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Purpose: Toludesvenlafaxine is a recently developed antidepressant that belongs to the triple reuptake inhibitor class. Despite the in vitro evidence that toludesvenlafaxine inhibits the reuptake of serotonin (5-HT), norepinephrine (NE) and dopamine (DA), there is no in vivo evidence that toludesvenlafaxine binds to DAT and increases DA level, a mechanism thought to contribute to its favorable clinical performance. Methods: Positron emission tomography/computed tomography (PET/CT) was used to examine the DAT binding capacity in healthy rats and human subjects and microdialysis was used to examine the striatal DA level in rats. [18F]FECNT and [11C]CFT were used as PET/CT radioactive tracer for rat and human studies, respectively. Results: In rats, 9 mg/kg of toludesvenlafaxine hydrochloride (i.v.) followed by an infusion of 3 mg/kg via minipump led to the binding rate to striatum DAT at 3.7 – 32.41% and to hypothalamus DAT at 5.91 – 17.52% during the 45 min scanning period. 32 mg/kg oral administration with toludesvenlafaxine hydrochloride significantly increased the striatal DA level with the AUC0 − 180 min increased by 63.9%. In healthy volunteers, 160 mg daily toludesvenlafaxine hydrochloride sustained-release tablets for 4 days led to an average occupancy rates of DAT at 8.04% ± 7.75% and 8.09% ± 7.00%, respectively, in basal ganglion 6 h and 10 h postdose. Conclusion: These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine. ClinicalTrials.gov identifiers: : NCT05905120. Registered 14 June 2023. (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: Most stroke patients suffer from an imbalance in blood supply, which causes severe brain damage leading to functional deficits in motor, sensory, swallowing, cognitive, emotional, and speech functions. Repetitive transcranial magnetic stimulation (rTMS) is thought to restore functions impaired during the stroke process and improve the quality of life of stroke patients. However, the efficacy of rTMS in treating post-stroke function impairment varies significantly. Therefore, we conducted a meta-analysis of the number of patients with effective rTMS in treating post-stroke dysfunction. Methods: The PubMed, Embase, and Cochrane Library databases were searched. Screening and full-text review were performed by three investigators. Single-group rate meta-analysis was performed on the extracted data using a random variable model. Then subgroup analyses were performed at the levels of stroke acuity (acute, chronic, or subacute); post-stroke symptoms (including upper and lower limb motor function, dysphagia, depression, aphasia); rTMS stimulation site (affected side, unaffected side); and whether or not it was a combination therapy. Results: We obtained 8955 search records, and finally 33 studies (2682 patients) were included in the meta-analysis. The overall analysis found that effective strength (ES) of rTMS was 0.53. In addition, we found that the ES of rTMS from acute/subacute/chronic post-stroke was 0.69, 0.45, and 0.52. We also found that the ES of rTMS using high-frequency stimulation was 0.56, while the ES of rTMS using low-frequency stimulation was 0.53. From post-stroke symptoms, we found that the ES of rTMS in sensory aspects, upper limb functional aspects, swallowing function, and aphasia was 0.50, 0.52, 0.51, and 0.54. And from the site of rTMS stimulation, we found that the ES of rTMS applied to the affected side was 0.51, while the ES applied to the unaffected side was 0.54. What's more, we found that the ES of rTMS applied alone was 0.53, while the ES of rTMS applied in conjunction with other therapeutic modalities was 0.53. Conclusions: By comparing the results of the data, we recommend rTMS as a treatment option for rehabilitation of functional impairment in patients after stroke. We also recommend that rehabilitation physicians or clinicians use combination therapy as one of the options for patients. [ABSTRACT FROM AUTHOR]

