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\usepackage[style=ieee, backend=biber]{biblatex}
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%! Author = alex
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%! Date = 3/7/25
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\section{Background}\label{sec:background}
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\subsection{Physiological Background}\label{subsec:physiological_background}
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@@ -13,13 +14,13 @@ During the follicular phase, the ovarian follicles mature, and the endometrium (
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in preparation for a potential implantation of a fertilized egg.
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Around day 14 of a typical cycle, ovulation occurs, marking the transition to the luteal phase.
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Ovulation refers to the rupture of the mature ovarian follicle and the release of an egg cell into the fallopian tube.
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Figure\ref{fig:background_basic_female_reproductive_system} illustrates the female reproductive system,
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Figure~\ref{fig:background_basic_female_reproductive_system} illustrates the female reproductive system,
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including the ovaries and the fallopian tubes.
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\\
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\begin{figure}
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\centering
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\includegraphics[width=0.4\textwidth]{background_female_reproductive_organs}
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\caption{The basic female reproductive system\cite{wikimedia_commons_basic_2019}.}
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\caption{The basic female reproductive system~\cite{wikimedia_commons_basic_2019}.}
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\label{fig:background_basic_female_reproductive_system}
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\end{figure}
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Ovulation is triggered by a surge in \textbf{luteinizing hormone (LH)}
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@@ -35,19 +36,19 @@ with the unfertilized egg.
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This process, known as menstruation, marks the beginning of a new cycle.
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\\
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The menstrual cycle typically lasts around 28 days, with ovulation occurring near the midpoint.
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However, variations, particularly in the follicular phase length, are common and can be influenced by factors such as stress, diet, exercise and age\cite{silberstein_physiology_2000}.
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However, variations, particularly in the follicular phase length, are common and can be influenced by factors such as stress, diet, exercise and age~\cite{silberstein_physiology_2000}.
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Figure~\ref{fig:background_menstrual_cycle_physiology} provides a detailed overview of the hormonal and physiological changes
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throughout the menstrual cycle.
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\begin{figure}
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\centering
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\includegraphics[width=0.6\textwidth]{background_menstrual_cycle_physiology}
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\caption{Physiological changes during the menstrual cycle\cite{pedroso_menstrual_2022}.}
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\caption{Physiological changes during the menstrual cycle~\cite{pedroso_menstrual_2022}.}
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\label{fig:background_menstrual_cycle_physiology}
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\end{figure}
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Not every cycle results in ovulation—a phenomenon known as anovulation—which leads to a monophasic temperature pattern.
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Anovulation can have various causes, including hormonal imbalances, stress, or underlying health conditions\cite{rosenfield_adolescent_2013}.
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Anovulation can have various causes, including hormonal imbalances, stress, or underlying health conditions~\cite{rosenfield_adolescent_2013}.
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Anovulation is reflected in temperature data as either an absence of a clear temperature rise or a rise
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that is insufficient in magnitude or duration to be considered a reliable indicator of ovulation.
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@@ -63,15 +64,15 @@ Even ultrasound imaging can only confirm that an egg was released from its folli
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Throughout the menstrual cycle, the chance of fertilization varies significantly.
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An egg cell released from the ovary during ovulation, can be fertilized for up to 24 hours.
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However, since male sperm cells can survive up to 6 days inside the female reproductive tract,
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the fertile window is typically defined as the five days before ovulation until one day after ovulation\cite{dunson_day-specific_1999}.
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Research by \citeauthor{dunson_day-specific_1999} has shown that the highest chance of fertilization is around one day before ovulation,
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the fertile window is typically defined as the five days before ovulation until one day after ovulation~\cite{dunson_day-specific_1999}.
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Research by~\citeauthor{dunson_day-specific_1999} has shown that the highest chance of fertilization is around one day before ovulation,
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as illustrated in Figure~\ref{fig:background_pregnancy_chance}.
