Sleep Medicine 85 (2021) 280e290

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Sleep Medicine
journal homepage: www.elsevier.com/locate/sleep

Original Article

Explainable fuzzy neural network with easy-to-obtain physiological

features for screening obstructive sleep apnea-hypopnea syndrome
Chia-Feng Juang a, Chih-Yu Wen a, Kai-Ming Chang b, Yu-Hsuan Chen c,
Ming-Feng Wu b, c, 1, Wei-Chang Huang b, d, e, f, g, *, 1
a
Department of Electrical Engineering, National Chung Hsing University, Taichung, 402, Taiwan
b
Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 407, Taiwan
c
Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, 406, Taiwan
d
Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, 350, Taiwan
e
School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan
f
Master Program for Health Administration, Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, 407, Taiwan
g
Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, 402, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Objective/background: Recently, several tools for screening obstructive sleep apnea-hypopnea syndrome
Received 18 February 2021 (OSAHS) have been devised with varied shortcomings. To overcome these drawbacks, we aimed to
Received in revised form propose a self-estimation method using an explainable prediction model with easy-to-obtain variables
7 July 2021
and evaluate its performance for predicting OSAHS.
Accepted 8 July 2021
Available online 16 July 2021
Patients/methods: This retrospective, cross-sectional study selected significant easy-to-obtain variables
from patients, suspected of having OSAHS by regression analysis, and fed these variables into the pro-
posed explainable fuzzy neural network (EFNN), a back propagation neural network (BPNN) and a
Keywords:
Apnea-hypopnea index
stepwise regression model to compare the screening performance for OSAHS.
Explainable artificial intelligence Results: Of the 300 participants, three easily available features, such as waist circumference, mean blood
Fuzzy neural networks pressure (BP) at the end of polysomnography and the difference in systolic BP between the end and start
Neural networks of polysomnography, were obtained from regression analysis with a five-fold cross-validation scheme.
Obstructive sleep apnea-hypopnea Feeding these three variables into the prediction models showed that the average prediction differences
syndrome for apnea-hypopnea index (AHI) when using the EFNN, BPNN, and regression model were respectively
1.5 ± 18.2, 3.5 ± 19.1 and 0.1 ± 19.3, indicating none of the tested methods had good efficacy to predict
the AHI values. The performance as determined by the sensitivity þ specificity-1 value for screening
moderate-to-severe OSAHS of the EFNN, BPNN and regression model were respectively 0.440, 0.414 and
0.380.
Conclusions: When fed with easy-to-obtain physiological features, the understandable EFNN should be
the preferred method to predict moderate-to-severe OSAHS.
© 2021 Elsevier B.V. All rights reserved.

1. Introduction polysomnography (PSG) involves an overnight stay in a sleep labo-

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is char-
acterized by repetitive airflow reduction (hypopnea) or cessation
(apnea) due to upper airway collapse during sleep, resulting in ox-
ygen desaturation and sleep fragmentation [1]. Full-night
ratory with multichannel monitoring for sleep physiology and ar-
chitecture, brain activity, and respiration during sleep, and it is the
standard method used to diagnose and grade OSAHS. In clinical
practice, the diagnosis of OSAHS is made according to an apnea-
hypopnea index (AHI) of 5 per hour, while the severity of OSAHS

* Corresponding author. 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan.