Predicting runoff, one of the fundamental operations in hydrology, is crucial for directing the complete exploitation and use of local water resources. However, influenced by factors such as human activities and climate change, runoff displays typical nonlinear, non-stationary dynamic characteristics, which means it is challenging to achieve accurate runoff prediction in the research on water resources. In this research, we developed a hybrid model named CEEMDAN-FE-VMD-SVM-GRU for runoff prediction, which was built on complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), fuzzy entropy (FE), variational mode decomposition (VMD), support vector machine (SVM), and gate recurrent unit (GRU). First, CEEMDAN was used to decompose the original daily runoff dataset into several intrinsic mode functions (IMF), followed by the introduction of FE to compute the complexity of each IMF component. The obtained FE calculation results greater than 0.4 were set as high-frequency sequences, and those lower than 0.4 as low-frequency sequences. Then, VMD was applied to perform the secondary decomposition of the high-frequency sequences, and SVM and GRU were trained to predict the primary and secondary decomposition parts, respectively. The results were finally obtained through linear combination. In this study, the daily runoff of the Minjiang River by this model was compared with those of other eight models. The findings demonstrate that the proposed model worked better than other models in a variety of evaluation metrics. In addition, this model showed better applicability in uncertainty interval estimation and flood prediction. Hence, this model proposed in this study has potential to be a preferred data-driven tool in hydrological prediction. [ABSTRACT FROM AUTHOR]

Purpose: This article aims to compare the diagnostic performance of 18-fluorodeoxyglucose ([18F]FDG) PET/CT and fibroblast activating protein inhibitor (FAPI) PET/CT in the assessment of primary tumors, lymph nodes, and distant metastases in lung cancer patients. Methods: A systematic search was conducted on the Cochrane Library, Embase, and PubMed/MEDLINE databases from inception until November 1, 2022. Included studies assessed the use of FAPI PET/CT and [18F]FDG PET/CT in patients with lung cancer. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to evaluate the risk of bias. A random variable model was used to analyze the diagnostic tests of the two imaging modalities. Results: The sensitivity of FAPI PET/CT in detecting primary lung cancer lesions was 0.98 (95% CI: 0.88–1.00), while the sensitivity of [18F]FDG PET/CT was 0.99 (95% CI: 0.74–1.00). For the detection of metastatic lesions (lymph node metastases and distant metastases), FAPI PET/CT had a sensitivity of 0.99 (95% CI: 0.90–1.00), while the sensitivity of [18F]FDG PET/CT was 0.77 (95% CI: 0.66–0.85). However, the specificity of the two imaging modalities could not be assessed due to the lack of sufficient information on pertinent true negatives. Conclusion: In the diagnosis of metastatic lung cancer lesions, FAPI PET/CT demonstrated a higher sensitivity compared to [18F]FDG PET/CT. Therefore, FAPI PET/CT may be considered an alternative imaging modality for the assessment of primary lung cancer tumors, lymph node metastases, and distant metastases. Clinical relevance statement: FAPI may be an alternative to [18F]FDG in the assessment of primary lung cancer tumors, lymph node metastases, and distant metastases, which plays a very important role in treatment. Key Points: • This article is to compare the performance of [18F]FDG PET/CT with FAPI PET/CT in the assessment of primary tumors, lymph nodes, and distant metastases in lung cancer. • However, FAPI PET/CT has a higher sensitivity for the diagnostic assessment of metastatic lung cancer lesions. [ABSTRACT FROM AUTHOR]

The indefinite separable quadratic knapsack problem (ISQKP) with box constraints is known to be NP-hard. In this paper, we propose a new branch-and-bound algorithm based on a convex envelope relaxation that can be efficiently solved by exploiting its special dual structure. Benefiting from a new branching strategy, the complexity of the proposed algorithm is quadratic in terms of the number of variables when the number of negative eigenvalues in the objective function of ISQKP is fixed. We then improve the proposed algorithm for the case that ISQKP has symmetric structures. The improvement is achieved by constructing tight convex relaxations based on the aggregate functions. Numerical experiments on large-size instances show that the proposed algorithm is much faster than Gurobi and CPLEX. It turns out that the proposed algorithm can solve the instances of size up to three million in less than twenty seconds on average and its improved version is still very efficient for problems with symmetric structures. [ABSTRACT FROM AUTHOR]

