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Background: There has been concern that individuals living with Hereditary Hemorrhagic Telangiectasia (HHT) could be at higher risk for poor outcomes if infected with SARS-CoV2, the virus that causes COVID-19 disease. As literature is lacking on outcomes on COVID-19 infection and vaccination in HHT, the objectives of this study were to determine and assess outcomes in HHT, as well as quantify vaccination rates and vaccination side effects in a large cohort of individuals with HHT. Method: Individuals previously recruited to OUR HHT Registry at St. Michael's Hospital, Toronto were contacted for participation in this study. Data were collected during annual assessment through a series of questionnaires asking specifically about HHT complications, treatments, and symptom management, along with COVID infection and vaccination data. Results: We attempted to contact all 262 subjects recruited to the registry. Of these, 215 (82.1%) responded at least once regarding COVID-19 related inquiries between April 2020 and August 2022, and these individuals formed our study sample. Forty-nine COVID-19 infections were reported in 47/215 (21.9%) individuals. Among 47 patients with recorded COVID-19 infection, 2/47 (4.3%) required urgent care and 7/47 (14.9%) were hospitalized following infection. Of the 7 individuals who were hospitalized, 3 (42.9%) required new supplemental oxygen. Zero deaths were reported due to COVID-19 infection. COVID vaccination history was available in 147/215 (68.4%). Of these, 135/147 (91.8%) of individuals reported vaccination and side effects were mild. Discussion: While our sample population is much like the general HHT population with regards to gender, HHT symptoms, and genetics, study limitations including survivor bias, lack of vaccine effectiveness assessment, and participant reported data should be acknowledged. Conclusion: Our results suggest that HHT patients are not at higher risk of severe infection with COVID-19 compared to the general population. Vaccination rates are high with only mild side effects being observed. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations (AVMs) are abnormal high flow shunts between arteries and veins with major negative impact on the cardiovascular system. Inherited loss-of-function (LOF) mutations in endoglin, encoding an endothelial cell (EC) expressed co-receptor for BMP9/10, causes the disease HHT1/Osler-Weber-Rendu, characterized by bleeding and AVMs. Here we observe increased activity of the downstream signalling complex mTORC1 within the retinal vasculature of HHT mouse models. To investigate its importance in AVM biology, concerning subvascular action, cell specificity, signalling strength and kinetics we combine timed genetic and antibody-based models of HHT with genetic mTORC1 inhibition or activation through EC specific deletion of Rptor or Tsc1. Results demonstrate that EC mTORC1 activation is secondary to endoglin LOF and mainly a consequence of systemic effects following AVM. While genetic EC inhibition of mTORC1 only showed tendencies towards reduced AVM severity, EC overactivation counterintuitively reduced it, implying that mTORC1 must be within a certain range to facilitate AVM. Complete inhibition of mTORC1 signalling by rapamycin provided the strongest therapeutic effect, pointing to potential involvement of RAPTOR-independent pathways or AVM-promoting effects of non-ECs in this pathology. [ABSTRACT FROM AUTHOR]

Lamb waves generated by high-speed blunt body penetrating a double - layer structure are subject to the effect of complex structural interfaces and test environment in the process of propagation, resulting in the effective signal containing damage characteristics easily disturbed by other factors. This study takes the double - layer steel plate structure as the object of study. The propagation characteristics of Lamb wave generated by penetration in steel plate are studied. For the nonlinear shock source signal, the transient non-smooth signal generated by the intrusion is analyzed and reconstructed based on the HHT (Hilbert - Huang Transform), and the Lamb wave So mode signal containing the shock source features is extracted. The results show that the proposed method can effectively eliminate the influence of other incoherent clutter in complex environment, and the reconstructed signal improves the localization accuracy. [ABSTRACT FROM AUTHOR]

Flywheels have been largely used in rotating machine engines to save inertial energy and to limit speed fluctuations. A stress distribution problem is created due to the centrifugal forces that are formed when the flywheel is spinning around, which leads to different levels of pressure and decompression inside its structure. Lack of balance leads to high energy losses through various mechanisms, which deteriorate both the flywheel’s expectancy and their ability to rotate at high speeds. Deviation in the design of flywheels from their optimum performance can cause instability issues and even a catastrophic failure during operation. This paper aims to analytically examine the stress distribution of radial and tangential directions along the flywheel structure within a linear elastic range. The eigenvalues and eigenvectors, which are representative of free vibrational features, were extracted by applying finite element analysis (FEA). Natural frequencies and their corresponding vibrating mode shapes and mass participation factors were identified. Furthermore, Kirchhoff–Love plate theory was employed to model the transverse vibration of the system. A general solution for the radial component of the equation of flywheel motion was derived with the help of the Bessel function. The results show certain modes of vibration identified as particularly influential in specific directions. Advanced time-frequency analysis techniques, including but not limited to continuous wavelet transform (CWT) and Hilbert–Huang transform (HHT), were applied to extract transverse vibration features of the flywheel system. It was also found that using CWT, low-frequency vibrations contribute to the majority of the energy in the extracted signal spectrum, while HHT exposes the high-frequency components of vibration that may cause significant structural damage if not addressed in time.

Electroencephalography (EEG) helps to assess the electrical activities of the brain so that the neuronal activities of the brain are captured effectively. EEG is used to analyze many neurological disorders, as it serves as a low-cost equipment. To diagnose and treat every neurological disorder, lengthy EEG signals are needed, and different machine learning and deep learning techniques have been developed so that the EEG signals could be classified automatically. In this work, five ensemble models are proposed for EEG signal classification, and the main neurological disorder analyzed in this paper is epilepsy. The first proposed ensemble technique utilizes an equidistant assessment and ranking determination mode with the proposed Enhance the Sum of Connection and Distance (ESCD)-based feature selection technique for the classification of EEG signals; the second proposed ensemble technique utilizes the concept of Infinite Independent Component Analysis (I-ICA) and multiple classifiers with majority voting concept; the third proposed ensemble technique utilizes the concept of Genetic Algorithm (GA)-based feature selection technique and bagging Support Vector Machine (SVM)-based classification model. The fourth proposed ensemble technique utilizes the concept of Hilbert Huang Transform (HHT) and multiple classifiers with GA-based multiparameter optimization, and the fifth proposed ensemble technique utilizes the concept of Factor analysis with Ensemble layer K nearest neighbor (KNN) classifier. The best results are obtained when the Ensemble hybrid model using the equidistant assessment and ranking determination method with the proposed ESCD-based feature selection technique and Support Vector Machine (SVM) classifier is utilized, achieving a classification accuracy of 89.98%. [ABSTRACT FROM AUTHOR]

