%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Jungnam Lee, Ivan Arisi, Ermanno Puxeddu, Lazarus K. Mramba, Massimo Amicosante, Carmen M. Swaisgood, Marco Pallante, Mark L. Brantly, C. Magnus Sköld, Cesare Saltini
Bronchoalveolar lavage (BAL) cells in idiopathic pulmonary fibrosis express a complex pro-inflammatory, pro-repair, angiogenic activation pattern, likely associated with macrophage iron accumulation
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 13 0 R/Contents 14 0 R/TrimBox[0 0 612 792]>>
endobj
13 0 obj
[15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R]
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref001)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref002)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref003)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref005)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref004)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref006)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref003)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref007)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref008)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref009)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref010)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref010)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref011)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref010)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref012)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref013)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref014)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref015)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref016)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref009)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref013)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref017)>>
endobj
37 0 obj
<>/Border[0 0 0]/A 38 0 R>>
endobj
38 0 obj
<>
endobj
14 0 obj
[39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R]
endobj
39 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
575.9997 680.2299 m
199.9998 680.2299 l
199.9998 680.73 l
575.9997 680.73 l
f*
0.83 0.64 0.02 0 k
436.5921 556.5543 m
441.2976 556.5543 l
h
f*
278.1354 530.5323 m
282.8409 530.5323 l
h
f*
449.2913 439.5402 m
454.0535 439.5402 l
h
f*
459.2693 439.5402 m
464.0315 439.5402 l
h
f*
456.548 413.5181 m
461.3102 413.5181 l
h
f*
465.789 413.5181 m
470.5512 413.5181 l
h
f*
468.9638 374.5134 m
473.726 374.5134 l
h
f*
387.1559 348.548 m
391.9181 348.548 l
h
f*
323.1496 296.5606 m
327.9118 296.5606 l
h
f*
416.2394 244.5165 m
421.0016 244.5165 l
h
f*
203.4142 231.5339 m
212.9386 231.5339 l
h
f*
288.9071 231.5339 m
298.4315 231.5339 l
h
f*
302.8535 231.5339 m
312.378 231.5339 l
h
f*
470.4945 231.5339 m
480.0189 231.5339 l
h
f*
484.4976 231.5339 m
493.9654 231.5339 l
h
f*
498.4441 231.5339 m
507.9685 231.5339 l
h
f*
282.9543 179.5465 m
292.4787 179.5465 l
h
f*
410.5134 179.5465 m
420.0378 179.5465 l
h
f*
519.2504 179.5465 m
528.7748 179.5465 l
h
f*
525.3732 166.5638 m
530.1354 166.5638 l
h
f*
535.3512 166.5638 m
544.8189 166.5638 l
h
f*
549.2976 166.5638 m
558.822 166.5638 l
h
f*
0 g
1 j
1 J
9.5 0 0 9.5 200.0125 707.7543 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(complex)Tj
3.9028 0 Td
(activation)Tj
4.3922 0 Td
(pattern,)Tj
3.5806 0 Td
(suggesting)Tj
4.9949 0 Td
(that)Tj
1.8739 0 Td
(iron)Tj
1.8619 0 Td
(accumulation)Tj
6.0392 0 Td
(may)Tj
2.1006 0 Td
(play)Tj
2.029 0 Td
(a)Tj
0.7639 0 Td
(role)Tj
1.8619 0 Td
(in)Tj
0.9847 0 Td
(macro-)Tj
-34.3856 -1.474 Td
(phage)Tj
2.9599 0 Td
(activation.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 626.6267 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 609.6188 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Idiopathic)Tj
4.3256 0 Td
(pulmonary)Tj
4.6488 0 Td
(fibrosis)Tj
3.1521 0 Td
(\(IPF\),)Tj
2.5512 0 Td
(a)Tj
0.6519 0 Td
(progressive)Tj
4.7452 0 Td
(interstitial)Tj
4.2973 0 Td
(pneumonia)Tj
4.8132 0 Td
(of)Tj
1.0148 0 Td
(unknown)Tj
4.0818 0 Td
(cause)Tj
-34.2819 -1.2982 Td
(disproportionately)Tj
7.6421 0 Td
(affecting)Tj
3.6567 0 Td
(older)Tj
2.296 0 Td
(adults,)Tj
2.8403 0 Td
(is)Tj
0.8504 0 Td
(defined)Tj
3.2258 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4684 0 Td
(histopathological)Tj
7.0582 0 Td
(pattern)Tj
3.1067 0 Td
(of)Tj
1.0205 0 Td
(usual)Tj
-34.3443 -1.3039 Td
(interstitial)Tj
4.2972 0 Td
(pneumonia)Tj
4.8132 0 Td
(\(UIP\))Tj
2.5399 0 Td
(that)Tj
1.7744 0 Td
(is)Tj
0.8504 0 Td
(characterized)Tj
5.5559 0 Td
(by)Tj
1.1849 0 Td
(patchy)Tj
2.8743 0 Td
(distribution)Tj
4.9663 0 Td
(of)Tj
1.0148 0 Td
(fibrosis)Tj
3.1521 0 Td
(areas)Tj
2.245 0 Td
(with)Tj
-35.2684 -1.2983 Td
(peripheral)Tj
4.3199 0 Td
(honeycombing)Tj
6.2192 0 Td
(and)Tj
1.7291 0 Td
(scattered)Tj
3.7814 0 Td
(fibroblastic)Tj
4.6942 0 Td
(foci)Tj
1.7064 0 Td
(resulting)Tj
3.7304 0 Td
(from)Tj
2.2053 0 Td
(microscopic)Tj
5.108 0 Td
(centers)Tj
3.0671 0 Td
(of)Tj
-36.561 -1.2983 Td
(acute)Tj
2.3243 0 Td
(alveolar)Tj
3.3392 0 Td
(epithelium)Tj
4.5354 0 Td
(injury)Tj
2.6476 0 Td
(of)Tj
1.0148 0 Td
(yet)Tj
1.3946 0 Td
(unrecognized)Tj
5.6693 0 Td
(cause)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(].)Tj
-22.1214 -1.3039 Td
(The)Tj
1.7858 0 Td
(role)Tj
1.7688 0 Td
(of)Tj
1.0148 0 Td
(alveolar)Tj
3.3335 0 Td
(macrophage-driven)Tj
8.09 0 Td
(lung)Tj
2.0069 0 Td
(inflammation)Tj
5.6977 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(pathogenesis)Tj
5.3517 0 Td
(of)Tj
1.0148 0 Td
(IPF)Tj
1.6498 0 Td
(has)Tj
-35.4158 -1.2982 Td
(been)Tj
2.1203 0 Td
(long)Tj
1.9899 0 Td
(debated)Tj
3.3618 0 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(].)Tj
1.5988 0 Td
(A)Tj
0.907 0 Td
(number)Tj
3.4129 0 Td
(of)Tj
1.0148 0 Td
(bronchoalveolar)Tj
6.7294 0 Td
(lavage)Tj
2.6816 0 Td
(\(BAL\))Tj
2.6986 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.0579 0 Td
(evaluated)Tj
-31.5607 -1.2983 Td
(human)Tj
3.0784 0 Td
(alveolar)Tj
3.3335 0 Td
(macrophage)Tj
5.142 0 Td
(activation)Tj
4.1556 0 Td
(in)Tj
1.0374 0 Td
(IPF)Tj
1.6441 0 Td
(using)Tj
2.3924 0 Td
(immunochemistry,)Tj
7.8803 0 Td
(immunocytochemis-)Tj
-28.6637 -1.3039 Td
(try,)Tj
1.5703 0 Td
(proteomics,)Tj
4.938 0 Td
(RT-PCR)Tj
3.651 0 Td
(or)Tj
1.0941 0 Td
(RNA)Tj
2.2621 0 Td
(microarrays)Tj
5.0343 0 Td
(to)Tj
1.0261 0 Td
(assess)Tj
2.5228 0 Td
(the)Tj
1.4683 0 Td
(production)Tj
4.7169 0 Td
(of)Tj
1.0148 0 Td
(cytokines)Tj
3.9968 0 Td
(and)Tj
1.7348 0 Td
(che-)Tj
-35.0303 -1.2983 Td
(mokines)Tj
3.6396 0 Td
(with)Tj
2.0013 0 Td
(pro-inflammatory)Tj
7.455 0 Td
(or)Tj
1.0942 0 Td
(pro-repair/fibrogenic)Tj
8.7477 0 Td
(activities.)Tj
3.9401 0 Td
(These)Tj
2.5682 0 Td
(studies)Tj
2.9877 0 Td
(reported)Tj
3.6623 0 Td
(the)Tj
-36.0961 -1.2983 Td
(expression)Tj
4.4617 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(chemokines)Tj
5.0173 0 Td
(appertaining)Tj
5.3121 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(classic)Tj
3.5206 0 Td
(M1)Tj
1.5874 0 Td
(pro-inflammatory)Tj
-28.4993 -1.2982 Td
(activation)Tj
4.1498 0 Td
(phenotype,)Tj
4.6658 0 Td
(as)Tj
1.0148 0 Td
(MIP-1)Tj
/F12 1 Tf
()Tj
/F8 1 Tf
3.4073 0 Td
(\(CCL3\),)Tj
3.4639 0 Td
(MIP-1)Tj
/F12 1 Tf
()Tj
/F8 1 Tf
3.3278 0 Td
(\(CCL4\),)Tj
3.4639 0 Td
(MIP-3)Tj
/F12 1 Tf
()Tj
/F8 1 Tf
(/LARC)Tj
6.2419 0 Td
(\(CCL20\))Tj
3.719 0 Td
(or)Tj
1.0942 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
-35.5745 -1.3039 Td
(alternative)Tj
5.2043 0 Td
(M2)Tj
1.5874 0 Td
(anti-inflammatory,)Tj
7.8293 0 Td
(pro-fibrotic)Tj
4.8982 0 Td
(activation)Tj
4.1499 0 Td
(phenotype)Tj
4.439 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(MCP-1)Tj
3.1634 0 Td
(\(CCL2\),)Tj
-33.7547 -1.2983 Td
(MCP-4)Tj
3.1577 0 Td
(\(CCL13\),)Tj
