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<title>20146086 Visualization</title>
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<h1>20146086 Visualization</h1>
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<div class="entities" style="line-height: 2.5; direction: ltr">A
<mark class="entity" style="background: #f6c3d0; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
54
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Age</span>
</mark>
-
<mark class="entity" style="background: #f6c3d0; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
year
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Age</span>
</mark>
-
<mark class="entity" style="background: #f6c3d0; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
old
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Age</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
woman
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sex</span>
</mark>
with
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
stage
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
IV
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
NSCLC
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
was treated with
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
carboplatin
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
and
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
paclitaxel
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
without
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
response
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
.</br>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
Molecular
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
analysis
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
tumor
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
tissue
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
was
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
unavailable
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
at that time.</br>However, her demographic profile (
<mark class="entity" style="background: #a0ced9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
Asian
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Personal_background</span>
</mark>
,
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
minimal
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Severity</span>
</mark>
<mark class="entity" style="background: #e2f0cb; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
smoking
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">History</span>
</mark>
<mark class="entity" style="background: #e2f0cb; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
history
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">History</span>
</mark>
,
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
non
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
-
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
small
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
cell
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
histology
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
) predicted
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
her
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
would harbor
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
EGFR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
TKI
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
sensitive
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
cells
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
[2].</br>Therefore, she then initiated
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
standard
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
daily
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
dosing
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
of
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
(
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
150
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mg
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
) and
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
her
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
responded
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
.</br>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
Twenty
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
-
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
eight
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
months
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
later
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
, she acquired
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
resistance
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Other_event</span>
</mark>
to
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
with
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
progression
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
of
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
systemically
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
.</br>Following further progression through an
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
experimental
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
angiogenesis
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
inhibitor
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
, she initiated
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
pemetrexed
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
and resumed
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
standard
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
dose
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
.</br>After initial response,
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
11
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
months
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
later
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
,
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
her
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
again
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
progressed
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
.</br>
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
DNA
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
was extracted from
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
biopsy
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of a
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
progressing
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
lung
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
lesion
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
and examined using established techniques for analysis of
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
EGFR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mutations
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
[5].</br>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
Direct
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
sequencing
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
exons
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
18–21 encoding the
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
kinase
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
domain
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
of
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
EGFR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
revealed the
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
L858R
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mutation
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
associated with
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
EGFR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
TKI
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
sensitivity
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
(Fig.1) [2].</br>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
It
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
also demonstrated the
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
T790M
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mutation
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
associated with
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
acquired
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
EGFR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
TKI
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
resistance
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
(Fig.1) [2].</br>She also developed
<mark class="entity" style="background: #bde0fe; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
headaches
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sign_symptom</span>
</mark>
and there was a high clinical suspicion of
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CNS
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
metastases
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
despite
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
negative
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
imaging
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
(not shown).</br>She refused a
<mark class="entity" style="background: #e6ccb2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
lumbar
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Therapeutic_procedure</span>
</mark>
<mark class="entity" style="background: #e6ccb2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
puncture
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Therapeutic_procedure</span>
</mark>
.</br>She initiated
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
empiric
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
temozolomide
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
plus
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
standard
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
dose
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
(
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
150
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mg
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
daily
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
) for presumed
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CNS
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
, but
<mark class="entity" style="background: #e9d8a6; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
after
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Time</span>
</mark>
<mark class="entity" style="background: #e9d8a6; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
one
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Time</span>
</mark>
<mark class="entity" style="background: #e9d8a6; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
cycle
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Time</span>
</mark>
her
<mark class="entity" style="background: #bde0fe; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
headaches
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sign_symptom</span>
</mark>
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
worsened
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
, and she developed
<mark class="entity" style="background: #bde0fe; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
nausea
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sign_symptom</span>
</mark>
and
<mark class="entity" style="background: #bde0fe; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
vomiting
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sign_symptom</span>
</mark>
concerning for
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CNS
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
metastases
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
with associated
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
raised
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
intracranial
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
pressure
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
.</br>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
Magnetic
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
resonance
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
imaging
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
(MRI)
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of the
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
brain
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
now demonstrated
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
LM
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
(Fig.2) confirmed by
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CSF
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
cytology
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
(not shown).</br>By
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
direct
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
sequencing
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
,
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
DNA
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
from
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CSF
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
cells
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
