ARTICLE | doi:10.20944/preprints202203.0140.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Left ventricular ejection fraction; Left ventricle segmentation; Convolutional long short-term memory; Echocardiography
Online: 10 March 2022 (04:19:30 CET)
Cardiovascular disease is the leading cause of death worldwide. A key factor in assessing the risk of cardiovascular disease is left ventricular functional evaluation. Left ventricular (LV) systolic function is evaluated by measuring the left ventricular ejection fraction (LVEF) using echocardiography data. Therefore, quick and accurate left ventricle segmentation is important for estimating the LVEF. However, it is difficult to accurately segment the left ventricle due to changes in the shape and area of the left ventricle during cardiac cycles. In this study, we proposed a framework that considers changes in the shape and area of the left ventricle during the cardiac cycle by applying the convolutional long short-term memory (CLSTM) approach. In addition, we evaluated the left ventricular segmentation and multidimensional quantification of the proposed system in comparison to manual and automated segmentation methods. In addition, to assess the validity of CLSTM, the values of multi-dimensional quantification metrics were compared and analyzed using graphs and Bland–Altman plots on a frame-by-frame basis. We demonstrated that the CLSTM method effectively segments the left ventricle by considering the LV activity. In conclusion, we demonstrated that LV segmentation based on our framework may be utilized to accurately estimate LVEF values.
ARTICLE | doi:10.20944/preprints201907.0139.v1
Subject: Medicine & Pharmacology, Behavioral Neuroscience Keywords: grip force modulation; embodied language; left hand; right hemisphere; left hemisphere; unimanual task
Online: 10 July 2019 (07:37:58 CEST)
Background and objectives: The language-induced grip force modulation (GFM) can be used to better understand the link between the language and motor functions as an expression of the embodied language. However, the contribution of each brain hemisphere to the language-induced GFM is still unclear. Using six different action verbs as stimuli, this study evaluated the GFM of the left hand in unimanual task to characterize the left- and right-hemisphere contributions. Materials and Methods: The left-hand GFM of 20 healthy consistent right-handers subjects was evaluated using the verbs “to write”, “to hold”, “to pull”(left-lateralized central processing actions), “to draw”, “to tie”, and “to drive” (bi-hemispheric central processing actions) as linguistic stimuli. The time between the word onset and the first interval of statistical significance regarding the baseline (RT) was also measured. Results: The six verbs produced language-induced GFM. The modulation intensity was similar for the six verbs, but the RT was variable. The verbs “to draw”, “to tie”, and “to drive”, whose central processing of the described action is bihemispheric showed a longer Rt compared to the other verbs. Conclusions: The possibility that an action is performed by the left-hand does not interfere with the occurrence of GFM when this action verb is employed as linguistic stimulus. Therefore, the language-induced GFM seems mainly rely on the left hemisphere, and the engagement of the right hemisphere seems to slow down the increase in the GFM intensity.
CASE REPORT | doi:10.20944/preprints202201.0190.v1
Online: 13 January 2022 (13:19:21 CET)
Retroaortic left renal veins are an often overlooked, but no so rare anatomic anomaly that might cause a few aspecific symptoms and signs, especially flank or inguinal pain, microscopic or even gross hematuria; in the vast majority of cases it is, thought, totally asymptomatic. The nutcracker syndrome that might arise in the case of RLRV is mainly due to the re- duced space between aorta and the vertebral body and the consequent compression on the venal rein; this might in turn cause upstream hypertension, hematuria, varicocele, pain. The compression of RLRV leads to hematuria because of renal venous hypertension, consequent left renal congestion. This upstream venous congestion might result, in some cases, in left-sided varicocele in men and pelvic congestion syndrome in women. From a radiologic point of view, the presence of RLRV and the precise reporting its subtypes is mandatory.
ARTICLE | doi:10.20944/preprints202201.0042.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Left ventricular hypertrophy; Echocardiography; Magnetic Resonance; Prognosis
Online: 5 January 2022 (13:10:00 CET)
Background: Left ventricular hypertrophy (LVH) may be due to different causes, ranging from benign secondary forms to severe cardiomyopathies. Transthoracic Echocardiography (TTE) and ECG are the first level examination for LVH diagnosis. Cardiac magnetic resonance (CMR) defines accurately LVH type, extent and severity. Objectives: to evaluate the diagnostic and prognostic role of CMR in patients with TTE and/or ECG evidence of LVH. Methods: We performed CMR in 300 consecutive patients with echocardiographic and/or ECG signs of LVH. Results: Overall, 275 patients had TTE evidence of LVH with initial suspicion of hypertrophic cardiomyopathy (HCM) in 132 (44%), cardiac amyloidosis in 41 (14%), hypertensive LVH in 48 (16%), aortic stenosis in 4 (1%), undetermined LVH in 50(16%). The initial echocardiographic diagnostic suspicion of LVH was confirmed in 172 patients (57.3%) and changed in 128 patients (42.7%, p<0.0001): the diagnosis of HCM increased from 44% to 71% of patients; hypertensive and undetermined LVH decreased significantly (respectively to 4% and 5%). CMR allowed a diagnosis in 41 out of 50 (82%) with undetermined LVH at TTE. CMR also identified HCM in 17 out of 25 patients with apparently normal echo but with ECG criteria for LVH. Finally, the reclassification of the diagnosis by CMR was associated with a change of survival risk of patients: after CMR reclassification no events occurred in patients with undetermined or hypertensive LVH. Conclusions: CMR changed echocardiographic suspicion in almost half of patients with LVH. In the subgroup of patient with abnormal ECG, CMR identified LVH (particularly HCM) in 80% of patients. This study highlights the indication of CMR to better characterize the type, extent and severity of LVH detected at echocardiography and suspected with ECG.
