tbuckley/cabot-search huggingface dataset:
Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparumpopulation divergence
Authors: Daniel E Neafsey, Stephen F Schaffner, Sarah K Volkman, Daniel Park, Philip Montgomery, Danny A Milner, Amanda Lukens, David Rosen, Rachel Daniels, Nathan Houde, Joseph F Cortese, Erin Tyndall, Casey Gates, Nicole Stange-Thomann, Ousmane Sarr, Daouda Ndiaye, Omar Ndir, Soulyemane Mboup, Marcelo U Ferreira, Sandra do Lago Moraes, Aditya P Dash, Chetan E Chitnis, Roger C Wiegand, Daniel L Hartl, Bruce W Birren, Eric S Lander, Pardis C Sabeti, Dyann F Wirth
Journal: Genome biology (2008)

Abstract Background The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum . Results Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, inter-population differentiation, and the degree to which allele frequencies are correlated between populations. Conclusions The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum , and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.
Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea
Authors: L. Kheirandish-Gozal, L. D. Serpero, E. Dayyat, J. Kim, J. L. Goldman, A. Snow, R. Bhattacharjee, D. Gozal
Journal: European Respiratory Journal (2008)

Intranasal corticosteroids (CS) are potentially useful interventions for children with obstructive sleep apnoea (OSA), and may reduce lymphadenoid tissue size in the upper airway. The present authors hypothesised that CS would reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system. Dissociated tonsils or adenoids harvested intra-operatively from children with polysomnographically diagnosed OSA were cultured in control medium (CO) or after stimulation with lipopolysaccharide and concanavalin A (STIM), and incubated with dexamethasone (DEX; 10 −5 –10 −7 M), fluticasone (FLU; 10 −5 –10 −14 M) and budesonide (BUD; 10 −4 –10 −14 M). Proliferation and apoptosis were assessed, and supernatants were assayed for the cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8. STIM increased tonsillar and adenoidal proliferation compared with CO (1,976±133 versus 404±69 counts·min −1 ; n = 54). DEX, FLU and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU&gt;BUD&gt;DEX (n = 25 per group). Conversely, CS increased cellular apoptosis (n = 20 per group). Furthermore, TNF-α, IL-8 and IL-6 concentrations in the supernatant were increased by STIM, and markedly reduced by all CS (n = 48 per group). Whole tissue cell cultures of adenoids and tonsils provide a useful approach for in vitro assessment of therapeutic efficacy of corticosteroids in the management of lymphadenoid hypertrophy that underlies obstructive sleep apnoea in children.
Sodium cromoglycate as a replacement for inhaled corticosteroids in mild‐to‐moderate childhood asthma
Authors: W. Petersen, F. Karup‐Pedersen, B. Friis, P. Howitz, F. Nielsen, L.‐H. Strömquist
Journal: Allergy (1996)

We investigated whether sodium cromoglycate 10 mg three times daily, delivered as an aerosol via Nebuhaler (in addition to terbutaline 0.5 mg three times daily), could replace inhaled steroid in children with mild‐to‐moderate asthma. Children (mean age 10.3 years) were randomly allocated to 12‐week treatment with sodium cromoglycate 10 mg plus terbutaline 0.5 mg (group A; n = 30) or placebo plus terbutaline 0.5 mg (group B; n = 32), both taken three times a day. The daily steroid dose was reduced by 50 μg/week for 4 weeks from a starting dose of 200 μg. Fewer patients withdrew owing to worsening asthma from group A ( n = 1) than group B ( n = 11). Symptom scores, morning and evening peak flows, and additional β 2 ‐agonist usage, recorded on diary cards, were better in group A than group B. Lung function measured at clinic visits was unchanged in either group. Overall opinions of efficacy favoured Group A. Adverse events were similar in the groups. Sodium cromoglycate plus terbutaline substituted effectively for inhaled steroid therapy.
Rebound nocturnal hypersecretion after four weeks treatment with an H2 receptor antagonist.
Authors: G M Fullarton, G McLauchlan, A Macdonald, G P Crean, K E McColl
Journal: Gut (1989)

