Explainable Deep-Learning Prediction for Brain-Computer Interfaces Supported Lower Extremity Motor Gains Based on Multistate Fusion.

Predicting the potential for recovery of motor function in stroke patients who undergo specific rehabilitation treatments is an important and major challenge. Recently, electroencephalography (EEG) has shown potential in helping to determine the relationship between cortical neural activity and motor recovery. EEG recorded in different states could more accurately predict motor recovery than single-state recordings. Here, we design a multi-state (combining eyes closed, EC, and eyes open, EO) fusion neural network for predicting the motor recovery of patients with stroke after EEG-brain-computer-interface (BCI) rehabilitation training and use an explainable deep learning method to identify the most important features of EEG power spectral density and functional connectivity contributing to prediction. The prediction accuracy of the multi-states fusion network was 82%, significantly improved compared with a single-state model. The neural network explanation result demonstrated the important region and frequency oscillation bands. Specifically, in those two states, power spectral density and functional connectivity were shown as the regions and bands related to motor recovery in frontal, central, and occipital. Moreover, the motor recovery relation in bands, the power spectrum density shows the bands at delta and alpha bands. The functional connectivity shows the delta, theta, and alpha bands in the EC state; delta, theta, and beta mid at the EO state are related to motor recovery. Multi-state fusion neural networks, which combine multiple states of EEG signals into a single network, can increase the accuracy of predicting motor recovery after BCI training, and reveal the underlying mechanisms of motor recovery in brain activity.

A real-world pilot study assessing treatment satisfaction with avanafil in patients with erectile dysfunction.

Background: Avanafil is a second-generation phosphodiesterase type 5 (PDE5) inhibitor, and offers a rapid onset of action (15 minutes). Its real-world data, including treatment satisfaction, are still lacking. Aim: The study sought to investigate the treatment outcomes of avanafil and the factors impacting treatment satisfaction in a real-world setting. Methods: Between November 2021 and February 2023, erectile dysfunction (ED) patients prescribed avanafil were consecutively enrolled in this phase 4, open-label, cross-sectional, observational study. At each follow-up visit (4-week intervals), participants completed a questionnaire for assessing the use and treatment-emergent adverse events of avanafil, ED severity, and treatment satisfaction. Outcomes: The outcome measures included the Sexual Health Inventory for Men (SHIM), and Erectile Dysfunction Inventory of Treatment Satisfaction. Results: Among 234 patients enrolled, 112 (47.9%) patients had follow-up visits and answered the questionnaire. Treatment with avanafil significantly improved the mean SHIM total score from 10.2 ± 5.6 at baseline to 17.5 ± 6.2 (P < .001). Of the patients treated with avanafil, 71.4% (n = 80 of 112) reported a >4-point improvement in the SHIM total score, and 33.1% (n = 37 of 112) reported normal erectile function. The proportion of patients satisfied with avanafil treatment (defined as Erectile Dysfunction Inventory of Treatment Satisfaction index score ≥60) was 87.5%. Several physical factors (younger age, lower waist circumference, and lower level of low-density lipoprotein), and sexual function factors (shorter duration of ED, higher SHIM total score at baseline, PDE5 inhibitor treatment naive, and acquired premature ejaculation) tended to contribute to satisfaction with avanafil treatment. Treatment-emergent adverse events occurred in 41.1% of patients, and all were mild in severity. Clinical Implications: This study identifies the factors associated with treatment satisfaction of avanafil, which may ultimately lead to better treatment outcomes. Strengths and Limitations: This is the first study to provide real-world evidence of avanafil for ED treatment, and validated questionnaires were used to assess erectile function and treatment satisfaction. However, the limitations of this study include single-center observational study design, small sample size, and short-term follow-up. Conclusion: Avanafil is an effective treatment for ED, and satisfaction rate is high in an outpatient setting. The awareness of identified factors related to patient satisfaction may improve treatment outcomes.

Multiscale Canonical Coherence for Functional Corticomuscular Coupling Analysis.

Functional corticomuscular coupling (FCMC) probes multi-level information communication in the sensorimotor system. The canonical Coherence (caCOH) method has been leveraged to measure the FCMC between two multivariate signals within the single scale. In this paper, we propose the concept of multiscale canonical Coherence (MS-caCOH) to disentangle complex multi-layer information and extract coupling features in multivariate spaces from multiple scales. Then, we verified the reliability and effectiveness of MS-caCOH on two types of data sets, i.e., a synthetic multivariate data set and a real-world multivariate data set. Our simulation results showed that compared with caCOH, MS-caCOH enhanced coupling detection and achieved lower pattern recovery errors at multiple frequency scales. Further analysis on experimental data demonstrated that the proposed MS-caCOH method could also capture detailed multiscale spatial-frequency characteristics. This study leverages the multiscale analysis framework and multivariate method to give a new insight into corticomuscular coupling analysis.