REVIEW | doi:10.20944/preprints201811.0075.v1
Subject: Medicine & Pharmacology, Other Keywords: sepsis cardiomyopathy; left ventricular function; global longitudinal strain
Online: 5 November 2018 (02:51:26 CET)
Myocardial deformation imaging (strain imaging) is a technique to directly quantify the extent of myocardial contractility and overcomes several of the limitations of ejection fraction. The application of the most commonly used strain imaging method; speckle-tracking echocardiography to patients with sepsis cardiomyopathy heralds an exciting development to the field. However; the body of evidence and knowledge on the utility, feasibility and prognostic value of left ventricular global longitudinal strain in sepsis cardiomyopathy is still evolving. We conducted a review of literature on utility of left ventricular global longitudinal strain in sepsis cardiomyopathy. We discuss the role of left ventricular global longitudinal strain in mortality prediction, utility and limitations of the technique in the context of sepsis cardiomyopathy.
ARTICLE | doi:10.20944/preprints202108.0533.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: glaucoma progression; nycthemeral intraocular pressure; right-left comparison; laterality
Online: 30 August 2021 (09:52:58 CEST)
Purpose: To determine whether 24-hour IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion and progression parameters. Methods: We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (Tmax), average IOP (Tavg), IOP variation (IOPvar) and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was conducted to check for various inter-eye relationships. Results: 217 eyes were included. The average IOP was 14.8±3.5 mmHg, with a 24-hour variation of 5.2±2.9 mmHg. 52% of eyes with RNFL data showed disease progression. There was no significant difference in Tmax, Tavg and IOPvar between progressors and non-progressors (all p>0.05). Except for Tavg and the temporal RNFL, there was no correlation between disease progression in any quadrant, Tmax, Tavg and IOPvar. 24-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak. Conclusion: In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other.
CASE REPORT | doi:10.20944/preprints202012.0704.v1
Subject: Medicine & Pharmacology, Allergology Keywords: left ventricular noncompaction; apical hypertrophic cardiomyopathy; next generation sequencing
Online: 28 December 2020 (13:19:41 CET)
Left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy (HCM) commonly occur as separate disorders with distinct clinical and pathoanatomical features. However, these cardiomyopathies may have a similar genetic origin with mutations encoding sarcomeric proteins. The described case demonstrates an example, in which phenotypic expression of both diseases occurs in the same patient.
ARTICLE | doi:10.20944/preprints202201.0358.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: left ventricular noncompaction; cardiomyopathy; imaging; echocardiography; cardiovascular magnetic resonance; children
Online: 24 January 2022 (13:59:45 CET)
Background: Left ventricular noncompaction (LVNC) is a distinct cardiomyopathy characterized by the presence of a two-layer myocardium with prominent trabeculation and deep intertrabecular recesses. The diagnosis of LVNC can be challenging because the diagnostic criteria are not uniform. The aim of our study was to evaluate echocardiographic and CMR findings in a group of children with isolated LVNC. Methods: From February 2008 to July 2021, pediatric patients under 18 years of age at the time of diagnosis with echocardiographic evidence of isolated LVNC were prospectively enrolled. The patients underwent echocardiography and contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement to assess myocardial noncompaction, ventricular size, and function. Results: A total of 34 patients with a median age of 11.9 years were recruited. Patients were followed prospectively for a median of 5.1 years. Of the 31 patients who met Jenni’s criteria in echocardiography, CMR was performed in 27 (79%). Further comprehensive analysis was performed in the group of 25 patients who met the echocardiographic and CMR criteria for LVNC. In echocardiography, the median NC/C ratio in systole was 2.60 and in diastole 3.40. In 25 out of 27 children (93%), LVNC was confirmed by CMR according to Petersen’s criteria, with a median NC/C ratio of 3.27. Conclusions: 1) Echocardiography precisely identifies patients with LVNC. 2) Echocardiography is a good method for monitoring LV systolic function, but CMR is indicated for the precise assessment of LV remodeling and RV size and function as well as for the detection of myocardial fibrosis.
