Use of Hydroxycarbamide Causes a Significant Increase in Haemoglobin Biology Ques

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Here is what I need to write about out of the article. The article is attached below. Please make sure all the instruction are followed from the article.

2) Read through your article’s Introduction and Discussion sections first to understand the overall study.
3) Read through the first data figure and write up a section ON THE FIRST DATA FIGURE ONLY for the following items IN YOUR OWN WORDS: NO QUOTES ALLOWED!
a) What was the hypothesis of the figure (NOT overall article)?
b) What question(s) did they ask to address the hypothesis in the figure (NOT overall article)?
c) What did the study do in this figure (NOT overall article)?
d) How did they do it in this figure (NOT overall article)?
e) What did they find in this figure (NOT overall article)?
f) What did it mean in this figure (NOT overall article)?
4) Spell and grammar check your work.

(20 pts) Including parts a-f in above “writing up the assignment”
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research paper The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia John Brewin,1 Sanjay Tewari,1 Stephan Menzel,1 Fenella Kirkham,2,3 Baba 4 Inusa, George Renney,5 Malcolm Ward5 and David C. Rees1 1 Red Cell Biology Unit, King’s College Hospital, King’s College London, 2 Developmental Neurosciences and Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, London, 3Clinical and Experimental Sciences, University of Southampton, Southampton, 4Paediatric Haematology, Evelina Children’s Hospital,Guy’s and St Thomas’ Hospital, London and 5Proteomics Laboratory, Institute of Psychiatry, King’s College London, UK Received 21 January 2019; accepted for publication 10 April 2019 Correspondence: David Rees, Department of Haematological Medicine, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. E-mail: david.rees2@nhs.net Summary We investigated changes in the plasma proteome of children with sickle cell anaemia (SCA) associated with hydroxycarbamide (HC) use, to further characterize the actions of HC. Fifty-one children with SCA consented to take part in this study. Eighteen were taking HC at a median dose of 22 mg/kg, and 33 were not on HC. Plasma was analysed using an unbiased proteomic approach and a panel of 92 neurological biomarkers. HC was associated with increased haemoglobin (Hb) (898 vs. 814 g/l, P = 0007) and HbF (67 vs. 153%, P < 0001). Seventeen proteins were decreased on HC compared to controls by a factor of 13 increased concentration. HC use was associated with reduced haemolysis (lower a, b, d globin chains, haptoglobin-related protein, complement C9; higher haemopexin), reduced inflammation (lower a-1-acid glycoprotein, CD5 antigen-like protein, ceruloplasmin, factor XII, immunoglobulins, cysteine-rich secretory protein 3, vitamin D-binding protein) and decreased activation of coagulation (lower factor XII, carboxypeptidase B2, platelet basic protein). There was a significant correlation between the increase in HbF% on HC and haemopexin levels (r = 0603, P = 0023). This study demonstrated three ways in which HC may be beneficial in SCA, and identified novel proteins that may be useful to monitor therapeutic response. Keywords: sickle cell anaemia, hydroxycarbamide, proteomics. Introduction The most prevalent and severe type of sickle cell disease is caused by homozygosity for the sickle mutation (HBB; c.20A>T, p.Glu7Val), and referred to as sickle cell anaemia (SCA). It is one of the commonest severe inherited disorders in the world, and is associated with unpredictable acute complications, progressive organ damage and shortened life expectancy (Brousse et al, 2014). Although outcomes have improved significantly in high-income countries over the last 40 years, there are still very few treatments available, with hydroxycarbamide (HC) continuing to be the only drug which has convincingly been shown to modify the natural history of the condition and prevent potential organ damage (McGann & Ware, 2015). Randomized controlled trials have shown that HC reduces the frequency of acute pain and acute chest syndrome (Charache et al, 1995; Wang et al, 2011), reduces the need for blood transfusion (Charache et al, 1995), reduces the risk of ª 2019 British Society for Haematology and John Wiley & Sons Ltd British Journal of Haematology, 2019, 186, 879–886 infection and malaria in some settings (Tshilolo et al, 2018), and is effective as part of the management of abnormal transcranial Doppler (TCD) velocities (Ware et al, 2016). Uncontrolled studies also suggest that HC increases oxygen saturations (Singh et al, 2008), decreases albuminuria (Tehseen et al, 2017) and may increase life expectancy in adults (Steinberg et al, 2003). In the USA and UK it is recommended that HC is offered