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Nonlinear projection equations (NPEs) provide a unified framework for solving various constrained nonlinear optimization and engineering problems. This paper presents a deep learning approach for solving NPEs by incorporating neurodynamic optimization and physics‐informed neural networks (PINNs). First, we model the NPE as a system of ordinary differential equations (ODEs) using neurodynamic optimization, and the objective becomes solving this ODE system. Second, we use a modified PINN to serve as the solution for the ODE system. Third, the neural network is trained using a dedicated algorithm to optimize both the ODE system and the NPE. Unlike conventional numerical integration methods, the proposed approach predicts the end state without computing all the intermediate states, resulting in a more efficient solution. The effectiveness of the proposed framework is demonstrated on a collection of classical problems, such as variational inequalities and complementarity problems. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the association of single nucleotide polymorphisms (SNPs) in protein C (PROC) and protein S (PROS1) genes with deep venous thrombosis (DVT) in a thrombophilia family. Methods: DNA were extracted from blood of participants. Five PROC SNPs and 11 PROS1 SNPs were selected from the Hapmap and 1000 Genomes databases. The minor allele frequencies (MAFs) of SNPs in the thrombophilia family (Group I) and healthy controls (Group II) were detected. SNPs were analysed by Chi‐square, logistic regression and linkage disequilibrium patterns. Results: MAFs for all 16 SNPs were greater than 0.05. Chi‐square analysis showed significant differences between Group I and Group II in the frequency of mutant alleles of rs1799808, rs5936, rs6123, rs12634349, rs6441600 and rs13062355 SNPs (P < .05). Logistic regression analysis found that mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT in this family (OR > 1, L95 > 1). Linkage disequilibrium was found among 15 of the PROC and PROS SNPs. Conclusions: Single nucleotide polymorphisms (SNPs) of PROC and PROS1 may be closely associated with DVT in this thrombophilia family. Mutant alleles of rs1799808, rs6441600 and rs13062355 SNPs may contribute to DVT, whereas mutant alleles of rs1799810, rs6123 and rs12634349 may protect individuals from DVT. With the exception of rs9681204, there was linkage disequilibrium between PROC and PROS1 SNPs. We found that 12 haplotypes were in linkage disequilibrium, but linkage disequilibrium was strong in only eight of these (frequency >5%). [ABSTRACT FROM AUTHOR]

Hamiltonian neural networks (HNNs) are state-of-the-art models that regress the vector field of a dynamical system under the learning bias of Hamilton's equations. A recent observation is that embedding a bias regarding the additive separability of the Hamiltonian reduces the regression complexity and improves regression performance. We propose separable HNNs that embed additive separability within HNNs using observational, learning, and inductive biases. We show that the proposed models are more effective than the HNN at regressing the Hamiltonian and the vector field. Consequently, the proposed models predict the dynamics and conserve the total energy of the Hamiltonian system more accurately.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH., Methods: Single-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining., Results: The results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression., Conclusion: CD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1β involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Wu, Shao, Lai, Lin, Chen, Wu, Chen, Lin, Huang, Chen, Yan, Chen, Li, Wu, Yang and Deng.)

Nonlinear projection equations (NPEs) provide a unified framework for addressing various constrained nonlinear optimization and engineering problems. However, when it comes to solving multiple NPEs, traditional numerical integration methods are not efficient enough. This is because traditional methods solve each NPE iteratively and independently. In this article, we propose a novel approach based on multitask learning (MTL) for solving multiple NPEs. The solution procedure is outlined as follows. First, we model each NPE as a system of ordinary differential equations (ODEs) using neurodynamic optimization. Second, for each ODE system, we use a physics-informed neural network (PINN) as the solution. Third, we use a multibranch MTL framework, where each branch corresponds to a PINN model. This allows us to solve multiple NPEs in parallel by training a single neural network model. Experimental results show that our approach has superior computational performance, especially when the number of NPEs to be solved is large.