ARTICLE | doi:10.20944/preprints202104.0403.v1
Subject: Medicine & Pharmacology, Allergology Keywords: echocardiography; speckle-tracking; frame rate; global longitudinal strain; left ventricle
Online: 15 April 2021 (09:39:24 CEST)
Background: global longitudinal strain (GLS) measures myocardial deformation and is a sensitive modality for detecting subclinical myocardial dysfunction and predicting cardiac outcomes. The accuracy of speckle-tracking echocardiography (STE) is dependent on temporal resolution. A novel software enables relatively high frame rate (Hi-FR) (~200 fps) echocardiographic images acquisition which empowers us to investigate the impact of Hi-FR imaging on GLS analysis. The goal of this pilot study was to demonstrate the feasibility of Hi-FR for STE. Methods: In this prospective study, we acquired echocardiographic images using clinical scanners on patients with normal left ventricular systolic function using Hi-FR and conventional frame rate (Reg-FR) (~50 FPS). GLS values were evaluated on apical 4-, 2- and 3-chamber images acquired in both Hi-FR and Reg-FR. Inter-observer and intra-observer variabilities were assessed in Hi-FR and Reg-FR. Results: There were 143 resting echocardiograms with normal LVEF included in this study. The frame rate of Hi-FR was 190 ± 25 and Reg-FR was 50 ± 3, and the heart rate was 71 ± 13. Strain values measured in Hi-FR were significantly higher than those measured in Reg-FR (all p < 0.001). Inter-observer and intra-observer correlations were strong in both Hi-FR and Reg-FR. Conclusions: We demonstrated that strain values were significantly higher using Hi-FR when compared with Reg-FR in patients with normal LVEF. It is plausible that higher temporal resolution enabled the measurement of myocardial strain at desired time point. The result of this study may inform clinical adoption of the novel technology. Further investigations are necessary to evaluate the value of Hi-FR to assess myocardial strain in stress echocardiography in the setting of tachycardia.
ARTICLE | doi:10.20944/preprints202003.0229.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: heart failure; left ventricular assist device; cardiac recovery; mechanical circulation
Online: 13 March 2020 (10:11:43 CET)
In this paper, we aim to assess the electric current parameters and report the analysis of the associated degree of ventricular recovery during left ventricular assist device (LVAD) support. An assumption was made there is a linear relationship between ventricular recovery degree and the pump electric current pulsatility index (PI). The experimental study was carried out using the ViVitro Pulse Duplicator System with Sputnik 1 LVAD connected. Cardiac output (CO) and cardiac power output (CPO) were used as a measure of ventricular recovery degree. Different heart rates (HR) (59, 73, 86 bpm) and pump speeds (7600–8400 rpm in 200 rpm steps) were investigated. Ventricular stroke volumes in the range of 30–80 ml for each heart rate at certain pump speed were used. The obtained relationships of CO and CPO vs. PI was linear as the coefficients of determination for each regression curve were more than 0.8. CO vs. PI: R2=0.9218; 0.9271; 0.9172 and CPO vs. PI: R2=0.8517; 0.841; 0.8244 for HR=59 bpm; 73 bpm; 86 bpm, respectively. Study findings suggest that adequate interpretation of parameters could potentially serve as a valuable clinical tool to assess ventricular recovery based on LVAD infrastructure without requiring any special hemodynamic assessment.
ARTICLE | doi:10.20944/preprints201608.0080.v2
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: left ventricle; myofibre; myocardium structure; rule-based model; mathematical anatomy
Online: 20 October 2016 (08:22:39 CEST)
Computer simulation of normal and diseased human heart activity requires a 3D anatomical model of the myocardium, including myofibres. For clinical applications, such a model has to be constructed based on routine methods of cardiac visualisation such as sonography. Symmetrical models are shown to be too rigid, so an analytical non-symmetrical model with enough flexibility is necessary. Based on previously made anatomical models of the left ventricle, we propose a new, much more flexible spline-based analytical model. The model is fully described and verified against DT-MRI data. We show a way to construct it on the basis of sonography data. To use this model in further physiological simulations, we propose a numerical method to utilise finite differences in solving the reaction-diffusion problem together with an example of scroll wave dynamics simulation.
ARTICLE | doi:10.20944/preprints202103.0382.v1
Subject: Medicine & Pharmacology, Allergology Keywords: diastolic dysfunction; heart failure; atrial fibrillation; atrial hypertension; left atrial pressure
Online: 15 March 2021 (13:02:14 CET)
Introduction: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n=204, AF group) or supraventricular tachycardia (n=34, control group) were analyzed (male n=183, 54±12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e’ (≥ 8) than in those with a low E/e’ (< 8). LAPR at a pacing interval of 400ms and E/e' were positively correlated (r=0.373, p<0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: The LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.
ARTICLE | doi:10.20944/preprints202103.0064.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: fractional integral inequalities, right and left - Hilfer and Hilfer fractional derivatives.