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Abstract Background Pulmonary arteriovenous malformations are a relatively uncommon medical condition, affecting roughly 1 in every 2500 individuals. Of those suffering from pulmonary arteriovenous malformations, 80% have an underlying genetic condition: hereditary hemorrhagic telangiectasia. Case presentation We present the case of a 20-year-old Pakistani male with a history of persistent slower-onset frontal headaches that increased in severity within the course of the day. His hemoglobin was 18 g/dl, indicating polycythemia, for which he had undergone seven venesections in a month previously. His physical examination was unremarkable. His computed tomography scan depicted multiple dilated tortuous vessels with branching linear opacities in the right lower lobe of the lungs. The multiple feeding arteries were supplied by the right main pulmonary artery, and the large draining veins led to the right inferior pulmonary vein. This was identified as a diffuse pulmonary arteriovenous malformation. He was recommended for a right pulmonary artery angiogram. It showed multiple tortuous vessels with a nidus and large draining veins—features of a diffuse arteriovenous malformation in the right lower lobe of the lung consistent with the computed tomography scan. Embolization of two of these vessels feeding the arteriovenous malformation was conducted, using Amplatzer Vascular plug 2, whereas multiple pushable coils (five coils) were used for embolizing the third feeding vessel. This achieved 70–80% successful embolization of right pulmonary AVM; however, some residual flow was still seen in the arteriovenous malformation given the complexity of the lesion. Immediately after, his oxygen saturation improved from 78% to 96%. Conclusion Diffuse pulmonary arteriovenous malformations, as seen in this patient, are rare, accounting for less than 5% of total pulmonary arteriovenous malformations diagnosed. The patient presented with a complaint of progressive frontal headaches, which can be attributed to low oxygen saturation or the presence of a cerebral arteriovenous malformation. There was no history of hereditary hemorrhagic telangiectasia in the patient’s family. Furthermore, although most patients with hereditary hemorrhagic telangiectasia and hence pulmonary arteriovenous malformation have complaints of iron-deficiency anemia, our patient in contrast was suffering from polycythemia. This can be explained as a compensatory mechanism in hypoxemic conditions. Moreover, the patient had no complaint of hemoptysis or epistaxis, giving a varied presentation in comparison with a typical pulmonary arteriovenous malformation.

Hereditary hemorrhagic telangiectasia (HHT) causes arteriovenous malformations (AVMs) in several organs. This report is the first to document and image a thyroid AVM complication in HHT. A 72-year-old woman with HHT was referred for thyroid nodule evaluation. Ultrasonography showed a hypervascularized nodule in the right thyroid lobe which was initially suspected to be malignant. However, 3-dimensional computed tomography angiography demonstrated a thyroid AVM with abnormal anastomosis of the superior thyroid artery and the inferior thyroid vein. In the formation of thyroid AVM, here, chronic thyroiditis and hypothyroidism complications may have been a second hit, due to the predisposing first-hit germline mutation. This report sheds light on overlooked thyroid lesions in HHT and advocates a noninvasive imaging approach in diagnosing thyroid AVMs. Furthermore, this case suggests a potential mechanism of AVM formation in human HHT, possibly supporting the second-hit hypothesis. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and complex vascular disorder characterized by abnormal blood vessel formation. It can present significant challenges in diagnosis and management, as it is currently estimated up to 90% of those affected are never diagnosed. Despite its rarity, HHT can carry substantial implications for patients and their families, at times requiring comprehensive medical care and support. This paper aims to provide an in-depth exploration of HHT, encompassing its epidemiology, genetics, clinical manifestations, diagnostic approaches, and current management strategies. Moreover, we hope to point out possible areas in need of future research. Description of the state knowledge: HHT is an autosomal dominant genetic disorder that affects 1 in 5-10,000 people. Its most prominent symptoms include telangiectasia of skin and mucous membranes, recurrent epistaxis, gastrointestinal bleeding and arteriovenous malformations in vital organs. In the vast majority of cases, it is caused by a mutation in one of the following genes: ENG, ACVRL1, SMAD4; however, mutations in other genes have been described to cause a similar or much the same constellation of symptoms. Treatment options are focused on managing symptoms and improving quality of life, but possible new treatment options are being researched that could change the landscape of HHT management. Summary: HHT is a severely underdiagnosed disease that has seen a surge of researchers’ interest in recent years. We firmly believe that, combined with plummeting costs of genetic testing and possible new treatment options, means that HHT will become increasingly important in physicians’ everyday practice. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arteriovenous malformations are a relatively uncommon medical condition, affecting roughly 1 in every 2500 individuals. Of those suffering from pulmonary arteriovenous malformations, 80% have an underlying genetic condition: hereditary hemorrhagic telangiectasia. Case presentation: We present the case of a 20-year-old Pakistani male with a history of persistent slower-onset frontal headaches that increased in severity within the course of the day. His hemoglobin was 18 g/dl, indicating polycythemia, for which he had undergone seven venesections in a month previously. His physical examination was unremarkable. His computed tomography scan depicted multiple dilated tortuous vessels with branching linear opacities in the right lower lobe of the lungs. The multiple feeding arteries were supplied by the right main pulmonary artery, and the large draining veins led to the right inferior pulmonary vein. This was identified as a diffuse pulmonary arteriovenous malformation. He was recommended for a right pulmonary artery angiogram. It showed multiple tortuous vessels with a nidus and large draining veins—features of a diffuse arteriovenous malformation in the right lower lobe of the lung consistent with the computed tomography scan. Embolization of two of these vessels feeding the arteriovenous malformation was conducted, using Amplatzer Vascular plug 2, whereas multiple pushable coils (five coils) were used for embolizing the third feeding vessel. This achieved 70–80% successful embolization of right pulmonary AVM; however, some residual flow was still seen in the arteriovenous malformation given the complexity of the lesion. Immediately after, his oxygen saturation improved from 78% to 96%. Conclusion: Diffuse pulmonary arteriovenous malformations, as seen in this patient, are rare, accounting for less than 5% of total pulmonary arteriovenous malformations diagnosed. The patient presented with a complaint of progressive frontal headaches, which can be attributed to low oxygen saturation or the presence of a cerebral arteriovenous malformation. There was no history of hereditary hemorrhagic telangiectasia in the patient's family. Furthermore, although most patients with hereditary hemorrhagic telangiectasia and hence pulmonary arteriovenous malformation have complaints of iron-deficiency anemia, our patient in contrast was suffering from polycythemia. This can be explained as a compensatory mechanism in hypoxemic conditions. Moreover, the patient had no complaint of hemoptysis or epistaxis, giving a varied presentation in comparison with a typical pulmonary arteriovenous malformation. [ABSTRACT FROM AUTHOR]