Purpose: To comprehensively reassess the efficacy and safety of different concentrations of atropine for retarding myopia progression and seek the most appropriate therapeutic concentration for clinical practice. Methods: We searched PubMed, Cochrane Library, Embase, Chinese Science and Technology Periodicals (VIP) and China National Knowledege Infrastructure (CNKI) from their inception to 23 March 2023, to obtain eligible randomized controlled trials (RCTs) and cohort studies that had atropine in at least one treatment arm and placebo/no intervention in another arm. We evaluated the risk of bias of the RCTs according to the recommendations of the Cochrane Collaboration for RCTs and quality of cohort studies by the Newcastle‒Ottawa Scale. Weighted mean difference (WMD), 95% confidence interval were calculated for meta-analysis. All data analyses were performed using Review Manager 5.3, STATA 12.0 and SPSS 26.0 software. Results: A total of 44 studies were included in the meta-analysis. Weighted mean difference (WMD) were 0.73 diopters (D), 0.65 D, 0.35 D per year in refraction progression ( χ 2 = 14.63, I 2 = 86.3%; p < 0.001) and -0.26 mm, -0.37 mm, -0.11 mm per year in axial length progression ( χ 2 = 5.80, I 2 = 65.5%; p = 0.06) for high (0.5%-1%), moderate (0.1%-0.25%), and low (0.005%-0.05%) dose atropine groups, respectively. Logarithmic dose‒response correlations were found between atropine and their effect on change of refraction, axial length, accommodation and photopic pupil diameter. Through these curves, we found that atropine with concentrations ≤0.05% atropine resulted in a residual value of accommodation of more than 5 D and an increase in pupil diameter no more than 3 mm. Higher doses of atropine resulted in a higher incidence of adverse effects, of which the incidence of photophobia was dose-dependent ( r = 0.477, p = 0.029). Conclusion: Both the efficacy and risk of adverse events for atropine treatment of myopia were mostly dose dependent. Comprehensively considered the myopia control effect and safety of each dose, 0.05% may be the best concentration of atropine to control myopia progression at present, at which myopia is better controlled and the side effects are tolerable. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, CRD42022377705., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hou, Wu, Nie, Wei, Liu and Yang.)