Daytime intragastric pH, fasting and meal stimulated serum gastrin and nocturnal acid output were studied in eight male duodenal ulcer patients before, during and two days after completing nizatidine 300 mg nocte (20:00 h) for four weeks. Median nocturnal acid output (mmol/10 h) decreased during treatment to 11.6 (range 0.4-26.7) compared with pretreatment value of 39.4 (9.8-91.2); median acid inhibition 77% (p less than 0.01) which was strongest between 24:00 and 04:00 h. Two days after discontinuing treatment, nocturnal acid output increased to 74.1 (11-181). Compared with the pretreatment value this represents median rebound hypersecretion of 77% (p less than 0.05), caused by increased H+ concentration and volume of secretion. Overall median daytime intragastric pH (09:00-21:00 h) was unchanged on the final day of treatment and two days after completing therapy, compared with the pretreatment values. Fasting serum gastrin measured between 09:30 and 10:00 h and the integrated gastrin response to an OXO breakfast taken out at 10:00 h were also similar during and after treatment, compared with pretreatment values. The rebound nocturnal hypersecretion may be relevant to the high ulcer relapse rates after stopping H2 receptor antagonists.
Current Management of Brain Metastases, With a Focus on Systemic Options
Authors: Corey J. Langer, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2005)

Brain metastases are an important sequelae of many types of cancer, most commonly lung cancer. Current treatment options include whole-brain radiation therapy (WBRT), surgical resection, stereotactic radiosurgery, and chemotherapy. Corticosteroids and antiepileptic medications are commonly used for palliation of mass effect and seizures, respectively. The overall median survival is only 4 months after WBRT. Combined-modality strategies of WBRT with either chemotherapy or novel anticancer agents are under clinical investigation. Promising results have been obtained with several experimental agents and confirmatory phase III trials are underway. Although improvement in overall survival has not been seen universally, reduction in death due to progression of brain metastases and prolongation of the time to neurologic and neurocognitive progression have been reported in selected series. On the basis of these findings, it might be possible to identify new agents that may enhance the efficacy of WBRT.
Effect of Aortic Clamping Strategy on Postoperative Stroke in Coronary Artery Bypass Grafting Operations
Authors: Danny Chu, Lara Schaheen, Victor O. Morell, Thomas G. Gleason, Chris C. Cook, Lawrence M. Wei, Vinay Badhwar
Journal: JAMA Surgery (2015)

Aortic clamping technique has been implicated in stroke risk at the time of on-pump coronary artery bypass grafting (CABG) procedures. We hypothesized that partial aortic clamping (PAC) use in performing proximal coronary anastomosis does not increase risk of stroke.To determine whether postoperative stroke incidence is influenced by single aortic clamping (SAC) or side-biting PAC use in performing proximal anastomosis during CABG procedures.In a retrospective cohort study, we analyzed data from 1819 patients who underwent conventional, isolated, nonemergent, first-time, arrested-heart, on-pump CABG at a single US major academic, tertiary/quaternary medical center from January 1, 2005, to December 31, 2013. Postoperative stroke was defined according to Society of Thoracic Surgeons (STS) criteria as any confirmed neurological deficit of abrupt onset that did not resolve within 24 hours. Institutional STS data including STS predicted risk of postoperative stroke score were used to compare patients receiving proximal aortic anastomoses performed with either SAC (n = 1107) or combined PAC (n = 712) techniques.Use of SAC or PAC in performing proximal coronary anastomosis.Thirty-day periprocedural postoperative stroke rates.There were no significant differences in preoperative risk or STS predicted risk of mortality between groups. Patients in the SAC group had longer myocardial ischemic time compared with those in the PAC group (mean [SD], 73.2 [22.8] vs 66.5 [22.8] minutes, respectively; P < .001) but shorter overall perfusion time (mean [SD], 96.6 [30.1] vs 102.2 [30.1] minutes, respectively; P < .001). The 30-day observed mortality rates between the SAC and PAC groups were equally low (21 of 1107 patients [1.9%] vs 13 of 712 patients [1.8%], respectively; P > .99) and congruent with STS predicted risk of mortality. Preoperative STS predicted risk of postoperative stroke scores were nearly identical between the SAC and PAC groups (mean [SD], 1.5% [1.4%] vs 1.6% [1.4%]; P = .95), and the 30-day actual observed postoperative stroke rates between the SAC and PAC groups were similar (17 of 1107 patients [1.5%] vs 10 of 712 patients [1.4%], respectively; P > .99).In this contemporary study of on-pump CABG, we did not identify any significant differences in the incidence of postoperative stroke regardless of the clamping method used to perform proximal anastomosis.
Adult cutaneous Langerhans cell histiocytosis: remission with thalidomide treatment
Authors: L. Meunier, Y. Marck, C. Ribeyre, J. Meynadier
Journal: British Journal of Dermatology (1995)