Motor-Respiratory Coupling Improves Endurance Performance during Rhythmic Isometric Handgrip Exercise.

PURPOSE: This study aimed to evaluate whether motor-respiratory coupling exists in rhythmic isometric handgrip exercises and its effect on endurance performance. In addition, the mechanism underlying observed effects was to be investigated if higher motor-respiratory coupling rate could enhance endurance performance. METHODS: Eleven subjects completed three rhythmic isometric handgrip trials to task failure in a randomized manner. After one pretraining session to determine personal grip frequency, one trial was performed without respiration requirement (CON), and two trials were performed with inspiration-motor coupling (IMC) or expiration-motor coupling. Changes in maximal voluntary contraction (MVC) and EMG were used to measure neuromuscular fatigue. Force data during test were used to assess exercise intensity. Another 10 subjects completed electrical stimulation-induced finger flexion and extension during normal inspiration, normal expiration, fast inspiration, fast expiration, and breath holding. Force changes of different breathing conditions were compared. RESULTS: Normalized exercise time to exhaustion was significantly longer in IMC (1.27 ± 0.23) compared with expiration-motor coupling (0.82 ± 0.18) and CON (0.91 ± 0.18, P < 0.001). ΔMVC, grip frequency, force, and EMG indices were not different among conditions (all P > 0.05). Electrical stimulation-induced finger extensor force was significant higher during fast inspiration (1.11 ± 0.09) than normal respiration (1.00 ± 0.05) and fast expiration (0.94 ± 0.08, P < 0.05). CONCLUSIONS: IMC is an effective way to improve endurance performance of rhythmic handgrip exercise. This is likely due to a reduction in the energy consumption of motion control, as evidenced by similar peripheral fatigue in different conditions and modulation of corticospinal excitability by respiration.

Effect of high-frequency repetitive transcranial magnetic stimulation in M1 region combined with dorsolateral prefrontal cortex on electroencephalogram θ frequency band amplitude of patients with neuropathic pain after spinal cord injury / 中国康复理论与实践

ObjectiveTo explore the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in M1 region combined with dorsolateral prefrontal cortex (DLPFC) on electroencephalogram (EEG) θ frequency band amplitude of patients with neuropathic pain (NP) after spinal cord injury. MethodsFrom June, 2022 to June, 2023, 50 NP patients after SCI in Qingdao University Affiliated Hospital were included and divided into M1 region stimulation group (n = 25) and M1 region combined with DLPFC stimulation group (the combined stimulation group, n = 25). M1 region stimulation group received 10 Hz rTMS in the left M1 region, while the combined stimulation group received same stimulation in left M1 region combined with DLPFC, for three weeks. Before and after intervention, the pain was assessed with Short Form of McGill Pain Questionnaire (SF-MPQ), the depression and anxiety status were evaluated using Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), and the EEG θ frequency band amplitude was recorded to detect the changes of brain electrophysiological activity. ResultsFour cases in M1 region stimulation group, and two cases in the combined stimulation group were dropped. After intervention, the total score of SF-MPQ and the scores of the subscales, the scores of HMMD and HAMA decreased in both groups (|t| > 2.523, P < 0.05). The EEG θ frequency band amplitude significantly reduced in the prefrontal and frontal regions in M1 region stimulation group (|t| > 5.243, P < 0.001), and it also significantly reduced in the prefrontal, frontal regions, central and parietal regions in the combined stimulation group (|t| > 4.630, P < 0.001). All the scores were lower (|t| > 2.270, Z = -1.973, P < 0.05), and the EEG θ frequency band amplitude in the prefrontal, frontal regions, central and parietal regions were lower (P < 0.05) in the combined stimulation group than in M1 region stimulation group. ConclusionHigh frequency rTMS is an effective analgesic method on NP after SCI, which can improve their depression and anxiety symptoms and reduce the EEG θ frequency band amplitude. Compared with M1 region rTMS stimulation, the combination of M1 region and DLPFC rTMS is more effective.

Lesion-specific cortical activation following sensory stimulation in patients with subacute stroke.