Online: 2 March 2021 (09:58:00 CET)
Here we present Hilfer-Polya, psi-Hilfer Ostrowski and psi-Hilfer-Hilbert- Pachpatte types fractional inequalities. They are univariate inequalities involving left and right Hilfer and -Hilfer fractional derivatives. All estimates are with respect to norms ||.||p, 1 <_ p <_infinite. At the end we provide applications.
ARTICLE | doi:10.20944/preprints201903.0103.v2
Subject: Physical Sciences, Particle & Field Physics Keywords: charged dark matters; left-handed neutrinos; Higgs mechanism, universe evolution; extended standard model
Online: 15 April 2019 (12:53:22 CEST)
In the present work, the charged dark matters of B1, B2 and B3 bastons are explained as the right-handed partners of the left-handed neutrinos. The new Higgs mechanism of SU(2)DM×SU(2)Weak×SU(2)Strong including electromagnetic and gravitational forces is applied. And the rest masses of the elementary particles depend on their charge configurations. The left-handed neutrinos have only the lepton charges (LC) and the right-handed dark matters have only the electric charges (EC). This explains the fact that the rest masses of the left-handed neutrinos are so small, and the rest masses of the right-handed dark matters are relatively very large. The proposed rest mass (26.12 eV/c2) of the B1 dark matter is indirectly confirmed from the supernova 1987A data. The missing neutrinos are newly explained by using the dark matters and lepton charge force. The neutrino excess anomaly of the MinibooNE data is explained by the B1 dark matter scattering within the Cherenkov detectors. The quark mixing and neutrino mixing are not required in the present model. It is shown that our matter universe and its partner antimatter universe can be created from the big bang in the point of view of time -, charge -, space -, and quantum state – symmetric universe evolution.
ARTICLE | doi:10.20944/preprints201810.0486.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: (left-, right-) pseudo-commutative; commutative; d/BCK-algebra; disjoint; (linear) groupoid
Online: 22 October 2018 (10:04:34 CEST)
In this paper, we investigate the effects of certain variants of the commutative laws on properties of several families of algebras which are in general not commutative, such as groups, linear algebras, or actually quite anti-commutative, such as $BCK$-algebras and $d$-algebras among others. From results obtained it becomes clear that by considering these variants in the presence of yet other axioms it is to be expected that a quite rich and varied set of results may be obtained both in the general and the particular setting of which what has been accomplished in this paper is a substantial sample.
ARTICLE | doi:10.20944/preprints202106.0276.v1
Subject: Medicine & Pharmacology, Allergology Keywords: left ventricular noncompaction; cardiomyopathy; heart failure; arrhythmia; conduction disturbances; molecular etiology; children
Online: 10 June 2021 (08:06:33 CEST)
Background: Left ventricular noncompaction (LVNC) is a genetically determined cardiomyopathy, that occurs following a disruption of endomyocardial morphogenesis. The purpose of this study was to identify the clinical characteristics and genetic profile of children with LVNC. Methods: From February 2008 to July 2020, a total of 32 children (median 11.5 years) with LVNC were prospectively enrolled and followed up for the median of 4.02 years. Diagnosis was made based on characteristic features of LVNC in echocardiography and cardiovascular magnetic resonance (CMR). Patients’ clinical symptoms, family history, ECG, Holter ECG and genetic tests were also evaluated. Results: The most common presenting symptom was heart failure (31% of children). ECG abnormalities were noted in 56% of patients. The most prominent features were ventricular arrhythmias, sinus bradycardia and paroxysmal third-degree atrioventricular block. Most of the patients (94%) met the criteria for LVNC and CMR confirmed this diagnosis in 82% of cases. The molecular etiology was found in 53% of children. Conclusion: Although heart failure and arrhythmias were very frequent in our study group, thromboembolic events and genetic syndromes were rare. For accurate and reliable assessment of children with LVNC, it is necessary to get to know their family history and detailed clinical profile.
ARTICLE | doi:10.20944/preprints202202.0243.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: left ventricular noncompaction; cardiomyopathy; sinus bradycardia; HCN4 mutation; late gado-linium enhancement; children
Online: 21 February 2022 (03:16:22 CET)
Background: Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous cardiomyopathy characterized by a two-layered myocardium consisting of compacted and noncompacted segments, prominent ventricular trabeculations, and intertrabecular recesses. Patients with LVNC are at increased risk to develop heart failure, atrial and ventricular arrhythmias, and/or systemic thromboembolic events. Familial forms of primary sinus bradycardia have been attributed to mutations in HCN4. There are very few reports about the association between HCN4 mutations and LVNC. The aim of our study was to characterize the clinical phenotype of families with LVNC and sinus bradycardia caused by mutation of the HCN4 gene. Methods: From March 2008 to July 2021 we prospectively enrolled 6 patients from 4 families with diagnosed isolated LVNC based on the clinical presentation, family history and echocardiographic and cardiovascular magnetic resonance (CMR) evidence of LVNC. Next generation sequencing (NGS) analysis was undertaken for evaluation of the molecular basis of the disease in each family. Results: A total of 6 children (median age 11 years) were enrolled and followed prospectively for the median of 12 years. All 6 patients were diagnosed with LVNC by echocardiography and 5 participants additionally by CMR. The presence of LGE was found in 3 children. Sinus bradycardia and dilation of the ascending aorta occurred in 5 studied patients. In 4 patients from 3 families the molecular studies demonstrated the presence of rare heterozygous HCN4 mutations. Conclusion: (1) The HCN4 mutation influences the presence of a complex LVNC phenotype, sinus bradycardia and dilation of the ascending aorta. (2) HCN4 mutation may be associated with the early presentation of clinical symptoms and the severe course of the disease. (3) It is particularly important to assess myocardial fibrosis not only within the ventricles, but also in the atria in patients with LVNC and sinus bradycardia.