3.9458 0 Td
(MIP-4/PARC)Tj
5.692 0 Td
(\(CCL18\),)Tj
3.9458 0 Td
(Eotaxin-2)Tj
4.1328 0 Td
(\(CCL24\))Tj
3.7134 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(].)Tj
2.5965 0 Td
(In)Tj
1.1112 0 Td
(addition,)Tj
3.8211 0 Td
(other)Tj
2.3471 0 Td
(studies)Tj
-34.4634 -1.2983 Td
(reported)Tj
3.6566 0 Td
(the)Tj
1.474 0 Td
(production)Tj
4.7112 0 Td
(of)Tj
1.0148 0 Td
(pro-inflammatory/)Tj
7.5684 0 Td
(angiogenic)Tj
4.5695 0 Td
(chemokines,)Tj
5.244 0 Td
(including)Tj
4.0365 0 Td
(GRO)Tj
/F12 1 Tf
()Tj
/F8 1 Tf
-32.275 -1.3039 Td
(\(CXCL1\),)Tj
4.1158 0 Td
(ENA78)Tj
3.1635 0 Td
(\(CXCL5\),)Tj
4.1159 0 Td
(PPBP)Tj
2.4774 0 Td
(\(CXCL7\))Tj
3.8948 0 Td
(and)Tj
1.7291 0 Td
(IL-8)Tj
1.9276 0 Td
(\(CXCL8\))Tj
3.8891 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(6)Tj
0 g
(].)Tj
1.2586 0 Td
(In)Tj
1.1112 0 Td
(particular,)Tj
4.3369 0 Td
(Schupp)Tj
-33.2841 -1.2982 Td
(and)Tj
1.7291 0 Td
(colleagues)Tj
4.2803 0 Td
(reported)Tj
3.6566 0 Td
(the)Tj
1.4684 0 Td
(production)Tj
4.7168 0 Td
(of)Tj
1.0148 0 Td
(anti-inflammatory/pro-fib)Tj
10.5278 0 Td
(rogenic)Tj
3.2258 0 Td
(chemokines)Tj
-30.6196 -1.2983 Td
(CCL2,)Tj
2.7836 0 Td
(CCL17,)Tj
3.2598 0 Td
(CCL18)Tj
3.0387 0 Td
(and)Tj
1.7291 0 Td
(CCL22,)Tj
3.2598 0 Td
(concomitantly)Tj
5.9981 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.474 0 Td
(pro-inflammatory)Tj
7.4551 0 Td
(chemokines)Tj
-30.9938 -1.3039 Td
(CXCL1)Tj
3.2144 0 Td
(and)Tj
1.7291 0 Td
(IL-8)Tj
1.9219 0 Td
(by)Tj
1.1849 0 Td
(BAL)Tj
2.0182 0 Td
(alveolar)Tj
3.3392 0 Td
(macrophage)Tj
5.1421 0 Td
(in)Tj
1.0374 0 Td
(IPF)Tj
1.6441 0 Td
(exacerbation)Tj
5.3234 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
-25.3585 -1.2983 Td
(Recent)Tj
2.9593 0 Td
(studies)Tj
2.9877 0 Td
(in)Tj
1.0375 0 Td
(murine)Tj
3.1748 0 Td
(models)Tj
3.1067 0 Td
(of)Tj
1.0148 0 Td
(pulmonary)Tj
4.6488 0 Td
(fibrosis)Tj
3.1464 0 Td
(have)Tj
2.0637 0 Td
(shown)Tj
2.8459 0 Td
(that)Tj
1.7802 0 Td
(alveolar)Tj
3.3335 0 Td
(macro-)Tj
-33.2955 -1.2983 Td
(phages)Tj
2.948 0 Td
(play)Tj
1.8708 0 Td
(a)Tj
0.652 0 Td
(key)Tj
1.5987 0 Td
(role)Tj
1.7688 0 Td
(in)Tj
1.0318 0 Td
(fibrosis)Tj
3.1521 0 Td
(pathogenesis)Tj
5.3518 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
1.6044 0 Td
(In)Tj
1.1055 0 Td
(particular,)Tj
4.337 0 Td
(Misharin)Tj
3.8891 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1282 0 Td
(showed)Tj
3.2485 0 Td
(that)Tj
-34.6278 -1.2982 Td
(both)Tj
2.0579 0 Td
(monocyte-derived)Tj
7.5514 0 Td
(alveolar)Tj
3.3336 0 Td
(macrophages)Tj
5.5048 0 Td
(and)Tj
1.7291 0 Td
(tissue-resident)Tj
6.0321 0 Td
(alveolar)Tj
3.3335 0 Td
(macrophages)Tj
5.5049 0 Td
(up-)Tj
-35.0473 -1.3039 Td
(regulated)Tj
3.9344 0 Td
(both)Tj
2.0636 0 Td
(M1)Tj
1.5874 0 Td
(and)Tj
1.7291 0 Td
(M2)Tj
1.5874 0 Td
(genes)Tj
2.4435 0 Td
(in)Tj
1.0375 0 Td
(response)Tj
3.7303 0 Td
(to)Tj
1.0262 0 Td
(bleomycin,)Tj
4.6431 0 Td
(with)Tj
1.9956 0 Td
(higher)Tj
2.8006 0 Td
(expression)Tj
4.4673 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(num-)Tj
-34.7128 -1.2983 Td
(ber)Tj
1.5193 0 Td
(of)Tj
1.0148 0 Td
(both)Tj
2.0636 0 Td
(M1)Tj
1.5874 0 Td
(and)Tj
1.7291 0 Td
(M2)Tj
1.5874 0 Td
(genes)Tj
2.4435 0 Td
(in)Tj
1.0318 0 Td
(monocyte-derived)Tj
7.5514 0 Td
(macrophages)Tj
5.5049 0 Td
(although)Tj
3.753 0 Td
(without)Tj
3.3279 0 Td
(a)Tj
0.6576 0 Td
(clear)Tj
-33.7717 -1.2983 Td
(shift)Tj
1.9615 0 Td
(toward)Tj
3.0444 0 Td
(either)Tj
2.5285 0 Td
(phenotype)Tj
4.439 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(].)Tj
-10.7772 -1.3039 Td
(Histopathological)Tj
7.2963 0 Td
(and)Tj
1.7291 0 Td
(BAL)Tj
2.0239 0 Td
(IPF)Tj
1.6441 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.0636 0 Td
(shown)Tj
2.846 0 Td
(that)Tj
1.7801 0 Td
(increased)Tj
3.9969 0 Td
(numbers)Tj
3.7814 0 Td
(of)Tj
1.0148 0 Td
(iron-laden)Tj
-32.3601 -1.2983 Td
(macrophages)Tj
5.5048 0 Td
(cluster)Tj
2.8686 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(alveolar)Tj
3.3391 0 Td
(and)Tj
1.7292 0 Td
(interstitial)Tj
4.2973 0 Td
(spaces)Tj
2.7439 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.6519 0 Td
(significant)Tj
4.388 0 Td
(proportion)Tj
4.6318 0 Td
(of)Tj
-33.698 -1.2982 Td
(affected)Tj
3.3278 0 Td
(individuals.)Tj
4.8699 0 Td
(In)Tj
1.1112 0 Td
(particular,)Tj
4.3369 0 Td
(alveolar)Tj
3.3336 0 Td
(macrophage)Tj
5.142 0 Td
(iron)Tj
1.9162 0 Td
(accumulation)Tj
5.6806 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.1203 0 Td
(described)Tj
-33.3805 -1.3039 Td
(in)Tj
1.0318 0 Td
(IPF,)Tj
1.8765 0 Td
(in)Tj
1.0318 0 Td
(association)Tj
4.6318 0 Td
(with)Tj
1.9955 0 Td
(increased)Tj
4.0025 0 Td
(capillary)Tj
3.6114 0 Td
(density)Tj
3.101 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(],)Tj
1.6044 0 Td
(pulmonary)Tj
4.6432 0 Td
(veno-occlusive)Tj
6.1398 0 Td
(disease)Tj
-33.6697 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(],)Tj
2.0749 0 Td
(microvasculitis,)Tj
6.4743 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(11)Tj
0 g
(])Tj
1.5137 0 Td
(and)Tj
1.7291 0 Td
(pulmonary)Tj
4.6488 0 Td
(arterial)Tj
3.0671 0 Td
(hypertension)Tj
5.4651 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(12)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(13)Tj
0 g
(].)Tj
1.7348 0 Td
(Iron)Tj
1.9899 0 Td
(accumu-)Tj
-33.5676 -1.2983 Td
(lation)Tj
2.5171 0 Td
(can)Tj
1.6271 0 Td
(drive)Tj
2.2677 0 Td
(macrophage)Tj
5.142 0 Td
(generation)Tj
4.5071 0 Td
(of)Tj
1.0147 0 Td
(reactive)Tj
3.3166 0 Td
(oxygen)Tj
3.084 0 Td
(species)Tj
2.9934 0 Td
(\(ROS\))Tj
2.7439 0 Td
(and)Tj
1.7348 0 Td
(a)Tj
0.652 0 Td
(pro-inflamma-)Tj
-31.6004 -1.3039 Td
(tory)Tj
1.8481 0 Td
(activation)Tj
4.1556 0 Td
(that)Tj
1.7745 0 Td
(persists,)Tj
3.4072 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(presence)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(concomitant)Tj
5.295 0 Td
(expression)Tj
4.4674 0 Td
(of)Tj
1.0148 0 Td
(anti-inflammatory/)Tj
-29.1966 -1.2982 Td
(pro-repair)Tj
4.3483 0 Td
(cytokines,)Tj
4.2292 0 Td
(leading)Tj
3.1295 0 Td
(to)Tj
1.0261 0 Td
(unrestrained,)Tj
6.3326 0 Td
(non-resolving)Tj
5.8166 0 Td
(inflammation,)Tj
5.9244 0 Td
(as)Tj
1.0148 0 Td
(shown)Tj
2.8516 0 Td
(in)Tj
1.0318 0 Td
(vari-)Tj
-35.7049 -1.2983 Td
(cose)Tj
1.9332 0 Td
(vein)Tj
1.9162 0 Td
(skin)Tj
1.8935 0 Td
(ulcer)Tj
2.211 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(],)Tj
2.075 0 Td
(haemophilia)Tj
5.193 0 Td
(hemarthrosis)Tj
5.4878 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(])Tj
1.8539 0 Td
(and)Tj
1.7291 0 Td
(spinal)Tj
2.5909 0 Td
(cord)Tj
2.0522 0 Td
(injury)Tj
2.6476 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(])Tj
1.8482 0 Td
(studies.)Tj
-32.2354 -1.2983 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(context)Tj
3.1861 0 Td
(and)Tj
1.7291 0 Td
(with)Tj
2.0013 0 Td
(the)Tj
1.4683 0 Td
(background)Tj
5.0286 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(above)Tj
2.5455 0 Td
(IPF)Tj
1.644 0 Td
(macrophage)Tj
5.1477 0 Td
(studies)Tj
2.9821 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(13)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
2.7325 0 Td
(17)Tj
0 g
(],)Tj
-34.9282 -1.3039 Td
(the)Tj
1.4683 0 Td
(present)Tj
3.1634 0 Td
(study)Tj
2.3925 0 Td
(was)Tj
1.6951 0 Td
(designed)Tj
3.7644 0 Td
(to)Tj
1.0261 0 Td
(explore)Tj
3.1748 0 Td
(the)Tj
1.4683 0 Td
(activation)Tj
4.1556 0 Td
(phenotype)Tj
4.4333 0 Td
(of)Tj
1.0148 0 Td
(BAL)Tj
2.0239 0 Td
(macrophages)Tj
5.5049 0 Td
(in)Tj
-35.2854 -1.2983 Td
(IPF)Tj
1.644 0 Td
(and)Tj
1.7292 0 Td
(its)Tj
1.1508 0 Td
(possible)Tj
3.4072 0 Td
(relation)Tj
3.3166 0 Td
(to)Tj
1.0261 0 Td
(iron)Tj
1.9105 0 Td
(accumulation.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 112.9889 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 95.9811 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Sixteen)Tj