BACKGROUND: Sensory stimulation can play a fundamental role in the activation of the primary sensorimotor cortex (S1-M1), which can promote motor learning and M1 plasticity in stroke patients. However, studies have focused mainly on investigating the influence of brain lesion profiles on the activation patterns of S1-M1 during motor tasks instead of sensory tasks. Therefore, the objective of this study is to explore the lesion-specific activation patterns due to different brain lesion profiles and types during focal vibration (FV). METHODS: In total 52 subacute stroke patients were recruited in this clinical experiment, including patients with basal ganglia hemorrhage/ischemia, brainstem ischemia, other subcortical ischemia, cortical ischemia, and mixed cortical-subcortical ischemia. Electroencephalograms (EEG) were recorded following a resting state lasting for 4 min and three sessions of FV. FV was applied over the muscle belly of the affected limb's biceps for 3 min each session. Beta motor-related EEG power desynchronization overlying S1-M1 was used to indicate the activation of S1-M1, while the laterality coefficient (LC) of the activation of S1-M1 was used to assess the interhemispheric asymmetry of brain activation. RESULTS: (1) Regarding brain lesion profiles, FV could lead to the significant activation of bilateral S1-M1 in patients with basal ganglia ischemia and other subcortical ischemia. The activation of ipsilesional S1-M1 in patients with brainstem ischemia was higher than that in patients with cortical ischemia. No activation of S1-M1 was observed in patients with lesions involving cortical regions. (2) Regarding brain lesion types, FV could induce the activation of bilateral S1-M1 in patients with basal ganglia hemorrhage, which was significantly higher than that in patients with basal ganglia ischemia. Additionally, LC showed no significant correlation with the modified Barthel index (MBI) in all patients, but a positive correlation with MBI in patients with basal ganglia lesions. CONCLUSIONS: These results reveal that sensory stimulation can induce lesion-specific activation patterns of S1-M1. This indicates FV could be applied in a personalized manner based on the lesion-specific activation of S1-M1 in stroke patients with different lesion profiles and types. Our study may contribute to a better understanding of the underlying mechanisms of cortical reorganization.

The impact of FOXP3 polymorphisms on oral cancer progression and clinicopathological characteristics.

Oral cancer is the sixth leading cause of cancer mortality worldwide. Genetic, epigenetic, and epidemiological risk factors were suggested to be correlated with the carcinogenesis of oral cancer. In this study, we focused on the correlations of FOXP3 single-nucleotide polymorphisms (SNPs) to oral cancer susceptibility and clinicopathological characteristics. The FOXP3 SNPs rs3761547, rs3761548, rs3761549, and rs2232365 in 1053 controls and 1175 male patients with oral cancer were analyzed with real-time polymerase chain reaction. The results showed that the betel quid chewer who carried the FOXP3 rs3761548 polymorphic variant "T" were significantly associated with lower risk to develop oral cancer [AOR (95% CI) = 0.649 (0.437-0.964); p = 0.032]. The betel quid chewers with genotypic variant "T" of FOXP3 rs3761548 in male oral cancer patients were associated with lower risk of cell differentiated grade [AOR (95% CI) = 0.592 (0.377-0.930); p = 0.023]. The carriers of FOXP3 rs3761548 polymorphic variant "T" in male oral cancer patients with alcohol consumption were associated with lower risk to develop greater tumor [AOR (95% CI) = 0.609 (0.378-0.983); p = 0.042] and lower risk of cell differentiated grade [AOR (95% CI) = 0.440 (0.248-0.779); p = 0.005]. In conclusion, our results have revealed that the FOXP3 rs3761548 polymorphic variant "T" was associated with lower risk of oral cancer susceptibility, greater tumor size, and cell differentiated grade among betel quid chewers. The FOXP3 rs3761548 polymorphisms may play a role as pivotal biomarkers to predict oral cancer disease development and prognosis.

Maternal diabetes mellitus and birth defects in Taiwan: A 5-year nationwide population-based cohort study.

