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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>A newborn development insights mining and recommendation system from scienti c literature and clinical guidelines?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Sergio Consoli</string-name>
          <email>sergio.consoli@ec.europa.eu</email>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Kees Wouters</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Renee Otte</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Adrienne Heinrich</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>European Commission, Joint Research Centre, Directorate A-Strategy, Work Programme and Resources, Scienti c Development Unit</institution>
          ,
          <addr-line>Via E. Fermi 2749, I-21027 Ispra (VA)</addr-line>
          ,
          <country country="IT">Italy</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Philips Research</institution>
          ,
          <addr-line>High Tech Campus 34, 5656 AE Eindhoven</addr-line>
          ,
          <country country="NL">The Netherlands</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>In this short contribution we describe a method that is able to automatically retrieve relevant newborn development content from scienti c documents, including scienti c papers and standard guidelines, and then to recommend parents automatically the most relevant personal advices, also known as insights, from the extracted knowledge. The approach cannot replace specialist advice but it rather provides quick information from reliable sources with a certain degree of speci city for the parents and the child. The system builds on recent technological developments on big data, knowledge engineering, and cognitive computing, in particular related to the task of extracting relations between conceptual entities in the data sources.</p>
      </abstract>
      <kwd-group>
        <kwd>Generation and aggregation of health semantics</kwd>
        <kwd>Ontologies</kwd>
        <kwd>Recommendations for health data</kwd>
        <kwd>Information Extraction</kwd>
        <kwd>Insights</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        The availability of abundant computing and storage resources combined with
the evolution of analytics has made a ordable the use of cognitive computing
technology to deliver industrial solutions of all kinds [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ]. Cognitive computing
systems depend on various aspects of arti cial intelligence (AI), such as machine
learning, reasoning, natural language processing, speech and vision,
humancomputer interaction, dialogue and narrative generation, and more. The
machine learning algorithms learn and acquire knowledge from the massive amount
of data fed into to them [
        <xref ref-type="bibr" rid="ref10 ref11">10, 11</xref>
        ].
      </p>
      <p>
        Nowadays there is a lot of interest in adopting cognitive computing
technologies in healthcare3, which is particularly characterized by a vast amount of
data coming from di erent sources [
        <xref ref-type="bibr" rid="ref4 ref7">7, 4</xref>
        ]. Through the application of natural
language processing (NLP), data mining, and advanced text analytics, cognitive
systems can assist doctors in diagnosing and faster decision making [
        <xref ref-type="bibr" rid="ref19 ref4">19, 4</xref>
        ]. They
optimize patient selection for clinical trials through intelligent matching. In
oncology, these systems can assist in the creation of individualized treatment plans
that enhance patient trust and experience [
        <xref ref-type="bibr" rid="ref19 ref4 ref7">7, 19, 4</xref>
        ].
      </p>
      <p>
        The idea is that a machine can process more information than a doctor and
potentially discover links and patterns not immediately visible at a rst glance or
that would require a complete overview of all possible interventions. An example
of this is Watson4, the popular question-answering (Q&amp;A) machine by IBM,
which has been recently employed to provide diagnosis and treatments to cancer
patients, enabling faster and better care for patients5 [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ]. It can analyse the
meaning and context of structured and unstructured data coming from a variety
of inputs including handwritten documents [
        <xref ref-type="bibr" rid="ref6 ref8">6, 8</xref>
        ], and derive data from various
sources including curated literature and rationales, as well as medical journals
and textbooks6.
      </p>
      <p>
        Currently, there is an increasing number of new data-driven solutions in the
market which provide pregnant women and new parents suggestions and
personal advices, also known as insights, which address their needs and wishes, on
the basis of behavioural and contextual data, scienti c literature and clinical
guidelines. It is important to underline that insights cannot replace specialist
advice but they rather provide quick information from reliable sources with a
certain degree of speci city for the parents and the child. Mor precisely, insights
refer to small pieces of text that are suggested to parents on the basis of a
technical rule [
        <xref ref-type="bibr" rid="ref16">16</xref>
        ]. This rule analyses parents-tracked data and the available scienti c
literature and guidelines, and de nes when an insight text is presented to the
user. For example, if a mother is keeping track of her newborn's breastfeeds,
an insight could be the following: \Recently, your tracked breast feeds with Sara
have taken around 14 minutes. In general, newborns feed for 10-30 minutes at a
time { occasionally even longer" [
        <xref ref-type="bibr" rid="ref16">16</xref>
        ].