Abstract Background Pulmonary arteriovenous malformation (PAVM), also known as pulmonary arteriovenous fistula, is a rare vascular developmental anomaly. Most cases of PAVM are associated with hereditary hemorrhagic telangiectasia (HHT). Hemothorax associated with PAVM is even rarer, and management concerning this complication still challenges. Case presentation A 55-year-old man with sudden onset of dyspnea and chest pain was admitted to our hospital. He had a medical history of epistaxis, intraperitoneal germ cell tumor and PAVM. Chest unenhanced CT revealed the left-sided pleural effusion together with partial passive atelectasis and gradual increase at the interval of six days. Diagnostic thoracocentesis further revealed hemorrhagic effusion. CT angiography (CTA) showed tortuously dilated lumen of the left lower pulmonary artery and PAVM with the formation of aneurysm. Due to his family's refusal of surgery, the patient underwent transcatheter embolization therapy. However, the left pleural effusion did not significantly reduce and there was a slow drop in hemoglobin value even after interventional treatment, indicating the possibility of ongoing active bleeding. Eventually, the patient received lobectomy of the left lower lobe with a satisfactory outcome. Conclusions Massive hemothorax resulting from PAVM rupture into the pleural space can lead to fatal outcomes. CTA can accurately diagnose this pathologic condition. Transcatheter embolization is frequently used in the treatment of PAVM, but it may be challenging to achieve the desirable effect in patients with hemothorax. Combined with our case and literature review, direct radical surgery can lead to a successful outcome when PAVM complicated with hemothorax and a large diameter of the draining vein.

Background: Pulmonary arteriovenous malformation (PAVM), also known as pulmonary arteriovenous fistula, is a rare vascular developmental anomaly. Most cases of PAVM are associated with hereditary hemorrhagic telangiectasia (HHT). Hemothorax associated with PAVM is even rarer, and management concerning this complication still challenges. Case presentation: A 55-year-old man with sudden onset of dyspnea and chest pain was admitted to our hospital. He had a medical history of epistaxis, intraperitoneal germ cell tumor and PAVM. Chest unenhanced CT revealed the left-sided pleural effusion together with partial passive atelectasis and gradual increase at the interval of six days. Diagnostic thoracocentesis further revealed hemorrhagic effusion. CT angiography (CTA) showed tortuously dilated lumen of the left lower pulmonary artery and PAVM with the formation of aneurysm. Due to his family's refusal of surgery, the patient underwent transcatheter embolization therapy. However, the left pleural effusion did not significantly reduce and there was a slow drop in hemoglobin value even after interventional treatment, indicating the possibility of ongoing active bleeding. Eventually, the patient received lobectomy of the left lower lobe with a satisfactory outcome. Conclusions: Massive hemothorax resulting from PAVM rupture into the pleural space can lead to fatal outcomes. CTA can accurately diagnose this pathologic condition. Transcatheter embolization is frequently used in the treatment of PAVM, but it may be challenging to achieve the desirable effect in patients with hemothorax. Combined with our case and literature review, direct radical surgery can lead to a successful outcome when PAVM complicated with hemothorax and a large diameter of the draining vein. [ABSTRACT FROM AUTHOR]

Aims BMP9 is a high affinity ligand of ALK1 and endoglin receptors that are mutated in the rare genetic vascular disorder hereditary hemorrhagic telangiectasia (HHT). We have previously shown that loss of Bmp9 in the 129/Ola genetic background leads to spontaneous liver fibrosis via capillarization of liver sinusoidal endothelial cells (LSEC) and kidney lesions. We aimed to decipher the molecular mechanisms downstream of BMP9 to better characterize its role in vascular homeostasis in different organs. Methods and results For this, we performed an RNA-seq analysis on LSEC from adult WT and Bmp9 -KO mice and identified over 2000 differentially expressed genes. Gene ontology analysis showed that Bmp9 deletion led to a decrease in BMP and Notch signalling, but also LSEC capillary identity while increasing their cell cycle. The gene ontology term 'glomerulus development' was also negatively enriched in Bmp9 -KO mice vs. WT supporting a role for BMP9 in kidney vascularization. Through different imaging approaches (electron microscopy, immunostainings), we found that loss of Bmp9 led to vascular enlargement of the glomeruli capillaries associated with alteration of podocytes. Importantly, we also showed for the first time that the loss of Bmp9 led to spontaneous arteriovenous malformations (AVMs) in the liver, gastrointestinal tract, and uterus. Conclusion Altogether, these results demonstrate that BMP9 plays an important role in vascular quiescence both locally in the liver by regulating endothelial capillary differentiation markers and cell cycle but also at distance in many organs via its presence in the circulation. It also reveals that loss of Bmp9 is sufficient to induce spontaneous AVMs, supporting a key role for BMP9 in the pathogenesis of HHT. [ABSTRACT FROM AUTHOR]

Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary. [ABSTRACT FROM AUTHOR]

