Personalized, intuitive & visual QT-prolongation monitoring using patient-specific QTc threshold with pseudo-coloring and explainable AI.

BACKGROUND: Drug-induced QT-prolongation increases the risk of TdP arrhythmia attacks and sudden cardiac death. However, measuring the QT-interval and determining a precise cut-off QT/QTc value that could put a patient at risk of TdP is challenging and influenced by many factors including female sex, drug-free baseline, age, genetic predisposition, and bradycardia. OBJECTIVES: This paper presents a novel approach for intuitively and visually monitoring QT-prolongation showing a potential risk of TdP, which can be adjusted according to patient-specific risk factors, using a pseudo-coloring technique and explainable artificial intelligence (AI). METHODS: We extended the development and evaluation of an explainable AI-based technique- visualized using pseudo-color on the ECG signal, thus intuitively 'explaining' how its decision was made -to detect QT-prolongation showing a potential risk of TdP according to a cut-off personalized QTc value (using Bazett's ∆QTc > 60 ms relative to drug-free baseline and Bazett's QTc > 500 ms as examples), and validated its performance using a large number of ECGs (n = 5050), acquired from a clinical trial assessing the effects of four known QT-prolonging drugs versus placebo on healthy subjects. We compared this new personalized approach to our previous study that used a more general approach using the QT-nomogram. RESULTS AND CONCLUSIONS: The explainable AI-based algorithm can accurately detect QT-prolongation when adjusted to a personalized patient-specific cut-off QTc value showing a potential risk of TdP. Using ∆QTc > 60 ms relative to drug-free baseline and QTc > 500 ms as examples, the algorithm yielded a sensitivity of 0.95 and 0.79, and a specificity of 0.95 and 0.98, respectively. We found that adjusting pseudo-coloring according to Bazett's ∆QTc > 60 ms relative to a drug-free baseline personalized to each patient provides better sensitivity than using Bazett's QTc > 500 ms, which could underestimate a potentially clinically significant QT-prolongation with bradycardia.

Assessment of General and Sports Nutrition Knowledge, Dietary Habits, and Nutrient Intake of Physical Activity Practitioners and Athletes in Riyadh, Saudi Arabia.

Physical performance and overall health are crucial in the athletic population, and their improvement relies on specific dietary guidelines and practices. Athletes and physical activity practitioners who participate in physical activity for specific health reasons need nutritional knowledge to improve physical performance. This study aimed to understand nutrient intake and nutritional knowledge among physical activity practitioners and athletes in Riyadh, Saudi Arabia. This cross-sectional study sampled 263 individuals divided into two groups: athletes (n = 121) and practitioners (n = 142). Their nutritional knowledge and dietary intake were measured with validated questionnaires: the Arabic Abridged Nutrition for Sport Knowledge Questionnaire and the Saudi Food Frequency Questionnaire. The majority of the sample (77.2%) had poor nutritional knowledge. Highest scoring domains for the dietary intake were protein from meat, fish, chicken (65.6%), vegetarian protein (62.4%), grains (51.0%), and the lowest were vegetables (41.1%), dairy (36.3%), and fruits (27.9%). In conclusion, athletes and practitioners in Riyadh, Saudi Arabia, have poor nutritional knowledge and dietary intake and may benefit from nutritional education and training to improve their knowledge, dietary intake, and performance.

Comprehensible Machine-Learning-Based Models for the Pre-Emptive Diagnosis of Multiple Sclerosis Using Clinical Data: A Retrospective Study in the Eastern Province of Saudi Arabia.

Multiple Sclerosis (MS) is characterized by chronic deterioration of the nervous system, mainly the brain and the spinal cord. An individual with MS develops the condition when the immune system begins attacking nerve fibers and the myelin sheathing that covers them, affecting the communication between the brain and the rest of the body and eventually causing permanent damage to the nerve. Patients with MS (pwMS) might experience different symptoms depending on which nerve was damaged and how much damage it has sustained. Currently, there is no cure for MS; however, there are clinical guidelines that help control the disease and its accompanying symptoms. Additionally, no specific laboratory biomarker can precisely identify the presence of MS, leaving specialists with a differential diagnosis that relies on ruling out other possible diseases with similar symptoms. Since the emergence of Machine Learning (ML) in the healthcare industry, it has become an effective tool for uncovering hidden patterns that aid in diagnosing several ailments. Several studies have been conducted to diagnose MS using ML and Deep Learning (DL) models trained using MRI images, achieving promising results. However, complex and expensive diagnostic tools are needed to collect and examine imaging data. Thus, the intention of this study is to implement a cost-effective, clinical data-driven model that is capable of diagnosing pwMS. The dataset was obtained from King Fahad Specialty Hospital (KFSH) in Dammam, Saudi Arabia. Several ML algorithms were compared, namely Support Vector Machine (SVM), Decision Tree (DT), Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGBoost), Adaptive Boosting (AdaBoost), and Extra Trees (ET). The results indicated that the ET model outpaced the rest with an accuracy of 94.74%, recall of 97.26%, and precision of 94.67%.

