tbuckley/cabot-search huggingface dataset:
SweeD: Likelihood-Based Detection of Selective Sweeps in Thousands of Genomes
Authors: Pavlos Pavlidis, Daniel Živković, Alexandros Stamatakis, Nikolaos Alachiotis
Journal: Molecular Biology and Evolution (2013)

The advent of modern DNA sequencing technology is the driving force in obtaining complete intra-specific genomes that can be used to detect loci that have been subject to positive selection in the recent past. Based on selective sweep theory, beneficial loci can be detected by examining the single nucleotide polymorphism patterns in intraspecific genome alignments. In the last decade, a plethora of algorithms for identifying selective sweeps have been developed. However, the majority of these algorithms have not been designed for analyzing whole-genome data. We present SweeD (Sweep Detector), an open-source tool for the rapid detection of selective sweeps in whole genomes. It analyzes site frequency spectra and represents a substantial extension of the widely used SweepFinder program. The sequential version of SweeD is up to 22 times faster than SweepFinder and, more importantly, is able to analyze thousands of sequences. We also provide a parallel implementation of SweeD for multi-core processors. Furthermore, we implemented a checkpointing mechanism that allows to deploy SweeD on cluster systems with queue execution time restrictions, as well as to resume long-running analyses after processor failures. In addition, the user can specify various demographic models via the command-line to calculate their theoretically expected site frequency spectra. Therefore, (in contrast to SweepFinder) the neutral site frequencies can optionally be directly calculated from a given demographic model. We show that an increase of sample size results in more precise detection of positive selection. Thus, the ability to analyze substantially larger sample sizes by using SweeD leads to more accurate sweep detection. We validate SweeD via simulations and by scanning the first chromosome from the 1000 human Genomes project for selective sweeps. We compare SweeD results with results from a linkage-disequilibrium-based approach and identify common outliers.
Prosurvival activity for airway neutrophils in severe asthma
Authors: M. Uddin, G. Nong, J. Ward, G. Seumois, L. R. Prince, S. J. Wilson, V. Cornelius, G. Dent, R. Djukanovic
Journal: Thorax (2010)

<h3>Background</h3> Airway neutrophilia is a recognised feature of chronic severe asthma, but the mechanisms that underlie this phenomenon are unknown. Evidence for factors present in airway secretions that prolong neutrophil survival has been sought and it has been hypothesised that these might be augmented in neutrophilic asthma. <h3>Methods</h3> Non-smoking subjects with severe asthma (SA) or mild asthma (MA) and healthy control subjects (HC) underwent sputum induction. The SA group was subdivided into subjects with neutrophil counts above (SA-high) and those within the normal range (SA-low). Apoptotic neutrophils were enumerated in the cellular phase while the fluid phase was assessed for its ability to prolong the in vitro survival of blood-derived neutrophils using morphometric and flow cytometric analyses. <h3>Results</h3> There was a significant difference between all four subject groups with respect to the percentage of apoptotic sputum neutrophils (Kruskal–Wallis, p=0.042). Cuzick test showed a highly significant (p=0.008) trend towards decreasing numbers of apoptotic neutrophils across the four groups with increasing asthma severity and neutrophil count. The sputum antiapoptotic activity was also different between the groups (p=0.039), with a highly significant (p=0.005) decreasing trend across the four groups. The survival effect could not be inhibited by blocking selective chemotaxin receptors, neutralising neutrophil survival factors, inhibiting phosphatidylinositol-3-kinase (using LY294002) or with pertussis toxin pretreatment. Similarly, it could not be explained by lipopolysaccharide contamination or by the presence of inhaled corticosteroids in sputum. <h3>Conclusions</h3> These data demonstrate the capacity of as yet unidentified factor(s) in the airways of subjects with asthma to delay human neutrophil apoptosis and extend their lifespan as a potential mechanism contributing to unresolving airways neutrophilia in severe asthma.
Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease
Authors: Patrick G. Kehoe, Carsten Russ, Stephen McIlroy, Hywel Williams, Peter Holmans, Clive Holmes, Danae Liolitsa, Djamil Vahidassr, John Powell, Bronagh McGleenon, Malcolm Liddell, Robert Plomin, Kevin Dynan, Nigel Williams, Jim Neal, Nigel J. Cairns, Gordon Wilcock, Peter Passmore, Simon Lovestone, Julie Williams, Michael J. Owen
Journal: Nature Genetics (1999)
Crohn's disease patients treated with adalimumab benefit from co-treatment with immunomodulators: Table 1
Authors: Mirthe E van der Valk, Martijn G H van Oijen, Marije Ammerlaan, Peter D Siersema, Bas Oldenburg
Journal: Gut (2011)