3.118 0 Td
(patients)Tj
3.3732 0 Td
(\(all)Tj
1.4854 0 Td
(Caucasians,)Tj
4.8982 0 Td
(4)Tj
0.6973 0 Td
(females\))Tj
3.5547 0 Td
(diagnosed)Tj
4.2803 0 Td
(according)Tj
4.1895 0 Td
(to)Tj
1.0262 0 Td
(international)Tj
5.4084 0 Td
(guidelines)Tj
4.2803 0 Td
(by)Tj
-36.3115 -1.2982 Td
(multidisciplinary)Tj
7.0638 0 Td
(discussion)Tj
4.371 0 Td
(\(MDD\).)Tj
3.4923 0 Td
(HRCT)Tj
2.88 0 Td
(scans)Tj
2.3527 0 Td
(were)Tj
2.1203 0 Td
(evaluated)Tj
3.9912 0 Td
(systematically)Tj
5.7429 0 Td
(according)Tj
4.1839 0 Td
(to)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 401.4425 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(BAL)Tj
2.0834 0 Td
(macropha)Tj
4.3725 0 Td
(ge)Tj
1.311 0 Td
(complex)Tj
3.8835 0 Td
(activation)Tj
4.3654 0 Td
(pattern)Tj
3.2812 0 Td
(in)Tj
0.9779 0 Td
(IPF)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01948)Tj
4.089 0 Td
(03)Tj
0 g
2.0906 0 Td
(April)Tj
2.1827 0 Td
(12,)Tj
1.5874 0 Td
(2018)Tj
35.1357 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(15)Tj
/F10 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(#603191)Tj
3.5362 0 Td
(\(I.A.\).)Tj
2.289 0 Td
(The)Tj
1.5874 0 Td
(funders)Tj
3.0402 0 Td
(had)Tj
1.5945 0 Td
(no)Tj
1.1622 0 Td
(role)Tj
1.6158 0 Td
(in)Tj
0.8858 0 Td
(study)Tj
-15.7111 -1.3748 Td
(design,)Tj
2.8984 0 Td
(data)Tj
1.7929 0 Td
(collection)Tj
3.7418 0 Td
(and)Tj
1.5874 0 Td
(analysis,)Tj
3.4087 0 Td
(decision)Tj
3.2953 0 Td
(to)Tj
-16.7245 -1.3749 Td
(publish,)Tj
3.1464 0 Td
(or)Tj
0.9993 0 Td
(preparation)Tj
4.4433 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F9 1 Tf
-10.9063 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F10 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
endstream
endobj
51 0 obj
<>stream
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
endstream
endobj
54 0 obj
<>stream
endstream
endobj
55 0 obj
<>stream
endstream
endobj
56 0 obj
<>stream
endstream
endobj
57 0 obj
<>stream
endstream
endobj
58 0 obj
<>stream
BT
10.3394 77.8399 Td
(exist.)Tj
ET
Q
endstream
endobj
59 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 63 0 R/Contents 64 0 R/TrimBox[0 0 612 792]>>
endobj
63 0 obj
[65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R]
endobj
65 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref001)>>
endobj
66 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref018)>>
endobj
67 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref019)>>
endobj
68 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref020)>>
endobj
69 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref017)>>
endobj
70 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref017)>>
endobj
71 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref021)>>
endobj
72 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.t001)>>
endobj
73 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref017)>>
endobj
74 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref022)>>
endobj
75 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref023)>>
endobj
76 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref023)>>
endobj
77 0 obj
<>/Border[0 0 0]/A 78 0 R>>
endobj
78 0 obj
<>
endobj
64 0 obj
[79 0 R 80 0 R 81 0 R 82 0 R 83 0 R 84 0 R 85 0 R 86 0 R 87 0 R 88 0 R 89 0 R]
endobj
79 0 obj
<>stream
q
0.83 0.64 0.02 0 k
346.7906 706.337 m
351.5528 706.337 l
h
f*
533.4803 680.315 m
542.948 680.315 l
h
f*
434.4378 641.3102 m
443.9622 641.3102 l
h
f*
266.0598 420.3213 m
275.5843 420.3213 l
h
f*
381.0331 420.3213 m
390.5575 420.3213 l
h
f*
404.8441 394.2992 m
414.3685 394.2992 l
h
f*
418.7906 394.2992 m
428.315 394.2992 l
h
f*
229.8331 355.3512 m
258.9732 355.3512 l
h
f*
203.4142 251.3197 m
212.9386 251.3197 l
h
f*
559.1622 172.9134 m
568.6866 172.9134 l
h
f*
222.463 146.948 m
231.9874 146.948 l
h
f*
557.2346 146.948 m
566.7591 146.948 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(the)Tj
1.4683 0 Td
(ATS/ERS/JRS/ALAT)Tj
8.5889 0 Td
(guidelines)Tj
4.2803 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(],)Tj
1.5987 0 Td
(including)Tj
4.0422 0 Td
(multiplanar)Tj
4.9323 0 Td
(HRCT)Tj
2.8856 0 Td
(chest)Tj
2.2507 0 Td
(scans)Tj
2.3471 0 Td
(with)Tj
2.0012 0 Td
(stan-)Tj
-34.3953 -1.3039 Td
(dard)Tj
2.0806 0 Td
(and)Tj
1.7291 0 Td
(Minimum)Tj
4.3653 0 Td
(Intensity)Tj
3.7587 0 Td
(Projection)Tj
4.3824 0 Td
(algorithms)Tj
4.5184 0 Td
(for)Tj
1.3833 0 Td
(improved)Tj
4.1102 0 Td
(detection)Tj
3.9344 0 Td
(of)Tj
1.0148 0 Td
(ground-glass)Tj
-31.2772 -1.2982 Td
(opacities,)Tj
3.9401 0 Td
(linear)Tj
2.5115 0 Td
(attenuation)Tj
4.8075 0 Td
(and)Tj
1.7291 0 Td
(honeycombing)Tj
6.2192 0 Td
(patterns)Tj
3.4752 0 Td
(of)Tj
1.0148 0 Td
(traction)Tj
3.3676 0 Td
(bronchiectasis)Tj
5.9414 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
2.0749 0 Td
(At)Tj
1.2019 0 Td
(the)Tj
-36.2832 -1.2983 Td
(time)Tj
2.0295 0 Td
(of)Tj
1.0148 0 Td
(evaluation,)Tj
4.5865 0 Td
(14)Tj
1.1678 0 Td
(patients)Tj
3.3676 0 Td
(had)Tj
1.7121 0 Td
(HRCT)Tj
2.88 0 Td
(definite)Tj
3.2655 0 Td
(UIP)Tj
1.8538 0 Td
(pattern.)Tj
3.3392 0 Td
(Two)Tj
2.0239 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
1.9955 0 Td
(possible)Tj
-32.6038 -1.2983 Td
(UIP)Tj
1.8538 0 Td
(underwent)Tj
4.5751 0 Td
(lung)Tj
2.0069 0 Td
(biopsy)Tj
2.8346 0 Td
(with)Tj
1.9956 0 Td
(histologically)Tj
5.4708 0 Td
(probable)Tj
3.7361 0 Td
(UIP.)Tj
2.0806 0 Td
(The)Tj
1.7801 0 Td
(final)Tj
2.0013 0 Td
(MDD)Tj
2.5852 0 Td
(diagnosis)Tj
3.9628 0 Td
(was)Tj
-34.8829 -1.3039 Td
(IPF.)Tj
1.8708 0 Td
(The)Tj
1.7802 0 Td
(GAP)Tj
2.1826 0 Td
(index)Tj
2.4491 0 Td
(was)Tj
1.7008 0 Td
(calculated)Tj
4.2066 0 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0261 0 Td
(Ley)Tj
1.6385 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1225 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(]:)Tj
2.0806 0 Td
(4)Tj
0.6916 0 Td
(patients)Tj
3.3732 0 Td
(were)Tj
2.1203 0 Td
(stage)Tj
2.1997 0 Td
(I,)Tj
0.788 0 Td
(10)Tj
1.1679 0 Td
(stage)Tj
-35.5235 -1.2982 Td
(II)Tj
0.9014 0 Td
(and)Tj
1.7291 0 Td
(stage)Tj
2.1997 0 Td
(III.)Tj
1.4683 0 Td
(Eleven)Tj
2.8856 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(IPF)Tj
1.6441 0 Td
(affected)Tj
3.3278 0 Td
(individuals)Tj
4.6488 0 Td
(reported)Tj
3.6623 0 Td
(comorbidities)Tj
5.7657 0 Td
(\(average)Tj
3.5659 0 Td
(=)Tj
0.7994 0 Td
(2,)Tj
-35.0813 -1.2983 Td
(Min)Tj
1.9275 0 Td
(0,)Tj
0.9184 0 Td
(Max)Tj
2.0126 0 Td
(5\),)Tj
1.2642 0 Td
(including)Tj
4.0422 0 Td
(gastro)Tj
2.6532 0 Td
(esophageal)Tj
4.5581 0 Td
(reflux)Tj
2.5455 0 Td
(\(31.3%\),)Tj
3.532 0 Td
(arterial)Tj
3.067 0 Td
(hypertension)Tj
5.4709 0 Td
(\(56.3%\),)Tj
3.5319 0 Td
(pul-)Tj
-35.5235 -1.3039 Td
(monary)Tj
3.3561 0 Td
(arterial)Tj
3.0614 0 Td
(hypertension)Tj
5.4709 0 Td
(\(18.8%\),)Tj
3.5376 0 Td
(coronary)Tj
3.8324 0 Td
(artery)Tj
2.5739 0 Td
(disease)Tj
3.0217 0 Td
(\(6.2%\),)Tj
3.0557 0 Td
(arrhythmia)Tj
4.7282 0 Td
(\(6.3%\),)Tj
3.0557 0 Td
(dys-)Tj
-35.6936 -1.2983 Td
(lipidemia)Tj
3.9911 0 Td
(\(25%\),)Tj
2.829 0 Td
(diabetes)Tj
3.4639 0 Td
(type)Tj
1.9162 0 Td
(II)Tj
0.8957 0 Td
(\(12.5%\),)Tj
3.5376 0 Td
(hepatitis)Tj
3.6114 0 Td
(B)Tj
0.805 0 Td
(\(6.3%\),)Tj
3.0557 0 Td
(depression)Tj
4.5298 0 Td
(\(6.3%\),)Tj
3.0557 0 Td
(and)Tj
1.7348 0 Td
(enlarged)Tj
-33.4259 -1.2983 Td
(prostate)Tj
3.4298 0 Td
(\(12.5%\).)Tj
3.532 0 Td
(At)Tj
1.2075 0 Td
(the)Tj
1.4684 0 Td
(time)Tj
2.0296 0 Td
(of)Tj
1.0148 0 Td
(evaluation)Tj
4.3596 0 Td
(3)Tj
0.6974 0 Td
(patients)Tj
3.3675 0 Td
(were)Tj
2.1203 0 Td
(not)Tj
1.576 0 Td
(receiving)Tj
3.8608 0 Td
(any)Tj
1.6611 0 Td
(medications,)Tj
5.3234 0 Td
(2)Tj
-35.6482 -1.3039 Td
(were)Tj
2.1203 0 Td
(taking)Tj
2.7325 0 Td
(acetylsalicylic)Tj
5.6239 0 Td
(acid)Tj
1.8709 0 Td
(alone,)Tj
2.6022 0 Td
(and)Tj
1.7291 0 Td
(one)Tj
1.7008 0 Td
(N-acetyl)Tj
3.5886 0 Td