harbored
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
L858R
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
predicting
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
EGFR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
TKI
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
sensitivity
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
(Fig.3, left panel) but not the
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
T790M
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
resistance
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mutation
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
(data not shown).</br>Because the result for
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
T790M
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
was
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
negative
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
in
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
this
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
sample
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
, we performed a
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
more
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
sensitive
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
fluorescence
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
detection
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
PCR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
-
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
based
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
assay
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
that takes advantage of a
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
PCR
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
restriction
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
fragment
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
length
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
polymorphism
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
generated by
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
the
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
specific
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
missense
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mutation
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
(Fig.3, right panel, arrow, positive control) [6].</br>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
That
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
<mark class="entity" style="background: #e3b5a4; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
result
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Coreference</span>
</mark>
was also
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
negative
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
, as only the
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
wild
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
type
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
peak
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
was detected (Fig.3, right panel, bottom).</br>Therefore, we hypothesized that the LM remained sensitive to an EGFR TKI if sufficiently high concentrations of drug could be achieved in the CSF.</br>The erlotinib concentration required to inhibit growth of cell lines harboring L858R by 50% (IC50) is 100 nM (nM) [2].</br>Standard dose erlotinib (150 mg daily) achieves 3000 nM in plasma [7], but CSF concentrations of EGFR TKIs are as low as 1% plasma levels below the IC50 [3, 8].</br>Increasing the daily dose of gefitinib to enhance CSF penetration has been an effective strategy [3], but gefitinib is no longer available in the United States following failure in phase III NSCLC trials.</br>An analogous increase of the daily erlotinib dose above 150–200 mg daily induces unacceptable toxicity.</br>However, weekly high-dose erlotinib up to 2000 mg is tolerable [4].</br>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
Pharmacokinetic
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
analysis
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CSF
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
from
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
another
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Subject</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
patient
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Subject</span>
</mark>
with
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
NSCLC
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
LM
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
(not shown) treated with
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
1500
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mg
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
weekly
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
demonstrated a
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
peak
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
plasma
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
concentration
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
11,300
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
nM
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
with a concurrent
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CSF
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
concentration
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
130
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
nM.</br>Therefore, such high dose weekly administration of erlotinib achieved a CSF concentration
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
exceeding
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
the
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
IC50
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
.</br>Therefore, to increase CSF penetrance over standard daily erlotinib dosing in this patient, we initiated
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
high
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
-
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
dose
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
weekly
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
at
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
1000
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mg
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
then
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
1200
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mg
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
;
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
persistent
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #bde0fe; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
nausea
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sign_symptom</span>
</mark>
precluded higher doses.</br>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
Pharmacokinetic
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
analysis
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
was not undertaken in this patient.</br>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
After
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
1
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
month
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
there was a
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
partial
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
radiographic
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
response
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
of
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
LM
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
on
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
brain
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
MRI
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
(Fig.2b) and
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
after
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
2
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
months
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
in the
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
cauda
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
equina
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
(not shown).</br>However,
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
hydrocephalus
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
and
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
persistent
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #bde0fe; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
symptoms
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sign_symptom</span>
</mark>
referable to
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
increased
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
intracranial
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
<mark class="entity" style="background: #c5b4e3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
pressure
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Diagnostic_procedure</span>
</mark>
led to a
<mark class="entity" style="background: #e6ccb2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
VP
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Therapeutic_procedure</span>
</mark>
<mark class="entity" style="background: #e6ccb2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
shunt
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Therapeutic_procedure</span>
</mark>
and
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
whole
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
-
<mark class="entity" style="background: #9ddfd3; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
brain
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Biological_structure</span>
</mark>
<mark class="entity" style="background: #e6ccb2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
radiation
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Therapeutic_procedure</span>
</mark>
<mark class="entity" style="background: #e6ccb2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
therapy
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Therapeutic_procedure</span>
</mark>
, after which she resumed treatment with
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
1500
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mg
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
weekly
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
.</br>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
One
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
month
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
later
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
,
<mark class="entity" style="background: #ffb347; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
progressive
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Detailed_description</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
intra
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
-
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
thoracic
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
<mark class="entity" style="background: #c4b7ea; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Disease_disorder</span>
</mark>
led to initiation of
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
cetixumab
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
and
<mark class="entity" style="background: #f9d5e5; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
erlotinib
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Medication</span>
</mark>
was continued but changed to
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
low
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
dose
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
(
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
100
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
<mark class="entity" style="background: #f4b3c2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
mg
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Lab_value</span>
</mark>
)
<mark class="entity" style="background: #b9e8d8; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
daily
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Dosage</span>
</mark>
.</br>She
<mark class="entity" style="background: #bde0fe; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
survived
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Sign_symptom</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
14
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
months
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
following
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
the
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
diagnosis
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
of
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
CNS
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
<mark class="entity" style="background: #f1f0d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em;">
disease
<span style="font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; vertical-align: middle; margin-left: 0.5rem">Date</span>
</mark>
.</br></div>
</body>
</html>
