group of patients. In order to deliver a systemic anti-lymphoma drug while avoiding the potential toxicity of chemotherapy, a phase I study program was designed combining the anti-CD20 Rituximab (Rb) monoclonal antibody with L-RT. Aim of the study was to assess toxicity profile, overall response rate and time to treatment failure. Methods: Since January 2000, patients with stage I-II Follicle Center Lymphoma (FCL) or low-grade MALT lymphoma, have been enrolled in a study program, including 4 Rb doses (375 mg/sqm) given at 1 week intervals, followed by L-RT, limited to involved sites with standard doses of 36–40 Gy. So far, 18 patients have been treated and are evaluable: 11 nodal FCL (9 inguinal, 1 cervical, 1 parothid gland involvement), 5 low-grade MALT lymphoma (1 parothid gland, 2 orbital and 2 breast involvement) and 2 primary cutaneous FCL. Results: Treatment was well tolerated. In 4 patients mild Rb-related side effects were observed (fever with chills); no hematological toxicity was seen. Mild RT-induced xerostomia (grade 1) was recorded at 2 years from RT in the patient treated for parothid gland MALT NHL. All patients were in CR at the end of the combined treatment. With a median follow-up of 20 months, all 18 patients are presently alive and well, 17 of them in continuous CR. One patient (inguinal FCL) relapsed out of radiation field, but with different histology (diffuse large B cell). Conclusions: Administration of 4 doses of Rb followed by L-RT appears to be a safe, tolerable and active combined modality regimen for patients with grade 1–2 FCL or low-grade MALT NHL presenting with limited stage disease. Among them, the use of Rb along with RT might result in prolonged event-free survival reducing outside-field relapse rate without the need of CT administration. Furthermore, the addition of Rb might allow to reduce RT doses and treatment volumes, minimizing RT toxicity. No significant financial relationships to disclose.
Treatment of Myasthenia Gravis with Germine Diacetate
Authors: Werner Flacke, Verne S. Caviness, Frederick G. Samaha
Journal: New England Journal of Medicine (1966)

MORE than three decades have passed since the first attempt to treat myasthenia gravis with veratrum alkaloids.1 , 2 At that time "Tinctura Veratri," given either intravenously or by mouth, was found to improve power in diseased bulbar and appendicular muscles of severely afflicted patients. Those who had previously been unable to sustain adequate nutrition and were in continued danger of aspiration gained weight and were again able to handle pharyngeal secretions safely. After these promising initial communications no more was heard of veratrum in the treatment of myasthenia gravis. For this the side effects of the preparation used were probably much . . .
Adaptive Immune Response Impairs the Efficacy of Autologous Transplantation of Engineered Stem Cells in Dystrophic Dogs
Authors: Clementina Sitzia, Andrea Farini, Luciana Jardim, Paola Razini, Marzia Belicchi, Letizia Cassinelli, Chiara Villa, Silvia Erratico, Daniele Parolini, Pamela Bella, Joao Carlos da Silva Bizario, Luis Garcia, Marcelo Dias-Baruffi, Mirella Meregalli, Yvan Torrente
Journal: Molecular Therapy (2016)

Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the best preclinical model of Duchenne muscular dystrophy, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in Golden Retriever muscular dystrophy. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected Golden Retriever muscular dystrophy dogs. The occurrence of T-cell response in three Golden Retriever muscular dystrophy dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin. Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the best preclinical model of Duchenne muscular dystrophy, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in Golden Retriever muscular dystrophy. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected Golden Retriever muscular dystrophy dogs. The occurrence of T-cell response in three Golden Retriever muscular dystrophy dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin.
Loss of Notch Receptor-Ligand Engagement Leads to Increased Hematopoietic Stem and Progenitor Cell Egress and Mobilization
Authors: Lan Zhou, Weihuan Wang, Grant Zimmerman, Jay Myers, Yuanshuai Huang, Vionnie W.C. Yu, Dan Huang, Shuiliang Yu, Yiwei Wang, Xiaoran Huang, Jeongsup Shim, Minhong Yan, John Lowe, Wei Xin, Pamela Stanley, David T. Scadden, Alex Y Huang, Christian W. Siebel
Journal: Blood (2014)
A Noninvasive Scintiphotographic Method for Detecting Regional Ventricular Dysfunction in Man
Authors: Barry L. Zaret, H. William Strauss, Peter J. Hurley, T. K. Natarajan, Bertram Pitt
Journal: New England Journal of Medicine (1971)

Regional left ventricular dysfunction (asynergy) can be detected by a noninvasive scintiphotographic technic. After intravenous injection of radionuclide (technetium-99m-albumin) electrocardiographically controlled cardiac images (scintiphotographs) are obtained in end-systole and in end-diastole with an Anger scintillation camera. By superimposition of end-systolic and end-diastolic traced images, an assessment of left ventricular wall contraction can be made, and the extent of wall movement quantified. The changes in scintiphotographic ventricular dimensions correlate well with measurements obtained with contrast cineangiography. Eleven patients with ventricular dysfunction were studied by scintiphotographic and contrast radiographic technics. In eight of these, a localized area of impaired left ventricular contraction was demonstrated by both methods. This noninvasive technic appears to offer a safe and repeatable means for assessing regional left ventricular function.