BACKGROUND: Birth defects (BDs) are the main causes of mortality and disability in infants and children. Associations between maternal diabetes mellitus (DM), including gestational DM (GDM) and pregestational DM (type 1 or type 2), and the risk of BDs have been reported. This study aims to determine the relationship between maternal DM and BDs and to investigate whether reducing the incidence of DM can decrease the incidence of BDs. METHODS: We identified all births in Taiwan from the National Birth Defects Surveillance Program between January 1, 2010, and December 31, 2014. Information on the infants' characteristics (sex, gestational age, and birth weight) and mothers' characteristics (age, parity, and associated diseases, including DM) were obtained from the National Birth Registry and National Health Insurance Research Database (NHIRD) in Taiwan. BDs were coded according to the International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) codes 740-759. RESULTS: Multiple logistic regression analysis with adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for all BDs showed that the aOR (95% CI) was 1.002 (0.965-1.041), and the p -value was 0.9139 in the GDM group. In the type 1 DM group, the aOR (95% CI) was 1.748 (1.110-2.754), and the p -value was 0.016. In the type 2 DM group, the aOR (95%CI) was 1.175 (1.005-1.375), 1.331 (1.196-1.482), and 1.391 (1.216-1.592), and the p -value was 0.0437, <0.0001, and <0.0001 for the duration of mothers with type 2 DM <2, 2 to 5, >5 years, respectively. CONCLUSION: Mothers with pregestational DM (type 1 or type 2) increase the incidence of BD. Appropriate maternal glycemic control may achieve good pregnancy and perinatal outcomes.

[Effects of different acupuncture and moxibustion methods on articular cartilage morphology and NF-κB p65/NLRP3 pathway in rats with knee osteoarthritis].

OBJECTIVE: To compare the effects of filiform needling, electroacupuncture (EA) and moxibustion on articular cartilage morphology and nuclear transcription factor-κB (NF-κB) p65/ Nod-like receptor protein 3 (NLRP3) pathway in rats with knee osteoarthritis (KOA). METHODS: Wistar rats were randomly divided into blank control， model, filiform needling, EA and moxibustion groups, with 8 rats in each group. The KOA model was established by injecting sodium iodoacetate into the right knee cavity. Filiform needling, EA and moxibustion groups were treated with the right side of "Dubi" (ST35) and "Neixiyan" (EX-LE5), and were given filiform needling, EA and mild moxibustion therapies for 15 min respectively, once every other day, for a total of 4 weeks. The diameter of the right knee joint was observed. The ultrastructure of knee chondrocytes was observed by transmission electron microscope. The contents of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-18 were determined by ELISA. The expression levels of NF-κB p65, NLRP3, apoptosis-related speckle like protein (ASC) and TNF-α in knee cartilage were dectected by Western blot. RESULTS: Compared with the blank control group, the right knee joint cavity was narrowed, chondrocytes were constricted significantly, mitochondria were moderately swollen, the diameter of the right knee was increased, and the contents of serum TNF-α, IL-1ß and IL-18 were increased (P<0.01), the expressions of NF-κB p65, NLRP3 and TNF-α in knee cartilage were increased (P<0.01) while the expression of ASC was decreased (P<0.01) in the model group.Compared with model group, the narrowed knee joint cavity and chondrocyte injury were improved， knee diameter decreased (P<0.01, P<0.05), and the content of serum TNF-α and the expression of NLRP3 in knee cartilage were decreased (P<0.05, P<0.01) in 3 treatment groups; the contents of serum IL-1ß and IL-18, and the expression of TNF-α in knee cartilage were decreased (P<0.01, P<0.05), while the expression of ASC in knee cartilage was increased (P<0.01) in EA and moxibustion groups; the expression of NF-κB p65 in knee cartilage was decreased (P<0.01) in moxibustion group. Compared with EA group, the content of serum IL-18 was decreased (P<0.05) in moxibustion group. CONCLUSION: Filiform needling, EA and moxibustion can all reduce the formation of knee osteophytosis in KOA rats, alleviate joint cavity narrowing, improve the ultrastructure of articular cartilage, reduce the level of inflammatory factors, regulate the NF-κB p65/NLRP3 pathway. Moxibustion has the most obvious regulatory effect among the 3 treatment methods.

Prognostic effects of microcirculation-assisted adjustment of venoarterial blood flow in extracorporeal membrane oxygenation: A prospective, pilot, randomized controlled trial.