ARTICLE | doi:10.20944/preprints202109.0244.v1
Subject: Engineering, Mechanical Engineering Keywords: Myocardium tissue; Left ventricle mechanics; right ventricle mechanics; cardiac septum mechanics; anisotropy index
Online: 14 September 2021 (15:12:23 CEST)
Heart myocardia are critical to the facilitation of heart pumping and blood circulating around the body. The biaxial mechanical testing of the Left Ventricle (RV) is utilised to build the computa-tional model of the whole heart with little importance given to the unique mechanical properties of Right Ventricle (RV) and Mid-wall (MDW). Most of those studies focussed on the LV of the heart, and then apply the obtained characteristics with a few modifications to the right side of the heart. However, that view has been contested over time with the realisation that the right side of the heart possesses its own unique mechanical properties that are widely distinct from that of the left side of the heart. This paper is aimed at reporting and evaluating the passive mechanical property dif-ferences in the three main walls of the rat heart based on biaxial tensile test data. Fifteen mature Wistar rats weighing 225 ± 25 g were euthanised by inhalation of 5 % halothane. The hearts were excised after which all the top chambers comprising the two atria, pulmonary and vena cava trunks, aorta and valves are all dissected out. Then 5 x 5 mm sections from the middle of each wall were carefully dissected with a surgical knife to avoid over-prestraining the specimens. The specimens were subjected tensile test. The elastic moduli, peak stresses in the toe region and stresses at 40 % strain, anisotropy indices as well as the stored strain energy in the toe and linear region up to 40 % strain are used for statistical significance tests. The following are the main findings of this study: (1) LV and MDW tissues have relatively shorter toe regions of 10 - 15 % strain as compared to RV tissue whose toe region extends up to twice as much as that (2) LV tissues have higher strain energy storage in the linear region despite being lower in stiffness than the RV (3) the MDW has the highest strain energy storage along both directions which might be directly related to its high level of anisotropy. These findings, though for a specific animal species at similar age and around the same body mass, emphasize the importance of application of wall specific material parameters to obtain accurate ventricular hyperelastic models. The findings further enhance our understanding of the desired mechanical behaviour of the different ventricle walls.
ARTICLE | doi:10.20944/preprints202106.0592.v1
Subject: Medicine & Pharmacology, Allergology Keywords: arterial stiffness; brachial-ankle pulse wave velocity; left ventricular mass index; echocardiography; hypertension
Online: 24 June 2021 (08:39:17 CEST)
Background: Brachial-ankle pulse wave velocity (baPWV) is widely used as a marker of arterial stiffness. It has been suggested as a simple method for detecting arterial loads that can trigger left ventricular hypertrophy in the heart. Increased left ventricular hypertrophy in hypertensive patients is a predictor that will have an impact on increasing morbidity and mortality. Objective: This study aimed to evaluate the correlation between the baPWV and the left ventricular mass index (LVMI) in hypertensive patients. Methods: This cross-sectional study was conducted by collecting secondary data from hypertensive patients at the Heart Outpatient Clinic, with inclusion: aged more than 40 years old, suffering hypertension more than one year, and had baPWV and echocardiography data. Correlation between baPWV and LVMI was evaluated using the Pearson correlation test. Results: A total of 40 hypertensive patients were enrolled in this study. 60% were women. The mean age was 52.92 ± 9.50 years. Mean LVMI was 107.20 + 21.01 gram/m2. LVMI showed a significant association with age and systolic blood pressure (p=0.001 and 0.019, respectively). Mean baPWV was 1832.90 + 336.22 cm/sec. A significant association was found between baPWV and age and systolic blood pressure (p=0.000 and 0.049, respectively). There was a significant positive correlation between baPWV and LVMI (r=0.493, p=0.001); and between baPWV and Relative Wall Thickness (RWT) (r=0.404, p=0.01). Conclusion: This study shows that elevated baPWV is an indicator of increased LVMI in hypertensive patients. Examination of baPWV should be carried out routinely to detect earlier arterial stiffness as a morbidity and mortality prevention strategy in hypertensive patients.