(cysteine)Tj
3.4186 0 Td
(alone.)Tj
2.6078 0 Td
(The)Tj
1.7802 0 Td
(other)Tj
2.3471 0 Td
(10)Tj
1.1735 0 Td
(patients)Tj
-33.2955 -1.2982 Td
(received)Tj
3.5319 0 Td
(different)Tj
3.6567 0 Td
(combination)Tj
5.3461 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(above)Tj
2.5455 0 Td
(drugs)Tj
2.4718 0 Td
(with)Tj
1.9955 0 Td
(proton)Tj
2.9707 0 Td
(pump)Tj
2.6022 0 Td
(inhibitors,)Tj
4.3654 0 Td
(statins)Tj
2.7892 0 Td
(and)Tj
-34.7638 -1.2983 Td
(anti-hypertensive)Tj
7.1886 0 Td
(drugs)Tj
2.4718 0 Td
(for)Tj
1.3889 0 Td
(a)Tj
0.652 0 Td
(total)Tj
2.0069 0 Td
(of)Tj
1.0148 0 Td
(7)Tj
0.6917 0 Td
(patients)Tj
3.3675 0 Td
(under)Tj
2.6192 0 Td
(proton)Tj
2.9707 0 Td
(pomp)Tj
2.5795 0 Td
(inhibitors)Tj
4.1442 0 Td
(therapy,)Tj
3.4696 0 Td
(6)Tj
-34.5654 -1.3039 Td
(under)Tj
2.6191 0 Td
(acetylsalicylic)Tj
5.6239 0 Td
(acid,)Tj
2.0977 0 Td
(6)Tj
0.6916 0 Td
(statins)Tj
2.7893 0 Td
(and)Tj
1.7291 0 Td
(anti-hypertensive)Tj
7.1943 0 Td
(drugs.)Tj
2.6986 0 Td
(No)Tj
1.4626 0 Td
(patient)Tj
3.0047 0 Td
(was)Tj
1.7008 0 Td
(under)Tj
2.6192 0 Td
(treat-)Tj
-34.2309 -1.2983 Td
(ment)Tj
2.3073 0 Td
(with)Tj
2.0013 0 Td
(immune-suppressants)Tj
9.0538 0 Td
(or)Tj
1.0998 0 Td
(antianticoagulants.)Tj
7.7896 0 Td
(Subjects)Tj
3.4922 0 Td
(were)Tj
2.1203 0 Td
(evaluated,)Tj
4.218 0 Td
(after)Tj
2.0352 0 Td
(written)Tj
-34.1175 -1.2982 Td
(informed)Tj
3.9741 0 Td
(consent)Tj
3.3279 0 Td
(was)Tj
1.7007 0 Td
(obtained)Tj
3.7304 0 Td
(\(Policlinico)Tj
4.8245 0 Td
(Tor)Tj
1.7065 0 Td
(Vergata)Tj
3.3448 0 Td
(Ethics)Tj
2.6646 0 Td
(Committee,)Tj
4.9663 0 Td
(Rome,)Tj
2.8176 0 Td
(Italy,)Tj
-33.0574 -1.2983 Td
(n.138/13\).)Tj
1.1962 -1.3039 Td
(Seven)Tj
2.5511 0 Td
(healthy)Tj
3.1295 0 Td
(controls)Tj
3.4809 0 Td
(\(all)Tj
1.491 0 Td
(Caucasian,)Tj
4.5354 0 Td
(4)Tj
0.6973 0 Td
(females\))Tj
3.5546 0 Td
(underwent)Tj
4.5751 0 Td
(fiberoptic)Tj
4.0876 0 Td
(bronchoscopy)Tj
-29.2987 -1.2983 Td
(\(FOB\))Tj
2.7552 0 Td
(and)Tj
1.7291 0 Td
(BAL)Tj
2.024 0 Td
(under)Tj
2.6135 0 Td
(an)Tj
1.2075 0 Td
(investigational)Tj
6.0378 0 Td
(protocol)Tj
3.6 0 Td
(\(Policlinico)Tj
4.8188 0 Td
(Tor)Tj
1.7122 0 Td
(Vergata)Tj
3.3391 0 Td
(Ethics)Tj
2.6703 0 Td
(Committee,)Tj
-32.5075 -1.2983 Td
(Rome,)Tj
2.8176 0 Td
(Italy:)Tj
2.2166 0 Td
(SCS/REDD/08)Tj
6.1115 0 Td
(n.123/08\))Tj
4.0365 0 Td
(after)Tj
2.0353 0 Td
(written)Tj
3.1124 0 Td
(informed)Tj
3.9741 0 Td
(consent.)Tj
-23.1078 -1.3039 Td
(BAL)Tj
2.0239 0 Td
(of)Tj
1.0148 0 Td
(controls)Tj
3.4809 0 Td
(and)Tj
1.7348 0 Td
(IPF)Tj
1.6441 0 Td
(patients)Tj
3.3675 0 Td
(was)Tj
1.7008 0 Td
(carried)Tj
3.0387 0 Td
(out)Tj
1.5534 0 Td
(using)Tj
2.3868 0 Td
(standard)Tj
3.7247 0 Td
(procedures,)Tj
4.8982 0 Td
(according)Tj
4.1896 0 Td
(to)Tj
-35.9544 -1.2982 Td
(ATS)Tj
1.9899 0 Td
(guidelines)Tj
4.2746 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(],)Tj
2.0806 0 Td
(as)Tj
1.0148 0 Td
(previously)Tj
4.3483 0 Td
(described)Tj
4.0535 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(].)Tj
2.075 0 Td
(Cell)Tj
1.8028 0 Td
(differentials)Tj
4.9606 0 Td
(were)Tj
2.126 0 Td
(counted)Tj
3.4752 0 Td
(on)Tj
1.2756 0 Td
(May-)Tj
-33.4769 -1.2983 Td
(Grunwald)Tj
4.2746 0 Td
(stained)Tj
3.0784 0 Td
(cytopreparations)Tj
6.9562 0 Td
(and)Tj
1.7291 0 Td
(iron)Tj
1.9162 0 Td
(macrophage)Tj
5.142 0 Td
(accumulation)Tj
5.6749 0 Td
(was)Tj
1.7008 0 Td
(assessed)Tj
3.4696 0 Td
(by)Tj
1.1849 0 Td
(Prus-)Tj
-35.1267 -1.3039 Td
(sian)Tj
1.8311 0 Td
(blue)Tj
1.9219 0 Td
(stain)Tj
2.1316 0 Td
(and)Tj
1.7292 0 Td
(scored)Tj
2.8346 0 Td
(according)Tj
4.1839 0 Td
(to)Tj
1.0261 0 Td
(Golde)Tj
2.6419 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
0.9014 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(21)Tj
0 g
(].)Tj
1.7348 0 Td
(All)Tj
1.4003 0 Td
(IPF)Tj
1.6441 0 Td
(patients)Tj
3.3675 0 Td
(included)Tj
3.7134 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
-34.7752 -1.2983 Td
(study)Tj
2.3867 0 Td
(had)Tj
1.7121 0 Td
(BAL)Tj
2.0183 0 Td
(macrophage)Tj
5.1477 0 Td
(differential)Tj
4.6034 0 Td
(counts)Tj
/F13 1 Tf
0 Tc
2.8856 0 Td
(>)Tj
/F8 1 Tf
-0.004 Tc
(80%,)Tj
2.9254 0 Td
(cell)Tj
1.559 0 Td
(viability,)Tj
3.6397 0 Td
(by)Tj
1.1849 0 Td
(trypan)Tj
2.8403 0 Td
(blue)Tj
1.9275 0 Td
(vital)Tj
1.9162 0 Td
(stain,)Tj
-34.7468 -1.2983 Td
(was)Tj
/F13 1 Tf
0 Tc
1.6951 0 Td
(>)Tj
/F8 1 Tf
-0.004 Tc
(95%;)Tj
2.9253 0 Td
(epithelial)Tj
3.8721 0 Td
(cells)Tj
1.9219 0 Td
(contamination)Tj
6.1228 0 Td
(was)Tj
/F13 1 Tf
0 Tc
1.6951 0 Td
(<)Tj
/F8 1 Tf
-0.004 Tc
(5%)Tj
2.228 0 Td
(and)Tj
1.7291 0 Td
(red)Tj
1.5421 0 Td
(blood)Tj
2.5171 0 Td
(cell)Tj
1.559 0 Td
(contamination)Tj
6.1228 0 Td
(was)Tj
1.6952 0 Td
(neg-)Tj
-35.6256 -1.2982 Td
(ligible)Tj
2.6418 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Table)Tj
2.7836 0 Td
(1)Tj
0 g
(\).)Tj
-4.2292 -1.3039 Td
(Generation)Tj
4.7565 0 Td
(of)Tj
1.0091 0 Td
(iron-dependent)Tj
6.5026 0 Td
(ROS)Tj
2.058 0 Td
(was)Tj
1.6951 0 Td
(measured)Tj
4.1045 0 Td
(by)Tj
1.1792 0 Td
(CM-H2DCFDA)Tj
6.7181 0 Td
(\(Invitrogen,)Tj
5.0059 0 Td
(Molecu-)Tj
-34.2252 -1.2983 Td
(lar)Tj
1.2699 0 Td
(Probes,)Tj
3.1747 0 Td
(Carlsbad,)Tj
3.9912 0 Td
(CA,)Tj
1.7915 0 Td
(USA\))Tj
2.4548 0 Td
(fluorescence)Tj
5.1873 0 Td
(on)Tj
1.2756 0 Td
(fresh,)Tj
2.4151 0 Td
(unstimulated)Tj
5.5049 0 Td
(BAL)Tj
2.0182 0 Td
(cells)Tj
1.9219 0 Td
(as)Tj
1.0148 0 Td
(spontane-)Tj
-32.0199 -1.2983 Td
(ously)Tj
2.313 0 Td
(generated)Tj
4.1386 0 Td
(fluorescence)Tj
5.1873 0 Td
(that)Tj
1.7802 0 Td
(could)Tj
2.4491 0 Td
(be)Tj
1.1509 0 Td
(inhibited)Tj
3.855 0 Td
(by)Tj
1.1793 0 Td
(the)Tj
1.4683 0 Td
(iron)Tj
1.9162 0 Td
(chelator)Tj
3.4526 0 Td
(deferiprone)Tj
4.8869 0 Td
(\(DFP,)Tj
-33.7774 -1.3039 Td
(Sigma)Tj
2.6815 0 Td
(Aldrich,)Tj
3.4923 0 Td
(St)Tj
0.9921 0 Td
(Louis,)Tj
2.6475 0 Td
(MO,)Tj
2.0863 0 Td
(USA\).)Tj
2.6816 0 Td
(BAL)Tj
2.0182 0 Td
(cells)Tj
1.9219 0 Td
(\(1x10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 407.5653 308.8629 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 411.137 304.3842 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5555 0 Td
(were)Tj
2.126 0 Td
(washed)Tj
3.1748 0 Td
(twice)Tj
2.3187 0 Td
(in)Tj
1.0375 0 Td
(PBS,)Tj
2.0579 0 Td
(and)Tj
1.7292 0 Td
(incu-)Tj
-34.1119 -1.2982 Td
(bated)Tj
2.4095 0 Td
(in)Tj
1.0374 0 Td
(RPMI)Tj
2.6306 0 Td
(without)Tj
3.3335 0 Td
(phenol)Tj
2.9877 0 Td
(red)Tj
1.542 0 Td
(\(Sigma)Tj
3.0218 0 Td
(Aldrich\))Tj
3.6113 0 Td
(in)Tj
1.0317 0 Td
(the)Tj
1.4683 0 Td
(dark)Tj
2.0523 0 Td
(for)Tj
1.3833 0 Td
(1)Tj
0.6973 0 Td
(hr)Tj
1.1225 0 Td
(\(37C,)Tj
2.7893 0 Td
(5%)Tj
1.4513 0 Td
(CO2\))Tj
2.4491 0 Td
(with/)Tj
-35.0189 -1.2983 Td
(out)Tj
1.5534 0 Td
(100)Tj
/F14 1 Tf
1.6441 0 Td
[()]TJ
/F8 1 Tf
(M)Tj
1.6214 0 Td
(DFP.)Tj
2.2677 0 Td
(CM-H2DCFDA)Tj
6.7181 0 Td
(\(5)Tj
1.0375 0 Td
(mM\))Tj
2.2677 0 Td
(was)Tj
1.7007 0 Td
(then)Tj
2.0183 0 Td
(added)Tj
2.6588 0 Td
(and)Tj
1.7348 0 Td
(fluorescence)Tj
5.1873 0 Td
(measured)Tj
4.1046 0 Td
(after)Tj
2.0352 0 Td
(1)Tj
-36.5496 -1.3039 Td
(h)Tj
0.7484 0 Td
(incubation)Tj
4.5467 0 Td
(\(LS50B)Tj
3.1068 0 Td
(LuminSpectrometer,)Tj
8.4982 0 Td
(Perkin)Tj
2.8856 0 Td
(Elmer,)Tj
2.8743 0 Td
(Waltham,)Tj
4.1725 0 Td
(MA,)Tj
2.024 0 Td
(USA\))Tj
2.4547 0 Td
(as)Tj
1.0148 0 Td
(described)Tj
-32.326 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(].)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 217.0204 cm
BT
/F15 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(RNA)Tj
2.3102 0 Td
(sequencing)Tj
4.8615 0 Td
(and)Tj
1.7905 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 200.0125 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Total)Tj
2.313 0 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.7008 0 Td
(obtained)Tj
3.7361 0 Td
(from)Tj
2.2053 0 Td
(un-fractionated)Tj
6.4686 0 Td
(BAL)Tj