      </p>
      <p>
        In this way, insights provide personal advice, tips, and information tailored to
the unique situation of the parent and the newborn [
        <xref ref-type="bibr" rid="ref16">16</xref>
        ].
      </p>
      <p>Currently these insights and articles are selected manually by curators, who
need to grasp and exploit a large number of scienti c documents and select the
most relevant content from that to be selected as candidate insights or articles
to users. However, manual generation of insights takes time and a lot of e ort,
because all the scienti c content needs to be read and the most relevant insights
or articles extracted. In addition, an optimal selection is hard to be manually
established by a human who can only rely on his intuition, bringing in most
cases non-optimal decisions. In addition, linking all the relationships among the
4 https://www.ibm.com/watson/
5
http://pulse.embs.org/may-2017/cognitive-computing-and-the-future-ofhealth-care/
6
https://mihin.org/wp-content/uploads/2015/06/The-Impact-of-Cognitive</p>
      <p>Computing-on-Healthcare-Final-Version-for-Handout.pdf
pregnancy or newborn concepts reported in the scienti c documents still remains
a challenge.</p>
      <p>The aim of the system proposed in this contribution is to support the process
of insights or article generation by recommending automatically a set of the
most important facts coming from the scienti c literature and clinical guidelines
given in input. The system leverages on state-of-art technologies on Cognitive
Computing, Natural Language Processing (NLP), Ontology Engineering, and
Big-Data, producing an advanced AI system for semantically mining information
from a scienti c pregnancy and newborn development domains repository.
2</p>
    </sec>
    <sec id="sec-2">
      <title>Description of the method</title>
      <p>The algorithm leverages the recent AI developments in cognitive computing and
applies them to automatically mining information from scienti c literature and
guidelines. In this way, new knowledge on the pregnancy or newborn
development domains can be extracted, automatically providing applications with a
recommendation of the most relevant insights or articles to give to users in a
personalized way. The schematic work ow of the system is depicted in Figure 1.</p>
      <p>The system is able to parse, extract, transform and load the unstructured
information coming from clinical guidelines and scienti c papers. It is able then to
structure the free-format text using machine reading from natural language
processing for extracting RDF7/OWL8 graphs that are linked to the Linked Open</p>
      <sec id="sec-2-1">
        <title>7 RDF: Resource Description Framework 8 OWL: Web Ontology Language</title>
        <p>
          Data cloud and compliant to Semantic Web and Linked Data patterns [
          <xref ref-type="bibr" rid="ref14">14</xref>
          ]. In
this way the information is translated into machine-readable semantic
information in RDF/OWL format, which is a W3C standard for exchanging semantic
data. Machine reading is typically much less accurate than human reading, but
can process massive amounts of text in reasonable time, can detect
regularities hardly noticeable by humans, and its results can be reused by machines for
applied tasks [
          <xref ref-type="bibr" rid="ref13">13</xref>
          ].
        </p>
        <p>
          The system recognizes and resolves named entities, links them to the existing
knowledge base, and gives them a type by using di erent cognitive computing
functionalities [
          <xref ref-type="bibr" rid="ref1 ref13 ref14 ref15 ref18">1, 13, 14, 15, 18</xref>
          ]: frame detection, topic extraction, named
entity recognition, resolution and co-reference, terminology extraction, sense
tagging, word-sense disambiguation, taxonomy induction, semantic-role labelling,
and type induction.
        </p>
        <p>
          In this way the algorithm recognizes the main entities and concepts, and most
importantly, it performs relations extraction to derive the main relationships
among them [
          <xref ref-type="bibr" rid="ref17">17</xref>
          ]. The main focus indeed is to extract the relationships among
the obtained conceptual entities and link them together to allow interoperability
among the information contained in the scienti c documents.
        </p>
        <p>
          Using named entity recognition (NER) and resolution (a.k.a. entity linking)
with standard biomedical ontologies in the pregnancy or newborn development
domains, the algorithm makes sure to restrict the extraction of the structured
information within the speci c pregnancy or newborn development domains.
Biomedical ontologies ensure both syntactic and semantic interoperability among
all heterogeneous data coming into the system [
          <xref ref-type="bibr" rid="ref9">9</xref>
          ].
        </p>
        <p>The extracted big data leverage the pregnancy and newborn development
knowledge-base, which is updated periodically by the system with new, updated
information coming from its input sources. Each concept in the system is linked
to other concepts in the knowledge-base by using ontologies and allowing
interoperability. The stored relationships may include, for example, sensitive user
status/conditions (e.g. pregnant, parent, infant, etc), and diseases (asthma,
allergies, etc.) linked to other conditions and information. The knowledge-base is
constantly maintained, updated, and integrated in the ontology model.</p>
        <p>The knowledge-base contains the semantic model with the updated
information coming from the scienti c literature and clinical guidelines. In order to
provide recommendation of the most relevant insights, a ranking is produced as
following:
1. Consider each sentence with all its extracted relationships. Sum the absolute
frequencies scores among all documents associated to the relationships. The
result will be a score associated to the sentence.