OBJECTIVE: The study explored the clinical efficacy of microcirculation-assisted blood flow adjustment in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: This prospective, pilot, randomized controlled trial was conducted from 2018 to 2021; enrolled patients were randomly assigned to the microcirculation or control group at a 1:1 ratio. Microcirculatory and clinical data were collected within 24 h (T1) and at 24-48 h (T2), 48-72 h (T3), and 72-96 h (T4) after ECMO initiation and were compared between the groups following the intention-to-treat (ITT) principle. The primary outcome was the Sequential Organ Failure Assessment (SOFA) score at T2. In addition to ITT analysis, analysis based on the as-treated (AT) principle was performed. RESULTS: A total of 35 patients were enrolled in this study. At T2, the SOFA score did not significantly differ between the microcirculation and control groups (16 [14.8-17] vs. 16 [12.5-18], P = 0.782). Generalized estimating equation analysis demonstrated a significantly greater reduction in the SOFA score over time in the microcirculation-AT group than in the control-AT group (estimated difference: -0.767, standard error: 0.327, P = 0.019). The lactate level at T2 was significantly lower in the microcirculation-AT group (2.7 [2.0-3.6] vs. 4.1 [3.0-6.6] mmol/L, P = 0.029). No significant difference in the 30-day survival rate was noted between the groups. CONCLUSION: This prospective pilot study demonstrated the feasibility of microcirculation-assisted VA-ECMO blood flow adjustment despite no significant clinical benefit for critically ill patients. More efforts in personnel training and newer technologies may help achieve microcirculation optimization.

Genotype and Phenotype of α-Thalassemia Fusion Gene in Huadu District of Guangzhou, Guangdong Province of China / 中国实验血液学杂志

OBJECTIVE@#To explore the carrier rate, genotype and phenotype of α-thalassemia fusion gene in Huadu district of Guangzhou, Guangdong province of China, and provide data reference for the prevention and control of thalassemia.@*METHODS@#A total of 10 769 samples who were screened for thalassemia in Maternal and Child Health Hospital of Huadu District from July 2019 to November 2020 were analyzed retrospectively. Blood cell analysis and hemoglobin (Hb) electrophoresis were performed. Thalassemia genes were analyzed by gap-PCR and PCR-reverse dot blot hybridization (PCR-RDB).@*RESULTS@#A total of 9 cases with α-thalassemia fusion gene were detected in 10 769 samples (0.08%). There were 7 cases with fusion gene heterozygote, 1 case with compound of α-thalassemia fusion gene and Hb G-Honolulu, 1 case with compound of α-thalassemia fusion gene and Hb QS. The MCV results of 4 samples of blood cell analysis were within the reference range, the Hb A2 value of 1 case was decreased, and there were no other abnormalities found.@*CONCLUSION@#The α-thalassemia fusion gene is common in Huadu district of Guangzhou, and heterozygotes are more common, and current screening methods easily lead to misdiagnosis.

Reducing Birth Defects by Decreasing the Prevalence of Maternal Chronic Diseases-Evaluated by Linked National Registration Dataset.

Birth defects (BDs) are an important cause of abortion, stillbirth, and infant mortality that may cause lifelong disability. The defects can be caused by genetics, environmental exposure, or maternal chronic diseases. We conducted a study to analyze the association between maternal chronic diseases and BDs and to evaluate the effect of decreasing the prevalence of maternal chronic diseases on reducing BDs. The data of newborns and their mothers were concatenated and analyzed from three national population databases: the National Health Insurance Research Database, the Birth Certificate Application, and the Birth Registration Database in Taiwan during the period of 2005 to 2014. Codes 740-759 of the International Classification of Diseases 9th Revision­Clinical Modification (ICD-9-CM) were used as the diagnosis of BDs. The prevalence of BDs was 2.72%. Mothers with cardiovascular diseases, hypertension, anemia, genitourinary tract infections, renal diseases, neurotic or psychotic disorders, gestational diabetes mellitus (DM), and pregestational type 1 or type 2 DM had a significantly higher prevalence of BDs. The population attributable risk percent (PAR%) of BDs was 1.63%, 0.55%, 0.18%, 1.06%, 0.45%, 0.22%, 0.48%, and 0.24% for maternal hypertension, cardiovascular disease, renal disease, genitourinary infection, anemia, neurotic and psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, respectively. The percentage change (−1%, −5%, and −10% of prevalence in 2034 compared with the prevalence in 2005−2014) of maternal disease and the predicted number of live births was used to estimate the decrease in the number of newly diagnosed BDs in 2034. By using the middle-estimated number of live births in 2034, we predicted that the number of BDs would decrease by 302, 102, 33, 196, 83, 41, 89, and 44 with a −5% prevalence of maternal hypertension, cardiovascular disease, renal disease, genitourinary infection, anemia, neurotic and psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, respectively. We conclude that mothers with chronic diseases, including cardiovascular diseases, hypertension, anemia, genitourinary tract infections, renal diseases, neurotic or psychotic disorders, gestational DM, and pregestational type 1 or type 2 DM, have a significantly higher (p < 0.01) prevalence of having offspring with BDs. Mothers with chronic diseases are associated with BDs. It is very important to set up a policy to decrease the prevalence of these maternal chronic diseases; then, we can reduce the incidence of BDs.