[Objective] To Compare and analyze the differences in multi-scale periodic calculation performance between different methods can provide more reference for the selection of regional hydrological periodic analysis methods. [Methods] In this study, two groups of artificial sequences with known period and trend characteristics were used to test, compare and analyze the difference between Hilbert-Huang Transform (HHT) based on Multivariate Empirical Mode Decomposition (MEMD) and wavelet analysis in multi-scale period calculation performance. On this basis, the improved HHT was used to analyze further the multi-time scale characteristics of the 39-year rainfall series at 11 stations in Mu Us Sandy Land. [Results] For artificial sequences, the wavelet analysis (symmetric extension) results are relatively large, and there is a significant difference from the preset period (Sig.=0.003＜0.05) . The periodic results of HHT and wavelet analysis (periodic extension) show no significant difference from the preset period, and the accuracy of HHT (Sig.=0.142＞0.05) is slightly higher than that of periodic extension wavelet (Sig.=0.109＞0.05) . For the measured rainfall series, HHT shows significant regional differences in the main period of rainfall in the Mu Us Sandy Land: the main period of rainfall at the hinterland station is 5.5 years, while at the edge station, it is 2.7～3.3 years. The decomposed residual component indicates that the rainfall at this region showed an upward trend in time and a gradually decreasing distribution state in space from east to west. [Conclusion] This study shows that HHT can extract more hydrological information while maintaining accuracy due to its data-driven, without considering the selection of many parameters, and has more advantages in the multi-scale analysis of regional rainfall series, thus it has important practical application value. [ABSTRACT FROM AUTHOR]

Background and purpose: Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right‐to‐left shunts was also assessed post hoc. Methods: This was a cross‐sectional population‐based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble‐echocardiography to detect vascular right‐to‐left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). Results: Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble‐echocardiography. The median age of participants was 54 years (IQR 45–62) and 19/57 (33%) were females compared with 59 years (IQR 48–68, p = 0.05) and 41/85 females (48%, p = 0.22) in non‐participants. Bubble‐echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06–11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. Conclusions: Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right‐to‐left shunts amongst brain abscess patients corresponds to the prevalence in the general population. [ABSTRACT FROM AUTHOR]

In the present study, a series of shaking table model tests were performed on a slope with a gabion reinforced retaining wall. Transfer functions were employed to compute the inherent frequencies of the slope. Furthermore, the investigation examined various aspects of the slope, including the peak acceleration amplification factor, incremental dynamic stresses, displacements, and tensile forces. Additionally, the study employed the Hilbert Huang transform (HHT) to analyze the slope's time-frequency characteristics and energy distribution. The findings of the study revealed that there is an inverse relationship between the amplitude of the input seismic wave and the natural frequency of the top of the gabion reinforced retaining wall slope. As the amplitude of the seismic wave increases, the natural frequency of the slope decreases. The amplification factors for peak acceleration were all found to be less than 1.9, suggesting a notable dissipation of seismic energy in comparison to typical slopes. The response of incremental dynamic stress was most pronounced in the middle section of the slope, followed by the top of the slope. The magnitude of the incremental displacement was found to be highest at layer 4, whereas the incremental tensile force exhibited its maximum value at layer 5. The dynamic response exhibited the least pronounced characteristics at the lower portion of the slope, demonstrating the most stable behavior. The peak frequencies observed in the Hilbert marginal spectrum displayed comparable characteristics to the natural frequencies. • Large-scale shaking table tests were conducted on the stepped gabion reinforced retaining wall slope. • The natural frequency, damping ratio, and dynamic shear modulus were used to analyze the dynamic characteristics of the gabion reinforced retaining wall slope under seismic action. • The energy dissipation mechanism of the gabion reinforced retaining wall slope was investigated by peak acceleration amplification factor, dynamic stress increment, displacement increment and tension increment. • The time-frequency domain and energy perspective of the gabion reinforced retaining wall slope under seismic action was analyzed by using HHT, and the damage evolution mechanism inside the slope when the amplitude of input seismic wave increases is revealed. [ABSTRACT FROM AUTHOR]

The comprehensive utility tunnel plays a crucial role in the urban development process. However, the integration of energy pipelines into the comprehensive utility tunnel can introduce a range of safety concerns. Therefore, researching the damage characteristics of urban comprehensive utility tunnels under internal gas explosions is of significant importance for optimizing tunnel design. The study involves designing and conducting explosion similarity model experiments in comprehensive utility tunnels. Through the use of piezoelectric smart aggregate monitoring technology, the tunnel model’s damage is monitored. This research aims to analyze the damage and destruction caused to the tunnel structure by internal gas explosions. It will provide a basis for determining the characteristics of tunnel damage. This paper first employs a combination of Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) and an improved wavelet threshold method to denoise the monitoring signals. Next, it compares the signal strength peaks before and after the explosion to conduct an initial analysis of the tunnel’s damage situation. Finally, through Hilbert-Huang Transform (HHT) transformation, comparisons were made between the energy and frequency distribution of signals from ‘RT5-Black5’ and ‘RT6-Black7’ before and after two explosions, further elucidating the damage characteristics of the tunnel. Upon analysis and verification, the combination of CEEMDAN and the improved wavelet thresholding method demonstrates superior denoising effects, it is confirmed that the accumulated energy decreases and the frequency band widens after the explosion.

We present a rare case of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia (LPL/WM) diagnosed in a 65‐year‐old female initially presenting with recurrent bilateral epistaxis. Despite multiple cauterizations and a history of ineffective conventional treatments, comprehensive evaluations led to the diagnosis, underscoring the critical need for thorough investigation in persistent epistaxis cases, particularly when standard approaches fail. This case emphasizes the importance of considering indolent lymphomas in the differential diagnosis of recurrent epistaxis and showcases the diagnostic pathway leading to successful identification and treatment of a rare etiology. Laryngoscope, 134:3974–3976, 2024 [ABSTRACT FROM AUTHOR]

Random and fluctuating wind speeds make it difficult to stabilize the wind-power output, which complicates the execution of wind-farm control systems and increases the response frequency. In this study, a novel prediction model for ultrashort-term wind-speed prediction in wind farms is developed by combining a deep belief network, the Elman neural network, and the Hilbert-Huang transform modified using an improved particle swarm optimization algorithm. The experimental results show that the prediction results of the proposed deep neural network is better than that of shallow neural networks. Although the complexity of the model is high, the accuracy of wind-speed prediction and stability are also high. The proposed model effectively improves the accuracy of ultrashort-term wind-speed forecasting in wind farms.