2. Rank the extracted sentences with respect to the scores and identify the
insight(s) having the largest score.
3. Put this sentence(s) set in the list of the insights to recommend.
4. Iteratively exclude from the remaining sentences the relationships that were
already considered in the previous insights selection, and recalculate
accordingly the scores of the sentences.
5. Re-order the sentence with the respect to the re-calculated scores, and
identify the insight(s) having the largest re-calculated score.
6. Go to Step 3, and continue until no further sentences are remaining.
7. The output will be the nal list of the insights to recommend.</p>
        <p>The output of the system is a document with the list of top recommended
insights that needs to be checked and validated by a curator, and successively
the next step would be to automatically provide those top insights directly to
end users. The recursive ranking re-calculation is aimed at increasing the
diversi cation of the top insights that are nally recommended.</p>
        <p>Based on a speci c user pro le the system may be also able to personalize
the insights that are recommended9. In this way the algorithm could provide
relevant insights to a pregnant woman or parent, linking validated information
on pregnancy and newborn development to user-speci c conditions. By
storing the speci c insights in the system for later usage, the method would be
able to re-adopt this information by, and share with, di erent products of the
user. The standardized RDF/OWL format of the produced information in the
knowledge-base guarantees standard communication among the di erent
products overcoming any incompatibility and interoperability issues.</p>
        <p>Summarizing, the described system is able to identify novel insights that go
beyond clinical guidelines, and provide relationships which can help parents and
pregnant women.
3</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>A controlled experiment</title>
      <p>In order to provide a business scenario as an example giving a detailed
description of the system, a controlled prototype experiment of relations extraction in
the pregnancy and newborn development domains from a small set of
scienti c paper and clinical guidelines as input (18 in total) has been carried out. In
this experiment the system produced 38878 relationships among the extracted
concepts from the 18 documents in the input repository.</p>
      <p>Table 1 shows some examples of the extracted relationships among some
concepts and their frequencies. Each entry in the subject and object columns
represents the label associated with the related concept from a standard
biomedical ontology. For example, \Child" is the label of the concept http://purl.
bioontology.org/ontology/HL7/C0008059 belonging to the Health Level 7 (HL7)
ontology. Similarly, \Asthma" is the label of the concept http://purl.bioontology.
org/ontology/MESH/D001249 from the Medical Subject Headings (MeSH)
ontology.</p>
      <p>Each concept in the ontology is uniquely identi ed by its corresponding URI,
which conveys other undirected information coming from the ontology, relations
to other concepts and its position in the hierarchy, and most important, it allows
disambiguation among terms and linking concepts together to ensure syntactic
as well semantic interoperability.</p>
      <sec id="sec-3-1">
        <title>9 Functionality not yet implemented, under current development.</title>
        <p>{ \Colostrum" is the concept: http://purl.obolibrary.org/obo/UBERON_
0001914 coming from the Uber-anatomy ontology (UBERON) ontology;
{ \Lactose" is the concept: http://purl.bioontology.org/ontology/HL7/</p>
        <p>C1696723 coming from the Health Level 7 (HL7) ontology;
{ \Decreased concentration" is the concept: http://purl.obolibrary.org/
obo/PATO_0001163 coming from the Phenotype And Trait Ontology (PATO)
ontology;</p>
        <p>
          The relationships can be also explored by interactive chord diagrams for
visualizations [
          <xref ref-type="bibr" rid="ref12 ref2">12, 2</xref>
          ]. A chord diagram is a graphical method of displaying
the inter-relationships between data in a matrix. The data is arranged
radially around a circle with the relationships between the points typically drawn
as arcs connecting the data together. When a speci c concept is selected
interactively, only its relationships are visualized in the diagram, helping users
to grasp and understand more intuitively the inter-relationships among the
different entities. The format of chord diagrams is aesthetically pleasing, making
it a popular choice in the world of data visualization [
          <xref ref-type="bibr" rid="ref12 ref3 ref5">12, 3, 5</xref>
          ]. For example,
Figure 3 shows the relationships of the extracted concept \Breast", i.e.
concept http://purl.obolibrary.org/obo/UBERON_0000310 from the UBERON
ontology with the other concepts.