E-mail addresses: cfjuang@dragon.nchu.edu.tw (C.-F. Juang), cwen@dragon.nchu.edu.tw (C.-Y. Wen), opencm@gmail.com (K.-M. Chang), yhchen2@ctust.edu.tw
(Y.-H. Chen), osmigo@seed.net.tw (M.-F. Wu), huangweichangtw@gmail.com (W.-C. Huang).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.sleep.2021.07.012
1389-9457/© 2021 Elsevier B.V. All rights reserved.
C.-F. Juang, C.-Y. Wen, K.-M. Chang et al.
Abbreviation list
AASM American Academy of Sleep Medicine
Ac accuracy
AHI apnea-hypopnea index
AI artificial intelligence
A_S systolic blood pressure measured at the end of
polysomnography
BMI body mass index
BP blood pressure
BPNN backpropagation neural network
Diff_M mean blood pressure measured at the end of
polysomnography minus that measured at the
beginning of polysomnography
Diff_S the difference of systolic blood pressure between the
end and start of polysomnography
is categorized as mild, moderate, and severe with AHI thresholds of
5, 15, and 30 per hour, respectively, as determined by PSG [2,3].
In-laboratory overnight PSG is complex, costly, and time-
consuming, thereby limiting its widespread use in the general
population. Accordingly, prediction models to assist in screening
patients at high-risk of OSAHS are urgently needed [4]. Several
formulas and screening tools to predict AHI scores and the diagnosis
and severity of OSAHS have been proposed, which are broadly
categorized into clinical regression and questionnaire models. The
results of these methods have shown that they could prevent un-
necessary PSG, although clinical models have shown marginally
better accuracy than questionnaire models to predict both the
diagnosis and severity of OSAHS [5e9]. Regarding the nature of the
input data, complex variables [10e15] such as physical findings of
the upper airway [10], pulse oxygen saturation [11], imaging anal-
ysis [12,14] and speech signals [15] have been widely used in clinical
regression models to assist in the diagnosis of OSAHS and assess its
severity. However, these variables are difficult to obtain for self-
evaluation and most of them suffer from continuous overnight
monitoring though good detection performance may be achieved.
Rapid screening for OSAHS with easily available physiological
measurements such as body mass index (BMI) by supersparse linear
integer models was reported to have a sensitivity (Sn) of 64.2% and a
specificity (Sp) of 77% [16]. Questionnaires such as Epworth Sleep-
iness Scale (ESS) etc. used to screen OSAHS have been proposed [17].
However, the low sensitivity of 66% in the identification of an AHI of
5 was still below the satisfaction level for clinical practice.
Recent advances in artificial intelligence (AI) models have led to
the development of automated medical diagnostic systems that can
aid in the diagnosis of disease states. Various neural networks (NNs)
have been proposed and shown promising results in medical di-
agnostics [18e21], including the prediction of apnea and hypopnea
episodes and the diagnosis and severity of OSAHS [22e25]. How-
ever, NNs suffer from the difficulty in explaining the inference
process behind their black-box-like models. Explainable AI that
enables a user to understand the inference process has thus
attracted increased research interest [26,27]. Fuzzy systems are
comprised of linguistic fuzzy if-then rules expressed in terms of
linguistic values. The behavior of the system is comprehensible, and
so the inference is understandable by the user. Accordingly, a fuzzy
system can be designed to be interpretable. The manual design of
fuzzy rules requires expert knowledge and time-consuming trial
and error to obtain good performance [28,29]. To address the
cumbersome system design problem, fuzzy NNs (FNNs), expressing
a fuzzy system in terms of nodes and link weights and automatically
281
Sleep Medicine 85 (2021) 280e290
EFNN explainable fuzzy neural network
ESS Epworth Sleepiness Scale
FNN fuzzy neural network
Mean_A mean blood pressure at the end of the sleep test
NN neural network
OSAHS obstructive sleep apnea-hypopnea syndrome
PSG polysomnography
SE sleep efficiency
SHAP SHapley Additive exPlanations
Sn sensitivity
Sp specificity
TCVGH Taichung Veterans General Hospital
TS Takagi-Sugeno
WC waist circumference
learning fuzzy rules from training data, have been proposed
[30e32]. For first-order Takagi-Sugeno (TS)-type FNNs [30,31], the
fuzzy rule consequent is a linear combination of input variables,
which is difficult to understand its meaning. For the zero-order TS-
type FNN [32], the fuzzy rule consequent is simply a real value,
which implies that the inference rule is comprehensible although
lacking transparency due to a large number of fuzzy sets (nodes).
We attempted to incorporate the fuzzy set merging process [31]
into the zero-order TS-type FNN [32], and the new network is called
explainable FNN (EFNN). Afterwards, the EFNN is applied to predict
the severity of OSAHS using simple and easy-to-obtain physiological
features extracted from sampled subjects. Meanwhile, the linguistic
relationship between the physiological features and the OSAHS
severity through inspecting the fuzzy rules in the EFNN and the
performance comparison with NNs and a clinical regression model
using the same easily available physiological variables were analyzed
under the hypothesis that the proposed EFNN fed with easily available
parameters may overcome the drawbacks mentioned above and
exhibit a promising performance for the screening of OSAHS.
2. Material and methods
2.1. Study design, setting and population
This retrospective, cross-sectional study reviewed and collected
demographic and clinical data from subjects who presented to
Taichung Veterans General Hospital (TCVGH) for the evaluation of
suspected OSAHS and underwent diagnostic standard full-night
PSG with sleep efficiency (SE) 70% and blood pressure (BP)
measurements just before sleeping for PSG and after awakening
from the sleep test between January 2013 and December 2016.
Those who took any medications before undergoing PSG, did not
complete the ESS questionnaire, and had a history of diabetes,
hyperlipidemia, and hypertension were excluded from this study.
For each severity of OSAHS (from normal to severe), 75 cases were
randomly sampled and enrolled in the final analysis. The Institu-
tional Review Board and Ethics Committee of TCVGH approved this
study (approval number: CE17085A) and waived the need for
informed consent from the participants because the study was
based on a retrospective electronic medical chart review.
2.2. Full-night diagnostic PSG
As detailed elsewhere, overnight PSG (Compumedics, E-series,
Victoria, Australia) was performed using standard recordings and
C.-F. Juang, C.-Y. Wen, K.-M. Chang et al. Sleep Medicine 85 (2021) 280e290

scored manually by well-trained medical technologists according
to the international criteria developed by the American Academy of
Sleep Medicine (AASM) in 2007 (AASM 2007) [33]. SE (%) was
defined as total sleep time (minutes) divided by total recording
time (minutes), and the arousal index was defined as the number of
arousal events divided by total sleep time (hours). The AHI was
defined as the total number of apneas and hypopneas divided by
the total sleep time (hours). The severity of OSAHS was graded as
mild, moderate, and severe if the AHI was 5e14, 15e30, and >30
events per hour, respectively [34e37].
3. Explainable fuzzy neural network
3.1. Neural network structure
The section describes the basic NN structure consisting of nodes
and link weights. Fig. 1 shows the structure of a backpropagation
NN (BPNN), also known as the multilayer perceptron. The BPNN
consists of three fully connected layers. The input layer transmits
scaled inputs x1 , .., xn 2[0, 1] to the next layer. Each node in the
BPNN uses the sigmoid activation function. The output of the qth
node in the hidden layer is given as follows:

 1 Xn
ð1Þ ð1Þ
2.3. Physiological parameters and questionnaires hq ¼ a Hq ¼ ; H ¼ wqi xi þ bq ; q ¼ 1; :::; Nh
q
1 þ eHq i¼1
Body weight and height were respectively measured in kilo- (1)
grams and centimeters using a digital scale (KONGHO INSTRU-
MENT, HW-2020, Taiwan) according to the manufacturer's ð1Þ
wherewqi is the link weight from input node i to hidden node q,
recommendations, and BMI was calculated as [(BMI ¼ weight (kg)/
ð1Þ
height (m)2]. BP was measured digitally using an upper arm BP bq is a bias connected to hidden node q and Nh is the number of
monitor (Omron, HEM-7230, Kyoto, Japan) according to the man- hidden nodes. The output node in the output layer uses the linear
ufacturer's recommendations at the beginning and end of the PSG activation function given as follows:
test. The difference in BP was defined as the measurement at the
end of the sleep test minus that measured at the beginning of PSG, X
Nh
ð2Þ
while the mean BP was defined as (systolic BP þ 2 x diastolic BP)/3. y ¼ aðYÞ ¼ Y; Y ¼ wq hq þ bð2Þ ; (2)
An inelastic tape with 1 mm precision was used to measure cir- q¼1
cumferences. The neck circumference was measured below the
ð2Þ
cricoid cartilage, and afterwards, at the level of the mid cervical wherewq and bð2Þ are the link weight and bias, respectively,
spine. Waist circumference (WC) was measured at the midpoint connected to the output node. When the BPNN is applied to predict
between the inferior costal margin and upper iliac crest [38]. The the real AHI score, the following error is defined
ESS is a self-administered questionnaire composed of eight ques-
tions to assess daytime sleepiness. Each item has a 4-point scale 1 
E¼ y  AHId (3)
(0e3), and the ESS score (the sum of all eight item scores) can range 2
from 0 to 24. ESS scores of 11e24 represent increasing levels of
excessive daytime sleepiness [39]. where AHId is the desired AHI value measured from PSG. All the
weights and biases in the BPNN are optimized by minimizing the
error function through the gradient descent algorithm.
2.4. Study protocol and statistics analysis

With stratified sampling based on the severity of OSAHS, par- 3.2. Explainable fuzzy neural network structure
ticipants were evenly grouped into five datasets. A five-fold cross-
validation scheme was performed. Fold-1 was built up with three In addition to the BPNN, this paper proposes the application of
datasets for training, one dataset for validation, and the rest dataset the EFNN to predict the AHI score. The EFNN comprises fuzzy if-
for test. Fold-2 to fold-5 were in the same way with sets turn. The then rules, with each rule described as follows:
validation dataset in each fold was created to determine the
optimal hyperparameters in a prediction model. The physiological
factors or questionnaires that had a Pearson correlation coefficient
>0.3 with AHI were extracted for stepwise regression on the
training and validation datasets in each fold. The selected physio-
logical features from the stepwise regression method in each fold
were fed as inputs into different prediction models.
All data were expressed as mean and standard deviation for
continuous variables or number (percentage) for categorical vari-
ables. Comparisons between sets were conducted using one-way
ANOVA for continuous variables and the chi-square test for cate-
gorical variables. BlandeAltman plots were used to determine the
agreement between AHI as measured by PSG and predicted values
derived from the test datasets in the five folds. Prediction model
characteristics, including Sn, Sp and accuracy (Ac) were computed
to compare the performance of the studied models. Statistical
analysis was performed using SPSS software version 18.0 (SPSS Inc., Fig. 1. The network structure of the BPNN. Abbreviations: BPNN, backpropagation
Chicago, IL, USA) with statistical significance of p < 0.05. neural network.

282
C.-F. Juang, C.-Y. Wen, K.-M. Chang et al. Sleep Medicine 85 (2021) 280e290

P
r
Rule k : If x1 isAk1 andx2 isAk2 :::andxn isAkn thenAHIiswk ; k¼1;:::;r wk mk
(4) AHI ¼ k¼1r (7)
P
mk
where Akj is a Gaussian fuzzy set, wk is a real number, and r is the k¼1
total number of rules. Following the network structure in the BPNN,
the EFNN expresses a fuzzy system in terms of nodes and weights,
as shown in Fig. 2. This network structure shows the advantage of 3.3. Explainable fuzzy neural network learning
visualization of the computation process in a fuzzy system. In
addition, the parallel structure of the nodes enables parallel The nodes (rules and fuzzy sets) in the EFNN are online gener-
implementations, such as through graphic processing unit [32], of ated through a data-driven technique with structure learning and
the EFNN output and parameter training for computation speedup parameter learning. Initially, there are no nodes in the EFNN. All
if necessary. Different from the BPNN that functions as a black box, nodes are built through structure learning. The rule node genera-
the nodes in the EFNN implement the rules in (4) and their func- tion approach in the FNN [32] is also used in the EFNN. Given the
tions are explainable. The functions of the nodes in different layers tth training datum, if the network is empty or if the maximum
of the EFNN are described as follows. firing strength mK from the node outputs in layer 3 is smaller than a
Layer 1: Each node in layer 1 corresponds to an input feature. predefined threshold mth , ie,
Node i transmits the scaled physiological features xi 2 [0, 1] to the
next layer. K ¼ arg max mk ; mK < mth (8)
1kr
Layer 2: Each node in layer 2 functions as a Gaussian fuzzy set.
Given an input value xi from the ith node in layer 1, the kth node in
then the (r þ 1) th node is added to layer 3. A new node (fuzzy set) is
layer 2 calculates the following membership value
also temporarily added to layer 2 for each of the input features. The
( !) center and width of the new fuzzy set are assigned by
ðxi  mki Þ2
Mki ðxi Þ ¼ exp  (5) mðrþ1Þi ¼ xi ðtÞ (9)
s2ki

where mki and ski denote the center and width of the fuzzy set. For X
n

the FNN in Ref. [32], the number of nodes (fuzzy sets) connected to
each input variable is equal to the number of rules. This structure
generates highly overlapped fuzzy sets, which degrades rule
interpretability. In the EFNN, the merging technique [31] is applied
to merge highly overlapped fuzzy sets, which reduces the number
of nodes in this layer and improves rule interpretability.
Layer 3: The kth node in layer 3 represents the kth fuzzy rule and
performs antecedent matching by calculating the firing strength
given as follows:
Y
n