Quantitative Analyses and Validation of Phospholipids and Sphingolipids in Ischemic Rat Brains.

Prior MALDI mass spectrometry imaging (MALDI-MSI) studies reported significant changes in phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), and sphingomyelins (SMs) in ischemic rat brains yet overlooked the information on other classes of PLs and SLs and provided very little or no validation on the detected lipid markers. Relative quantitation of four classes of PLs and two classes of SLs in the ischemic and normal temporal cortex (TCX), parietal cortex (PCX), and striatum (ST) of rats was performed with hydrophilic interaction chromatography (HILIC)-tandem mass spectrometry (MS/MS) analyses, and the marker lipid species was identified by multivariate data analysis and validated with additional tissue cohorts. The acquired lipid information was sufficient in differentiating individual anatomical regions under different pathological states, identifying region-specific ischemic brain lipid markers and revealing additional PL and SL markers not reported previously. Validation of orthogonal partial least square discriminating analysis (OPLS-DA) identified ischemic brain lipid markers yielded much higher classification accuracy, precision, specificity, sensitivity, and lower false positive and false negative rates than those from the volcano plot analyses using conventional statistical significance and a fold change of two as the cutoff and provided a wider prospective to ischemia-associated brain lipid changes.

A Transferable Deep Learning Prognosis Model for Predicting Stroke Patients' Recovery in Different Rehabilitation Trainings.

Since the underlying mechanisms of neurorehabilitation are not fully understood, the prognosis of stroke recovery faces significant difficulties. Recovery outcomes can vary when undergoing different treatments; however, few models have been developed to predict patient outcomes toward multiple treatments. In this study, we aimed to investigate the potential of predicting a treatment's outcome using a deep learning prognosis model developed for another treatment. A total of 15 stroke survivors were recruited in this study, and their clinical and physiological data were measured before and after the treatment (clinical measurement, biomechanical measurement, and electroencephalography (EEG) measurement). Multiple biomarkers and clinical scale scores of patients who had completed manual stretching rehabilitation training were analyzed. Data were used to train deep learning prognosis models, yielding an 87.50% prognosis accuracy. Pre-trained prognosis models were then applied to patients who completed robotic-assisted stretching training, yielding a prognosis accuracy of 91.84%. Interpretation of the deep learning models revealed several key factors influencing patients' recoveries, including the plantar-flexor active range of movement (r = 0.930, P = 0.02), dorsiflexor strength (r = 0.932, P = 0.002), plantar-flexor strength (r = 0.930, P = 0.002), EEG power spectrum density and EEG functional connectivities in the occipital, central parietal, and parietal areas. Our results suggest (i) that deep learning can be a promising method for accurate prediction of the recovery potential of stroke patients in clinical scenarios and (ii) that it can be successfully applied to different rehabilitation trainings with explainable factors.

Association of dipeptidyl peptidase IV polymorphism with clinicopathological characters of oral cancer.

OBJECTIVE: To evaluate the associations between dipeptidyl peptidase IV (DPP4) single-nucleotide polymorphism (SNP) and clinicopathological characteristics of oral cancer. METHODS: Four loci of DPP4 SNPs (rs7608798 A/G, rs3788979 C/T, rs2268889 T/C, and rs6741949 G/C) were genotyped by using the TaqMan allelic discrimination in 1238 oral cancers patients and 1197 non-cancer individuals. RESULTS: The percentage of DPP4 SNP rs2268889 TC + CC was significantly higher in the oral cancer participants compared to the control group (odds ratio [OR]: 1.178, 95% confidence interval (CI): 1.004-1.382, p = 0.045). Among 1676 smokers, DPP4 polymorphisms carriers with betel quid chewing were found to have an 8.785- to 10.903-fold risk to have oral cancer compared to DPP4 wild-type carriers without betel quid chewing. Similar trend was found in individuals with alcohol consumption. Moreover, the oral cancer individuals without cigarette smoking history with at least one varied C allele of DPP4 rs2268889 had a significantly higher percentage of large tumor size with the wild-type TT homozygote (p = 0.011). CONCLUSIONS: The DPP4 SNP may correlate to the development of oral cancer in those with cigarette smoking and alcohol consumption. Besides, the DPP4 SNP rs2268889 could relate to worse clinical course of oral cancer in non-smokers.