We read with interest the study by Sokol et al in Gut , emphasising the need for co-treatment with immunomodulators in patients receiving infliximab maintenance therapy. Concomitant use of immunosuppressives was associated with reduced disease activity and infliximab dose escalation, presumably through a lowered frequency of antibody formation.1

Although adalimumab is a 100% human anti-tumour necrosis factor monoclonal antibody, it is not devoid of immunogenicity. Antibodies against adalimumab have been reported in 2.6–38% of patients treated for Crohn's disease or rheumatoid arthritis.2 However, the long-term efficacy of the combination of adalimumab plus immunosuppressives in this setting is not known. One observational study from Karmiris et al performed at …
Drug Points: Iritis after treatment with streptokinase
Authors: M Y G. a. J H Lazarus
Journal: BMJ (1994)

South Glamorgan CF64 2XX) write: Several allergic reactions have been described in association with streptokinase. Immediate reactions include bronchospasm, urticaria, and anaphylaxis.1 Delayed reactions include vasculitis and an illness like serum sickness.2 3 Kinshuk suggested that iritis may be associated with streptokinase treatment.4 We report a case of severe bilateral …
Metabolic Studies in Familial Hypercholesterolemia
Authors: David W. Bilheimer, Neil J. Stone, Scott M. Grundy
Journal: Journal of Clinical Investigation (1979)

To investigate the gene-dosage effect in familial hypercholesterolemia (FH), metabolic studies were conducted in a group of well-characterized patients with either heterozygous (n = 7) or homozygous (n = 7) FH and the results were compared to those obtained in normal subjects (n = 6). The turnover of 125I-labeled low-density lipoprotein (LDL) was measured in all of the normals, all but one of the FH heterozygotes, and in all of the homozygotes. Chemical cholesterol balance was performed simultaneously with the 125I-LDL turnover in all seven of the homozygotes.
A prospective study of Mohs’ micrographic surgery in two English centres
Authors: C.G. JULIAN, P.W. BOWERS
Journal: British Journal of Dermatology (1997)

In this study we report the results of using Mohs' micrographic surgery (MMS) to treat 228 basal cell carcinomas (BCCs) in both a teaching and a district general hospital. The criteria for case selection and the 5-year recurrence rate of 3.8% are comparable with figures from the U.S.A. Our experience shows that high cure rates in difficult and, especially, recurrent tumours are obtainable using MMS in both a teaching and a district general hospital setting. Such treatment should be more widely available in the U.K. particularly as the incidence of BCCs is rising.
More people opt to use assisted dying laws for greater variety of reasons:
Authors: Ingrid Torjesen
Journal: BMJ (2015)

<h3>ABSTRACT</h3> The human fetal period is associated with a rapid emergence of body organ functions and systems, including establishment of the functional brain connectome. In order to characterise developmental features of in-utero functional activity, we introduce a novel perspective on resting-state functional networks, which we call “maturational networks”, or “matnets”. The key feature of this framework is that it incorporates age-related changes in connectivity into network estimation, thereby characterising functional networks as an emerging property of the brain. We find that fetal matnets reveal several spatially distributed patterns of connections with remarkable anatomical specificity. The framework also enables construction of a whole-brain view of maturational relationships across the early brain’s functional organisation, which we term the “maturational connectome”. We find that the fetal maturational connectome is composed of several groups of maturational networks, among which two groups which are associated with active environmental interaction through perceptual and motor-planning mechanisms, assume a central role.
Targeting cap-dependent translation blocks converging survival signals by AKT and PIM kinases in lymphoma
Authors: Jonathan H. Schatz, Elisa Oricchio, Andrew L. Wolfe, Man Jiang, Irina Linkov, Jocelyn Maragulia, Weiji Shi, Zhigang Zhang, Vinagolu K. Rajasekhar, Nen C. Pagano, John A. Porco, Julie Teruya-Feldstein, Neal Rosen, Andrew D. Zelenetz, Jerry Pelletier, Hans-Guido Wendel
Journal: The Journal of Experimental Medicine (2011)