ARTICLE | doi:10.20944/preprints202105.0677.v1
Subject: Medicine & Pharmacology, Allergology Keywords: heart failure, phenotype, left ventricular ejection fraction, primary care, artificial intelligence, supervised analysis
Online: 27 May 2021 (14:08:53 CEST)
Artificial Intelligence are creating a paradigm shift in health care, being phenotyping patients through clustering techniques one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data in Electronic Health Records (EHR). Subjects and methods: 2854 subjects more than 25 years old with diagnose of HF and LVEF measured by echocardiography were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. Performance of the algorithm developed were tested in heart failure patients from Primary Care. To select the most influencing variables, LASSO algorithm setting was used and to tackle the issue of one class exceed the other one by a large proportion we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: Full XGBoost model obtained the maximized accuracy, a high negative predictive value and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence FE value. Applied in the EHR data set with a total 25594 patients with an ICD-code of HF and no regular follow-up in Cardiology clinics, 6170 (21.1%) were identified as those pertaining to the reduced EF group. Conclusion: The algorithm obtained is able to rescue a number of HF patients with reduced ejection fraction that can be take benefit for a protocol with strong recommendation to succeed. Furthermore, the methodology can be used for studies with data extracted from the Electronic Health Records.
ARTICLE | doi:10.20944/preprints202005.0313.v1
Subject: Social Sciences, Business And Administrative Sciences Keywords: Vehicle Routing Problem; Delivery and Pickup; Time Windows; Left-over Cost; Reusable Container
Online: 19 May 2020 (09:27:52 CEST)
A lot of previous research have proposed various frameworks and algorithms to optimize routes to reduce the total transportation cost, which accounts for over 70% of overall logistics cost. However, it is very hard to find the cases applied the mathematical models or algorithms to the practical business environment cases, especially daily operating logistics services like convenient stores. Most of previous research have considered the developing an optimal algorithm which can solve the mathematical problem within the practical time while satisfying all constraints such as the capacity of delivery and pick-up, and time windows. For the daily pick-up and delivery service like supporting several convenient stores, it is required to consider the unit transporting container as well as the demand, capacity of trucks, traveling distance and traffic congestion. Especially, the reusable transporting container, trays, should be regarded as the important asset of logistics center. However, if the mathematical model focuses on only satisfying constraints related delivery and not considering the cost of trays, it is often to leave the empty trays on the pick-up points when there is not enough space in the track. In this research, it has been proposed to build the mathematical model for optimizing pick-up and delivery plans by extending the general vehicle routing problem of simultaneous delivery and pickup with time windows while considering left-over cost. With the numerical experiments, it has been proved that the proposed model may reduce the total delivery cost. It may be possible to apply the proposed approach to the various logistics business which uses the reusable transporting container like shipping containers, refrigerating containers, trays, and pallets.
ARTICLE | doi:10.20944/preprints202002.0066.v3
Subject: Keywords: information theory; causal inference; causal tensors; transfer entropy; partial information decomposition; left monotonicity; identity property; unobserved common cause
Online: 27 February 2020 (10:55:05 CET)
We propose a partial information decomposition based on the newly introduced framework of causal tensors, i.e., multilinear stochastic maps that transform source data into destination data. The innovation that causal tensors introduce is that the framework allows for an exact expression of an indirect association in terms of the constituting, direct associations. This is not possible when expressing associations only in measures like mutual information or transfer entropy. Instead of a priori expressing associations in terms of mutual information or transfer entropy, the a posteriori expression of associations in these terms results in an intuitive definition of a nonnegative and left monotonic redundancy, which also meets the identity property. Our proposed redundancy satisfies the three axioms introduced by Williams and Beer. Symmetry and self-redundancy axioms follow directly from our definition. The data processing inequality ensures that the monotonicity axiom is satisfied. Because causal tensors can describe both mutual information as transfer entropy, the partial information decomposition applies to both measures. Results show that the decomposition closely resembles the decomposition of other another approach that expresses associations in terms of mutual information a posteriori. A negative synergistic term could indicate that there is an unobserved common cause.
ARTICLE | doi:10.20944/preprints202101.0031.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: ERPs; selective attention; global/local; cerebral hemispheres; VEPs; spatial frequency; Attentional tuning; Left hemisphere
Online: 4 January 2021 (12:27:21 CET)
A hemispheric asymmetry is known for the processing of global vs. local visual information. In this study, we investigated the existence of a hemispheric asymmetry for visual processing of low vs. high spatial frequency gratings. Event-related potentials were recorded in a group of healthy right-handed volunteers from 30 scalp sites. Six types of stimuli (1.5, 3 and 6 c/deg gratings) were randomly flashed 180 times in the left and right upper hemi-fields. Stimulus duration was 80 ms and ISI ranged between 850-1000 ms. Participants had to pay attention and respond to targets based on their spatial frequency and location, or to passively look at the stimuli. C1 and P1 visual responses, as well as a later Selection negativity and a P300 components of ERPs were quantified and subjected to repeated-measure ANOVAs. Overall, performance was faster for the RVF, thus suggesting a left hemispheric advantage for attentional selection of local elements. Similarly, the analysis of mean area amplitude of C1 (60-110 ms) sensory response showed a stronger attentional effect (F+L+ vs. F-L+) at left occipital areas, thus suggesting the sensory nature of this hemispheric asymmetry.