2.0183 0 Td
(cells)Tj
1.9218 0 Td
(\(5x10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 448.611 204.4346 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(6)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 454.337 200.0125 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cells\),)Tj
2.4888 0 Td
(kept)Tj
1.9558 0 Td
(on)Tj
1.2756 0 Td
(ice)Tj
1.3323 0 Td
(until)Tj
2.109 0 Td
(RNA)Tj
-34.5937 -1.3039 Td
(extraction)Tj
4.2576 0 Td
(\(RNA/DNA/Protein)Tj
8.3905 0 Td
(Purification)Tj
4.9776 0 Td
(Kit,)Tj
1.6838 0 Td
(Norgen)Tj
3.2711 0 Td
(Biotech)Tj
3.2484 0 Td
(Corp.,)Tj
2.7326 0 Td
(Thorold,)Tj
3.7417 0 Td
(ON,)Tj
1.9275 0 Td
(Can-)Tj
-34.2308 -1.2982 Td
(ada\).)Tj
2.177 0 Td
(As)Tj
1.2699 0 Td
(previous)Tj
3.6453 0 Td
(studies)Tj
2.9877 0 Td
(showed)Tj
3.2542 0 Td
(generalized)Tj
4.7621 0 Td
(gene)Tj
2.0807 0 Td
(under-expression)Tj
7.2111 0 Td
(in)Tj
1.0375 0 Td
(IPF)Tj
1.6498 0 Td
(macrophages)Tj
5.5048 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(],)Tj
-35.5801 -1.2983 Td
(libraries)Tj
3.4696 0 Td
(were)Tj
2.1203 0 Td
(prepared)Tj
3.804 0 Td
(with)Tj
2.0013 0 Td
(the)Tj
1.4683 0 Td
(FFPE)Tj
2.4038 0 Td
(RNA-seq)Tj
3.9004 0 Td
(system)Tj
2.9424 0 Td
(\(NuGEN)Tj
3.8436 0 Td
(Technologies,)Tj
5.7543 0 Td
(San)Tj
1.6781 0 Td
(Carlos,)Tj
-33.3861 -1.2983 Td
(CA\))Tj
1.9048 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(],)Tj
2.0807 0 Td
(as)Tj
1.0148 0 Td
(recommended)Tj
6.032 0 Td
(for)Tj
1.389 0 Td
(clinical)Tj
3.0727 0 Td
(samples)Tj
3.3846 0 Td
(potentially)Tj
4.4617 0 Td
(affected)Tj
3.3277 0 Td
(by)Tj
1.1793 0 Td
(low)Tj
1.6554 0 Td
(RNA)Tj
2.262 0 Td
(integrity)Tj
3.617 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(].)Tj
-35.3817 -1.3039 Td
(The)Tj
1.7801 0 Td
(260/280)Tj
3.4016 0 Td
(nm)Tj
1.593 0 Td
(ratio)Tj
2.0977 0 Td
(was)Tj
1.6951 0 Td
(2.05)Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(0.05)Tj
4.0932 0 Td
(using)Tj
2.3924 0 Td
(NanoDrop)Tj
4.5751 0 Td
(\(Thermo)Tj
3.821 0 Td
(Scientific,)Tj
4.1272 0 Td
(Wilmington,)Tj
5.3801 0 Td
(DE,)Tj
-34.9565 -1.2982 Td
(USA\).)Tj
2.6815 0 Td
(Total)Tj
2.3131 0 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.7008 0 Td
(quantified)Tj
4.3086 0 Td
(using)Tj
2.3925 0 Td
(a)Tj
0.6519 0 Td
(Qubit)Tj
2.5682 0 Td
(RNA)Tj
2.262 0 Td
(High)Tj
2.245 0 Td
(Sensitivity)Tj
4.3369 0 Td
(Assay)Tj
2.5172 0 Td
(\(invitrogen,)Tj
4.9322 0 Td
(Ther-)Tj
-35.1719 -1.2983 Td
(moFisher)Tj
4.0251 0 Td
(Scientific,)Tj
4.1273 0 Td
(Waltham,)Tj
4.1725 0 Td
(MA,)Tj
2.0183 0 Td
(USA\))Tj
2.4548 0 Td
(and)Tj
1.7348 0 Td
(RNA)Tj
2.262 0 Td
(integrity)Tj
3.6113 0 Td
(number)Tj
3.4185 0 Td
(\(R.I.N.\))Tj
3.2768 0 Td
(was)Tj
1.6951 0 Td
(measured)Tj
-32.7965 -1.3039 Td
(using)Tj
2.3867 0 Td
(an)Tj
1.2019 0 Td
(Agilent)Tj
3.1578 0 Td
(2100)Tj
2.1203 0 Td
(Bioanalyzer)Tj
4.8982 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.474 0 Td
(Total)Tj
2.3131 0 Td
(RNA)Tj
2.262 0 Td
(pico)Tj
1.9389 0 Td
(kit)Tj
1.2812 0 Td
(\(Agilent)Tj
3.4922 0 Td
(Technologies,)Tj
5.7543 0 Td
(Santa)Tj
-34.2762 -1.2983 Td
(Clara,)Tj
2.5908 0 Td
(CA,)Tj
1.7972 0 Td
(USA\).)Tj
2.6815 0 Td
(RINs)Tj
2.2791 0 Td
(of)Tj
1.0148 0 Td
(controls)Tj
3.4809 0 Td
(and)Tj
1.7291 0 Td
(IPF)Tj
1.6498 0 Td
(patients)Tj
3.3675 0 Td
(were)Tj
2.1203 0 Td
(on)Tj
1.2756 0 Td
(average)Tj
3.2257 0 Td
(6.3)Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(2.55)Tj
3.617 0 Td
(and)Tj
1.7348 0 Td
(5.4)Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(2.02,)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 401.4425 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(BAL)Tj
2.0834 0 Td
(macropha)Tj
4.3725 0 Td
(ge)Tj
1.311 0 Td
(complex)Tj
3.8835 0 Td
(activation)Tj
4.3654 0 Td
(pattern)Tj
3.2812 0 Td
(in)Tj
0.9779 0 Td
(IPF)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01948)Tj
4.089 0 Td
(03)Tj
0 g
2.0906 0 Td
(April)Tj
2.1827 0 Td
(12,)Tj
1.5874 0 Td
(2018)Tj
35.1357 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
80 0 obj
<>stream
endstream
endobj
81 0 obj
<>stream
endstream
endobj
82 0 obj
<>stream
endstream
endobj
83 0 obj
<>stream
endstream
endobj
84 0 obj
<>stream
endstream
endobj
85 0 obj
<>stream
endstream
endobj
86 0 obj
<>stream
endstream
endobj
87 0 obj
<>stream
endstream
endobj
88 0 obj
<>stream
endstream
endobj
89 0 obj
<>stream
BT
66.402 0 Td
(15)Tj
ET
Q
endstream
endobj
90 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 92 0 R/Contents 93 0 R/TrimBox[0 0 612 792]>>
endobj
92 0 obj
[94 0 R 95 0 R 96 0 R 97 0 R 98 0 R 99 0 R]
endobj
94 0 obj
<>/Border[0 0 0]/A 100 0 R>>
endobj
100 0 obj
<>
endobj
95 0 obj
<>/Border[0 0 0]/A 101 0 R>>
endobj
101 0 obj
<>
endobj
96 0 obj
<>/Border[0 0 0]/Dest(Rpone.0194803.ref024)>>
endobj
97 0 obj
<>/Border[0 0 0]/Dest(Lpone.0194803.t001)>>
endobj
98 0 obj
<>/Border[0 0 0]/A 102 0 R>>
endobj
102 0 obj
<>
endobj
99 0 obj
<>/Border[0 0 0]/A 103 0 R>>
endobj
103 0 obj
<>
endobj
93 0 obj
[104 0 R 105 0 R 106 0 R]
endobj
104 0 obj
<>stream
q
0.83 0.64 0.02 0 k
470.0409 178.5827 m
575.5465 178.5827 l
h
f*
200.0126 165.6 m
351.2693 165.6 l
h
f*
420.6614 113.6126 m
430.1858 113.6126 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 426.6708 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(respectively.)Tj
5.1079 0 Td
(Libraries)Tj
3.7588 0 Td
(were)Tj
2.1259 0 Td
(prepared,)Tj
4.0309 0 Td
(as)Tj
1.0148 0 Td
(above,)Tj
2.7722 0 Td
(and)Tj
1.7292 0 Td
(fragmented)Tj
4.8188 0 Td
(to)Tj
1.0262 0 Td
(an)Tj
1.2018 0 Td
(average)Tj
3.2259 0 Td
(size)Tj
1.6837 0 Td
(of)Tj
1.0148 0 Td
(200)Tj
1.6498 0 Td
(bp)Tj
-35.1607 -1.2982 Td
(using)Tj
2.3867 0 Td
(the)Tj
1.4683 0 Td
(Covaris)Tj
3.2825 0 Td
(S2)Tj
1.1679 0 Td
(\(Covaris,)Tj
3.8438 0 Td
(Woburn,)Tj
3.8721 0 Td
(MA,)Tj
2.0239 0 Td
(USA\).)Tj
2.6815 0 Td
(Fragmented)Tj
5.0627 0 Td
(cDNA)Tj
2.7949 0 Td
(was)Tj
1.7008 0 Td
(end-repaired,)Tj
5.6353 0 Td
(A-)Tj
-35.9204 -1.3039 Td
(tailed)Tj
2.4151 0 Td
(and)Tj
1.7291 0 Td
(ligated)Tj
2.8856 0 Td
(with)Tj
1.9956 0 Td
(barcoded)Tj
3.9401 0 Td
(Illumina)Tj
3.651 0 Td
(adapters.)Tj
3.8098 0 Td
(Ligated)Tj
3.1748 0 Td
(DNA)Tj
2.381 0 Td
(was)Tj
1.6952 0 Td
(treated)Tj
2.999 0 Td
(with)Tj
1.9956 0 Td
(NuGEN)Tj
-32.6719 -1.2983 Td
(mouse)Tj
2.8573 0 Td
(Insert)Tj
2.5625 0 Td
(Dependent)Tj
4.6658 0 Td
(Adaptor)Tj
3.5602 0 Td
(Cleavage)Tj
3.7644 0 Td
(\(InDA-C\))Tj
4.2236 0 Td
(reagent)Tj
3.1862 0 Td
(to)Tj
1.0261 0 Td
(deplete)Tj
3.0784 0 Td
(cDNA)Tj
2.8006 0 Td
(corresponding)Tj
-31.7251 -1.2983 Td
(to)Tj
1.0261 0 Td
(ribosomal)Tj
4.2349 0 Td
(RNA,)Tj
2.4888 0 Td
(and)Tj
1.7291 0 Td
(PCR)Tj
2.0637 0 Td
(amplified.)Tj
4.2406 0 Td
(Final)Tj
2.2393 0 Td
(library)Tj
2.8743 0 Td
(yield)Tj
2.1373 0 Td
(was)Tj
1.7008 0 Td
(measured)Tj
4.1102 0 Td
(using)Tj
2.3868 0 Td
(the)Tj
1.4683 0 Td
(Qubit)Tj
-32.7002 -1.2982 Td
(High)Tj
2.245 0 Td
(Sensitivity)Tj
4.337 0 Td
(DNA)Tj
2.3754 0 Td
(assay)Tj
2.2677 0 Td
(\(Thermo)Tj
3.8211 0 Td
(Fisher)Tj
2.6985 0 Td
(Scientific\))Tj
4.2406 0 Td
(and)Tj
1.7291 0 Td
(library)Tj
2.8744 0 Td
(size)Tj
1.6837 0 Td
(assessed)Tj
3.4696 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
1.4684 0 Td
(Agi-)Tj
-35.6029 -1.3039 Td
(lent)Tj
1.7347 0 Td
(2100)Tj
2.126 0 Td
(Bioanalyzer)Tj
4.8982 0 Td
(\(Agilent)Tj
3.4923 0 Td
(Technologies,)Tj
5.7543 0 Td
(Santa)Tj
2.4094 0 Td
(Clara,)Tj
2.5966 0 Td
(CA,)Tj
1.7914 0 Td
(USA\).)Tj
2.6816 0 Td
(Libraries)Tj
3.7644 0 Td
(were)Tj
2.1203 0 Td
(then)Tj
-33.3692 -1.2983 Td
(pooled,)Tj
3.1747 0 Td
(and)Tj
1.7292 0 Td
(sequenced)Tj
4.3823 0 Td
(using)Tj
2.3924 0 Td
(single-end)Tj
4.3824 0 Td
(75)Tj
1.1678 0 Td
(bp)Tj
1.2473 0 Td
(reads)Tj
2.3357 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(Illumina)Tj
3.651 0 Td
(NextSeq500)Tj
4.9776 0 Td
(\(Illumina,)Tj
-32.1843 -1.2983 Td
(San)Tj
1.678 0 Td