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\begin{figure}
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\centering
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\includegraphics[width=0.7\textwidth]{background_pregnancy_chance_over_time}
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\caption{Chance of fertilization depending on the day of the menstrual cycle.
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The highest chance is around one day before ovulation\cite{dunson_day-specific_1999}.}
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The highest chance is around one day before ovulation~\cite{dunson_day-specific_1999}.}
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\label{fig:background_pregnancy_chance}
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\end{figure}
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@@ -86,7 +87,7 @@ Several physiological signs correlate with ovulation and can be used for predict
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As shown in Figure~\ref{fig:background_menstrual_cycle_physiology}, these include hormonal fluctuations (LH and FSH surges) and
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changes in body temperature.
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Additionally, variations in cervical mucus consistency, salivary ferning patterns,
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and electrical resistance of the skin and vaginal mucosa have been observed\cite{silberstein_physiology_2000}.
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and electrical resistance of the skin and vaginal mucosa have been observed~\cite{silberstein_physiology_2000}.
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Among these, ultrasonography provides the most accurate confirmation of ovulation by detecting follicular changes,
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but it is costly and requires specialized equipment.
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@@ -95,7 +96,7 @@ but they require frequent testing.
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Temperature-based methods, particularly body temperature tracking, offer a non-invasive alternative by
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detecting the slight temperature rise that follows ovulation.
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Advances in wearable technology have further enabled continuous and automated temperature monitoring,
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improving accessibility and usability\cite{alexander_fertilitatsmonitoring_2014, luo_detection_2020, yu_tracking_2022}.
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improving accessibility and usability~\cite{alexander_fertilitatsmonitoring_2014, luo_detection_2020, yu_tracking_2022}.
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\subsection{Technical Background}\label{subsec:technological_background}
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@@ -103,65 +104,111 @@ improving accessibility and usability\cite{alexander_fertilitatsmonitoring_2014,
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Time series analysis is a fundamental tool for studying sequential data that evolves over time.
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Unlike other data types, time series data has an inherent temporal order, where each data point is associated
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with a timestamp, capturing its dependence on past values.
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There are usually two main goals:
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understanding the underlying mechanisms that lead to the observed data and predicting future data points based on the
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historical information and potentially external factors\cite{cryer_time_2008}
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Time series analysis typically serves two main goals:
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Understanding the underlying mechanisms that lead to the observed data and predicting future data points based on the
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historical information and potentially external factors~\cite{cryer_time_2008}
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\\
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Time series analysis encompasses various methods, ranging from simple statistical models to complex deep learning architectures.
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Classical methods
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\subsubsection{Transformer Models}\label{subsubsec:transformer_models}
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\subsubsection{Temporal-Fusion-Transformer Models}\label{subsubsec:temporal_fusion_transformer_models}
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The Temporal Fusion Transformer (TFT) is a deep learning model designed for time series forecasting.
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It's a novel approach at time series analysis and forecasting presented by Google in 2020\cite{lim_temporal_2020}.
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The main focus of this architecture is to both achieve high prediction accuracy while maintaining interpretability.
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It differs from a traditional implementation of a transformer architecture by incorporating the support for:
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In the following, we will introduce the two most common approaches used for machine learning on time series data,
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LSTMs and transformers.
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\subsubsection{RNN and LSTM Networks}\label{subsubsec:lstm_networks}
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Recurrent Neural Networks (RNNs) are extensions of classical neural networks that incorporate cyclic connections between neurons.
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These recurrent connections allow the network to retain information from previous inputs by feeding the hidden state
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from a prior time step into the current one, enabling a form of temporal memory.
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In practice, this means that input data is processed sequentially, one step at a time.
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At each step \(t\), the input \(x_t\) is combined with the previous hidden state \(h_{t-1}\) to produce a new
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hidden state \(h_t\), which contributes to the output \(o_t\).