Introduction and purpose: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and complex vascular disorder characterized by abnormal blood vessel formation. It can present significant challenges in diagnosis and management, as it is currently estimated up to 90% of those affected are never diagnosed. Despite its rarity, HHT can carry substantial implications for patients and their families, at times requiring comprehensive medical care and support. This paper aims to provide an in-depth exploration of HHT, encompassing its epidemiology, genetics, clinical manifestations, diagnostic approaches, and current management strategies. Moreover, we hope to point out possible areas in need of future research. Description of the state knowledge: HHT is an autosomal dominant genetic disorder that affects 1 in 5-10,000 people. Its most prominent symptoms include telangiectasia of skin and mucous membranes, recurrent epistaxis, gastrointestinal bleeding and arteriovenous malformations in vital organs. In the vast majority of cases, it is caused by a mutation in one of the following genes: ENG, ACVRL1, SMAD4; however, mutations in other genes have been described to cause a similar or much the same constellation of symptoms. Treatment options are focused on managing symptoms and improving quality of life, but possible new treatment options are being researched that could change the landscape of HHT management. Summary: HHT is a severely underdiagnosed disease that has seen a surge of researchers’ interest in recent years. We firmly believe that, combined with plummeting costs of genetic testing and possible new treatment options, means that HHT will become increasingly important in physicians’ everyday practice.

In this paper, the method of embedding piezoelectric ceramic sensors is used to test the damage of the materials and models of the urban comprehensive pipe gallery. The monitoring signal is processed by HHT method, and the frequency and energy changes of the piezoelectric signal before and after the explosion were analyzed, thus the damage characteristics of the urban comprehensive pipe gallery under the internal gas explosion are determined. The results show that in the gas explosion test inside the pipe gallery model, the waveform and peak value of the piezoelectric signal before and after the explosion did not change significantly, indicating that there was no obvious damage to the side wall of the integrated pipe gallery. However, after further time-frequency analysis of the piezoelectric signal by HHT, it is found that the dominant frequency of the piezoelectric signal after explosion has a downward trend, so it is judged that there is a small damage in the pipe gallery after explosion. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety, technical success and short-term effectiveness of polyurethane-covered stent (PK Papyrus, BioTronik, Berlin) in the treatment of pulmonary arteriovenous malformations (PAVMs) that are not amenable to embolotherapy. Materials and Methods: In this IRB-approved, retrospective study, data from patients who received polyurethane-covered stents for exclusion of PAVMs were analyzed. The study included 5 patients (all women) with a median age of 40 years (range 25–60). Patients presented with hypoxemia, TIAs, and/or epistaxis; 4 were confirmed to have HHT. All had multiple PAVMs diagnosed on chest CT and underwent embolization with other devices in addition to the polyurethane-covered stent. The indication for stent placement in all cases was a short and/or tortuous feeding artery. Safety was assessed by immediate or short-term complications, e.g., migration, stent thrombosis, and fracture. Technical success was defined as the ability to accurately place the stent at the intended location. Effectiveness was defined as successful exclusion of PAVM with no perfusion across the AVM. Results: Technical success of stent placement was 100%. AVM exclusion rate was 80% after single stent deployment; in the case of incomplete exclusion, success was achieved using an overlapping stent to completely cover a second feeding artery. During the median follow-up period of 5 months (range 2–10), all stents remained patent, and AVMs were excluded without other complications. Conclusion: Exclusion of PAVMs with polyurethane-covered stents is technically feasible, safe, and shows short-term effectiveness for PAVMs with a short/tortuous feeding artery when traditional embolization techniques are not possible. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was twofold: to determine the prevalence of arterial and venous thromboembolic events in the Norwegian Hereditary Hemorrhagic Telangiectasia (HHT) population, and to explore potential factors linked to such events, with particular emphasis on FVIII. Methods: Patients with an HHT diagnosis attending the Otorhinolaryngology Department at Oslo University Hospital—Rikshospitalet were included consecutively between April 2021 and November 2022. We recorded the participants' medical history with an emphasis on thromboembolic events. Measurements of blood constituents, including FVIII, FIX, vWF, hemoglobin, iron, ferritin, and CRP were performed. Results: One hundred and thirty‐four patients were included in the study. The total prevalence of thromboembolic events among the participants was 23.1%. FVIII levels were high (>150 IU/dL) in the majority of HHT patients (n = 84) (68.3%) and were significantly associated with thromboembolic events (p <.001), as was age. Of the patients with high FVIII levels, 28 (33%) had experienced a thromboembolic event. Furthermore, FVIII levels were measured consecutively in 51 patients and were found to fluctuate above or below 150 IU/dL in 25% of these cases. Conclusion: Thromboembolic events are highly prevalent in the Norwegian HHT population and are significantly associated with FVIII levels. FVIII levels can fluctuate, and measurements should be repeated in HHT patients to assess the risk of thromboembolic events. Level of Evidence: 4. [ABSTRACT FROM AUTHOR]

Background: The Epistaxis Severity Score (ESS) is the gold-standard patient-reported outcome measure for evaluating nosebleed severity in patients with hereditary hemorrhagic telangiectasia (HHT). To date, the ESS has been assessed only for content validity and concurrent validity. Objective: We evaluate the internal consistency and test–retest reliability of the ESS. Materials and Methods: After receiving institutional review board approval, we sent an online survey battery, including the ESS survey, to 305 (39% male) English-speaking HHT patients ≥18 years old at a single center. Of those, 140 (46%) patients completed the battery, and 110/140 (79%) reported epistaxis. Cronbach's alpha and correlation analyses were used to evaluate internal consistency. For the test–retest reliability evaluation, we recruited 69 HHT patients during HHT clinic to complete 2 self-administered ESS surveys 2 weeks apart. Participants also completed a modified Clinical Global Impression-Improvement scale with readministration of the ESS survey. We calculated the intraclass correlation coefficient in a 2-way mixed model with absolute agreement. Results: The ESS survey demonstrated low internal consistency (Cronbach's alpha = 0.495), suggesting that it measured multiple unrelated concepts. Factor analysis revealed 3 latent factors with moderate intercorrelation, suggesting the presence of 3 related but distinct constructs underlying the ESS. However, the ESS demonstrated excellent test–retest reliability (intraclass correlation coefficient = 0.955; 95% CI, 0.91-0.98). Conclusion: Although the ESS demonstrates high test–retest reliability, it may not adequately assess different dimensions of nosebleed severity. Additional correlated survey questions and sub-scores may be needed to increase internal consistency to accurately measure each component of epistaxis severity. It is necessary to acknowledge epistaxis severity from different dimensions and to consider evaluating individual ESS items separately for a comprehensive understanding. [ABSTRACT FROM AUTHOR]