Survey of Approaches for Investigation of Atherosclerosis In Vivo.

Although in vitro model systems are useful for investigation of atherosclerosis-associated processes, they represent simplification of complex events that occur in vivo, which involve interactions between many different cell types together with their environment. The use of animal model systems is important for more in-depth insights of the molecular mechanisms underlying atherosclerosis and for identifying potential targets for agents that can prevent plaque formation and even reverse existing disease. This chapter will provide a survey of such animal models and associated techniques that are routinely used for research of atherosclerosis in vivo.

Monitoring Modified Lipoprotein Uptake and Macropinocytosis Associated with Macrophage Foam Cell Formation.

Macrophage foam cell formation plays a crucial role in the initiation and progression of atherosclerosis. Macrophages uptake native and modified low density lipoprotein (LDL) through either receptor-dependent or receptor-independent mechanisms to transform into lipid laden foam cells. Foam cells are involved in the formation of fatty streak that is seen during the early stages of atherosclerosis development and therefore represents a promising therapeutic target. Normal or modified lipoproteins labeled with fluorescent dyes such as 1,1'-dioctadecyl-3-3-3',3'-tetramethylindocarbocyanine perchlorate (Dil) are often used to monitor their internalization during foam cell formation. In addition, the fluorescent dye Lucifer Yellow (LY) is widely used as a marker for macropinocytosis activity. In this chapter, we describe established methods for monitoring modified lipoprotein uptake and macropinocytosis during macrophage foam cell formation.

Evaluation of Plaque Burden and Lipid Content in Atherosclerotic Plaques.

Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid-rich, fibrous plaques within the arterial wall of medium and large arteries. Plaques prone to rupture are typically rich in lipids and pro-inflammatory markers. Cells within the plaque can take up lipids via different mechanisms leading to the formation and accumulation of lipid-rich foam cells, a key hallmark of the disease. Evaluation of plaque burden and lipid content is hence important to determine disease progression and severity. This chapter describes the most commonly used staining methods that enable visualization and analysis of mouse atherosclerotic plaques. These methods include en face preparation of mouse aorta, and staining sections of arteries using hematoxylin and eosin, Oil Red O, and Masson's Trichrome.

Monitoring Cellularity and Expression of Key Markers in Atherosclerotic Plaques.

Atherosclerotic plaques are highly diverse and heterogeneous structures, even within the same individual, and can vary depending on its anatomical location within the vascular bed. Early in the disease and throughout its progression, immune cells infiltrate the lesion, contributing to the plaque phenotype via different mechanisms. Detailed characterization of constituent cell populations within plaques is hence required for more accurate assessment of disease severity and inflammatory burden. A wide range of fluorophore-conjugated antibodies targeted to key cell types implicated in all stages of the disease are commercially available, enabling visualization of the dynamic cellular landscape present within lesions. This chapter describes the use of immunofluorescence staining of atherosclerotic plaque sections to study plaque cellularity and expression of key markers.

Understanding Cardiology Practitioners' Interpretations of Electrocardiograms: An Eye-Tracking Study.