The singly linearly constrained separable binary quadratic programming problem (SLSBQP) has a wide variety of applications in practice. In real-life applications, the coefficients in the objective function and constraints generally appear with symmetric structure. In this paper, we propose an extremely efficient global optimization algorithm for solving SLSBQP with symmetric structure. We first develop a reformulation of SLSBQP based on an aggregate function defined on the symmetric structure in the problem, and derive the convex envelop function for the aggregate function. A branch-and-bound algorithm is then proposed to find the global solution of the reformulation of SLSBQP. Computational experiments show that the proposed algorithm is able to solve test instances with thousands of variables in less than 0.04 seconds on average, whereas the current state-of-the-art algorithms may fail to solve the same test instances in 200 seconds. The superior performance of the proposed algorithm clearly indicates the potential of the proposed algorithm in real-life applications. [ABSTRACT FROM AUTHOR]

Purpose: Digestive system tumors are a group of tumors with high incidence in the world nowadays. The assessment of digestive system tumor metastasis by conventional imaging seems to be unsatisfactory. [68Ga]Ga-FAPI, which has emerged in recent years, seems to be able to evaluate digestive system tumor metastasis. We aimed to summarize the current evidence of [68Ga]Ga-FAPI PET/CT or PET/MR for the assessment of primary tumors, lymph node metastases, and distant metastases in digestive system tumors. Besides, we also aimed to perform a meta-analysis of the sensitivity of [68Ga]Ga-FAPI PET diagnosis to discriminate between digestive system tumors, primary lesions, and non-primary lesions (lymph node metastases and distant metastases). Materials and methods: PubMed, MEDLINE and Cochrane Library databases were searched from the beginning of the database build to August 12, 2022. All studies undergoing [68Ga]Ga-FAPI PET for the evaluation of digestive tumors were included in the screening and review. Screening and full text review was performed by 3 investigators and data extraction was performed by 2 investigators. Risk of bias was examined with the QUADAS-2 criteria. Diagnostic test meta-analysis was performed with a random-effects model. Results: A total of 541 studies were retrieved. Finally, 22 studies were selected for the systematic review and 18 studies were included in the meta-analysis. In the 18 publications, a total of 524 patients with digestive system tumors, 459 primary tumor lesions of digestive system tumors, and 1921 metastatic lesions of digestive system tumors were included in the meta-analysis. Based on patients, the sensitivity of [68Ga]Ga-FAPI PET for the diagnosis of digestive system tumors was 0.98 (95% CI: 0.94–0.99). Based on lesions, the sensitivity of [68Ga]Ga-FAPI PET for the diagnostic evaluation of primary tumor lesions of the digestive system was 0.97 (95% CI: 0.93–0.99); the sensitivity of [68Ga]Ga-FAPI PET for the diagnostic evaluation of non-primary lesions (lymph node metastases and distant metastases) of the digestive system tumors was 0.94 (95% CI: 0.79–0.99). Conclusion: [68Ga]Ga-FAPI PET has high accuracy and its sensitivity is at a high level for the diagnostic evaluation of digestive system tumors. Clinicians, nuclear medicine physicians, and radiologists may consider using [68Ga]Ga-FAPI PET/CT or PET/MR in the evaluation of primary tumors, lymph node metastases, and distant metastases in digestive system tumors. [ABSTRACT FROM AUTHOR]