(Diego)Tj
2.6192 0 Td
(CA,)Tj
1.7915 0 Td
(USA\).)Tj
2.6816 0 Td
(In)Tj
1.1112 0 Td
(average,)Tj
3.4469 0 Td
(82,247,297)Tj
/F14 1 Tf
4.4787 0 Td
[()]TJ
/F8 1 Tf
0.788 0 Td
(27,317,568)Tj
4.4787 0 Td
(reads)Tj
2.3358 0 Td
(were)Tj
2.1203 0 Td
(generated)Tj
4.1385 0 Td
(of)Tj
1.0148 0 Td
(which)Tj
-32.6832 -1.3039 Td
(69,860,529)Tj
/F14 1 Tf
4.473 0 Td
[()]TJ
/F8 1 Tf
0.7937 0 Td
(24,683,386)Tj
4.473 0 Td
(\(84.51)Tj
/F14 1 Tf
2.6873 0 Td
[()]TJ
/F8 1 Tf
0.788 0 Td
(1.58%\))Tj
2.9707 0 Td
(were)Tj
2.1259 0 Td
(uniquely)Tj
3.7191 0 Td
(aligned)Tj
3.1351 0 Td
(\(Cofactor)Tj
4.0478 0 Td
(Genomics,)Tj
4.5128 0 Td
(Saint)Tj
-33.7264 -1.2983 Td
(Louis,)Tj
2.6475 0 Td
(MO,)Tj
2.0806 0 Td
(USA\).)Tj
2.6816 0 Td
(Raw)Tj
1.9615 0 Td
(sequence)Tj
3.8551 0 Td
(data)Tj
1.9162 0 Td
(in)Tj
1.0375 0 Td
(FASTQ)Tj
3.2655 0 Td
(format)Tj
2.9367 0 Td
(were)Tj
2.1203 0 Td
(assessed)Tj
3.4752 0 Td
(for)Tj
1.3833 0 Td
(Per)Tj
1.5761 0 Td
(Base)Tj
2.0182 0 Td
(Sequence)Tj
-32.9553 -1.2982 Td
(Quality)Tj
3.1917 0 Td
(\(Phred)Tj
2.9707 0 Td
(average)Tj
3.2258 0 Td
(score)Tj
2.3074 0 Td
(=)Tj
0.7994 0 Td
(33,)Tj
1.3946 0 Td
(ribosomal)Tj
4.2406 0 Td
(RNA)Tj
2.2621 0 Td
(content)Tj
/F13 1 Tf
0 Tc
3.2711 0 Td
(<)Tj
/F8 1 Tf
-0.004 Tc
0.9921 0 Td
(2%\))Tj
1.7915 0 Td
(\(Cofactor)Tj
4.0535 0 Td
(Genomics,)Tj
4.5071 0 Td
(Saint)Tj
-35.0076 -1.3039 Td
(Louis,)Tj
2.6475 0 Td
(MO,)Tj
2.0806 0 Td
(USA\).)Tj
-3.5319 -1.2983 Td
(Raw)Tj
1.9615 0 Td
(read)Tj
1.9786 0 Td
(counts)Tj
2.8856 0 Td
(were)Tj
2.1203 0 Td
(mapped)Tj
3.4583 0 Td
(on)Tj
1.2756 0 Td
(UCSC)Tj
2.7609 0 Td
(mRNA)Tj
3.0841 0 Td
(transcript)Tj
4.1102 0 Td
(human)Tj
3.0784 0 Td
(database)Tj
3.634 0 Td
(based)Tj
2.4775 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
-35.2967 -1.2983 Td
(GRCh37/hg19)Tj
5.9697 0 Td
(version)Tj
3.1578 0 Td
(of)Tj
1.0147 0 Td
(the)Tj
1.4684 0 Td
(Genome)Tj
3.6567 0 Td
(Reference)Tj
4.1669 0 Td
(Consortium)Tj
5.0909 0 Td
(consensus)Tj
4.2803 0 Td
(representation)Tj
6.0151 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-35.8353 -1.2982 Td
(human)Tj
3.0784 0 Td
(genome)Tj
3.4072 0 Td
(using)Tj
2.3867 0 Td
(the)Tj
1.4684 0 Td
(NovoAlign)Tj
4.6374 0 Td
(tool.)Tj
2.0069 0 Td
(Raw)Tj
1.9559 0 Td
(counts)Tj
2.8857 0 Td
(per)Tj
1.5364 0 Td
(transcript)Tj
4.1102 0 Td
(were)Tj
2.1203 0 Td
(then)Tj
2.0182 0 Td
(aggregated)Tj
-31.6117 -1.3039 Td
(onto)Tj
2.0806 0 Td
(unique)Tj
3.0217 0 Td
(UCSC)Tj
2.7552 0 Td
(gene)Tj
2.0807 0 Td
(symbols)Tj
3.4809 0 Td
(\(26,605)Tj
3.1634 0 Td
(unique)Tj
3.0217 0 Td
(gene)Tj
2.0807 0 Td
(symbols\).)Tj
4.0421 0 Td
(Raw)Tj
1.9559 0 Td
(counts)Tj
2.8857 0 Td
(were)Tj
2.1259 0 Td
(filtered)Tj
3.0614 0 Td
(by)Tj
-35.7559 -1.2983 Td
(keeping)Tj
3.3618 0 Td
(only)Tj
1.9729 0 Td
(protein-coding)Tj
6.2475 0 Td
(genes)Tj
2.4378 0 Td
(satisfying)Tj
3.9685 0 Td
(the)Tj
1.4683 0 Td
(following)Tj
3.9799 0 Td
(condition:)Tj
4.3369 0 Td
(Counts)Tj
3.1295 0 Td
(Per)Tj
1.5703 0 Td
(Million)Tj
-32.4734 -1.2983 Td
(\(CPM\))Tj
/F13 1 Tf
0 Tc
3.016 0 Td
(>)Tj
/F8 1 Tf
-0.004 Tc
0.9921 0 Td
(1.0)Tj
1.3947 0 Td
(in)Tj
1.0374 0 Td
(at)Tj
0.9525 0 Td
(least)Tj
1.9785 0 Td
(4)Tj
0.6973 0 Td
(samples.)Tj
3.6057 0 Td
(The)Tj
1.7858 0 Td
(final)Tj
2.0013 0 Td
(data)Tj
1.9162 0 Td
(table)Tj
2.1259 0 Td
(comprised)Tj
4.4391 0 Td
(19,696)Tj
2.8233 0 Td
(gene)Tj
2.0806 0 Td
(symbols.)Tj
3.702 0 Td
(Data)Tj
-34.5484 -1.3039 Td
(are)Tj
1.4456 0 Td
(publicly)Tj
3.4129 0 Td
(available)Tj
3.668 0 Td
(from)Tj
2.2054 0 Td
(the)Tj
1.4683 0 Td
(Gene)Tj
2.3301 0 Td
(Expression)Tj
4.6091 0 Td
(Omnibus)Tj
4.0025 0 Td
(database,)Tj
0.83 0.64 0.02 0 k
3.8607 0 Td
(https://www.ncbi.nlm.)Tj
8.9801 0 Td
(nih.)Tj
-35.9827 -1.2983 Td
(gov/geo/query/acc.cgi?acc=GSE)Tj
12.7501 0 Td
(79544)Tj
0 g
(.)Tj
-11.5539 -1.2982 Td
(Normalization)Tj
6.0717 0 Td
(of)Tj
1.0148 0 Td
(RNA-sequences)Tj
6.6104 0 Td
(was)Tj
1.7008 0 Td
(obtained)Tj
3.7303 0 Td
(using)Tj
2.3925 0 Td
(the)Tj
1.4683 0 Td
(upper-quartile)Tj
6.0037 0 Td
(method)Tj
3.3222 0 Td
(provided)Tj
-33.5109 -1.3039 Td
(by)Tj
1.1792 0 Td
(EDASeq)Tj
3.6169 0 Td
(package)Tj
3.4129 0 Td
(in)Tj
1.0375 0 Td
(R)Tj
0.8391 0 Td
(Bioconductor,)Tj
5.9357 0 Td
(followed)Tj
3.651 0 Td
(by)Tj
1.1792 0 Td
(removing)Tj
4.0762 0 Td
(unwanted)Tj
4.2122 0 Td
(variation)Tj
3.8041 0 Td
(\(RUV\))Tj
-32.944 -1.2983 Td
(technique)Tj
4.1669 0 Td
(using)Tj
2.3867 0 Td
(RUVg)Tj
2.7383 0 Td
(function)Tj
3.6283 0 Td
(provided)Tj
3.8154 0 Td
(by)Tj
1.1849 0 Td
(R)Tj
0.839 0 Td
(Bioconductor)Tj
5.709 0 Td
(package)Tj
3.4128 0 Td
(RUVSeq,)Tj
3.9062 0 Td
(where)Tj
2.6475 0 Td
(a)Tj
0.6576 0 Td
(set)Tj
1.304 0 Td
(of)Tj
-36.3966 -1.2983 Td
(20)Tj
1.1678 0 Td
(house)Tj
2.5625 0 Td
(keeping)Tj
3.3562 0 Td
(genes)Tj
2.4378 0 Td
(were)Tj
2.1203 0 Td
(used)Tj
2.0579 0 Td
(as)Tj
1.0092 0 Td
(negative)Tj
3.5319 0 Td
(controls)Tj
3.4809 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
2.075 0 Td
(RUVg)Tj
2.7326 0 Td
(has)Tj
1.542 0 Td
(the)Tj
1.4627 0 Td
(potential)Tj
3.7587 0 Td
(to)Tj
1.0205 0 Td
(normal-)Tj
-34.316 -1.3039 Td
(ize)Tj
1.3209 0 Td
(RNA-sequences)Tj
6.6103 0 Td
(using)Tj
2.3925 0 Td
(housekeeping)Tj
5.7089 0 Td
(genes)Tj
2.4435 0 Td
(to)Tj
1.0204 0 Td
(successfully)Tj
4.8642 0 Td
(remove)Tj
3.2202 0 Td
(unwanted)Tj
4.2122 0 Td
(effects)Tj
2.7269 0 Td
(thereby)Tj
-34.52 -1.2983 Td
(producing)Tj
4.3653 0 Td
(an)Tj
1.1905 0 Td
(accurate)Tj
3.5433 0 Td
(evaluation)Tj
4.354 0 Td
(of)Tj
1.0035 0 Td
(gene)Tj
2.0692 0 Td
(differential)Tj
4.5921 0 Td
(expression.)Tj
4.6828 0 Td
(After)Tj
2.2734 0 Td
(removing)Tj
4.0705 0 Td
(the)Tj
1.457 0 Td
(unwanted)Tj
ET
Q
q
0.45 0.36 0.35 0.01 k
1 j
1 J
0 w
36 703.8893 m
576 703.8893 l
576 703.3893 l
36 703.3893 l
f*
204.6934 688.8892 m
36 688.8892 l
36 690.8893 l
204.6934 690.8893 l
f*
204.6934 703.3893 m
204.6934 690.8893 l
204.1934 690.8893 l
204.1934 703.3893 l
f*
204.1934 690.8893 m
36 690.8893 l
36 691.3894 l
204.1934 691.3894 l
f*
337.0808 688.8892 m
204.6934 688.8892 l
204.6934 690.8893 l
337.0808 690.8893 l
f*
337.0808 703.3893 m
337.0808 690.8893 l
336.5807 690.8893 l
336.5807 703.3893 l
f*
336.5807 690.8893 m
204.6934 690.8893 l
204.6934 691.3894 l
336.5807 691.3894 l
f*
465.7096 688.8892 m
337.0808 688.8892 l
337.0808 690.8893 l
465.7096 690.8893 l
f*
465.7096 703.3893 m
465.7096 690.8893 l
465.2096 690.8893 l
465.2096 703.3893 l
f*
465.2096 690.8893 m
337.0808 690.8893 l
337.0808 691.3894 l
465.2096 691.3894 l
f*
575.9994 688.8892 m
465.7096 688.8892 l
465.7096 690.8893 l
575.9994 690.8893 l
f*
575.9994 690.8893 m
465.7096 690.8893 l
465.7096 691.3894 l
575.9994 691.3894 l
f*
204.6934 688.8892 m
204.6934 676.3893 l
204.1934 676.3893 l
204.1934 688.8892 l
f*
204.1934 676.3893 m
36 676.3893 l
36 676.8893 l
204.1934 676.8893 l
f*
337.0808 688.8892 m
337.0808 676.3893 l
336.5807 676.3893 l
336.5807 688.8892 l
f*
336.5807 676.3893 m
204.6934 676.3893 l
204.6934 676.8893 l
336.5807 676.8893 l
f*
465.7096 688.8892 m
465.7096 676.3893 l
465.2096 676.3893 l
465.2096 688.8892 l
f*
465.2096 676.3893 m
337.0808 676.3893 l
337.0808 676.8893 l
465.2096 676.8893 l
f*
575.9994 676.3893 m
465.7096 676.3893 l
465.7096 676.8893 l
575.9994 676.8893 l
f*
204.6934 676.3893 m
204.6934 663.8893 l
204.1934 663.8893 l
204.1934 676.3893 l
f*
204.1934 663.8893 m
36 663.8893 l
36 664.3894 l
204.1934 664.3894 l
f*
337.0808 676.3893 m
337.0808 663.8893 l
336.5807 663.8893 l
336.5807 676.3893 l
f*
336.5807 663.8893 m
204.6934 663.8893 l
204.6934 664.3894 l
336.5807 664.3894 l
f*
465.7096 676.3893 m
465.7096 663.8893 l
465.2096 663.8893 l
465.2096 676.3893 l
f*
465.2096 663.8893 m
337.0808 663.8893 l
337.0808 664.3894 l
465.2096 664.3894 l
f*
575.9994 663.8893 m
465.7096 663.8893 l
465.7096 664.3894 l
575.9994 664.3894 l
f*
204.6934 663.8893 m
204.6934 651.3894 l
204.1934 651.3894 l