mk ðx1 ; :::; xn Þ ¼ Mkj xj :
j¼1
Layer 4: The node in layer 4 finds the predicted AHI value. The
consequent parameter wk in (4) functions as a link weight con-
necting the kth node in layer 3 the output node in this layer. The
node functions as a defuzzifier by using the weighted average
operation given as follows:
sðrþ1Þi ¼ 0:5, ðxi ðtÞ  mKi Þ2 (10)
i¼1
Different from the FNN in Ref. [32], highly overlapped fuzzy sets
are merged in the EFNN to generate transparent fuzzy sets. To this
end, the similarity between the new and each of the existing fuzzy
sets in an input variable is found. The metric SðA; BÞthat finds the
similarity of two fuzzy sets A and B by finding the cardinality of
their intersection jA ∩Bj over union jA ∪Bj is used. For each input
variable, if the maximum similarity value is smaller than a pre-
defined threshold (set to 0.5) then the new node (fuzzy set) in
layer 2 is reserved. Otherwise, the new node (fuzzy set) is merged
(6) into the node (fuzzy set) with the maximum S value. Fig. 3 shows an
example when a new input datum “a” causes the generation of
rule 3 according to (8), where two nodes (fuzzy sets C1 and C2 ) are
initially added to layer 2 accordingly. Because the new fuzzy set
C1 is highly overlapped with A1 , ie, SðA1 ; C1 Þ> 0.5, in input variable
x1 , it is merged to A1 . Therefore, only one node (fuzzy set C2 ) is
added to layer 2 after the measuring and merging process. This
operation helps obtain transparent fuzzy sets and improve rule
interpretability accordingly.
Parameter learning follows the structure learning for each training
datum. In this learning process, all of the free parameters in layer 2
(center mki and width ski ) and 4 (link weightwk ) are optimized by
minimizing the error function in (3). The parameters in layer 4 are
updated through the following recursive least square algorithm [31]:

. .
h.T i
. .
wðtÞ ¼ wðt  1Þ  SðtÞ m ðtÞ w ðt  1Þ m ðtÞ  AHId (11)

 . .T 
1 Sðt  1Þ m ðtÞ m ðtÞSðt  1Þ
SðtÞ ¼ Sðt  1Þ  : (12)
l .T
l þ m ðtÞSðt  1Þ m ðtÞ
.

. . P
r P
r
where w ¼ ½w1 ; :::; wr T , m ¼ ½m1 = mk ; :::; mr = mk T , and l is a
k¼1 k¼1
Fig. 2. The network structure of the EFNN. Abbreviations: EFNN, explainable fuzzy forgetting factor. The parameters in layer 2 are updated through the
neural network. gradient descent algorithm.
283
C.-F. Juang, C.-Y. Wen, K.-M. Chang et al.
Fig. 3. The distribution of fuzzy rules and fuzzy sets in the input space and the cor-
responding EFNN structure when a new rule is generated before and after the
measuring and merging operation. Abbreviations: EFNN, explainable fuzzy neural
network.
4. Results
A total of 300 participants were enrolled in the final analysis and
categorized into five sets (Table 1). The mean age of the participants
was 41.3 ± 3.2 years, and the majority were male. There were no
significant differences in the demographics and clinical data be-
tween the sets. As described in the study protocol, the five-fold
cross-validation scheme was used. For fold-1, based on the anal-
ysis of the training and validation datasets, 10 variables showed a
significant correlation (Pearson correlation coefficient > 0.3) with
AHI (Table 2a). These 10 variables were entered into stepwise
regression analysis, and three independent variables, WC, mean BP
at the end of the sleep test (Mean_A) and the difference of systolic
BP between the end and beginning of polysomnography (Diff_S),
were obtained from the feature extraction process (Table 2b). These
variables could not individually differentiate the presence of OSAHS
and diagnose the severity of OSAHS (Fig. 4). Meanwhile, the same
selection process applied to the other four folds. Table 2b shows the
selected variables in each fold. The systolic BPs measured at the end
of PSG (A_S) were selected in fold-2 and fold-3, while mean BPs
measured at the end of PSG minus that obtained at the beginning of
PSG (Diff_M) were selected in fold-3 and fold-4. Table 2c presents
the regression models for apnea-hypopnea index prediction that
were built depending on the significant factors from each fold.
The three selected variables were fed as inputs into the EFNN to
predict the AHI values in each of the five folds. In training the EFNN,
the hyperparameter mth determined the number of fuzzy rules and
the optimal one in each fold was selected from the candidate values
in {0.05, 0.1, …, 0.25} according to validation performance evalu-
ated in terms of the Sn þ Sp-1 values. The learning constant in the
284
Sleep Medicine 85 (2021) 280e290
gradient descent algorithm was set to 0.2. The maximum number of
training epochs was set to 150. After the training-validation pro-
cess, the optimal numbers of fuzzy rules in the five folds were
found to be 6, 9, 8, 7, and 5.
For comparison, the BPNN and linear regression models were
applied to the same prediction problem using the selected variables
in each fold. The optimal hyperparameter Nh (number of hidden
nodes) in each fold was selected from the candidate values in {5, 10,
15, 20, 25} according to validation performance. The maximum
number of training epochs in training the BPNN was set to 70,000.
After the training-validation process, the optimal numbers of Nh in
the five folds were found to be 10, 15, 10, 10, and 15. In addition to
the performance comparison of different models, the fuzzy pre-
diction model using the three different variables BMI, ESS and
Diff_S [40], denoted as B-E-D model, was also applied to the same
prediction problem to see the effect of the selected variables.
Table 3 shows that the predicted AHI scores were at variance
with the actual scores over the test datasets in the five folds when
using different prediction methods because of the high standard
deviation. Fig. 5 shows the obvious inconsistency between the
predicted AHI values and the observed values when using different
models. The results indicated that all the studied models did not
have a good performance to accurately predict AHI values. There-
fore, instead of predicting accurate AHI values, this paper applies
these models to predict the severity of OSAHS.
Table 4 shows the average Ac, Sn, Sp, and Sn þ Sp-1 values of
different prediction methods when diagnosing and grading OSAHS
of the test dataset over the five folds. With regards to the diagnosis
of OSAHS with an AHI threshold of 5 per hour, all of the studied
models had a high Ac along with a low Sp value. This suggested that
none of the studied models were suitable for the prediction of the
diagnosis of OSAHS.
With regards to predicting moderate-to-severe OSAHS at an AHI
threshold of 15 per hour, all studied models had an acceptable
ability to detect moderate-to-severe OSAHS while the EFNN ach-
ieved the highest Sn þ Sp-1 value of 0.44 (Table 4).
Finally, with regards to the prediction of severe OSAHS at an AHI
threshold of 30 per hour, Table 4 shows that all studied models had
a low Sn value. This indicated that none of the studied models were
suitable for screening severe OSAHS. In conclusion, all the predic-
tion models were most suitable for the detection of moderate-to-
severe OSAHS. Overall, the EFNN showed the advantage of high
interpretability in the inference process with better performance
than the other models in screening moderate-to-severe OSAHS.
Table 5 shows the overall confusion matrix using the EFNN
model. The wrong detection of a severe subject as mild or normal
would lead to reduced awareness of treatment priority. Of the 75
participants with severe OSAHS in the experiment, the EFNN pre-
dicted that six (8.0%) had mild OSAHS and no severe subject was
predicted as normal. Only one participant with moderate OSAHS
was detected as being a normal subject. Through further analysis, it
was found that all of these seven patients had a BMI <27.0 kg/m2
and four had an ESS >10, which suggests that a significant under-
estimation of the severity of OSAHS may occur in non-obese sub-
jects with suspected OSAHS as well as in those with excessive
daytime sleepiness.
Fig. 6 illustrates the understandable advantage of the EFNN with
the learned rules and distributions of the fuzzy sets in each input
variable in fold-1 and provides new knowledge from the inference
rules. For example, rule 6 in Fig. 6 showed that a very high Mean_A
and a positive large Diff_S inferred a high AHI value of 79.7 even
though the WC value was small. For WC, a special rule (rule 2) was
found. In this rule, the linguistic values of very large WC, medium
Mean_A, and negative medium Diff_S inferred a small AHI value of
1.6. To see why this special rule was generated, Fig. 7 shows the
C.-F. Juang, C.-Y. Wen, K.-M. Chang et al. Sleep Medicine 85 (2021) 280e290