ARTICLE | doi:10.20944/preprints202202.0017.v1
Subject: Biology, Other Keywords: protein-protein interactions; interactome; congenital heart disease; developmental disorder; hypoplastic left heart syndrome; web application
Online: 1 February 2022 (16:00:59 CET)
Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.
ARTICLE | doi:10.20944/preprints202112.0461.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Hypertrophic Cardiomyopathy; Left ventricular outflow tract obstruction; single nucleus RNA-sequencing; dendritic cells; integrin-b1.
Online: 29 December 2021 (09:43:00 CET)
Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.
DATA DESCRIPTOR | doi:10.20944/preprints202108.0153.v1
Subject: Engineering, Mechanical Engineering Keywords: Cardiac mechanics; Biaxial testing; Rat heart; Left ventricle mechanics; Mid-wall mechanics; Right ventricle mechanics
Online: 6 August 2021 (08:24:19 CEST)
This article presents raw data of biaxial tensile measurements of rat heart passive myocardium conducted in lab scale environment. The passive myocardium of the rat was divided into three regions, namely: left ventricle, mid-wall and right ventricle. The biaxial dataset of passive rat myocardia is presented as stress vs strain of the passive rat myocardium in various regions. The determination of valid material properties of the heart plays an important role in the development computational models. These computational models are useful in studying various scenarios and mechanisms of heart diseases. In addition, valid and accurate materials are critical in the development of new therapies. The dataset presented here is useful in the area of soft tissue mechanics including studying the mechanisms of heart diseases such as myocardial infarction. Accordingly, the evaluation of stress and strain in left ventricle, mid-wall and right ventricle was performed.
ARTICLE | doi:10.20944/preprints202208.0343.v1
Subject: Life Sciences, Molecular Biology Keywords: 14-3-3; interactome; protein-protein interaction; mitochondria; metabolism; protein quality control; homeostasis; left ventricule; network
Online: 18 August 2022 (10:54:49 CEST)
Rationale: The 14-3-3 protein family is known to interact with many proteins in non-cardiac cell types to regulate multiple signaling pathways, particularly those relating to energy and protein homeostasis; and the 14-3-3 network is a therapeutic target of critical metabolic and proteostatic signaling in cancer and neurological diseases. Although the heart is critically sensitive to nutrient and energy alterations, and multiple signaling pathways coordinate to maintain the cardiac cell homeostasis, neither the structure of cardiac 14-3-3 protein interactome, nor potential functional roles of 14-3-3 protein-protein interactions (PPIs) in heart has been explored. Objective: To establish the comprehensive landscape and characterize the functional role of cardiac 14-3-3 PPIs. Methods and Results: We evaluated both RNA expression and protein abundance of 14-3-3 isoforms in mouse heart, followed by co-immunoprecipitation of 14-3-3 proteins and mass spectrometry in left ventricle. We identified 52 proteins comprising the cardiac 14-3-3 interactome. Multiple bioinformatic analyses indicated that more than half of the proteins bound to 14-3-3 are related to mitochondria; and the deduced functions of the mitochondrial 14-3-3 network are to regulate cardiac ATP production via interactions with mitochondrial inner membrane proteins, especially those in mitochondrial complex I. Binding to ribosomal proteins, 14-3-3 proteins likely coordinate protein synthesis and protein quality control. Localizations of 14-3-3 proteins to mitochondria and ribosome were validated via immunofluorescence assays. The deduced function of cardiac 14-3-3 PPIs is to regulate cardiac metabolic homeostasis and proteostasis. Conclusions: Thus, the cardiac 14-3-3 interactome may be a potential therapeutic target in cardiovascular metabolic and proteostatic disease states, as it already is in cancer therapy.
Subject: Medicine & Pharmacology, Allergology Keywords: Heart failure with reduced ejection fraction; Real-life practice; Sacubitril/valsartan; Left ventricular ejection fraction recovery; Implantable cardioverter defibrillator
Online: 5 May 2021 (10:30:13 CEST)
Background: our purpose is to assess the effectiveness and safety of sacubitril/valsartan (SV) in “real-world” patients with heart failure and reduced ejection fraction (HFrEF), including a broader spectrum of patients than those in clinical trials and evaluating variables not previously described in the literature. Methods: real-world study in HFrEF patients (N:204), both in and out-patients, who started SV between October 2017 and December 2018. We performed a prospective analysis with a 12-month follow-up. The study outcomes were effectiveness and safety, measured by individual parameters and combined endpoints, comparing the pre and post practice periods. Results: at the end of follow-up, an improvement of left ventricle ejection fraction (LVEF): 29.8% vs 33.7; p<0.0001, a decrease in NT-proBNP levels (3928 pg/mL vs 2902 pg/mL; p=0.012), number of hospital admissions (141 vs 35; p<0.0001) and percentage of patients with implantable cardioverter defibrillator (ICD) indication (79.9% vs 49.5%; p<0.0001) were observed. Of our population, 81.3% met a combined efficacy endpoint (defined by increase of LVEF, reduction of hospital admission or improvement in functional class). No differences were observed in parameters regarding safety. Conclusions: Sacubitril/valsartan has brought about a revolution in the therapeutic management of HFrEF patients and its use may raise questions about what is considered "optimal medical therapy" prior to implantation of cardiac devices.