Picrasidine I Triggers Heme Oxygenase-1-Induced Apoptosis in Nasopharyngeal Carcinoma Cells via ERK and Akt Signaling Pathways.

Nasopharyngeal carcinoma (NPC) has a higher incidence in Taiwan than worldwide. Although it is a radiosensitive malignancy, cancer recurrence is still high in the advanced stages because of its ability to induce lymph node metastasis. Picrasidine I from Picrasma quassioides has been reported as a potential drug for targeting multiple signaling pathways. The present study aimed to explore the role of picrasidine I in the apoptosis of NPC cells. Our results show that picrasidine I induced cytotoxic effects in NPC cells and caused cell cycle arrest in the sub-G1, S, and G2/M phases. Western blot analysis further demonstrated that the modulation of apoptosis through the extrinsic and intrinsic pathways was involved in picrasidine I-induced cell death. Downregulation of the ERK1/2 and Akt signaling pathways was also found in picrasidine I-induced apoptosis. Additionally, the apoptosis array showed that picrasidine I significantly increased heme oxygenase-1 (HO-1) expression, which could act as a critical molecule in picrasidine I-induced apoptosis in NPC cells. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets also revealed that the HMOX1 mRNA level (HO-1) is lower in patients with head and neck squamous carcinoma (HNSCC) and NPC than in patients without cancer. Our study indicated that picrasidine I exerts anticancer effects in NPC by modulating HO-1 via the ERK and Akt signaling pathways.

Causative organisms and antimicrobial susceptibility in jaundiced infants with significant bacteriuria.

BACKGROUND: Jaundice may be one of the first signs of urinary tract infection (UTI) in infants. The most common pathogen is Escherichia coli. Currently recommended antibiotic treatment for neonatal UTI is ampicillin and an aminoglycoside. Recently, increasing ampicillin and gentamicin resistance in strains of E. coli has been isolated. The aim of this study was to determine causative organisms and antimicrobial susceptibility in jaundiced infants with significant bacteriuria (SB). METHODS: We evaluated admitted afebrile, asymptomatic infants younger than 1-month old with hyperbilirubinemia (total bilirubin >15 mg/dl) requiring phototherapy between January 2011 and December 2015. A total of 615 asymptomatic jaundiced infants were enrolled. Urinalysis and urine cultures were performed on all jaundiced infants. A urine culture was defined as SB if a single pathogen with more than 105-colony forming units per milliliter (CFU/ml) by sterile urinary collection bag or 104 CFU/ml by catheterization was isolated. RESULTS: A total of 88 (14.3%) of 615 asymptomatic jaundiced infants had positive urinary culture. E coli was the most common cultured bacteria (40 cases, [45.5%]). Enterococcus faecalis was the second most common bacteria (17 cases, [19.3%]). Seven cases (8.0%) of Streptococcus agalactiae and six cases (6.8%) of Klebsiella pneumoniae were also identified. Ampicillin sensitivity was found in 22.5% of E. coli infections, gentamicin sensitivity was found in 84.2%, and extended-spectrum ß-lactamases were found in 7.5%. CONCLUSION: E. coli was the most common causative organism for infants with SB. We suggest modifying current empiric antibiotics by changing gentamicin to amikacin for neonatal Gram-negative bacterial infections.

[Complex network analysis on regularities of acupoint combinations and application characteristics of acupuncture and moxibustion in the treatment of knee osteoarthritis].