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This process allows the network to learn temporal dependencies and model sequential data effectively~\cite{medsker_recurrent_1999}.
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However, this approach has the downside that the model cannot explicitly control how it remembers or forgets information at each step,
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limiting its ability to manage long-term dependencies.
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During training via backpropagation, the weights of a neural network are updated based on the partial derivatives of the loss function.
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The more propagations required (e.g., in deeper networks), the more multiplications are needed to compute gradients for earlier weights.
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RNNs are typically trained using \textit{backpropagation through time} (BPTT), in which gradients are propagated through many time steps,
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leading to numerical instability.
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If the gradients shrink exponentially, the model suffers from the \emph{vanishing gradient} problem;
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if they grow exponentially, it results in \emph{exploding gradients}~\cite{hochreiter_vanishing_1998}.
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In both cases, learning is significantly impaired.
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Exploding gradients can often be mitigated using techniques such as \emph{gradient clipping},
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where the magnitude of the gradient is capped---typically within a range of \([-1, 1]\)---to stabilize training.
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Figure~\ref{fig:rnn_unfolded} illustrates the unfolded structure of an RNN across three time steps.
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This technique, known as \emph{unfolding}, clarifies how sequential inputs update the hidden state and generate
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outputs at each time step.
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\begin{figure}
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\centering
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\includegraphics[width=0.7\textwidth]{recurrent_neural_network_unfold}
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\caption{Schematic diagram of the unfolded structure of a recurrent neural network~\cite{fdeloche_english_2017}}
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\label{fig:rnn_unfolded}
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\end{figure}
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To address the vanishing gradient problem and enable better long-term memory,
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\emph{Long Short-Term Memory} (LSTM) networks were introduced by \citeauthor{hochreiter_long_1997}~\cite{hochreiter_long_1997}.
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LSTMs extend the RNN architecture by incorporating a memory cell and a series of gates that regulate the flow of
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information: the \emph{forget gate}, the \emph{input gate}, and the \emph{output gate}.
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\begin{itemize}
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\item Multiple inputs (static, past and future variables)
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\item Long sequences
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\item Uncertainty
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\item The \emph{forget gate} determines which information from the previous cell state should be discarded.
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\item The \emph{input gate} controls what new information is added to the cell state.
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\item The \emph{output gate} selects relevant parts of the current cell state to produce the output and the next hidden state.
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\end{itemize}
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Figure~\ref{fig:background_tft_architecture} provides an overview of the TFT architecture.
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\paragraph{1. Gating Mechanisms}
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As the precise relationship between input variables is hard to anticipate in advance, the authors introduce a mechanisms,
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that allows the model to learn this relationship, giving it the ability to choose whether to apply a non-linear
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transformation to the inputs.
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Sometimes, the relationship between variables is linear, and applying a non-linear transformation would only add noise.
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They call this mechanism Gated Residual Network (GRN).
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GRNs take the primary input vector $a$ and an optional context vector $c$ and compute the output as follows:
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\begin{align}
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\text{GRN}_{\omega}(a, c) &= \text{LayerNorm}(a + \text{GLU}_{\omega}(\eta_1)) \label{eq:grn} \\
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\eta_1 &= W_{1,\omega} \eta_2 + b_{1,\omega} \label{eq:eta1} \\
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\eta_2 &= \text{ELU}(W_{2,\omega} a + W_{3,\omega} c + b_{2,\omega}) \label{eq:eta2}
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\end{align}
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ELU refers to the Exponential Linear Unit activation function, which is a variant of the ReLU function,
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that speeds up training and alleviates the vanishing gradient problem\cite{clevert_fast_2016}.
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LayerNorm refers to a more robust normalization technique compared to batch normalization, which is used to stabilize
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and speed up training in deep neural networks\cite{ba_layer_2016}.
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Here, $\omega$ denotes weight sharing.