Background: Chronic intermittent hypoxia (CIH) involves substantial cortico-hippocampal injury, causing impairments of neurocognitive, respiratory, and cardiovascular functions. Long non-coding RNAs (lncRNAs) participate in CIH functions and development. Therefore, we explored the mechanisms involving lncRNA maternally expressed gene 3 (MEG3) regulating the aortic endothelial function of CIH mice via regulation of microRNA-135a (miR-135a) and the hypoxia-inducible factor (HIF)-1α., Methods: Expression of MEG3, miR-135a, and HIF-1α in CIH mice and CIH-treated cells was detected. Then, the apoptosis and proliferation of the aortic endothelial cells were examined to verify whether miR-135a and HIF-1α participated in CIH. Next, the interactions between MEG3, miR-135a, and HIF-1α were explored. Later, the effects of MEG3/miR-135a/HIF-1α on the expression of proliferation- and apoptosis-related factors and aortic injury were investigated via gain- and loss-of function studies both in vivo and in vitro ., Results: MEG3 and HIF-1α were highly expressed while miR-135a was poorly expressed in CIH mice and CIH-modeled cells. Moreover, miR-135a targeted HIF-1α to promote cell proliferation and inhibit apoptosis. MEG3 regulated HIF-1α expression by competitively binding to miR-135a. More importantly, we found that the silencing of MEG3/HIF-1α and the overexpression of miR-135a inhibited the apoptosis and injury of aortic endothelial cells while promoting cell proliferation in CIH mice., Conclusions: Altogether, silencing of MEG3 suppressed the aortic endothelial injury and cell apoptosis in CIH mice by downregulating HIF-1α through sponging miR-135a, providing evidence of a potential therapeutic target for CIH., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-19-2472). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition arising from the thrombus and obstructive remodeling of the pulmonary arteries, which causes a significant morbidity and mortality. Although the modern treatment in CTEPH has been significant advanced both in surgical and medical treatment, none can claim to cure the disease, largely because of our limited understanding of the underlying pathogenesis of the disease and lack of a reliable CTEPH animal model to study for. Recently, inflammation has been accepted as a common pathway through which various risk factors trigger venous thrombo-embolism (VTE) formation, we describe a novel mouse model of CTEPH which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of CTEPH in humans, to open a new horizons of inflammation in CTEPH., Methods: By administering a pulmonary embolism (PE) protocol (comprising 3 sequential left jugular vein injections of autologous blood clots) to 8-week-old male Sprague Dawley (SD) rats using tranexamic acid (200 mg/kg . d) to inhibit fibrinolysis and injecting additional carrageenan (20 mg/kg, once a week) to create perivascular inflammation, we successfully generated a CTEPH animal model. By monitoring the mean pulmonary artery pressure (mPAP) and the histopathological change to evaluate the CTEPH model. By detecting the RT-PCR, western blot, TUNEL, and immunohistochemistry in the sub-groups to find the potential mechanism of inflammation may work in the pulmonary vascular remolding., Results: In this study, rats with CTEPH exhibited pronounced pulmonary vascular remolding with higher vessel wall area/total area (WA/TA) ratio in comparison to the control rats (85.41%±7.37% vs. 76.41%±5.97%, P<0.05), the mPAP (25.51±1.13 vs. 15.92±1.13 mmHg, P<0.05). Significant differences in mean pulmonary artery pressure (mPAP) values were observed between rats injected solely with clots and those injected with both clots and carrageenan (25.51±1.13 vs. 29.82±1.26 mmHg, P<0.05, respectively). Furthermore, following the third embolization, thrombi and intimal hyperplasia occurred in the pulmonary artery. In addition, repeated embolization elevated mRNA and protein levels of tumor necrosis factor-α (TNF-α), NF-κB/p65, and B-cell lymphoma-2 (BCL-2), but decreased BAX expression in a time-dependent manner., Conclusions: Take advantage of the inflammation to trigger VTE formation, we successfully generated a CTEPH animal model. Inflammation may play a crucial role in the pathogenesis and progression of CTEPH by inhibiting endothelial cell apoptosis. Understanding the role of inflammation in CTEPH may not only help to determine the optimal treatment options but also may aid in the development of future preventative strategies, since current anticoagulation treatment regimens are not designed to inhibit inflammation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.02.86). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

To explore the role of FoxO1 and apoptosis in a rat model of chronic thromboembolic pulmonary hypertension (CTEPH). Rats were randomly divided into a sham group (n = 45) and an experimental group (n = 45). Autologous blood clots were injected into rats three times to induce CTEPH. Rats were further divided into three subgroups: a 1-week subgroup (n = 15), a 2-week subgroup (n = 15), and a 4-week subgroup (n = 15). Mean pulmonary arterial pressure (mPAP) and histopathology were evaluated at each time point. FoxO1, Bad, and Bcl-2 levels were examined at each time point using reverse transcription PCR and western blotting. The mPAP and vessel wall area/total area (WA/TA) ratio in the experimental group gradually increased in a time-dependent manner (P < 0.05). Both the mRNA and protein levels of FoxO1 decreased in the CTEPH rats compared to in the sham group. In addition, embolization led to the up-regulation of Bad and the down-regulation of Bcl-2 (P < 0.05). FoxO1 and apoptosis play an important role in the pathogenesis of CTEPH. Apoptosis-resistant pulmonary artery endothelial cells may play an important role in remodeling of the rat pulmonary artery.