Table 1
Baseline demographics and clinical characteristics of enrolled participants.

Total (n ¼ 300) Set 1 (n ¼ 60) Set 2 (n ¼ 60) Set 3 (n ¼ 60) Set 4 (n ¼ 60) Set 5 (n ¼ 60) P-value

Age (years) 41.3 ± 13.2 40.6 ± 13.6 42.2 ± 13.1 39.8 ± 13.2 39.0 ± 12.7 44.7 ± 13.1 0.137
Male gender 238 (79.3%) 44 (73.3%) 46 (76.7%) 51 (85.0%) 50 (83.3%) 47 (78.3%) 0.497
NC (cm) 37.6 ± 3.6 37.6 ± 3.3 37.1 ± 3.6 38.0 ± 3.3 37.5 ± 3.5 37.8 ± 4.3 0.742
WC (cm) 89.9 ± 10.9 90.5 ± 10.4 88.9 ± 10.7 90.8 ± 11.7 89.9 ± 9.6 89.5 ± 12.1 0.895
BMI (kg/m2) 26.2 ± 4.1 26.6 ± 4.3 25.9 ± 4.3 26.5 ± 3.9 26.0 ± 3.7 25.9 ± 4.5 0.788
TRT (minutes) 374.2 ± 12.7 375.2 ± 13.6 372.6 ± 11.7 375.6 ± 12.3 372.1 ± 12.5 374.8 ± 13.2 0.358
TST (minutes) 331.5 ± 28.8 332.4 ± 30.1 327.5 ± 30.2 332.7 ± 27.0 332.3 ± 23.8 332.7 ± 32.6 0.829
AHI (events per hour) 23.0 ± 23.9 22.2 ± 22.9 22.5 ± 23.4 22.9 ± 23.8 23.3 ± 24.5 23.9 ± 25.9 0.996
SE (%) 88.5 ± 7.2 87.7 ± 7.1 88.1 ± 7.4 88.6 ± 6.8 89.5 ± 6.6 88.8 ± 8.0 0.705
Sleep stage
REM (%) 13.3 ± 6.2 12.0 ± 6.2 13.6 ± 6.6 13.7 ± 5.8 13.4 ± 6.1 13.8 ± 6.2 0.474
N1 (%) 19.3 ± 14.2 18.8 ± 14.2 18.8 ± 12.8 19.6 ± 13.2 18.6 ± 13.3 20.6 ± 17.4 0.935
N2 (%) 55.0 ± 13.2 56.7 ± 13.6 56.6 ± 12.3 54.8 ± 11.5 54.2 ± 12.4 52.5 ± 11.8 0.276
N3 (%) 12.7 ± 10.4 12.6 ± 9.4 11.1 ± 10.0 11.9 ± 10.3 13.9 ± 11.3 13.8 ± 10.8 0.520
Arousal index (events per hour) 24.7 ± 20.6 23.7 ± 18.5 24.4 ± 18.7 25.1 ± 21.0 25.0 ± 20.1 25.2 ± 24.8 0.994
SpO2nadir (%) 82.4 ± 9.4 83.3 ± 8.5 82.6 ± 8.7 81.9 ± 10.2 83.2 ± 9.4 80.9 ± 10.1 0.617
ESS 10.9 ± 4.6 11.5 ± 4.8 9.9 ± 4.4 11.1 ± 4.1 10.5 ± 4.6 11.6 ± 5.0 0.215
B_S (mmHg) 127.1 ± 15.4 128.0 ± 16.5 128.1 ± 18.1 126.4 ± 15.2 127.2 ± 12.2 125.7 ± 14.7 0.899
B_D (mmHg) 83.6 ± 11.6 85.9 ± 12.6 83.7 ± 12.8 83.2 ± 11.0 82.5 ± 9.7 82.7 ± 11.7 0.494
A_S (mmHg) 127.0 ± 7.5 128.0 ± 20.1 128.8 ± 21.5 127.0 ± 15.6 125.3 ± 13.7 125.6 ± 15.5 0.777
A_D (mmHg) 86.8 ± 13.5 88.4 ± 14.3 86.9 ± 15.2 87.0 ± 13.3 85.7 ± 10.8 86.3 ± 13.7 0.847