OBJECTIVE: To analyze the regularities of combination of acupoints in the existing clinical trial literature by using complex network technique, so as to provide reliable evidence for selecting appropriate acupoint recipes in the treatment of knee osteoarthritis (KOA) with acupuncture and moxibustion therapies. METHODS: Clinical papers about acupuncture treatment of KOA published from January of 2000 to April of 2020 were searched from Chinese and English databases including CNKI, Wanfang, VIP, Pubmed and ScienceDirect by using keywords of "acupuncture", "moxibustion" and "knee osteoarthritis". According to the inclusive and exclusive criteria, the collected papers were screened out to set up a database. SPSS Modeler18.0 software was used to analyze the association rules of acupoints (including the core acupoint nodes and compatibility relationship), and Gephi0.9.2 software was employed to conduct a complex network analysis about the compatibility rules of acupoints and their application characteristics of moxibustion and needling methods in the treatment of KOA (shown by a complex network schematic diagram). RESULTS: A total of 444 acupuncture prescriptions were extracted, including 6 single-acupoint prescriptions (1.35%) and 438 multiple-acupoint prescriptions (98.65%). A total of 112 acupoints were involved, with the application frequency of 3 389. Among them, the application frequency of the Neixiyan (EX-LE4)is the highest (354 times, 10.45%), followed by Dubi (ST35), Xuehai(SP10), Yanglingquan(GB34), Liangqiu(ST34), Zusanli(ST36), etc. The mainly involved meridians are the Stomach Meridian of Foot-Yangming and the Spleen Meridian of Foot-Taiyin. The involved specific acupoints are the Five-shu (stream) acupoints, being the most commonly used, followed by the crossing points, and lower confluent (sea) acupoints. CONCLUSION: In the treatment of KOA with acupuncture and moxibustion, the regularities and characteristics of acupoint combinations (acupoint prescriptions) are: 1) often selecting local acupoints at the lower limbs, 2) frequently applying the Five-shu acupoints (specific acupoints), and 3) matching the acupoints of the outside meridians and inside meridians, especially those of the Spleen Meridian and Stomach Meridian.

CNN-Based Prognosis of BCI Rehabilitation Using EEG From First Session BCI Training.

Stroke is a world-leading disease for causing disability. Brain-computer interaction (BCI) training has been proved to be a promising method in facilitating motor recovery. However, due to differences in each patient's neural-clinical profile, the potential of recovery for different patients can vary significantly by conducting BCI training, which remains a major problem in clinical rehabilitation practice. To address this issue, the objective of this study is to prognosticate the outcome of BCI training using motor state electroencephalographic (EEG) collected during the first session of BCI tasks, with the aim of prescribing BCI training accordingly. A Convolution Neural Network (CNN) based prognosis model was developed to predict the outcome of 11 stroke patients' recovery following a 2-week rehabilitation training with BCI. In our study, functional connectivity and power spectrum have been evaluated and applied as the inputs of CNN to regress patients' recovery rate. A saliency map was used to identify the correlation between EEG channels with the recovery outcome. The performance of our model was assessed using the leave-one-out cross-validation. Overall, the proposed model predicted patients' recovery with R2 0.98 and MSE 0.89. According to the saliency map, the highest functional connectivity occurred in Fp2/Fpz-AF8, Fp2/F4/F8-P3, P1/PO7-PO5 and AF3-AF4. Our results demonstrated that deep learning method has the potential to predict the recovery rate of BCI training, which contributes to guiding individualized prescription in the early stage of clinical rehabilitation.

Luteolin-7-O-glucoside inhibits cell proliferation and modulates apoptosis through the AKT signaling pathway in human nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an unnoticeable malignant tumor with a high potential of lymphatic metastasis, and its prevalence is high in Asia. Ionizing radiation is the mainstay of treatment for patients with NPC without metastasis. However, patients with metastatic lesions require advanced treatments such as chemotherapy. The present study investigated the apoptotic effect of luteolin-7-O-glucoside on NPC cells and elucidated its underlying signaling mechanisms. The results revealed that luteolin-7-O-glucoside significantly reduced the proliferation of NPC cell lines (NPC-039 and NPC-BM). Flow cytometry and morphological analysis results demonstrated that luteolin-7-O-glucoside treatment induced S and G2 /M cell cycle arrest, chromatin condensation, and apoptosis. In addition, mitochondrial membrane potential was observed to be depolarized with an increasing concentration of luteolin-7-O-glucoside. Proteins involved in the extrinsic and intrinsic pathways of apoptosis, such as death receptor, caspase-3, caspase-8, caspase-9, and Bcl-2 family proteins (Bax, t-Bid, Bcl-2, and Bcl-xL), were downregulated and upregulated after treatment with luteolin-7-O-glucoside, respectively. Moreover, the addition of a PI3K/AKT inhibitor enhanced the activation of poly-ADP-ribose-polymerase (PARP) and attenuated cell viability, indicating that luteolin-7-O-glucoside induced apoptosis in NPC cells through the AKT signaling pathway. These results indicated that the apoptosis of NPC cells modulated by luteolin-7-O-glucoside may be preceded by mitochondrial depolarization, cell cycle arrest, extrinsic and intrinsic apoptosis pathway activation, and AKT signaling modulation. Thus, luteolin-7-O-glucoside can be a promising anticancer agent against human NPC.