Journal Article Adult cutaneous Langerhans cell histiocytosis: remission with thalidomide treatment Get access L. Meunier, L. Meunier Department of Dermatology, Hôpital St Charles, 300 rue Auguste Broussonnet, University of Montpellier, Montpellier, France Search for other works by this author on: Oxford Academic Google Scholar Y. Marck, Y. Marck Department of Dermatology, Hôpital St Charles, 300 rue Auguste Broussonnet, University of Montpellier, Montpellier, France Search for other works by this author on: Oxford Academic Google Scholar C. Ribeyre, C. Ribeyre Department of Dermatology, Hôpital St Charles, 300 rue Auguste Broussonnet, University of Montpellier, Montpellier, France Search for other works by this author on: Oxford Academic Google Scholar J. Meynadier J. Meynadier Department of Dermatology, Hôpital St Charles, 300 rue Auguste Broussonnet, University of Montpellier, Montpellier, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 1, 1 January 1995, Page 168, https://doi.org/10.1111/j.1365-2133.1995.tb08659.x Published: 01 January 1995
Unstable alpha‐chain hemoglobin variants with factitious beta‐thalassemia biosynthetic ratio: Hb questembert (α131[H14] Ser→Pro) and Hb Caen (α132[H15] Val→Gly)
Authors: H. Wajcman, C. Vasseur, Y. Blouquit, J. Rosa, D. Labie, A. Najman, O. Reman, M. Leporrier, F. Galacteros
Journal: American Journal of Hematology (1993)

Abstract Hb Questembert [α131(H14) Ser→Pro] was found in several members of a French family suffering from congenital Heinz body anemia. The unstable hemoglobin was expressed in the peripheral red blood cells at a very low level. Globin biosynthetic studies revealed a high specific activity of the abnormal chain and an α‐/β‐labeling ratio similar to that of β‐thalassemia trait. Hb Caen [α132(H15) Val→Gly] is another unstable variant with the same globin biosynthesis abnormality. In both cases the structural modification is localized at the end of the H helix, a region encoded by the third exon. The mechanism for the unbalanced globin synthesis is not yet clear. It may be related 1) to a defect in chain assembly, 2) to an increased rate of degradation of the variant chain followed by the release of unlabeled β‐chains from the abnormal hemoglobin, thus leading to an apparent suppression of β‐chain synthesis, or 3) to a modified stability of the abnormal α‐globin mRNA. © 1993 Wiley‐Liss, Inc.
P240 Assessing the Accuracy and Confidence of Chest X-Ray Reporting by Medical Doctors
Authors: IF Satia, S Bashagha, A Bibi, F Zaman, S Mellor
Journal: Thorax (2012)

<h3>Introduction</h3> The reporting of CXRs for medical patients admitted to hospital vary across Europe. Our local policy is that all admission x-rays are reported but this may not be available at the time of senior medical review on the assessment unit. Comparison between physicians and radiology reporting has suggested radiologists provide improved quality (1) and accuracy (2) of reporting. There are no current curriculum competencies for trainees nor is CXR reporting formally assessed in undergraduate or post-graduate examinations. <h3>Aim</h3> To assess the accuracy and confidence of CXR reporting by all grades within the medical division for common chest diagnoses presenting to the medical assessment unit. <h3>Method</h3> 10 CXRs were presented to all grades within the medical division with a short clinical history and one digital CXR. Doctors were asked to give a pre-test confidence (out of 5) in reporting CXRs and then also give individual confidence levels for each of their CXR diagnoses. <h3>Results</h3> A total of 138 doctors completed the CXR quiz with average results and 95% confidence intervals shown in figure 1. The least well answered CXR diagnoses were left lower lobe collapse (38%), emphysema (45%), and mediastinal widening (57%). When correlated with average % confidence for each diagnosis, doctors were on average over-confident in the incorrect CXRs they answered; left lower lobe collapse (64%), emphysema (62%), bilateral pneumothoraces (74%). Interestingly, for the correct diagnosis, the average confidence for diagnosing effusions, TB and pneumonia were much less. <h3>Conclusion</h3> SPRs and Consultants scored the highest marks with the highest average confidence levels. Junior trainees felt least confident about making their diagnosis and were less likely to be correct. We recommend that SPRs and consultants must review all the CXRs requested to ensure accuracy of diagnosis. There also needs to be discussion with the JRCPTB and educationalist about including CXR competency as part of a trainee’s generic curriculum on the e-portfolio, something which is currently lacking. <h3>References</h3> Weiner SN. Radiology by non-radiologists: is report documentation adequate? Am J Manag Care. 2005 Dec; 11(12). Zohair Al Aseri. Accuracy of chest radiograph interpretation by emergency physicians. Emergency Radiology, 2009; 16(2).
A sensor at the lipid‐protein interface: Lipid peroxidation controls hepatitis C virus replication
Authors: David Paul, Ralf Bartenschlager
Journal: Hepatology (2014)