BackgroundVascular malformations in the central nervous system are difficult to monitor and treat due to their inaccessible location. Angiogenic and inflammatory proteins are secreted into the bloodstream and may serve as useful biomarkers for identifying patients at risk for complications or with certain disease phenotypes.MethodsA validated multiplex protein array consisting of 26 angiogenic and inflammatory biomarkers (Angiome) was assessed in plasma isolated from healthy controls and patients with either sporadic brain arteriovenous malformation (BAVM), familial cerebral cavernous malformation (CCM), or hereditary hemorrhagic telangiectasia (HHT). These samples were obtained from archives of ongoing research studies at the University of California San Francisco and through prospective collection at the Toronto HHT Centre at St. Michael's Hospital.ResultsWe compared circulating biomarker levels from each patient group to healthy controls and analyzed each pairwise combination of patient groups for differences in biomarker levels. Additionally, we analyzed the HHT samples to determine the association between biomarker levels and the following HHT-specific phenotypes, BAVM, pulmonary arteriovenous malformation (PAVM), liver vascular malformation (LVM), and gastrointestinal (GI) bleeding. Compared to controls, levels of SDF1 were significantly elevated in HHT patients (Proportional Increase [PI] = 1.87, p

Background: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations. Individuals with HHT often identify low humidity and temperature as detrimental to epistaxis severity. We set out to assess the relationship between humidity and temperature on epistaxis severity in patients with HHT. Methods: Retrospective cross‐sectional study at an academic hospital with an HHT center between July 1, 2014 and January 1, 2022. The primary outcome of this study was ESS. Pearson correlation analyses and multiple linear regression analyses were performed to test the association between weather variables and epistaxis severity scre (ESS). Results were reported as coefficient and 95% confidence interval (CI). Results: Four hundred twenty‐nine patients were included in the analysis. Through a Pearson correlation analysis, neither humidity (regression coefficient = −0.01; 95% CI, −0.006 to 0.003; p = 0.50), daily low temperature (regression coefficient = 0.01; 95% CI, −0.011 to 0.016; p = 0.72), or daily high temperature (regression coefficient = 0.01; 95% CI, −0.004 to 0.013; p = 0.32) were significantly correlated with ESS. In a multiple linear regression analysis, adjusting for both daily low temperature and humidity, medications taken, demographics, and genotype, neither daily low temperature (regression coefficient = −0.02; 95% CI, −0.04 to 0.01; p = 0.14) nor humidity (regression coefficient = 0.01; 95% CI, −0.01 to 0.01; p = 0.64) were significantly associated with ESS. Conclusion: We have shown in a large clinical sample that neither humidity nor temperature were strongly correlated with HHT patient epistaxis severity. [ABSTRACT FROM AUTHOR]

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting the patient's quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and the need for blood transfusions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT. Methods: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5–2 mg/day) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. The epistaxis severity score (ESS) and hemoglobin levels were the parameters used to evaluate the impact of tacrolimus. The occurrence of side effects was also recorded. Results: Tacrolimus was well tolerated in all of the patients except 2 (who stopped the treatment). The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced when comparing the ESS before and after the treatment. Hemoglobin levels significantly increased, overcoming the anemia, during the course of the treatment. Conclusion: Tacrolimus at low doses should be considered as a promising treatment for epistaxis and gastrointestinal bleeding in HHT. [ABSTRACT FROM AUTHOR]

The transforming growth factor β (TGF-β)/ALK1/ENG signaling pathway maintains quiescent state of endothelial cells, but at the same time, it regulates neutrophil functions. Importantly, mutations of this pathway lead to a rare autosomal disorder called hereditary hemorrhagic telangiectasia (HHT), characterized with abnormal blood vessel formation (angiogenesis). As neutrophils are potent regulators of angiogenesis, we investigated how disturbed TGF-β/ALK1/ENG signaling influences angiogenic properties of these cells in HHT. We could show for the first time that not only endothelial cells, but also neutrophils isolated from such patients are ENG/ALK1 deficient. This deficiency obviously stimulates proangiogenic switch of such neutrophils. Elevated proangiogenic activity of HHT neutrophils is mediated by the increased spontaneous degranulation of gelatinase granules, resulting in high release of matrix-degrading matrix metalloproteinase 9 (MMP9). In agreement, therapeutic disturbance of this process using Src tyrosine kinase inhibitors impaired proangiogenic capacity of such neutrophils. Similarly, inhibition of MMP9 activity resulted in significant impairment of neutrophil-mediated angiogenesis. All in all, deficiency in TGF-β/ALK1/ENG signaling in HHT neutrophils results in their proangiogenic activation and disease progression. Therapeutic strategies targeting neutrophil degranulation and MMP9 release and activity may serve as a potential therapeutic option for HHT. We demonstrate a key role of ENG/ALKlow neutrophils in MMP9-dependent support of angiogenesis in HHT, providing a rationale for therapeutical targeting of neutrophils. [ABSTRACT FROM AUTHOR]

Purpose of Review: To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. Recent Findings: Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Summary: Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned. [ABSTRACT FROM AUTHOR]

With the advancement of computer and mathematical techniques, significant progress has been made in the 3D modeling of foundation piles. Existing methods include the 3D semi-analytical model for non-destructive low-strain integrity assessment of large-diameter thin-walled pipe piles and the 3D soil-pile dynamic interaction model. However, these methods have complex analysis procedures and substantial limitations. This paper introduces an innovative and streamlined 3D imaging technique tailored for the detection of pile damage. The approach harnesses the power of an eight-channel ring array transducer to capture internal reflection signals within foundation piles. The acquired signals are subsequently processed using the Hilbert-Huang Transform (HHT), a robust analytical tool known for its effectiveness in handling non-stationary signals. Through the development of a sophisticated multi-channel ring array imaging algorithm, this technique empowers engineers and researchers to identify various pile defects, including their specific type, precise location, and obtain detailed 3D imaging representations. The findings of this research offer a valuable blend of theoretical insights and practical guidance, significantly advancing the state-of-the-art in the realm of concrete pile integrity inspection. By simplifying and enhancing the assessment process, this innovative approach not only addresses the complexities of existing methods but also contributes to the overall safety and reliability of concrete engineering structures. [ABSTRACT FROM AUTHOR]