204.1934 663.8893 l
f*
204.1934 651.3894 m
36 651.3894 l
36 651.8894 l
204.1934 651.8894 l
f*
337.0808 663.8893 m
337.0808 651.3894 l
336.5807 651.3894 l
336.5807 663.8893 l
f*
336.5807 651.3894 m
204.6934 651.3894 l
204.6934 651.8894 l
336.5807 651.8894 l
f*
465.7096 663.8893 m
465.7096 651.3894 l
465.2096 651.3894 l
465.2096 663.8893 l
f*
465.2096 651.3894 m
337.0808 651.3894 l
337.0808 651.8894 l
465.2096 651.8894 l
f*
575.9994 651.3894 m
465.7096 651.3894 l
465.7096 651.8894 l
575.9994 651.8894 l
f*
204.6934 651.3894 m
204.6934 638.8894 l
204.1934 638.8894 l
204.1934 651.3894 l
f*
204.1934 638.8894 m
36 638.8894 l
36 639.3895 l
204.1934 639.3895 l
f*
337.0808 651.3894 m
337.0808 638.8894 l
336.5807 638.8894 l
336.5807 651.3894 l
f*
336.5807 638.8894 m
204.6934 638.8894 l
204.6934 639.3895 l
336.5807 639.3895 l
f*
465.7096 651.3894 m
465.7096 638.8894 l
465.2096 638.8894 l
465.2096 651.3894 l
f*
465.2096 638.8894 m
337.0808 638.8894 l
337.0808 639.3895 l
465.2096 639.3895 l
f*
575.9994 638.8894 m
465.7096 638.8894 l
465.7096 639.3895 l
575.9994 639.3895 l
f*
204.6934 638.8894 m
204.6934 626.3895 l
204.1934 626.3895 l
204.1934 638.8894 l
f*
204.1934 626.3895 m
36 626.3895 l
36 626.8895 l
204.1934 626.8895 l
f*
337.0808 638.8894 m
337.0808 626.3895 l
336.5807 626.3895 l
336.5807 638.8894 l
f*
336.5807 626.3895 m
204.6934 626.3895 l
204.6934 626.8895 l
336.5807 626.8895 l
f*
465.7096 638.8894 m
465.7096 626.3895 l
465.2096 626.3895 l
465.2096 638.8894 l
f*
465.2096 626.3895 m
337.0808 626.3895 l
337.0808 626.8895 l
465.2096 626.8895 l
f*
575.9994 626.3895 m
465.7096 626.3895 l
465.7096 626.8895 l
575.9994 626.8895 l
f*
204.6934 626.3895 m
204.6934 613.8896 l
204.1934 613.8896 l
204.1934 626.3895 l
f*
204.1934 613.8896 m
36 613.8896 l
36 614.3896 l
204.1934 614.3896 l
f*
337.0808 626.3895 m
337.0808 613.8896 l
336.5807 613.8896 l
336.5807 626.3895 l
f*
336.5807 613.8896 m
204.6934 613.8896 l
204.6934 614.3896 l
336.5807 614.3896 l
f*
465.7096 626.3895 m
465.7096 613.8896 l
465.2096 613.8896 l
465.2096 626.3895 l
f*
465.2096 613.8896 m
337.0808 613.8896 l
337.0808 614.3896 l
465.2096 614.3896 l
f*
575.9994 613.8896 m
465.7096 613.8896 l
465.7096 614.3896 l
575.9994 614.3896 l
f*
204.6934 613.8896 m
204.6934 601.3896 l
204.1934 601.3896 l
204.1934 613.8896 l
f*
204.1934 601.3896 m
36 601.3896 l
36 601.8897 l
204.1934 601.8897 l
f*
337.0808 613.8896 m
337.0808 601.3896 l
336.5807 601.3896 l
336.5807 613.8896 l
f*
336.5807 601.3896 m
204.6934 601.3896 l
204.6934 601.8897 l
336.5807 601.8897 l
f*
465.7096 613.8896 m
465.7096 601.3896 l
465.2096 601.3896 l
465.2096 613.8896 l
f*
465.2096 601.3896 m
337.0808 601.3896 l
337.0808 601.8897 l
465.2096 601.8897 l
f*
575.9994 601.3896 m
465.7096 601.3896 l
465.7096 601.8897 l
575.9994 601.8897 l
f*
204.6934 601.3896 m
204.6934 588.8897 l
204.1934 588.8897 l
204.1934 601.3896 l
f*
204.1934 588.8897 m
36 588.8897 l
36 589.3897 l
204.1934 589.3897 l
f*
337.0808 601.3896 m
337.0808 588.8897 l
336.5807 588.8897 l
336.5807 601.3896 l
f*
336.5807 588.8897 m
204.6934 588.8897 l
204.6934 589.3897 l
336.5807 589.3897 l
f*
465.7096 601.3896 m
465.7096 588.8897 l
465.2096 588.8897 l
465.2096 601.3896 l
f*
465.2096 588.8897 m
337.0808 588.8897 l
337.0808 589.3897 l
465.2096 589.3897 l
f*
575.9994 588.8897 m
465.7096 588.8897 l
465.7096 589.3897 l
575.9994 589.3897 l
f*
204.6934 588.8897 m
204.6934 576.3898 l
204.1934 576.3898 l
204.1934 588.8897 l
f*
204.1934 576.3898 m
36 576.3898 l
36 576.8898 l
204.1934 576.8898 l
f*
337.0808 588.8897 m
337.0808 576.3898 l
336.5807 576.3898 l
336.5807 588.8897 l
f*
336.5807 576.3898 m
204.6934 576.3898 l
204.6934 576.8898 l
336.5807 576.8898 l
f*
465.7096 588.8897 m
465.7096 576.3898 l
465.2096 576.3898 l
465.2096 588.8897 l
f*
465.2096 576.3898 m
337.0808 576.3898 l
337.0808 576.8898 l
465.2096 576.8898 l
f*
575.9994 576.3898 m
465.7096 576.3898 l
465.7096 576.8898 l
575.9994 576.8898 l
f*
204.6934 576.3898 m
204.6934 563.8898 l
204.1934 563.8898 l
204.1934 576.3898 l
f*
204.1934 563.8898 m
36 563.8898 l
36 564.3899 l
204.1934 564.3899 l
f*
337.0808 576.3898 m
337.0808 563.8898 l
336.5807 563.8898 l
336.5807 576.3898 l
f*
336.5807 563.8898 m
204.6934 563.8898 l
204.6934 564.3899 l
336.5807 564.3899 l
f*
465.7096 576.3898 m
465.7096 563.8898 l
465.2096 563.8898 l
465.2096 576.3898 l
f*
465.2096 563.8898 m
337.0808 563.8898 l
337.0808 564.3899 l
465.2096 564.3899 l
f*
575.9994 563.8898 m
465.7096 563.8898 l
465.7096 564.3899 l
575.9994 564.3899 l
f*
204.6934 563.8898 m
204.6934 551.3899 l
204.1934 551.3899 l
204.1934 563.8898 l
f*
204.1934 551.3899 m
36 551.3899 l
36 551.8899 l
204.1934 551.8899 l
f*
337.0808 563.8898 m
337.0808 551.3899 l
336.5807 551.3899 l
336.5807 563.8898 l
f*
336.5807 551.3899 m
204.6934 551.3899 l
204.6934 551.8899 l
336.5807 551.8899 l
f*
465.7096 563.8898 m
465.7096 551.3899 l
465.2096 551.3899 l
465.2096 563.8898 l
f*
465.2096 551.3899 m
337.0808 551.3899 l
337.0808 551.8899 l
465.2096 551.8899 l
f*
575.9994 551.3899 m
465.7096 551.3899 l
465.7096 551.8899 l
575.9994 551.8899 l
f*
204.6934 551.3899 m
204.6934 538.89 l
204.1934 538.89 l
204.1934 551.3899 l
f*
204.1934 538.89 m
36 538.89 l
36 539.39 l
204.1934 539.39 l
f*
337.0808 551.3899 m
337.0808 538.89 l
336.5807 538.89 l
336.5807 551.3899 l
f*
336.5807 538.89 m
204.6934 538.89 l
204.6934 539.39 l
336.5807 539.39 l
f*
465.7096 551.3899 m
465.7096 538.89 l
465.2096 538.89 l
465.2096 551.3899 l
f*
465.2096 538.89 m
337.0808 538.89 l
337.0808 539.39 l
465.2096 539.39 l
f*
575.9994 538.89 m
465.7096 538.89 l
465.7096 539.39 l
575.9994 539.39 l
f*
204.6934 538.89 m
204.6934 526.39 l
204.1934 526.39 l
204.1934 538.89 l
f*
204.1934 526.39 m
36 526.39 l
36 526.89 l
204.1934 526.89 l
f*
337.0808 538.89 m
337.0808 526.39 l
336.5807 526.39 l
336.5807 538.89 l
f*
336.5807 526.39 m
204.6934 526.39 l
204.6934 526.89 l
336.5807 526.89 l
f*
465.7096 538.89 m
465.7096 526.39 l
465.2096 526.39 l
465.2096 538.89 l
f*
465.2096 526.39 m
337.0808 526.39 l
337.0808 526.89 l
465.2096 526.89 l
f*
575.9994 526.39 m
465.7096 526.39 l
465.7096 526.89 l
575.9994 526.89 l
f*
575.9994 468.6401 m
36 468.6401 l
36 469.1401 l
575.9994 469.1401 l
f*
0.83 0.64 0.02 0 k
36 455.5843 m
186.7465 455.5843 l
h
f*
0 g
7.9999 0 0 7.9999 36 708.7181 cm
BT
/F15 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Table)Tj
2.5512 0 Td
(1.)Tj
1.1763 0 Td
(Study)Tj
2.6079 0 Td
(populati)Tj
3.5079 0 Td
(on)Tj
1.2898 0 Td
(characterist)Tj
4.8827 0 Td
(ics)Tj
1.304 0 Td
(of)Tj
1.063 0 Td
(IPF)Tj
1.7362 0 Td
(patients)Tj
3.5504 0 Td
(and)Tj
1.7859 0 Td
(controls)Tj
3.6142 0 Td
(undergoin)Tj
4.3158 0 Td
(g)Tj
0.7086 0 Td
(fiberopt)Tj
3.3591 0 Td
(ic)Tj
0.9284 0 Td
(bronchosc)Tj
4.2732 0 Td
(opy)Tj
1.7433 0 Td
(with)Tj
2.0693 0 Td
(BAL.)Tj
0 Tc
-25.1293 -1.8567 Td
(Control)Tj
ET
Q
q
1 j
1 J
0 w
5.5998 0 0 5.5998 233.1212 696.8125 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 339.0803 693.8645 cm
BT
/F15 1 Tf
1 TL
0 0 Td
(IPF)Tj
1.7574 0 Td
(patients)Tj
ET
Q
q
1 j
1 J
0 w
5.5998 0 0 5.5998 380.1259 696.8125 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 467.7165 693.8645 cm
BT
/F15 1 Tf
1 TL
0 0 Td
(Pvalue)Tj
/F8 1 Tf
-53.9649 -1.8071 Td
(N)Tj
21.4584 0 Td
(7)Tj
16.5545 0 Td
(16)Tj
-38.0129 -1.5661 Td
(Age)Tj
21.4584 0 Td
(46.9)Tj
1.8921 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(6.23\))Tj
14.6624 0 Td
(67)Tj
1.1834 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(8.62\))Tj
20.1615 0 Td
(0.001)Tj
-59.3578 -1.5591 Td
(Gender)Tj
3.2527 0 Td
(\(Male)Tj
2.5725 0 Td
()Tj
0.3898 0 Td
(Female\))Tj
15.2434 0 Td
(3)Tj
0.7087 0 Td
()Tj
0.3897 0 Td
(4)Tj
15.4561 0 Td
(12)Tj
1.1834 0 Td
()Tj
0.3827 0 Td
(4)Tj
19.7788 0 Td
(0.182)Tj