New anticancer drugs that target oncogenic signaling molecules have greatly improved the treatment of certain cancers. However, resistance to targeted therapeutics is a major clinical problem and the redundancy of oncogenic signaling pathways provides back-up mechanisms that allow cancer cells to escape. For example, the AKT and PIM kinases produce parallel oncogenic signals and share many molecular targets, including activators of cap-dependent translation. Here, we show that PIM kinase expression can affect the clinical outcome of lymphoma chemotherapy. We observe the same in animal lymphoma models. Whereas chemoresistance caused by AKT is readily reversed with rapamycin, PIM-mediated resistance is refractory to mTORC1 inhibition. However, both PIM- and AKT-expressing lymphomas depend on cap-dependent translation, and genetic or pharmacological blockade of the translation initiation complex is highly effective against these tumors. The therapeutic effect of blocking cap-dependent translation is mediated, at least in part, by decreased production of short-lived oncoproteins including c-MYC, Cyclin D1, MCL1, and the PIM1/2 kinases themselves. Hence, targeting the convergence of oncogenic survival signals on translation initiation is an effective alternative to combinations of kinase inhibitors.
Effects of Renal Hypertension on Coronary Blood Flow, Cardiac Oxygen Consumption and Related Circulatory Dynamics of the Dog
Authors: JAMES W. WEST, HERMANN MERCKER, HERBERT WENDEL, ELWOOD L. FOLTZ
Journal: Circulation Research (1959)

A comparative study is presented on the circulatory dynamics of the renal hypertensive state, the stability (repeatability) of the findings in a given subject, the effect of anemia as a complicating factor and the amount of cardiac hypertrophy present in each animal at the end of the series of observations. The results indicate that in nonanemic renal hypertensive dogs with cardiac hypertrophy the coronary blood flow and cardiac oxygen consumption are the same per unit weight of myocardial tissue as in normal dogs. However, when a mild chronic anemia is a complicating factor, the coronary blood flow and the myocardial oxygen uptake are both increased. The coronary sinus venous oxygen saturation is essentially unchanged in the nonanemic hypertensives, whereas in the anemic hypertensives it is significantly lowered.
Gender differences in survival following hospitalisation for COPD
Authors: A. V. Gonzalez, S. Suissa, P. Ernst
Journal: Thorax (2010)

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Gender differences in the clinical expression of COPD are increasingly recognised, but outcome differences have not been systematically examined. Gender differences in survival and rate of rehospitalisation were investigated in a large cohort of elderly patients with chronic airflow obstruction hospitalised for COPD. <h3>Methods</h3> The databases from the Québec provincial health insurance plan were used. The study population included subjects aged &gt;66 years who received ≥3 prescriptions for respiratory medications in any 1-year period between 1 January 1990 and 31 December 2001. The study cohort consisted of patients with a first hospitalisation for COPD, after selection into the study population. Patients were followed until death or 31 December 2003. The Kaplan–Meier method was used to estimate time to death and time to first hospitalisation for obstructive airways disease (COPD or asthma). The Cox proportional hazards model was used to determine the effect of male gender on all-cause mortality and rehospitalisation. <h3>Results</h3> The cohort consisted of 19 260 women and 23 893 men with a mean age of 77 years. 11 245 (58.4%) women and 16 754 (70.1%) men died after cohort entry. Male sex was associated with a significantly increased risk of death (adjusted HR 1.45, 95% CI 1.42 to 1.49) and with a significantly increased risk of rehospitalisation for obstructive airways disease (adjusted HR 1.12, 95% CI 1.09 to 1.15). <h3>Conclusion</h3> Mean survival and time to rehospitalisation for obstructive airways disease are significantly better for female patients.
Long-Term Prognostic Importance of Diabetes After a Myocardial Infarction Depends on Left Ventricular Systolic Function
Authors: Charlotte Andersson, Gunnar H. Gislason, Charlotte Mérie, Ulrik M. Mogensen, Scott D. Solomon, Christian Torp-Pedersen, Lars Køber
Journal: Diabetes Care (2011)