BACKGROUND: Visual expertise refers to advanced visual skills demonstrated when performing domain-specific visual tasks. Prior research has emphasized the fact that medical experts rely on such perceptual pattern-recognition skills when interpreting medical images, particularly in the field of electrocardiogram (ECG) interpretation. Analyzing and modeling cardiology practitioners' visual behavior across different levels of expertise in the health care sector is crucial. Namely, understanding such acquirable visual skills may help train less experienced clinicians to interpret ECGs accurately. OBJECTIVE: This study aims to quantify and analyze through the use of eye-tracking technology differences in the visual behavior and methodological practices for different expertise levels of cardiology practitioners such as medical students, cardiology nurses, technicians, fellows, and consultants when interpreting several types of ECGs. METHODS: A total of 63 participants with different levels of clinical expertise took part in an eye-tracking study that consisted of interpreting 10 ECGs with different cardiac abnormalities. A counterbalanced within-subjects design was used with one independent variable consisting of the expertise level of the cardiology practitioners and two dependent variables of eye-tracking metrics (fixations count and fixation revisitations). The eye movements data revealed by specific visual behaviors were analyzed according to the accuracy of interpretation and the frequency with which interpreters visited different parts/leads on a standard 12-lead ECG. In addition, the median and SD in the IQR for the fixations count and the mean and SD for the ECG lead revisitations were calculated. RESULTS: Accuracy of interpretation ranged between 98% among consultants, 87% among fellows, 70% among technicians, 63% among nurses, and finally 52% among medical students. The results of the eye fixations count, and eye fixation revisitations indicate that the less experienced cardiology practitioners need to interpret several ECG leads more carefully before making any decision. However, more experienced cardiology practitioners rely on their skills to recognize the visual signal patterns of different cardiac abnormalities, providing an accurate ECG interpretation. CONCLUSIONS: The results show that visual expertise for ECG interpretation is linked to the practitioner's role within the health care system and the number of years of practical experience interpreting ECGs. Cardiology practitioners focus on different ECG leads and different waveform abnormalities according to their role in the health care sector and their expertise levels.

Pro-atherogenic actions of signal transducer and activator of transcription 1 serine 727 phosphorylation in LDL receptor deficient mice via modulation of plaque inflammation.

Atherosclerosis is a chronic inflammatory disorder of the vasculature regulated by cytokines. We have previously shown that extracellular signal-regulated kinase-1/2 (ERK1/2) plays an important role in serine 727 phosphorylation of signal transducer and activator of transcription-1 (STAT1) transactivation domain, which is required for maximal interferon-γ signaling, and the regulation of modified LDL uptake by macrophages in vitro. Unfortunately, the roles of ERK1/2 and STAT1 serine 727 phosphorylation in atherosclerosis are poorly understood and were investigated using ERK1 deficient mice (ERK2 knockout mice die in utero) and STAT1 knock-in mice (serine 727 replaced by alanine; STAT1 S727A). Mouse Atherosclerosis RT² Profiler PCR Array analysis showed that ERK1 deficiency and STAT1 S727A modification produced significant changes in the expression of 18 and 49 genes, respectively, in bone marrow-derived macrophages, with 17 common regulated genes that included those that play key roles in inflammation and cell migration. Indeed, ERK1 deficiency and STAT1 S727A modification attenuated chemokine-driven migration of macrophages with the former also impacting proliferation and the latter phagocytosis. In LDL receptor deficient mice fed a high fat diet, both ERK1 deficiency and STAT1 S727A modification produced significant reduction in plaque lipid content, albeit at different time points. The STAT1 S727A modification additionally caused a significant reduction in plaque content of macrophages and CD3 T cells and diet-induced cardiac hypertrophy index. In addition, there was a significant increase in plasma IL-2 levels and a trend toward increase in plasma IL-5 levels. These studies demonstrate important roles of STAT1 S727 phosphorylation in particular in the regulation of atherosclerosis-associated macrophage processes in vitro together with plaque lipid content and inflammation in vivo, and support further assessment of its therapeutical potential.

The Lab4P Consortium of Probiotics Attenuates Atherosclerosis in LDL Receptor Deficient Mice Fed a High Fat Diet and Causes Plaque Stabilization by Inhibiting Inflammation and Several Pro-Atherogenic Processes.

SCOPE: Previous studies show that Lab4 probiotic consortium plus Lactobacillus plantarum CUL66 (Lab4P) reduces diet-induced weight gain and plasma cholesterol levels in C57BL/6J mice fed a high fat diet (HFD). The effect of Lab4P on atherosclerosis is not known and is therefore investigated. METHODS AND RESULTS: Atherosclerosis-associated parameters are analyzed in LDL receptor deficient mice fed HFD for 12 weeks alone or supplemented with Lab4P. Lab4P increases plasma HDL and triglyceride levels and decreases LDL/VLDL levels. Lab4P also reduces plaque burden and content of lipids and macrophages, indicative of dampened inflammation, and increases smooth muscle cell content, a marker of plaque stabilization. Atherosclerosis arrays show that Lab4P alters the liver expression of 19 key disease-associated genes. Lab4P also decreases the frequency of macrophages and T-cells in the bone marrow. In vitro assays using conditioned media from probiotic bacteria demonstrates attenuation of several atherosclerosis-associated processes in vitro such as chemokine-driven monocytic migration, proliferation of monocytes and macrophages, foam cell formation and associated changes in expression of key genes, and proliferation and migration of vascular smooth muscle cells. CONCLUSION: This study provides new insights into the anti-atherogenic actions of Lab4P together with the underlying mechanisms and supports further assessments in human trials.