        </p>
        <p>In the controlled prototype experiment with the 18 scienti c paper and
clinical guidelines as input, a total of 2573 di erent sentences were extracted. Figure
4 shows a chart with the ranked sentences extracted from the input pregnancy
and newborn development repository for the controlled experiment.</p>
        <p>If in Figure 4 we consider a threshold to cut the tail of the curve, so that
to have 95% of AUC for the given chart (corresponding to a minimum scoring
threshold equal to 10), we can reduce the total number of insights that are
recommended to 1523. If we aim for a more selective selection, if we cut at a
score of 100, we have only 53 most relevant insights to look at. For example, the
following are the top ones:</p>
        <p>\Demonstrating the bioactivity of breast milk, a study on shed epithelial cells
in the faeces of infants has shown that gene expression in the neonatal
gastrointestinal tract is in uenced by breastfeeding, with di erential expression found
between formula fed and breast fed infants in genes regulating intestinal cell
proliferation, di erentiation and barrier function."</p>
        <p>\Protein concentration is highest in breast milk of mothers aged 20-30,
however, maternal age does not seem to in uence either lipid or lactose
concentrations, and maternal age does not have a large impact on breast milk
composition."</p>
        <p>\Infants and young children have a higher resting metabolic rate and rate of
oxygen consumption per unit body weight than adults because they have a larger
surface area per unit body weight and because they are growing rapidly."
\The total protein content of human breast milk consists of 13% casein,
the lowest casein concentration of any studied species, corresponding to the slow
growth rate of human infants."</p>
        <p>\Exposure to tobacco smoke in utero was associated with an increased risk
of stillbirth (odds ratio = 2.0, 95% con dence interval: 1.4, 2.9), and infant
mortality was almost doubled in children born to women who had smoked
during pregnancy compared with children of nonsmokers (odds ratio = 1.8, 95%
con dence interval: 1.3, 2.6)."</p>
        <p>\Human milk oligosaccharides (HMO) also make up a signi cant fraction of
breast milk carbohydrate, but are indigestible by the infant, their function instead
is to nourish the gastrointestinal microbiota."</p>
        <p>A preferred, ideal deployment of the system, not yet implemented but at a
prototype stage, is shown in Figure 5, schematically depicting a
recommendation device (e.g. a smartphone) comprising at least one (or more) communication
unit(s) and a user interface, and a processing unit embedded in a remote server
controlling the suggestions of the most relevant insights to the device. The
processing unit comprises a cognitive system, of which the pipeline is described in
Figure 5, and is connected to the recommendation device via the communication
unit. In various embodiments, the cognitive system in the processing unit maybe
connected to di erent input data sources, including, but not limited to, a
repository of scienti c papers and clinical guidelines. The output information interface
could be any device able to provide useful insights to a pregnant woman or a
parent, for example a smartphone hosting an appropriate application. It might
comprise a user interface for data input/output and a data display. Through
a user interface, the user might input his pro le details, e.g. sex, age, eventual
health diseases (like allergies, asthma, etc.), and others, and then save these
details for later usage. The recommendation device sends the user details to the
processing unit via the communication unit.</p>
        <p>Alternatively, the system may include also some automatic trackers, i.e. either
devices embedded into the main system able to track and store automatically
users' activities, or also special tracking devices that are external to the main
system but directly linked to it.</p>
        <p>The remote server is connected to the knowledge-base, which is a
semantic triplestore containing the semantic information in the W3C standard format
RDF/OWL, as described previously, and enabling semantic interoperability,
reasoning and inferencing, containing the relationships among conceptual pregnancy
and newborn development actors involved in speci c situations, including health
conditions, sensitivity information (manually set or derived by the system).</p>
        <p>The cognitive system in the processing unit receives the user pro le details
and combines this information with the information in the knowledge-base. The
system uses this knowledge to nally provide personalized insights to the
recommendation device which is then displayed to the user.</p>
        <p>Fig. 5: Schematic illustration showing the ideal deployment of the system.</p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>Conclusion</title>
      <p>In this short contribution it has been described a method which is able to
automatically retrieve relevant clinical content on newborn development from
scienti c papers and standard guidelines. The system may be used to feed in real-time
a connected application to provide feedbacks and suggestion of useful insights
to pregnant women and new parents derived from scienti c literature and
clinical guidelines. This method has the potential to be used in real pregnancy or
newborn development recommendation systems. In addition, the method may
be generalizable and applicable to other domains after choosing the relevant
ontologies and information sources.</p>
    </sec>
  </body>
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