Background: Nowadays, small peripheral pulmonary lesions (PPLs) are frequently detected and the prognosis of lung cancer depends on the early diagnosis. Because of the high fee and requiring specialized training, many advanced techniques are not available in many developing countries and rural districts., Methods: Three sets of opaque soft copper wires visible under the fluoroscopy (Flu) in the Flu-flexible bronchoscopy (FB) group (n = 24), which determined the three planes of the lesion, were respectively placed firmly on the surface of the chest wall with adhesive tape on the chest wall. The FB tip was advanced into the bronchus toward the crosspoint of the three perpendicular planes under Flu with careful rotation of a C-arm unit. Then the specimen were harvested focusing around the crosspoint for pathologic diagnosis. The rapid on-site evaluation (ROSE) procedure was also performed. The average Flu time during FB procedures were recorded and diagnostic accuracy rates in the Flu-FB group were compared with the other group guided by radial endobronchial ultrasound (R-EBUS) (n = 23)., Results: The location of the core point of the lesion, whether it was visible or not under the fluoroscopy could be recognized by three-dimensional localization technique. The accuracy rates of diagnostic yields were 62.5% in the Flu-FB group, and was similar as 65.2% in the R-EBUS group (P > 0.05). However, in the Flu-FB group, there was a decreasing tendency on accurate diagnosis rates of lower lobe (LL) lesions when comparing with non-LL lesions (3/8 = 37.5% vs 12/16 = 75%, P = 0.091) while in the R-EBUS group it was similar (9/12 = 75% vs 6/11 = 54.6%, P = 0.278). In the Flu-FB group, fluoroscopy time was negatively correlated with the lesion length (r = -0.613, P = 0.001), however, there was no significant difference between the lesions invisible or not (5.83 ± 1.45 min vs 7.67 ± 2.02 min, P = 0.116) under the fluoroscopy, as well as no significant difference among SPN, mGGO and GGO (6.12 ± 2.05 min, 7.25 ± 1.33 min and 7.80 ± 2.02 min, P > 0.05)., Conclusions: Small PPL whether it is visible or not under fluoroscopy can be located accurately by our three-dimensional localization technique on chest wall surface and performed bronchoscopy procedures to increase diagnostic yields. It is more convenient, economical and reliable with the similar diagnostic yields than R-EBUS guided method., Trial Registration: Current Controlled Trials ChiCTR-DDD-16009715 . The date of registration: 3rd Nov, 2016. Retrospectively registered.

Background: Few reports have examined tissue factor (TF) and autophagy expression in chronic pulmonary thromboembolic hypertension (CTEPH) animal models., Objectives: To investigate the role of tissue factor (TF), autophagy and their interactions during chronic thromboembolic pulmonary hypertension (CTEPH) pathogenesis in a rat model., Methods: Autologous blood clots were repeatedly injected into the left jugular vein of rats with injecting endogenous fibrinolysis inhibitor tranexamic acid (TXA). Mean pulmonary arterial pressure (mPAP), histopathology and TF, Beclin-1 and microtubule-associated protein 1 light chain (LC3) expression levels were detected., Results: The mPAP and vessel wall area/total area (WA/TA) ratio in the experiment group increased significantly (P < 0.05). TF mRNA and protein expression levels in the experiment group increased significantly (P < 0.05). Beclin-1 and LC3B mRNA and protein expression levels were lower in the experiment group (P < 0.05). The mPAP had a positive correlation with WA/TA ratio (r = 0.955, P < 0.05). Beclin-1 and LC3B protein expression had a negative correlation with the WA/TA ratio (r = -0.963, P < 0.05, r = -0.965, P < 0.05, respectively). TF protein expression had a negative correlation with both Beclin-1 and LC3B protein expression (r = -0.995, P <0.05, r = -0972, P < 0.05, respectively)., Conclusions: A rat model of CTEPH can be established by repeatedly introducing autologous blood clots into the pulmonary artery with injecting TXA. TF and autophagy may play a key role during CTEPH pathogenesis, especially in vascular remodeling.