This study was performed to understand how left ventricular function modulates the prognostic importance of diabetes after myocardial infarction (MI).Consecutively hospitalized MI patients screened for three clinical trials were followed for a median of 7 years. Multivariable Cox regression models were used to assess the risk of mortality associated with diabetes, and the importance of diabetes was examined independently within defined left ventricular ejection fraction (LVEF) subgroups.A total of 16,912 patients were included; 1,819 (11%) had diabetes. Diabetes and 15% unit depression in LVEF were of similar prognostic importance: hazard ratios (HRs) were 1.45 (95% CI 1.37-1.54) and 1.41 (1.37-1.45) for diabetes and LVEF depression, respectively. LVEF modified the outcomes associated with diabetes, with HRs being 1.29 (1.19-1.40) and 1.61 (1.49-1.74) in patients with LVEF <40% and LVEF ≥ 40%, respectively (P = 0.03).Patients within the higher LVEF categories have a greater mortality risk attributable to diabetes than patients within the lower LVEF categories.
Pregestational Diabetes and Pregnancy
Authors: Aidan McElduff, Glynis P. Ross, Janet A. Lagström, Bernard Champion, Jeff R. Flack, Sue-Mei Lau, Robert G. Moses, Sivanthi Seneratne, Mark McLean, N. Wah Cheung
Journal: Diabetes Care (2005)

We examined the current status of pregnancy complicated by preexisting diabetes in Australia. Data were collected on 180 pregnancies from 10 teaching hospitals (in NSW, Victoria, and Western Australia) with an interest in pregnancy complicated by diabetes, for the period from July 2003 to June 2004.

The majority of the pregnancies were complicated by type 2 (55%) rather than type 1 diabetes. The women with type 2 diabetes were significantly older (32.8 ± 5.4 years) than those with type 1 diabetes (30.9 ± 5.1 years, P = 0.014, independent t test). Type 2 diabetic women also had a shorter diabetes duration (4.4 ± 3.3 vs. 13.3 ± 8.2 years, …
Interventions That Restore Awareness of Hypoglycemia in Adults With Type 1 Diabetes: A Systematic Review and Meta-analysis
Authors: Ester Yeoh, Pratik Choudhary, Munachiso Nwokolo, Salma Ayis, Stephanie A. Amiel
Journal: Diabetes Care (2015)

OBJECTIVE Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia (SH) sixfold and affects 30% of adults with type 1 diabetes (T1D). This systematic review and meta-analysis looks at the educational, technological, and pharmacological interventions aimed at restoring hypoglycemia awareness (HA) in adults with T1D. RESEARCH DESIGN AND METHODS We searched The Cochrane Library, MEDLINE, Embase, Science Citation Index Expanded, Social Sciences Citation Index, PsycINFO, and CINAHL from inception until 1 October 2014. Included studies described HA status at baseline. Outcome measures were SH rates, change in HA, counterregulatory hormone responses, and glycemic control. RESULTS Forty-three studies (18 randomized controlled trials, 25 before-and-after studies) met the inclusion criteria, comprising 27 educational, 11 technological, and 5 pharmacological interventions. Educational interventions included structured diabetes education on flexible insulin therapy, including psychotherapeutic and behavioral techniques. These were able to reduce SH and improve glycemic control, with greater benefit from the latter two techniques in improving IAH. Technological interventions (insulin pump therapy, continuous glucose monitoring, and sensor-augmented pump) reduced SH, improved glycemic control, and restored awareness when used in combination with structured education and frequent contact. Pharmacological studies included four insulin studies and one noninsulin study, but with low background SH prevalence rates. CONCLUSIONS This review provides evidence for the effectiveness of a stepped-care approach in the management of patients with IAH, initially with structured diabetes education in flexible insulin therapy, which may incorporate psychotherapeutic and behavioral therapies, progressing to diabetes technology, incorporating sensors and insulin pumps, in those with persisting need.
Complete remission of treatment-refractory advanced angiosarcoma of the scalp by protracted intralesional interleukin-2 therapy
Authors: C. Gebhardt, B. Ziegler, S. Stadler, S. Goerdt, J. Utikal
Journal: British Journal of Dermatology (2014)