1Department of Infectious DiseasesMolecular Virology, University of HeidelbergHeidelbergGermany 2Division of Virus‐Associated CarcinogenesisGerman Cancer Research Center (DKFZ)HeidelbergGermany
Dose-intensive cyclophosphamide with etoposide and vincristine for pediatric solid tumors: a phase I/II pilot study by the Australia and New Zealand Childhood Cancer Study Group.
Authors: L White, G McCowage, G Kannourakis, V Nayanar, L Colnan, S Kellie, P Shaw, R Seshadri, L Lockwood, K Tiedemann
Journal: Journal of Clinical Oncology (1994)

PURPOSE This pilot study of the Australia and New Zealand Childhood Cancer Study Group investigated the effectiveness and toxicity of a regimen incorporating vincristine (VCR), etoposide, and divided-dose, escalating cyclophosphamide (CPA) (VETOPEC) in 23 patients aged 1 to 20 years with solid tumors. PATIENTS AND METHODS Seventeen patients (group A) had recurrent or refractory tumors after prior multiagent therapy, and six patients (group B) with adverse prognostic indicators were treated at initial presentation. Treatment cycles were 21 to 28 days and consisted of vincristine (0.05 mg/kg) on days 1 and 14, with etoposide (2.5 mg/kg/d) plus escalating CPA on days 1, 2, and 3. The CPA dosage was escalated from 30 mg/kg/d in cycle no. 1 by 5 mg/kg/d in each cycle to a maximum of 55 mg/kg/d in cycle no. 6. RESULTS Of 20 patients assessable for tumor response, 19 (95%) responded after two to six cycles of VETOPEC: seven complete responses (CRs); eight very good partial responses (VGPRs); and four partial responses (PRs). In group A, 13 of 14 (93%) assessable patients responded (five CRs, four VGPRs, four PRs), and in group B, five stage IV and one stage III patient achieved two CRs and four VGPRs. The principal toxicity was myelosuppression. Grade IV neutropenia occurred after 98% of cycles, and the incidence of grade IV thrombocytopenia increased from 37% after cycle no. 1 to 91% after cycle no. 6 (P = .002). A total of 115 cycles delivered were followed by 62 febrile admissions (54%), and showed a significant rise with increasing cycles (P = .001). One patient died of septicemia. CONCLUSION This combination and scheduling produced a high response rate in patients with recurrent, refractory, or advanced solid tumors of childhood. Further studies of this regimen and of strategies to reduce hematologic toxicity are warranted.
Remarks on a Method of Fixing the Bones in the Operation of Excision of the Knee-Joint
Authors: W. M. Baker
Journal: BMJ (1887)

THE BRITlSH MEUDICAL OUBNAL.32gj tion of the growth, if its nature is simple, or it may even suffice, as in Case v. to draiv it away, when small, and secure it with a stitch, so that it will rot pAss between the joint-surfaces and interfere with th-ir Itree movements.1 n the American Mfedical Record for JlTne 26th, 1886, there is an initeresting paper on this subj-ct by Dr. R. F. Weir.Dr. Weir records two cases of his own and one of his colleaguie, Dr. Bull, in which tuuiours were removed froua the knee-joint.In one case, the tumour was composed of " vancalar connective tissue, rich in fat and connective-tissuie cells."In the secondl case, the growth was a "fibro-sircoma," andl in the thirdl the growth was a "giant-celled sarcoma."Weir also refers to other cases published by.Simon, Volkmasan, K6nio, and Lanenstein.Barwell (International Encyclopedica of Sargery) mentions that he removed two fatty growths from the knee, one being situa.tedupon each side of the ligamentum patellme.He expresses the opinion that some of these growths are formed in the subsynoviAl tissue, andl gradually bulge into the joint.VolkinauL, under the term " lipouna arborescens articulorum," has de- scribed a condition of multiple fatty growths having their origin in connection with tho fringes of synovial membrane.III. Crotwth from.the Bone protrtuding into the Joint.CAsnF visi.
TRANYLCYPROMINE (PARNATE) IN THE AMBULATORY TREATMENT OF DEPRESSED PATIENTS
Authors: MAX L. LURIE, HARRY M. SALZER
Journal: American Journal of Psychiatry (1961)