Subject: Mathematics & Computer Science, Numerical Analysis & Optimization Keywords: equipment vendor selection; fuzzy TOPSIS; fuzzy weighted average left and right score; multi-choice goal programming; multi-aspiration goal programming
Online: 30 May 2019 (08:42:27 CEST)
The airport ground handling service (AGHS) equipment vendor selection (AGHSEVS) problem is critical for ramp work safety management, because AGHS equipment malfunctions affect airport ramp work safety. Appropriate vendor selection can prevent aircraft damage and delays in airlines schedules, and ensure reliable and high-quality ground handling service. The AGHSEVS problem is a time-consuming and complex process that requires professional knowledge and experience to make judgments. Specifically, AGHSEVS is a multi-criteria decision-making (MCDM) problem. Previous research has seldom integrated MCDM methods with linear and goal programming to solve the AGHSEVS problem. The objective of this study was to develop a new system evaluation model for AGHSEVS by considering both qualitative and quantitative methods. We test the proposed approach on an AGHS company in Taiwan.
ARTICLE | doi:10.20944/preprints202203.0026.v1
Subject: Physical Sciences, Particle & Field Physics Keywords: Tc symmetry; CTP symmetry; Photon space; Elementary particles; Quantum wave functions; Modified Lorenz transformations; Left-handed neutrinos; Right-handed dark matters
Online: 1 March 2022 (15:01:52 CET)
The time symmetry of Tc = CT is redefined based on the 4-D Euclidean space. The time inversion symmetry of Tc = CT changes the signs of the charge (q) and absolute time (ct) of the particle. The P symmetry changes the signs of the space momenta and handedness of the particle. The Tc symmetry changes the signs of the time momentum (Pt=E/c) and charges. The handedness are classified as the left-handedness and right-handedness on the 3-D space. The charges (|q| = cDt) and energies (E= cDtDV) of the particles are originated from the upward warping (q>0) and downward warping (q<0) of the particles along the time axis. The evolution of our matter universe with Pt > 0 since the big bang can be interpreted based on the CTP symmetry with the partner antimatter universe with pt < 0. The photon space is called as the vacuum space. Then the E and M waves are the space fluctuations, and the gravitational G wave is the time fluctuations. And the E, M and G fields are newly explained. The zero E and M fields of the photon space indicates that the photon space and gamma ray are the 2EM waves. The rest mass energy of the particle is the 4-D space volume of the warped photon space. In the present work, the quantum wave function is considered as the 4-D vector with the space wave function and time axis wave function in the 4-D Euclidean space. The warped photon space corresponds to the squared wave function which is the probability density. It is concluded that, in the quantum mechanics, the imaginary number concept is introduced in the quantum wave functions instead of the time axis component of the 4-D wave function vector. The left-handed neutrino puzzle is explained from the handedness partner relation with the right-handed dark matters. Finally, the modified Lorentz transformations derived in the 4-D Euclidean space are compared with the Lorentz transformations of the special and general relativity theories in the 4-D Minkowski space.
ARTICLE | doi:10.20944/preprints202108.0157.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: reptile, ventricular septation, endocardial cushions, semilunar valves, outflow tract, cartilage, foramen of Panizza, left aorta, right aorta, pulmonary trunk, pharyngeal arch arteries, coronary arter
Online: 6 August 2021 (11:08:56 CEST)
The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortae originating from either the right or left ventricular cavum. Mixing of blood in crocodilians cannot occur at ventricular level as in other reptiles, but instead takes place at aortic root level by a shunt, the Foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods. Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris, have been studied. Results and Conclusions. The outflow tract septation complex can be divided into 2 components. The aorto-pulmonary septum divides the pulmonary trunk from both aortae, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.
REVIEW | doi:10.20944/preprints201912.0385.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: dilated cardiomyopathy (DCM); hypertrophic cardiomyopathy (HCM); restrictive cardiomyopathy (RCM); arrhythmogenic right ventricular cardiomyopathy (ARVC); left ventricular non-compaction cardiomyopathy (LVNC); Duchenne muscular dystrophy; dystrophin; genome editing; CRISPR/Cas9; Cpf1 (Cas12a)
Online: 29 December 2019 (13:41:48 CET)
Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.