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For large $W_{2,\omega}\ a + W_{3\omega}\ c + b_{2,\omega} \gg 0$ the output of the ELU is approximately $a$, acting
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as identity function.
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For negative values, it generates a constant output, resulting in a linear transformation of the input.
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Gating layers based on the Gated Linear Unit (GLU)\cite{dauphin_language_2017} provide the model with the ability to
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suppress any parts of the architecture not needed for the prediction in a dataset.
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\paragraph{2. Variable Selection Networks (VSNs)}
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Variable Selection Networks (VSNs) are a key component of the TFT architecture, allowing the model to both
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select input variables most relevant to the prediction and removing unnecessary, noisy inputs, that could negatively
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impact prediction performance.
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Each component, i.e., static, past, and future variables, use separate VSNs to select the most relevant features.
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Inputs to the VSN use entity embeddings for categorical features or a linear transformation for continuous features.
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This transforms the inputs into the ($d_{model}$)-dimensional space, where $d_{model}$ is the model's hidden dimension.
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Each gate employs a sigmoid activation function to regulate the flow of information,
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allowing LSTMs to preserve and update memory over long sequences.
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\begin{figure}
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\centering
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\includegraphics[width=0.8\textwidth]{background_tft_architecture}
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\caption{TFT architecture overview\cite{lim_temporal_2020}.}
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\label{fig:background_tft_architecture}
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\includegraphics[width=0.6\textwidth]{lstm_cell_diagram}
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\caption{Diagram of a LSTM cell showing the flow of information \cite{chevalier_english_2018}}
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\label{fig:lstm_architecture}
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\end{figure}
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Figure~\ref{fig:lstm_architecture} illustrates the architecture of an LSTM cell.
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On the left, the previous cell state \(C_{t-1}\) represents the long-term memory,
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while the hidden state \(h_{t-1}\) encodes the short-term memory from the preceding time step.
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The current input \(x_t\) is processed together with these states to update the cell.
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The resulting new cell state \(C_t\) and hidden state \(h_t\) are passed forward to the next time step or used to produce the model’s output.
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Within the cell, the forget gate determines how much of the previous cell state \(C_{t-1}\) is retained.
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The input gate updates the cell state with new information derived from the current input and previous hidden state.
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Finally, the output gate controls how much of the updated cell state contributes to the hidden state \(h_t\),
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which is passed on to the next time step or used for prediction.
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Mathematically, the core LSTM operations are given by:
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\[
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\begin{aligned}
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f_t &= \sigma(W_f [h_{t-1}, x_t] + b_f) \\
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i_t &= \sigma(W_i [h_{t-1}, x_t] + b_i) \\
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\tilde{c}_t &= \tanh(W_c [h_{t-1}, x_t] + b_c) \\
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c_t &= f_t \odot c_{t-1} + i_t \odot \tilde{c}_t \\
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o_t &= \sigma(W_o [h_{t-1}, x_t] + b_o) \\
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h_t &= o_t \odot \tanh(c_t)
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\end{aligned}
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\]
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Here, \( \odot \) denotes element-wise multiplication, and \( \sigma \) is the sigmoid function.
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These equations allow for more stable training and long-range temporal modeling.
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\\
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LSTMs are widely used in biomedical applications due to their capacity to handle sequences of variable length and complexity.
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In the context of ovulation prediction, where hormonal patterns exhibit periodicity but also irregularity,
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LSTMs are well-suited to learn relevant time-dependent signals from sequential physiological measurements.
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While powerful, LSTMs can be computationally intensive and sensitive to hyperparameter tuning.
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Therefore, they are often compared with alternative architectures,
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including simpler feedforward networks and more recent attention-based models,
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to evaluate trade-offs in performance, interpretability, and computational cost.
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The next section introduce the \emph{Transformer} architecture, a more recent alternative that forgoes
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recurrence in favor of attention mechanisms
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\subsubsection{Transformer Models}\label{subsubsec:transformer_models}
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