Tranylcypromine is a safe and potent mono-amine oxidase inhibitor which, when used in combination with sedatives, produced improvement in 74% of 84 ambulatory depressed patients of both psychotic and psychoneurotic types. The onset of benefit was rapid, occurring within an average of 7-9 days. The improvement was more rapid and more dramatic when the drug was combined with trifluoperazine. The incidence of significant side effects was low. No case of blood dyscrasia or jaundice occurred in our series. Some of these cases have been followed for over one year and have had no relapse.
New, emerging roles for cardiac connexins. Mitochondrial Cx43 raises new questions
Authors: S DHEIN
Journal: Cardiovascular Research (2005)

See also article by Boengler et al.  [9]  (pages 234–244) in this issue .

Connexins are protein subunits that constitute the gap junction channel, a dodecameric channel connecting two neighbouring cells formed by two hexameric hemichannels provided by either cell. The gap junction channel permits intercellular communication by allowing the propagation of the action potential and the transfer of small molecules such as cAMP. Six different gap junctional proteins (connexins; Cx) have been identified in the cardiovascular system: Cx31.9, Cx37, Cx40, Cx43, Cx45, Cx46, Cx50, and Cx57 (the molecular mass in kDa is given by the number) [1,2]. In the heart, there are mainly three isoforms that differ in their molecular weight: connexin 43 (a 43-kDa connexin; Cx43), which is found in most parts of the heart; connexin 40 (Cx40), which is mainly expressed in atria and in the conduction system; and connexin 45 (Cx45), which is expressed predominantly in embryonic stages and has been identified in parts of the ventricular conduction system of mice and rats [3]. Moreover, Cx45 was shown to be expressed in co-cultures of neonatal rat cardiomyocytes with fibroblasts [4] and is involved in myocyte/fibroblast coupling in the sinoatrial node [5]. Cx50 has been found in valvular tissue of the rat heart [6].

Connexins have four transmembrane regions, one intracellular and two extracellular loops, and intracellular N- and C-terminal tails. The length of the C-terminus differs among the various isoforms and is subject to phosphorylation by a number of kinases (for review, see Ref. [2]). Connexins are synthesized in the rough endoplasmic reticulum, folded, and transported to the Golgi apparatus … 

*Tel.: +49 341 865 1551; fax: +49 341 865 1421. Email address: dhes{at}medizin.uni-leipzig.de
Squamous metaplasia without atypia
Authors: Shuko Ishida, Masaaki Masuhara, Kazuo Mizumoto, Shingo Yamagata, Nobuyuki Takahashi, Yutaka Ishibashi, Kazutaka Kurokohchi
Journal: Endoscopy (2015)

An 89-year-old man presented with a 1-month history of anemia. The results of a physical examination were normal. Diagnostic gastrointestinal endoscopy showed advanced atrophic gastritis, multiple ulcer scars, and a whitish, slightly depressed lesion 15 mm in size in the lesser curvature of the antrum ([Fig. 1]). Squamous metaplasia without atypia was diagnosed based on examination of the specimen obtained from the depressed lesion ([Fig. 2]).
The Open Microscopy Environment (OME) Data Model and XML file: open tools for informatics and quantitative analysis in biological imaging.
Authors: Ilya G Goldberg, Chris Allan, Jean-Marie Burel, Doug Creager, Andrea Falconi, Harry Hochheiser, Josiah Johnston, Jeff Mellen, Peter K Sorger, Jason R Swedlow
Journal: Genome biology (2005)

The Open Microscopy Environment (OME) defines a data model and a software implementation to serve as an informatics framework for imaging in biological microscopy experiments, including representation of acquisition parameters, annotations and image analysis results. OME is designed to support high-content cell-based screening as well as traditional image analysis applications. The OME Data Model, expressed in Extensible Markup Language (XML) and realized in a traditional database, is both extensible and self-describing, allowing it to meet emerging imaging and analysis needs.