Journal Article Complete remission of treatment‐refractory advanced angiosarcoma of the scalp by protracted intralesional interleukin‐2 therapy C. Gebhardt, C. Gebhardt Skin Cancer Unit German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Dermatology, Venereology and Allergology University Medical Center Mannheim Ruprecht‐Karl University of Heidelberg Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany Search for other works by this author on: Oxford Academic Google Scholar B. Ziegler, B. Ziegler Department of Dermatology, Venereology and Allergology University Medical Center Mannheim Ruprecht‐Karl University of Heidelberg Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany Search for other works by this author on: Oxford Academic Google Scholar S. Stadler, S. Stadler Skin Cancer Unit German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Dermatology, Venereology and Allergology University Medical Center Mannheim Ruprecht‐Karl University of Heidelberg Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany Search for other works by this author on: Oxford Academic Google Scholar S. Goerdt, S. Goerdt Department of Dermatology, Venereology and Allergology University Medical Center Mannheim Ruprecht‐Karl University of Heidelberg Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany Search for other works by this author on: Oxford Academic Google Scholar J. Utikal J. Utikal Skin Cancer Unit German Cancer Research Center (DKFZ) Heidelberg GermanyDepartment of Dermatology, Venereology and Allergology University Medical Center Mannheim Ruprecht‐Karl University of Heidelberg Theodor‐Kutzer‐Ufer 1‐3 68167 Mannheim Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 4, 1 April 2015, Pages 1156–1158, https://doi.org/10.1111/bjd.13400 Published: 01 April 2015
Relationship between structural joint damage and urate deposition in gout: a plain radiography and dual-energy CT study
Authors: Nicola Dalbeth, Opetaia Aati, Ramanamma Kalluru, Gregory D Gamble, Anne Horne, Anthony J Doyle, Fiona M McQueen
Journal: Annals of the Rheumatic Diseases (2014)

Objectives The aim of this work was to examine the relationship between joint damage and monosodium urate (MSU) crystal deposition in gout. Methods Plain radiographs and dual-energy CT (DECT) scans of the feet were prospectively obtained from 92 people with tophaceous gout. Subcutaneous tophus count was recorded. The ten metatarsophalangeal joints were scored on plain radiography for Sharp–van der Heijde erosion and joint space narrowing (JSN) scores, and presence of spur, osteophyte, periosteal new bone and sclerosis (920 total joints). DECT scans were analysed for the presence of MSU crystal deposition at the same joints. Results DECT MSU crystal deposition was more frequently observed in joints with erosion (OR (95% CI) 8.5 (5.5 to 13.1)), JSN (4.2 (2.7 to 6.7%)), spur (7.9 (4.9 to 12.8)), osteophyte (3.9 (2.5 to 6.0)), periosteal new bone (7.0 (4.0 to 12.2)) and sclerosis (6.9 (4.6 to 10.2)), p&lt;0.0001 for all. A strong linear relationship was observed in the frequency of joints affected by MSU crystals with radiographic erosion score (p&lt;0.0001). The number of joints at each site with MSU crystal deposition correlated with all features of radiographic joint damage (r&gt;0.88, p&lt;0.05 for all). In linear regression models, the relationship between MSU crystal deposition and all radiographic changes except JSN and osteophytes persisted after adjusting for subcutaneous tophus count, serum urate concentration and disease duration. Conclusions MSU crystals are frequently present in joints affected by radiographic damage in gout. These findings support the concept that MSU crystals interact with articular tissues to influence the development of structural joint damage in this disease.
Further Studies on the Relationship Between Allotransplantability and the Presence of the Cell Surface Glycoprotein Epiglycanin in the TA3-MM Mouse Mammary Carcinoma Ascites Cell&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Scott C. Miller, John F. Codington, George Klein
Journal: JNCI Journal of the National Cancer Institute (1982)

The loss of strain specificity in the TA3-St mammary carcinoma ascites cell during passage in ascites form in diseased syngeneic strain A mice was confirmed by the observation that TA3-MM/2 ascites cells were capable of progressive growth in 7 foreign mouse strains. Support for the hypothesis that allotransplantability in the TA3-MM lines may be due to masking of cell surface histocompatibility H-2a antigens by large glycoprotein (epiglycanin) molecules was obtained from the finding that the capacity of the TA3-MM/2 ascites cell to absorb anti-H-2a antibody was several times less than that of the parent TA3-St ascites cell, although it was greater than the capacity of the non-strain-specific TA3-Ha line. Further support for the location of epiglycanin molecules at the cell surface was obtained by transmission electron-microscopic observation of a high concentration of filamentous structures, usually 20–40 nm long, but often extending to 200–300 nm length at the TA3-MM/2 cell surface. Similar structures were also observed at the TA3-Ha cell surface but were not observed at the surface of the TA3-St ascites cell, a cell known to contain no detectable epiglycanin. Epiglycanin molecules, obtained by two different methods from TA3-MM/1, TA3-MM/2, and TA3-Ha ascites cells, were shown to be similar with respect to their capacities to inhibit the binding of 125I-labeled epiglycanin to its antibody, induced in the rabbit by TA3-Ha ascites cells in a radioimmunoassay.