In view that the conventional harmonic detection algorithms cannot support analysis on nonlinear and non-stationary harmonics in the traction power supply systems, this paper proposes a harmonic detection algorithm based on the improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) and Teager energy operator (TEO). The first step is to process the signal to be detected into a set of intrinsic mode function (IMF) components through ICEEMDAN, and then obtain the true IMF components by filtering out the false ones. Then, performing TEO demodulation on each IMF component can generate the variation charts of amplitude and frequency of harmonic components over time. It is revealed through analysis that ICEEMDAN, as an improved algorithm for empirical mode decomposition (EMD), an important step in the Hilbert-Huang transform (HHT), has the best effect in suppressing mode aliasing, compared with other improved algorithms of EMD. Thanks to its good adaptability, it also has good performance in processing nonlinear and non-stationary signals. On the other hand, TEO can accurately detect the instantaneous amplitude and frequency of harmonics, and quickly respond to signal changes. The proposed algorithm was simulated and analyzed by constructing harmonic signals of the traction network characteristics. The results show that the average detection errors of amplitude and frequency were 3.56% and 1.74% respectively when analyzing steady-state current harmonics, and 3.39% and 2.44% respectively when analyzing transient current harmonics. This indicates that the algorithm proposed in this paper can accurately detect the amplitude and frequency of harmonics in the traction power supply systems, and can accurately locate harmonic signal singularity.

Abstract Background Identifying therapeutic targets and prognostic biomarkers significantly contributes to individualized treatment of acute myeloid leukemia (AML). Dihydropyrimidinase‐like 2 (DPYSL2) expression was decreased in homoharringtonine (HHT)‐resistant AML cells, which were established by our group. DPYSL2 plays an important role in axon growth and has oncogene effect in glioblastoma. However, little research has been conducted to investigate the function of DPYSL2 in AML pathogenesis. Methods Auto‐docking was used to reveal the targeting relationship between HHT and DPYSL2. Overall survival (OS), event‐free survival (EFS), and relapse‐free survival (RFS) were used to evaluate the prognostic impact of DPYSL2 for AML. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. In vivo growth and survival were assessed using a xenotransplantation mice model. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML and were confirmed by Western blot. Results We found DPYSL2 was the target of HHT. Next, we found AML cell lines and patients had higher DPYSL2 expression levels than the normal samples. Further multivariate analysis demonstrated that high DPYSL2 expression was an independent poor prognostic factor for OS, EFS, and RFS in AML. Inhibition of DPYSL2 expression suppressed cell growth, induced apoptosis in AML cell lines, and prolonged the survival of AML xenograft NCG mice. Through RNA‐seq analysis from TCGA and our data, the JAK2/STAT3/STAT5‐PI3K P85/AKT/GSK3b axis was thought to be the critical pathway in regulating DPYSL2 in AML development. Conclusions We first time confirmed that DPYSL2 was a target of HHT and played an oncogene role in AML by regulating JAK/STAT signaling pathway. Therefore, DPYSL2 could serve as a novel prognostic marker and therapeutic target for AML treatment.

Making clear the vibration response law of buildings(structures)due to blasting is of great significance both engineeringly and the economically. By conducting blasting experiment at subway station entrance A, the vibration signal of building NO.2 was analyzed through Hilbert-Huang transform. Results indicate that as height increases, the three-vector peak vibration velocity attenuate sharply, and then shows a wave-shaped change in the middle and amplify on the top floor, which was divided into attenuation area(0~26.15 m], fluctuation area(26.15~71.75 m]and amplification area(71.75~94.55 m]. The shape of the Hilbert spectrum gradually changes from three-peak to single-peak, the dominant frequency band attenuates from 75~125 Hz to 10~40 Hz and the energy amplitude decreases. This demonstrates that the lower vibration frequency of the floor in the amplification area could easily cause resonance. Based on the composition of the top-level energy spectrum fitted by the ground measuring points, it is verified that the essence of the top-level amplification effect is to selectively amplify the energy close to the natural frequency of the building in the blasting seismic wave.

Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu–Osler–Weber Syndrome (ROW) is an autosomal dominant vascular disease, with an estimated prevalence of 1:5000. Genes associated with HHT are ACVRL1, ENG, SMAD4, and GDF2, all encoding for proteins involved in the TGFβ/BMPs signaling pathway. The clinical diagnosis of HHT is made according to the “Curaçao Criteria,” based on the main features of the disease: recurrent and spontaneous epistaxis, muco-cutaneous telangiectases, arteriovenous malformations in the lungs, liver, and brain, and familiarity. Since the clinical signs of HHT can be misinterpreted, and the primary symptom of HHT, epistaxis, is common in the general population, the disease is underdiagnosed. Although HHT exhibits a complete penetrance after the age of 40, young subjects may also present symptoms of the disease and are at risk of severe complications. Here we review the literature reporting data from clinical, diagnostic, and molecular studies on the HHT pediatric population.

Introduction: Hereditary haemorrhagic telangiectasia (HHT) is a rare multi-organ vascular disease. It is characterised by mucocutaneous telangiectasia, epistaxis, and arteriovenous malformations. Some 70% of patients with HHT are thought to have issues with gastrointestinal (GI) bleeding. Traditional management of GI bleeding in HHT includes monitoring for iron deficiency anaemia, iron replacement, antifibrinolytic therapy and control of identifiable bleeding sites with argon photocoagulation during gastrointestinal endoscopy. Blood transfusion may also be required. Case description: Our case describes a man in his 40s with confirmed HHT, with transfusion-dependent anaemia secondary to GI bleeding. He was commenced on fortnightly bevacizumab (5 mg/kg) for 12 weeks in an attempt to reduce his blood transfusion requirement and manage his anaemia. In the months prior to starting bevacizumab, our patient’s transfusion requirement ranged from 3–5 units of packed red cells per month to maintain an Hb >8 g/dl. He had a marked improvement in his symptoms within the first month of treatment and did not require any further blood transfusion during the three months of treatment. He was given one further IV iron infusion in the final month of his 3-month bevacizumab treatment and did not experience any adverse side effects from bevacizumab. Discussion: HHT results from alterations to genes which encode proteins involved in blood vessel formation. This provides the rationale for using anti VEGF drugs such as bevacizumab. Current evidence for this treatment approach is limited. Conclusion: Bevacizumab can be an effective treatment option in patients with HHT refractory to traditional management.