to all children with SCA (Yawn et al, 2014; Qureshi et al, 2018), and approximately 80% children take it in some large centres in the USA; in Europe practice varies widely, but HC is offered to most symptomatic children. The main mechanism of action of HC is to increase haemoglobin F (HbF) production, which decreases the rate of HbS polymerization, with subsequent improvement in many downstream pathologies, including reductions in vaso-occlusion, inflammation, anaemia and haemolysis (Ware, 2010). HC has some other actions beyond the b-globin locus, including reducing white cell numbers, decreasing expression First published online 29 May 2019 doi: 10.1111/bjh.15996 J. Brewin et al of adhesion molecules on the vascular endothelium and possibly improving nitric oxide metabolism (Rees, 2011), although it is unclear how much these contribute to its therapeutic actions. In a mouse model of sickle cell disease in which HC caused no increase in HbF levels, there was no evidence of improvement in clinical or laboratory parameters (Lebensburger et al, 2010). Another important unanswered question involves variability in the therapeutic response to HC. It is unclear why some patients appear not to respond as well as others. Some of this may be related to drug adherence, although all studies show a variable response. In the HUSTLE study, the HbF level varied from 162–278% after one year in patients achieving the maximum tolerated dose (Estepp et al, 2017); some of this variability is related to baseline HbF levels, although analysis of data from the HUG-KIDS study showed that this explained only about 18% of the HbF response (Ware et al, 2002). Previous studies have measured the effects of HC on selected biomarkers, such as indicators of inflammation (Penkert et al, 2018) or vasculopathy (Lapoumeroulie et al, 2005), but we have adopted an unbiased proteomic approach to identify changes in plasma protein levels associated with HC use. We hypothesized that there would be significant differences in the plasma proteome between children with SCD taking and not taking HC, and that these differences would shed light on the mechanism of action of HC and may identify novel biomarkers associated with response to HC. Methods Patients and setting The data were collected as part of a study of silent cerebral infarcts (SCIs), funded by the Stroke Association (Grant TSA 2012/06) (Tewari et al, 2018). The study was approved by the UK National Research Ethics Committee (reference 13/ LO/0709) and all patients/parents gave written consent. Children with SCA were recruited from clinics at King’s College Hospital and the Evelina Children’s Hospital, London. The aim was to recruit 50 patients, with approximately equal numbers of those with SCIs and controls with normal brain magnetic resonance imaging (MRI) scans. Children already known to have SCIs from previous MRI scans were selectively recruited and eligible patients without previous MRIs were recruited sequentially as they attended clinic. Children taking HC were recruited to both arms and had been on a stable dose of HC for at least 6 months. Inclusion criteria were: sickle cell anaemia (HbSS), age 8–18 years old, normal or conditional TCD velocities (13-fold higher concentrations in children taking HC. It is difficult to know the significance of increased levels of a-1B-glycoprotein and a2-macroglobulin: a-1B-glycoprotein is an immunoglobulinlike protein of unknown function and a-2-macroglobulin is a multi-functional proteinase inhibitor, which has been found at 881 J. Brewin et al Table I. Comparison of laboratory and clinical measurements of those taking hydroxycarbamide with those who were not Controls Age (years) Hb (g/l) MCV (fl) HbF (%) HbF (g/l) Neutrophil count (3109/l) Reticulocyte count (3109/l) Bilirubin AST LDH Hydroxycarbamide n Mean SD n Mean SD P value 33 33 33 33 33 33 33 33 33 32 116 814 832 67 55 50 389 427 598 601 383 729 743 414 36 150 922 163 245 141 18 18 18 18 18 18 18 18 18 18 124 898 943 153 141 38 227 389 517 505 250 1085 1370 802 818 181 891 194 219 113 034 0007 0004
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correctedThat was supposed to be full citation

1

Write Up Assignment

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2

Write Up Assignment
a)What was the hypothesis of the figure (NOT the overall article)?
The use of hydroxycarbamide causes a significant increase in haemoglobin F in sickle cell
anaemia patients.
b) What question(s) did they ask to address the hypothesis in the figure (NOT the overall
article)?
To address the hypothesis, the following questions were asked; The age of the patient? Is the
patient on hydroxycarbamide?
c) What did the study do in this figure (NOT the overall article)?
The figure's study was comparing both clinical and...


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