Abbreviations: A_D, diastolic blood pressure measured at the end of polysomnography; AHI, apnea-hypopnea index; A_S, systolic blood pressure measured at the end of
polysomnography; B_D, diastolic blood pressure measured at the beginning of polysomnography; BMI, body mass index; B_S, systolic blood pressure measured at the
beginning of polysomnography; ESS, Epworth Sleepiness Scale; NC, neck circumference; REM, rapid eye movement; SE, sleep efficiency; SpO2nadir, minimum of arterial
oxyhemoglobin saturation by pulse oximetry; TRT, total recording time; TST, total sleep time; WC, waist circumference.

Table 2
(a) The Pearson correlation between apnea-hypopnea index and physiological fea- AHI value in contrast to those with large WC values. This subject led
tures of interest in the training and validation sets of fold-1. (b) The extarcted var-
to the generation of rule 2, and therefore the width of the fuzzy set
iables in each fold. (c) Regression models for apnea-hypopnea index prediction
dependent on significant factors from each fold.
in the WC feature for this rule was automatically learned to be small
to mainly cover only this subject. To see the effect of this training
(a)
subject and rule 2, another experiment with the same training data
Variable r Variable r with the exclusion of this subject was performed. After training, a
Age 0.152* A_S 0.492* total of five rules were generated. The rules were similar to those in
NC 0.435* A_D 0.509* Fig. 6, except that rule 2 was not generated. The Ac, Sn, and Sp
WC 0.519* Mean_B 0.309* values in the test dataset were the same as those in the original six-
BMI 0.515* Mean_A 0.523*
rule EFNN. These results showed that the special subject did not
ESS 0.162* Diff_S 0.371*
B_S 0.290* Diff_D 0.350* bias the validation performance of the EFNN.
B_D 0.299* Diff_M 0.396* Fig. 8 shows the corresponding structure of the EFNN. A total of
(b)
six rules (rule nodes) were generated from the training data. There
were 3, 4 and 4 fuzzy sets (nodes) in WC, Mean_A, and Diff_S,
Extracted variables
respectively. In the test, the Ac, Sn, and Sp values were 0.75, 0.867,
Fold 1 Mean_A, WC, Diff_S and 0.633, respectively, for screening moderate-to-severe OSAHS.
Fold 2 A_S, WC, Diff_S
Fig. 9 shows the actual and predicted AHI values from the EFNN.
Fold 3 A_S, WC, Diff_M
Fold 4 Mean_A, WC, Diff_M
Among the 14 subjects with severe OSAHS, subjects 3 and 53 with
Fold 5 Mean_A, WC, Diff_S the feature sets of (WC, Mean_A, Diff_S; AHI) ¼ (83, 107, 11; 63.7)
(c)
and (86, 97.7, and 14; 43.6), respectively, were wrongly predicted
to have mild OSAHS. These may be due to the normal BP dipping.
linear regression equation R2
Nevertheless, these subjects were still non-obese (BMI ¼ 24.2 and
Fold 1 98.6 þ 0.524  Mean_A þ 0.770  WC þ 0.281  Diff_S 0.367 23 kg/m2, respectively).
Fold 2 94.8 þ 0.379  A_S þ 0.763  WC þ 0.354  Diff_S 0.426
Fold 3 91.3 þ 0.304  A_S þ 0.828  WC þ 0.608  Diff_M 0.462
Fold 4 93.6 þ 0.245  Mean_A þ 1.012  WC þ 0.685  Diff_M 0.452
Fold 5 99.6 þ 0.411  Mean_A þ 0.913  WC þ 0.334  Diff_S 0.369 5. Discussion
*p < 0.05.
Abbreviations: Diff_D, diastolic blood pressure measured at the end of poly- Three significant, easy-to-obtain physiological features obtained
somnography minus that measured at the beginning of polysomnography; Diff_M, from the stepwise regression analysis were fed as inputs into
mean blood pressure measured at the end of polysomnography minus that
measured at the beginning of polysomnography; Diff_S, systolic blood pressure
different prediction models. None of the studied models had good
measured at the end of polysomnography minus that measured at the beginning of performance for the prediction of AHI values and OSAHS diagnosis
polysomnography; Mean_A, mean blood pressure measured at the end of poly- at an AHI threshold of 5 per hour while all of the tested methods
somnography; Mean_B, mean blood pressure measured at the beginning of poly- could differentiate moderate-to-severe OSAHS from normal-to-
somnography; also see Table 1.
mild OSAHS well. Moreover, the EFNN showed the best perfor-
mance for the screening of moderate-to-severe OSAHS among the
relationship between all training values of WC and AHI in fold-1. studied models although a clinically significant misclassification
We observed that the subject with the largest WC value, ie, (WC, may occur in subjects with non-obesity and excessive sleepiness
Mean_A, Diff_S; AHI) ¼ (136, 83.67, 6; 14), had an unusually small during daytime hours.
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Fig. 4. The distribution of individual extracted variables by OSAHS diagnosis and severity. Abbreviations: OSAHS, obstructive sleep apnea-hypopnea syndrome.