Pulmonary arterial hypertension (PAH) is a rare cardiovascular disorder leading to pulmonary hypertension and, often fatal, right heart failure. Sex differences in PAH are evident, which primarily presents with a female predominance and increased male severity. Disturbed signalling of the transforming growth factor-β (TGFβ) family and gene mutations in the bone morphogenetic protein receptor 2 (BMPR2) are risk factors for PAH development, but how sex-specific cues affect the TGFβ family signalling in PAH remains poorly understood. In this review, we aim to explore the sex bias in PAH by examining sex differences in the TGFβ signalling family through mechanistical and translational evidence. Sex hormones including oestrogens, progestogens, and androgens, can determine the expression of receptors (including BMPR2), ligands, and soluble antagonists within the TGFβ family in a tissue-specific manner. Furthermore, sex-related genetic processes, i.e. Y-chromosome expression and X-chromosome inactivation, can influence the TGFβ signalling family at multiple levels. Given the clinical and mechanistical similarities, we expect that the conclusions arising from this review may apply also to hereditary haemorrhagic telangiectasia (HHT), a rare vascular disorder affecting the TGFβ signalling family pathway. In summary, we anticipate that investigating the TGFβ signalling family in a sex-specific manner will contribute to further understand the underlying processes leading to PAH and likely HHT. [ABSTRACT FROM AUTHOR]

Disturbances in bone morphogenetic protein (BMP) signalling contribute to onset and development of a number of rare genetic diseases, including Fibrodysplasia ossificans progressiva (FOP), Pulmonary arterial hypertension (PAH), and Hereditary haemorrhagic telangiectasia (HHT). After decades of animal research to build a solid foundation in understanding the underlying molecular mechanisms, the progressive implementation of iPSC-based patient-derived models will improve drug development by addressing drug efficacy, specificity, and toxicity in a complex humanized environment. We will review the current state of literature on iPSC-derived model systems in this field, with special emphasis on the access to patient source material and the complications that may come with it. Given the essential role of BMPs during embryonic development and stem cell differentiation, gain- or loss-of-function mutations in the BMP signalling pathway may compromise iPSC generation, maintenance, and differentiation procedures. This review highlights the need for careful optimization of the protocols used. Finally, we will discuss recent developments towards complex in vitro culture models aiming to resemble specific tissue microenvironments with multi-faceted cellular inputs, such as cell mechanics and ECM together with organoids, organ-on-chip, and microfluidic technologies. [ABSTRACT FROM AUTHOR]

With the rapid development of underground space utilization, the excavation of new tunnels with ultra-shallow under crossing buildings using the drilling and blasting method is gradually increasing. The blasting vibration will undoubtedly affect the surrounding buildings. Reducing the impact of blasting vibration on ground buildings has become an important technical challenge faced by tunnel blasting technicians. The inlet end of the Xi'an-Chengdu High-Speed Railway Xiannvyan Tunnel passes below a village through an ultra-shallow buried section; as a result, blasting vibration control is a major concern. A design scheme for a 0.6 m footage in tunnel was proposed and verified through field tests. A 0.8 m footage scheme and 1.8 m footage millisecond interference vibration reduction scheme were proposed, respectively. Based on the HHT analysis, by comparing the surface vibration velocities and instantaneous energy obtained from the millisecond delay detonation of cutting holes and the detonation of different charging schemes, we found that the free surface, mass of single dynamite charges, and tunnel burial depth had significant influences on the surface vibration. [ABSTRACT FROM AUTHOR]

The interplay between hypoxia-inducible factors (HIFs) and transforming growth factor beta (TGF-β) is critical for both inflammation and angiogenesis. In hereditary hemorrhagic telangiectasia (HHT), we have previously observed that impairment of the TGF-β pathway is associated with downregulation of HIF-1α. HIF-1α accumulation is mandatory in situations of altered energy demand, such as during infection or hypoxia, by adjusting cell metabolism. Leukocytes undergo a HIF-1α-dependent switch from aerobic mitochondrial respiration to anaerobic glycolysis (glycolytic switch) after stimulation and during differentiation. We postulate that the decreased HIF-1α accumulation in HHT leads to a clinically observed immunodeficiency in these patients. Examination of HIF-1α and its target genes in freshly isolated peripheral blood mononuclear cells (PBMCs) from HHT patients revealed decreased gene expression and protein levels of HIF-1α and HIF-1α-regulated glycolytic enzymes. Treatment of these cells with the HIF–prolyl hydroxylase inhibitor, Roxadustat, rescued their ability to accumulate HIF-1α protein. Functional analysis of metabolic flux using a Seahorse FX extracellular flux analyzer showed that the extracellular acidification rate (indicator of glycolytic turnover) after Roxadustat treatment was comparable to non-HHT controls, while oxygen consumption (indicator of mitochondrial respiration) was slightly reduced. HIF stabilization may be a potential therapeutic target in HHT patients suffering from infections. [ABSTRACT FROM AUTHOR]

The DL (Deep Learning) method is the standard for forecasting tourist arrivals. This method provides very good forecasting results but needs improvement if the data is small. Statistical data from the BPS (Central Bureau of Statistics) needs to be corrected, resulting in forecasts that tend to be invalid. This study uses statistical data and GT (Google Trends) as a solution so that the data is sufficient. GT data has a lot of noise because there is a shift between web searches and departures. This difference will produce noise that needs to be cleaned. We use monthly data from January 2008 to December 2021 from BPS sources combined with GT. Hilbert-Huang Transform (HHT) is proposed to clean data from various disturbances. The DL used in this study is long short-time memory (LSTM) and was evaluated using the root mean squared error RMSE and mean absolute percentage error (MAPE). The evaluation results show that the HHT-LSTM results are better than without data cleaning. [ABSTRACT FROM AUTHOR]