Water resources matters considerably in maintaining the biological survival and sustainable socio-economic development of a region. Affected by a combination of factors such as geographic characteristics of the basin and climate change, runoff variability is non-linear and non-stationary. Runoff forecasting is one of the important engineering measures to prevent flood disasters. The improvement of its accuracy is also a difficult problem in the research of water resources management. To this end, an ensemble deep learning model was hereby developed to forecast daily river runoff. First, variational mode decomposition (VMD) was used to decompose the original daily runoff series data set into discrete internal model function (IMF) and distinguish signals with different frequencies. Then, for each IMF, a convolutional neural network (CNN) was introduced to extract the features of each IMF component. Subsequently, a bi-directional long short-term memory network (BiLSTM) based on an attention mechanism (AM) was used for prediction. A Bayesian optimization algorithm (BOA) was also introduced to optimize the hyperparameters of the BiLSTM, thereby further improving the estimation precision of the VMD-CNN-AM-BOA-BiLSTM model. The model was applied to the daily runoff data from January 1, 2010 to November 30, 2021 at the Wushan and Weijiabao Hydrological Stations in the Wei River Basin, and the RMSEs of 3.54 and 15.23 were obtained for the test set data at the two stations respectively, which were much better than those of EEMD-VMD-SVM and CNN-BiLSTM-AM models. Additionally, the hereby proposed model is proven to have better peak flood prediction capability and adaptability under different hydrological environments. Based on this sound performance, the model becomes an effective data-driven tool in hydrological forecasting practice, and can also provide some reference and practical application guidance for water resources management and flood warning. [ABSTRACT FROM AUTHOR]

Purpose: Patients with severe obstructive sleep apnea–hypopnea syndrome are often accompanied by symptoms such as decreased cognitive function and daytime sleepiness, while cognitive function is often associated with biomarkers of Alzheimer's disease. Therefore, this study aims to explore the level of Alzheimer's disease biomarkers in the plasma of obstructive sleep apnea–hypopnea syndrome patients as well as the relationship between cognitive function and daytime sleepiness. Methods: Between May and July 2019, 35 patients requiring hospitalization for severe obstructive sleep apnea–hypopnea syndrome and 16 normal control patients were selected from West China Hospital. Alzheimer's disease biomarkers (Aβ40, Aβ42, t-tau, p-tau) in plasma were detected by ELISA in all 51 subjects. The differences in Alzheimer's disease biomarkers between the two groups were compared. In addition, a correlation analysis of disease-related indicators and univariate analysis of the risk factors of obstructive sleep apnea–hypopnea syndrome was conducted using the logistic regression model. Results: The plasma levels of Alzheimer's disease biomarkers (Aβ40, t-tau, p-tau) in patients with severe obstructive sleep apnea–hypopnea syndrome were significantly higher than those in the control group (29.24 ± 32.52, 13.18 ± 10.78, p = 0.049; 11.88 ± 7.05, 7.64 ± 4.17, p = 0.037; 26.31 ± 14.41, 17.34 ± 9.12, p = 0.027). Aβ42, Aβ40, t-tau, and p-tau were significantly negatively correlated with mean oxygen saturation, low oxygen saturation and Mini-Mental State examination scale scores, and positively correlated with oxygen desaturation index and Epworth Sleepiness Scale scores. T-tau and p-tau can be used as new risk factors for obstructive sleep apnea–hypopnea syndrome. Conclusion: Alzheimer's disease biomarkers in the plasma of obstructive sleep apnea–hypopnea syndrome patients are higher than those in the control group, and the mechanism of action may be related to sleep disorders and night hypoxia. The Alzheimer's disease biomarkers deposited in plasma may also cause the decline of patients' cognitive function, increased daytime sleepiness and accelerate the progression of obstructive sleep apnea–hypopnea syndrome. [ABSTRACT FROM AUTHOR]

The patient then underwent video-assisted thoracoscopic surgery (VATS) biopsies of the pericardium, mediastinal lymph nodes and pulmonary nodule, pathologically revealing necrotizing granulomatous inflammation. Chest CT image showed the thickened pericardium and several pulmonary nodules in the upper lobe of lungs. [Extracted from the article]