Table 3
The differences between the observed and predicted apnea-hypopnea indexes by studied models derived from each fold.

Actual AHI EFNN BPNN Regression B-E-D Model

Fold 1
Average 23.9 ± 25.8 19.8 ± 16.0 15.9 ± 13.4 22.4 ± 15.8 21.7 ± 13.8
Difference 4.2 ± 20.0 8.0 ± 21.6 1.6 ± 19.6 2.2 ± 20.0
Fold 2
Average 23.3 ± 24.5 21.6 ± 12.9 19.0 ± 12.5 20.7 ± 12.5 20.6 ± 11.5
Difference 1.7 ± 18.8 4.3 ± 19.5 2.6 ± 20.4 2.7 ± 21.0
Fold 3
Average 22.9 ± 23.8 23.2 ± 17.3 20.9 ± 16.3 24.8 ± 12.8 21.0 ± 12.6
Difference 0.3 ± 19.6 2.0 ± 18.6 1.9 ± 21.0 1.9 ± 23.8
Fold 4
Average 22.5 ± 23.4 22.8 ± 16.8 20.5 ± 18.4 21.9 ± 16.3 23.4 ± 16.7
Difference 0.3 ± 16.9 2.0 ± 20.4 0.7 ± 18.8 0.8 ± 19.6
Fold 5
Average 22.2 ± 22.9 20.2 ± 13.4 21.2 ± 16.8 24.9 ± 14.1 20.5 ± 11.6
Difference 2.0 ± 15.3 1.0 ± 13.9 2.7 ± 16.3 1.7 ± 18.1
Total
Average 22.9 ± 23.9 21.5 ± 15.3 19.5 ± 15.6 22.9 ± 14.4 21.6 ± 13.3
Difference 1.5 ± 18.2 3.5 ± 19.1 0.1 ± 19.3 1.5 ± 20.5

Abbreviations: BPNN, back propagation neural network; EFNN, explainable fuzzy neural network; also see Table 1.

Previously, Wu MF et al. proposed the screening method using
the combination of physiological measurements and question-
naires with a fuzzy system prediction model [40]. Three easily
available measurements, including BMI, Diff_S and ESS, were
entered into the prediction model. With the consideration of
screening of moderate-to-severe OSAHS and the objects sampled
with SE  80%, the prediction model showed the performance of a
Sn of 75.6% and a Sp of 77.2%, which were acceptable for clinical
practice. By contrast, this study enrolled subjects with SE  70% for
assessment in order to apply a screening method to a larger pop-
ulation. A similar efficacy (Sn of 79.3% and Sp of 64.7%) was ach-
ieved when compared to that reported by Wu et al. (Sn: 75.6%
versus 79.3%; Sp: 77.2% versus 64.7%) while different easily avail-
able features were chosen to predict moderate-to-severe OSAHS or
not in our study [40]. The inconsistent feature extraction between
the present study and that reported by Wu MF et al. may arise from
the different enrolled requirement of sleep efficiency that would
affect blood pressure and dipping [40e42].
In contrast to our findings that none of the tested models had a
good performance for the prediction of AHI scores and OSAHS
diagnosis at an AHI threshold of 5 per hour, previous studies have
shown that NNs and clinical regression models can reliably predict
AHI values and the diagnosis of OSAHS when using a large set of
complex and difficult to self-estimate input signals
[6,7,10e15,24,39]. This implies that it may suffer from a major in-
adequacy in those studies that performed well in the prediction of
AHI values and the diagnosis of OSAHS. That is, subjects suspected
to have OSAHS and clinicians have barriers in adopting these
methods to improve the management for OSAHS because of diffi-
culties in obtaining these input data.
In addition to the predicting performance, this paper also
considered building an explainable prediction model. Methods for
explaining AI models could be classified as intrinsic model inter-
pretation or post hoc interpretation approaches according to the
focus on the modeling or post hoc analysis stage [43], respectively.
For the latter approach, one popular method is applying the
SHapley Additive exPlanations (SHAP) [44] to interpret the pre-
dictions of any machine learning models. The SHAP is a unified and
model-agnostic method that measures contributions of each
feature to model predictions by using Shapely values. This paper
focused on the former approach and built the EFNN so that the
constructed fuzzy rule-based model could provide insights into the
relationship it had learned. For example, by inspecting the lin-
guistic relationship between each of the input variables and the
inferred AHI values, a higher Mean_A value tended to cause a
higher AHI value. A positive Diff_S value was also found to be

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Fig. 5. The agreement between observed AHI and that predicted by (a) EFNN, (b) BPNN, (c) B-E-D model and (d) stepwise regression. Abbreviations: AHI, apnea-hypopnea index;
BPNN, backpropagation neural network; EFNN, explainable fuzzy neural network.