An explainable algorithm for detecting drug-induced QT-prolongation at risk of torsades de pointes (TdP) regardless of heart rate and T-wave morphology.

Torsade de points (TdP), a life-threatening arrhythmia that can increase the risk of sudden cardiac death, is associated with drug-induced QT-interval prolongation on the electrocardiogram (ECG). While many modern ECG machines provide automated measurements of the QT-interval, these automated QT values are usually correct only for a noise-free normal sinus rhythm, in which the T-wave morphology is well defined. As QT-prolonging drugs often affect the morphology of the T-wave, automated QT measurements taken under these circumstances are easily invalidated. An additional challenge is that the QT-value at risk of TdP varies with heart rate, with the slower the heart rate, the greater the risk of TdP. This paper presents an explainable algorithm that uses an understanding of human visual perception and expert ECG interpretation to automate the detection of QT-prolongation at risk of TdP regardless of heart rate and T-wave morphology. It was tested on a large number of ECGs (n=5050) with variable QT-intervals at varying heart rates, acquired from a clinical trial that assessed the effect of four known QT-prolonging drugs versus placebo on healthy subjects. The algorithm yielded a balanced accuracy of 0.97, sensitivity of 0.94, specificity of 0.99, F1-score of 0.88, ROC (AUC) of 0.98, precision-recall (AUC) of 0.88, and Matthews correlation coefficient (MCC) of 0.88. The results indicate that a prolonged ventricular repolarisation area can be a significant risk predictor of TdP, and detection of this is potentially easier and more reliable to automate than measuring the QT-interval distance directly. The proposed algorithm can be visualised using pseudo-colour on the ECG trace, thus intuitively 'explaining' how its decision was made, which results of a focus group show may help people to self-monitor QT-prolongation, as well as ensuring clinicians can validate its results.

Pseudo-colouring an ECG enables lay people to detect QT-interval prolongation regardless of heart rate.

Drug-induced long QT syndrome (diLQTS), characterized by a prolongation of the QT-interval on the electrocardiogram (ECG), is a serious adverse drug reaction that can cause the life-threatening arrhythmia Torsade de Points (TdP). Self-monitoring for diLQTS could therefore save lives, but detecting it on the ECG is difficult, particularly at high and low heart rates. In this paper, we evaluate whether using a pseudo-colouring visualisation technique and changing the coordinate system (Cartesian vs. Polar) can support lay people in identifying QT-prolongation at varying heart rates. Four visualisation techniques were evaluated using a counterbalanced repeated measures design including Cartesian no-colouring, Cartesian pseudo-colouring, Polar no-colouring and Polar pseudo-colouring. We used a multi-reader, multi-case (MRMC) receiver operating characteristic (ROC) study design within a psychophysical paradigm, along with eye-tracking technology. Forty-three lay participants read forty ECGs (TdP risk n = 20, no risk n = 20), classifying each QT-interval as normal/abnormal, and rating their confidence on a 6-point scale. The results show that introducing pseudo-colouring to the ECG significantly increased accurate detection of QT-interval prolongation regardless of heart rate, T-wave morphology and coordinate system. Pseudo-colour also helped to reduce reaction times and increased satisfaction when reading the ECGs. Eye movement analysis indicated that pseudo-colour helped to focus visual attention on the areas of the ECG crucial to detecting QT-prolongation. The study indicates that pseudo-colouring enables lay people to visually identify drug-induced QT-prolongation regardless of heart rate, with implications for the more rapid identification and management of diLQTS.

Exploring the effect of lexical inferencing and dictionary consultation on undergraduate EFL students' vocabulary acquisition.