-59.3578 -1.5661 Td
(Current/Ex/N)Tj
5.6622 0 Td
(ever)Tj
1.9063 0 Td
(smokers)Tj
13.8899 0 Td
(6)Tj
0.7087 0 Td
()Tj
0.3897 0 Td
(0)Tj
0.7087 0 Td
()Tj
0.3827 0 Td
(1)Tj
14.3647 0 Td
(4)Tj
0.7086 0 Td
()Tj
0.3827 0 Td
(10)Tj
1.1835 0 Td
()Tj
0.3897 0 Td
(2)Tj
18.6804 0 Td
(1.000)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 527.9811 645.4488 cm
BT
/F8 1 Tf
1 TL
0 0 Td
($)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 36 629.4047 cm
BT
/F8 1 Tf
1 TL
0 0 Td
(Smoke)Tj
2.9622 0 Td
(history)Tj
3.0331 0 Td
(\(pack)Tj
2.452 0 Td
(years\))Tj
13.0111 0 Td
(19.3\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(13.06\))Tj
16.5544 0 Td
(21.2\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(1)Tj
3.0473 0 Td
(6.34\))Tj
18.2978 0 Td
(0.806)Tj
-59.3579 -1.5661 Td
(FVC)Tj
2.1189 0 Td
(\(%\))Tj
19.3395 0 Td
(115.05\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(16.72)Tj
5.6693 0 Td
(\))Tj
10.8851 0 Td
(80.6\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(2)Tj
3.0473 0 Td
(7\))Tj
18.2978 0 Td
(0.009)Tj
-59.3579 -1.5591 Td
(Dlco)Tj
2.1543 0 Td
(\(%\))Tj
19.3041 0 Td
(82.06\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(7.59\))Tj
16.5544 0 Td
(48.6\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(1)Tj
3.0473 0 Td
(6\))Tj
18.2978 0 Td
(0.001)Tj
-59.3579 -1.5661 Td
(BAL)Tj
2.0338 0 Td
(cell)Tj
1.5804 0 Td
(count)Tj
-2.615 -1.5591 Td
(Macropha)Tj
4.1173 0 Td
(ges)Tj
1.4882 0 Td
(\(%\))Tj
14.8537 0 Td
(83.4)Tj
1.8921 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(7.68\))Tj
14.6623 0 Td
(86.1)Tj
1.8922 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(3.84\))Tj
19.4529 0 Td
(0.671)Tj
-58.3587 -1.5661 Td
(Neutrophil)Tj
4.4433 0 Td
(s)Tj
0.5953 0 Td
(\(%\))Tj
15.4206 0 Td
(3.5)Tj
1.4173 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(0.90\))Tj
15.1371 0 Td
(7.3)Tj
1.4103 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(4.04\))Tj
19.9348 0 Td
(0.019)Tj
-58.3587 -1.5591 Td
(Lymphocy)Tj
4.252 0 Td
(tes)Tj
1.3252 0 Td
(\(%\))Tj
14.882 0 Td
(8.3)Tj
1.4173 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(8.31\))Tj
15.1371 0 Td
(3.0)Tj
1.4103 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(2.49\))Tj
19.9348 0 Td
(0.047)Tj
-58.3587 -1.5662 Td
(Eosinophi)Tj
4.089 0 Td
(ls)Tj
0.8433 0 Td
(\(%\))Tj
15.5269 0 Td
(1.2)Tj
1.4173 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(1.70\))Tj
15.1371 0 Td
(3.0)Tj
1.4103 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(1.87\))Tj
19.9348 0 Td
(0.026)Tj
-58.3587 -1.559 Td
(Basophi)Tj
3.2031 0 Td
(ls)Tj
0.8434 0 Td
(\(%\))Tj
16.4127 0 Td
(0.0)Tj
1.4173 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(0.00\))Tj
15.1371 0 Td
(0.0)Tj
1.4103 0 Td
(\()Tj
/F14 1 Tf
[()]TJ
/F8 1 Tf
(0.12\))Tj
19.9348 0 Td
(0.557)Tj
-59.3579 -2.3457 Td
(Definition)Tj
4.4008 0 Td
(of)Tj
1.0346 0 Td
(abbreviat)Tj
3.7134 0 Td
(ions:)Tj
2.1544 0 Td
(FVC)Tj
2.1189 0 Td
(=)Tj
0.815 0 Td
(Forced)Tj
3.0189 0 Td
(Vital)Tj
2.1827 0 Td
(Capacity,)Tj
3.9685 0 Td
(Dlco)Tj
2.1544 0 Td
(=)Tj
0.8078 0 Td
(Diffusing)Tj
3.9969 0 Td
(Capacity,)Tj
ET
Q
q
1 j
1 J
0 w
5.5998 0 0 5.5998 36 501.5622 cm
BT
/F16 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 39.2881 498.6141 cm
BT
/F8 1 Tf
1 TL
0 0 Td
(Data)Tj
2.1401 0 Td
(is)Tj
0.8646 0 Td
(expressed)Tj
4.1244 0 Td
(as)Tj
1.0276 0 Td
(mean)Tj
2.4662 0 Td
(and)Tj
1.7433 0 Td
(standard)Tj
3.7488 0 Td
(deviation)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 36 490.1669 cm
BT
/F8 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 38.948 486.6519 cm
BT
/F8 1 Tf
1 TL
0 0 Td
(Comparis)Tj
3.9543 0 Td
(ons)Tj
1.6512 0 Td
(between)Tj
3.5575 0 Td
(the)Tj
1.4811 0 Td
(groups)Tj
2.9977 0 Td
(were)Tj
2.1402 0 Td
(performe)Tj
3.7346 0 Td
(d)Tj
0.7583 0 Td
(by)Tj
1.1977 0 Td
(Mann-Whit)Tj
4.8472 0 Td
(ney)Tj
1.6654 0 Td
(test)Tj
1.6229 0 Td
(or)Tj
1.1126 0 Td
(Fisher's)Tj
3.3024 0 Td
(exact)Tj
2.2889 0 Td
(test)Tj
1.6158 0 Td
(for)Tj
1.4032 0 Td
(frequencies)Tj
ET
Q
q
1 j
1 J
0 w
5.9998 0 0 5.3325 36 478.2047 cm
BT
/F8 1 Tf
1 TL
0 0 Td
($)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 38.8913 474.633 cm
BT
/F8 1 Tf
1 TL
0 0 Td
(Curren)Tj
2.9126 0 Td
(t)Tj
0.5315 0 Td
(and)Tj
1.7504 0 Td
(ex-smokers)Tj
4.826 0 Td
(compared)Tj
4.2733 0 Td
(to)Tj
1.0417 0 Td
(never)Tj
2.4591 0 Td
(smokers)Tj
0.83 0.64 0.02 0 k
/F10 1 Tf
-0.025 Tc
-18.156 -2.2464 Td
(https://do)Tj
3.5574 0 Td
(i.org/10.1371/j)Tj
5.4426 0 Td
(ournal.pone)Tj
4.4079 0 Td
(.0194803.t001)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 401.4425 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(BAL)Tj
2.0834 0 Td
(macropha)Tj
4.3725 0 Td
(ge)Tj
1.311 0 Td
(complex)Tj
3.8835 0 Td
(activation)Tj
4.3654 0 Td
(pattern)Tj
3.2812 0 Td
(in)Tj
0.9779 0 Td
(IPF)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01948)Tj
4.089 0 Td
(03)Tj
0 g
2.0906 0 Td
(April)Tj
2.1827 0 Td
(12,)Tj
1.5874 0 Td
(2018)Tj
35.1357 0 Td
(4)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
105 0 obj
<>stream
endstream
endobj
106 0 obj
<>stream
BT
66.402 0 Td
(15)Tj
ET
Q
endstream
endobj
107 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 12 0 R/Annots 110 0 R/Contents 111 0 R/TrimBox[0 0 612 792]>>
endobj
109 0 obj
<>
endobj
112 0 obj
<>
endobj
113 0 obj
<>stream
%!PS-AdobeFont-1.0
11 dict begin
/FontName /PI_chars_3 def
/FontType 1 def
/FontBBox {-11 -345 1373 718} readonly def
/FontMatrix [0.001 0 0 0.001 0 0] readonly def
/PaintType 0 def
/FontInfo 8 dict dup begin
/FullName (PI_chars_3) readonly def
/BaseFontName (PI_chars_3) def
end def
/Encoding 256 array
0 1 255 {1 index exch /.notdef put} for
dup 33 /exclam put
dup 34 /quotedbl put
dup 35 /numbersign put
dup 36 /dollar put
dup 37 /percent put
dup 38 /ampersand put
dup 39 /quoteright put
dup 40 /parenleft put
dup 41 /parenright put
dup 42 /asterisk put
dup 43 /plus put
dup 44 /comma put
dup 45 /hyphen put
dup 46 /period put
dup 47 /slash put
dup 49 /one put
dup 50 /two put
dup 51 /three put
dup 52 /four put
dup 53 /five put
dup 54 /six put
dup 55 /seven put
dup 56 /eight put
dup 58 /colon put
dup 60 /less put
dup 61 /equal put
dup 62 /greater put
dup 63 /question put
dup 64 /at put
dup 65 /A put
dup 66 /B put
dup 67 /C put
dup 68 /D put
dup 69 /E put
dup 70 /F put
dup 71 /G put
dup 72 /H put
dup 73 /I put
dup 74 /J put
dup 75 /K put
dup 76 /L put
dup 77 /M put
dup 78 /N put
dup 79 /O put
dup 80 /P put
dup 81 /Q put
dup 82 /R put
dup 83 /S put
dup 84 /T put
dup 85 /U put
dup 86 /V put
dup 87 /W put
dup 88 /X put
dup 89 /Y put
dup 90 /Z put
dup 91 /bracketleft put
dup 92 /backslash put
dup 93 /bracketright put
dup 94 /asciicircum put
dup 97 /a put
dup 98 /b put
dup 99 /c put
dup 100 /d put
dup 101 /e put
dup 102 /f put
dup 103 /g put
dup 104 /h put
dup 105 /i put
dup 106 /j put
dup 107 /k put
dup 108 /l put
dup 109 /m put
dup 110 /n put
dup 111 /o put
dup 112 /p put
dup 113 /q put
dup 114 /r put
dup 115 /s put
dup 116 /t put
dup 117 /u put
dup 118 /v put
dup 119 /w put
dup 120 /x put
dup 121 /y put
dup 122 /z put
dup 123 /braceleft put
dup 124 /bar put
dup 125 /braceright put
dup 126 /asciitilde put
readonly def
currentdict end
currentfile eexec
M#1H5 J6o\&rtS(#v\0\V7Fe༙OYx5-cY9^%Y6
(efIOldN"wȰ;)UƽoFg/rvV$JS8_oc@
o9-eGJp}[Do]mN=4*{ܯq=eU^t6¤/{zM4aܪ
Q:д'B-r^ܦ6y?rRnu S\U{Oλrs(Βƚ
#d29%s'ƈT1F8&\0Xd&&Zug'VPd]:>u=Q,?#(CV4'..|ӱ5 h
sȀg)fɘ`UXK^>] q\l#5pE"JO}rquáQBr/E7
QW5\GSlu{7ZH(PSf/O;̟w{ɴ}-K hA8!b!U>`#u?Vlnǝ19V+mg'QmA}S Y$í8n uJ ڒx3>[x0Z]
ͩw4M&1+pkC,sr"%q&OjbH{:5$65*S`cr;%s4Oӆe>T+6~pBOD!$c]"~r#nh6$38i˞[~Z}}rHmte9(1½=j{<\ ;? RA?c{Rf1'VԞ_-Lwo]`.l|zjf"![G1BYro˓9[-+z g!}RN+pX!M~HcFh@g%J6B)6!Lq>TX\ݪGF
PiQݓX~Fs;Ölo4/(C?+,ɖxۼ:xU^)
fd,`*>-:}=q$:\Xzcw1Nf(
ZkEeJXfэi@zXc\{a5qKg\5ݩv\Qe%1>OY̗$Y#P[)."^+{"bP]Bt&zeN6
іijDE% 0;̅
~~lfB>u'i4znym%tfԟ^נBTDS6-ghiWk/(r!!˶fc>趕%U