Table 4 Table 5
The sensitivity, specificity, and accuracy in the diagnosis and grading of obstructive The overall confusion matrix in the EFNN prediction.
sleep apnea-hypopnea syndrome by the tested prediction models.
Predicted AHI Actual AHI
AHI AHI AHI
<5 5-14 15-30 S30 <15 S15
threshold ¼ 5 threshold ¼ 15 threshold ¼ 30
(n ¼ 75) (n ¼ 75) (n ¼ 75) (n ¼ 75) (n ¼ 150) (n ¼ 150)
EFNN Sn 0.982 0.793 0.573
<5 4 3 1 0 NA NA
Sp 0.053 0.647 0.876
(n ¼ 8)
Sn þ Sp-1 0.035 0.440 0.449
5-14 52 38 24 6 NA NA
Ac 0.750 0.720 0.800
(n ¼ 120)
BPNN Sn 0.928 0.787 0.560
15-30 18 27 30 26 NA NA
Sp 0.360 0.627 0.876
(n ¼ 101)
Sn þ Sp-1 0.288 0.414 0.436
>30 1 7 20 43 NA NA
Ac 0.757 0.707 0.797
(n ¼ 71)
Regression Sn 0.942 0.900 0.627
<15 NA NA NA NA 97 31
Sp 0.293 0.480 0.827
(n ¼ 128)
Sn þ Sp-1 0.236 0.380 0.453
S15 NA NA NA NA 53 119
Ac 0.780 0.690 0.777
(n ¼ 172)
B-E-D Model Sn 0.978 0.720 0.520
Sp 0.267 0.627 0.916 Abbreviations: NA, not applicable; also see Tables 1 and 3
Sn þ Sp-1 0.004 0.347 0.436
Ac 0.740 0.675 0.817

Abbreviations: Ac, accuracy; Sn, sensitivity; Sp, specificity; also see Tables 1 and 3
closely related to a high AHI value. A higher WC value was also
related to a higher AHI value. Taken together, the relationship be-
tween each individual variable and the AHI value was similar to the
statistical results as shown in Fig. 4. Thus, the proposed EFNN
shows the advantage of making the inference of AI models inter-
pretable and understandable in the process of predicting AHI when
using easily available physiologic features as the input data.
There are some limitations in this study. First, when applying
the proposed EFNN to screen moderate-to-severe OSAHS, caution
should be taken when interpreting the results as the severity of
OSAHS may be underestimated in non-obese subjects and in those
with excessive daytime sleepiness. Second, given the inherent
limitations of studies on OSAHS and the possible effects of medi-
cations and co-morbidities on PSG results and BP measurements,
our results are subject to selection bias toward young male adults,
ie, nearly 80% of our participants were young men, which may
make the results not generalizable to other populations.

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Fig. 6. The rules generated from training data and distribution of fuzzy sets in each input variable. Where (ms) denotes (center, width) of a fuzzy set.

Fig. 7. The relationships between all WC and AHI values in the fold-1 training dataset,
where the largest WC value is marked by a circle. Abbreviations: AHI, apnea-hypopnea Fig. 8. The structure of the EFNN corresponding to the fuzzy rules in Fig. 6. Abbrevi-
index; WC, waist circumference. ations: EFNN, explainable fuzzy neural network.

288
C.-F. Juang, C.-Y. Wen, K.-M. Chang et al.
Fig. 9. The actual and predicted AHI values from the EFNN in the fold-1 test dataset.
Abbreviations: AHI, apnea-hypopnea index; EFNN, explainable fuzzy neural network.
Different from previous studies which adopted difficult to self-
estimate input measurements to diagnose OSAHS and assess the
severity of OSAHS [10e15], we used easily available physiological
parameters to predict moderate-to-severe OSAHS, making it easy to
apply for self-screening by both subjects suspected of having
OSAHS and clinicians with a competitive performance and helpful
to optimize the utility of sleep center resources in real-world
practice. Future AI research should keep using easily available
characteristics as the input data and enroll more diverse patient
populations to develop a more practical and precise screening
method.
6. Conclusions
Out of the tested methods, the EFNN, which was based on three
easily available physiological features, showed the advantage of
model interpretability with competitive performance for screening
subjects who were suspected of having OSAHS. Therefore, it is
suggested that the EFNN would be the preferred method for self-
estimation of moderate-to-severe OSAHS.
Funding
This work was supported by the Taichung Veterans General
Hospital, Taiwan and National Chung Hsing University, Taiwan
(grant number TCVGH-NCHU1067608); the Taichung Veterans
General Hospital, Taiwan and Nan kai University of Technology,
Taiwan (grant number TCVGH-NK1079005).
Data statement
The research data is confidential.
Author contribution statement
Chia-Feng Juang: Conceptualization, Methodology, Formal
analysis, Investigation, Resources, Data curation, Writing- Original
draft preparation, Funding acquisition.
Chih-Yu Wen: Conceptualization, Methodology, Formal analysis,
Investigation, Validation, Writing- Reviewing and Editing.
Kai-Ming Chang: Conceptualization, Methodology, Formal
analysis, Investigation, Validation, Writing- Reviewing and Editing.
Yu-Hsuan Chen: Conceptualization, Methodology, Formal anal-
ysis, Investigation, Validation, Writing- Reviewing and Editing.
Ming-Feng Wu: Conceptualization, Methodology, Formal anal-
ysis, Investigation, Resources, Data curation, Writing- Reviewing
289
Sleep Medicine 85 (2021) 280e290
and Editing, Visualization, Project administration, Funding
acquisition.
Wei-Chang Huang: Conceptualization, Methodology, Validation,
Formal analysis, Investigation, Resources, Writing- Reviewing and
Editing, Visualization, Supervision. Having full access to all of the
data in the study, taking responsibility for the integrity of the data
and the accuracy of the data analysis, and being the guarantor of the
content of the manuscript, including the data and analysis.
Acknowledgements
The authors thank Dr. Gwan-Han Shen, who supervised Labo-
ratory No. 114 at Taichung Veterans General Hospital and passed
away in 2014. We hold you dear in our memory.
Conflict of interest
None.
The ICMJE Uniform Disclosure Form for Potential Conflicts of
Interest associated with this article can be viewed by clicking on the
following link: https://doi.org/10.1016/j.sleep.2021.07.012
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