This study compares how lexical inferencing and dictionary consultation affect L2 vocabulary acquisition. Sixty-one L1 Arabic undergraduates majoring in English language read target words in semi-authentic English reading materials and were either asked to guess their meaning or look it up in a dictionary. A pre- and delayed post-test measured participants' knowledge of target words and overall vocabulary size. The results show a significant and comparable learning effect for both vocabulary learning strategies (VLS), with a higher pre-test vocabulary size related to a larger learning effect for both VLS. In addition, the better participants were at guessing correctly, the better they learned words through inferencing. The results suggest that both VLS are equally effective for our learner group and that learners' overall vocabulary size influences the amount of learning that occurs when using these VLS.

Effects of Language Skills and Strategy Use on Vocabulary Learning Through Lexical Translation and Inferencing.

This study explores how vocabulary learning strategy usage and skills in the four language domains relate to participants' increase in vocabulary size and to the learning of specific vocabulary items over a certain period of time. Sixty-one advanced L1 Arabic L2 learners of English read target words in semi-authentic reading materials and were instructed to either guess the meaning from context or consult a dictionary. Pre- and delayed post-tests assessed vocabulary size and knowledge of the target vocabulary items. Results showed that learning through inferencing, but not learning through dictionary use, depended on learners' familiarity with the particular learning strategy. Additionally, note taking and reading comprehension influenced lexical knowledge and acquisition in complex ways.

Revisited maxillary sinus pneumatization narrative of observation in Al-Madinah Al-Munawwarah, Saudi Arabia: A retrospective cross-sectional study.

OBJECTIVES: Maxillary sinus pneumatization (MSP), is linked worldwide to number of factors. MSP measurements and assessment alongside potential correlates in Al-Madinah Al-Munawwarah, Saudi Arabia (SA) awaits identification. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted at Taibah University Dental-College and Hospital, Al-Madinah Al-Munawwarah; SA. The analysis included 700 female patients digital Orthopantomogram (OPG), of which 535 (76%) OPGs were usable. MSP was established according to the distance between the maxillary sinus floor and posterior teeth apices number 15, 16, 17, 18, 25, 26, 27 and 28. MSP categorized as followed: Sever MSP (Category I), Moderate MSP (Category II) and No MSP/normal (Category III). Descriptive statistics, and inferential analysis were carried out. RESULTS: Mean age of the patients was 30.11 (±10.26) and 290 (54.5%) were Saudi nationals. Severe pneumatization (category I) was prominent in the right and left first and second molars, 16, 26, 17, 27 (66%, 64%, 63% and 62%, respectively). A statistically significant difference (P < 0.0005) was observed between pneumatization categories in all sites. Furthermore, the impact of young age on levels of MSP was statistically significant (P < 0.05) on most teeth. However, nationality was non-significantly (P > 0.05) associated with MSP levels. CONCLUSION: High percentages of female patients showed bilateral sever MSP in the upper molar area, specifically, young age group. CLINICAL SIGNIFICANCE: The oro-antral communication during extraction and surgical cases of female patients' maxillary teeth is possible. This should be considered during dentists' daily practice in this geographic area of SA.

Can laypeople identify a drug-induced QT interval prolongation? A psychophysical and eye-tracking experiment examining the ability of nonexperts to interpret an ECG.

OBJECTIVE: The study sought to quantify a layperson's ability to detect drug-induced QT interval prolongation on an electrocardiogram (ECG) and determine whether the presentation of the trace affects such detection. MATERIALS AND METHODS: Thirty layperson participants took part in a psychophysical and eye-tracking experiment. Following training, participants completed 21 experimental trials, in which each trial consisted of 2 ECGs (a baseline and a comparison stimulus, both with a heart rate of 60 beats/min). The experiment used a 1 alternative forced-choice paradigm, in which participants indicated whether or not they perceived a difference in the QT interval length between the 2 ECGs. The ECG trace was presented in 3 ways: a single complex with the signals aligned by the R wave, a single complex without alignment, and a 10-second rhythm strip. Performance was analyzed using the psychometric function to estimate the just noticeable difference threshold, along with eye-tracking metrics. RESULTS: The just noticeable difference 50% and 75% thresholds were 30 and 88 ms, respectively, showing that the majority of laypeople were able to detect a clinically significant QT-prolongation at a low normal heart rate. Eye movement data indicated that people were more likely to appraise the rhythm strip stimulus systematically and accurately. CONCLUSIONS: People can quickly be trained to self-monitor, which may help with more rapid identification of drug-induced long QT syndrome and prevent the development of life-threatening complications. The rhythm strip is a better form of presentation than a single complex, as it is less likely to be misinterpreted due to artifacts in the signal.