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Objective: To evaluate the predictive performance of metagenomic next-generation sequencing (mNGS) in identifying and predicting pulmonary infections following liver transplantation and to investigate its association with patient outcomes within the initial four-week post-transplantation period. Methods: We retrospectively analyzed 41 liver transplant patients with suspected pulmonary infections from August 2022 to May 2023. Bronchoalveolar lavage fluid (BALF) samples were collected on the first postoperative day for metagenomic next generation sequencing (mNGS) and culture. The predictive capability of mNGS for subsequent infections was assessed by monitoring inflammatory biomarkers and comparing the detection rates with culture methods. Real-time Polymerase Chain Reaction (Rt-PCR) was used to monitor Human betaherpesvirus 5 (CMV) and Human parvovirus B19 (B19) weekly during a four-week postoperative period. Inflammatory biomarkers and blood coagulation function were evaluated on specific days throughout the first, third, fifth, and during four weeks following surgery. The study was conducted until August 2023 to evaluate the patients' prognostic survival outcome, classifying them into groups based on the mortality and survival. Results: The analysis included a total of 41 patients, comprising 32 males and 9 females, with an average age of 52 (47, 63) years. Within one week after liver transplantation, there were 7 cases of bacterial infections, 5 cases of fungal infections, 19 cases of mixed infections, 8 cases without any infection, and 2 cases with unidentified pathogen-associated infections. mNGS successfully predicted 39 (72 %) strains of pathogens, while culture-based methods only detected 28 (52 %) strains. Among the 8 patients diagnosed as non-infected, culture methods identified positive results in 4 cases (50 %), whereas mNGS yielded positive results in 7 cases (87.5 %). The detection rates of CMV and B19 by Rt-PCR within 4 weeks after liver transplantation were 61 % and 17 %, respectively (25/41, 7/41) among the patients. During the study period, a total of 9 patients succumbed while 32 patients survived. The death group and the survival group exhibited significant differences in CRP, HGB, and INR levels at specific monitoring time points. The proportion of CMV detection in blood was significantly higher in the death group compared to the surviving group. Elevated CRP level was identified as a prognostic risk factor. Conclusions: Despite the presence of false positives, mNGS still presents a potential advantage in predicting pulmonary infection pathogens following liver transplantation. Furthermore, the levels of CRP and CMV carrier status within four weeks post-surgery exhibit significant associations with patient survival and prognosis.

ObjectiveTo evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests.MethodsPatients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms.ResultsThirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis.ConclusionBoth platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.

Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction, however, the molecular pathways resulting in endothelial barrier dysfunction and vascular leakage are only sparsely understood. Here, Biering et al. show that SARS-CoV-2 spike protein is sufficient to induce barrier dysfunction and vascular leak. They show a role for integrins, TGF-beta, ECM remodeling enzymes, and glycosaminoglycans in this S-mediated barrier dysfunction.

Abstract SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir’s apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir.

Despite approved vaccines and anti-virals to prevent and treat SARS-CoV-2 infection, there is a need for further development of efficient antiviral therapeutic strategy. Here, Zhu et al. develop locked nucleic acid antisense oligonucleotides (LNA ASOs) targeting the 5’ leader sequence of SARS-CoV-2 RNA to interfere with replication of wildtype virus and variants of concern. Daily intranasal administration in K18-hACE2 humanized mice suppresses viral infection in lung.

Summary: Bromodomain-containing protein 8 (BRD8) is a subunit of the NuA4/TIP60-histone acetyltransferase complex. Although BRD8 has been considered to act as a co-activator of the complex, its biological role remains to be elucidated. Here, we uncovered that BRD8 accumulates in colorectal cancer cells through the inhibition of ubiquitin-dependent protein degradation by the interaction with MRG domain binding protein. Transcriptome analysis coupled with genome-wide mapping of BRD8-binding sites disclosed that BRD8 transactivates a set of genes independently of TIP60, and that BRD8 regulates the expression of multiple subunits of the pre-replicative complex in concert with the activator protein-1. Depletion of BRD8 induced cell-cycle arrest at the G1 phase and suppressed cell proliferation. We have also shown that the bromodomain of BRD8 is indispensable for not only the interaction with histone H4 or transcriptional regulation but also its own protein stability. These findings highlight the importance of bromodomain as a therapeutic target.

Increasing evidence has shown that thirdhand smoke (THS) exposure is likely to induce adverse health effects. An important knowledge gap remains in our understanding of THS exposure related to cancer risk in the human population. Population-based animal models are useful and powerful in investigating the interplay between host genetics and THS exposure on cancer risk. Here, we used the Collaborative Cross (CC) mouse population-based model system, which recapitulates the genetic and phenotypic diversity observed in the human population, to assess cancer risk after a short period of exposure, between 4 and 9 weeks of age. Eight CC strains (CC001, CC019, CC026, CC036, CC037, CC041, CC042 and CC051) were included in our study. We quantified pan-tumor incidence, tumor burden per mouse, organ tumor spectrum and tumor-free survival until 18 months of age. At the population level, we observed a significantly increased pan-tumor incidence and tumor burden per mouse in THS-treated mice as compared to the control (p = 3.04E-06). Lung and liver tissues exhibited the largest risk of undergoing tumorigenesis after THS exposure. Tumor-free survival was significantly reduced in THS-treated mice compared to control (p = 0.044). At the individual strain level, we observed a large variation in tumor incidence across the 8 CC strains. CC036 and CC041 exhibited a significant increase in pan-tumor incidence (p = 0.0084 and p = 0.000066, respectively) after THS exposure compared to control. We conclude that early-life THS exposure increases tumor development in CC mice and that host genetic background plays an important role in individual susceptibility to THS-induced tumorigenesis. Genetic background is an important factor that should be taken into account when determining human cancer risk of THS exposure.

Lan et al. report RNA structure ensembles across the entire SARSCoV-2 genome in infected human cells at single nucleotide resolution. They find alternative RNA conformations critical for promoting near-native frameshifting rates in ORF1ab.

BackgroundWith the development of metagenomic sequencing technologies, more and more cases of pneumonia caused with Chlamydia psittaci (C. psittaci) have been reported. However, it remains unknown about the characteristics of patients with pneumonia caused by different strains of C. psittaci. Here, we shared the clinical characteristics of two cases of pneumonia caused with C. psittaci strains SZ18-2 and SZ15 which were rarely identified in humans.Case presentationCase 1: A 69-year-old male farmer who fed ducks presented to hospital for cough, diarrhea and lethargy with the temperature of 39.8°C. Case 2: A 48-year-old male worker who slaughtered ducks was transferred to hospital for high fever, cough, myalgia, diarrhea and loss of appetite. Both patients did not take any protective measures (wearing face masks or gloves) while processing ducks. C. psittaci pneumonia was diagnosed by metagenomic next-generation sequencing and polymerase chain reaction. After treatment with doxycycline and azithromycin individually, they recovered well and discharged from hospital. Through OmpA sequencing, two different strains of SZ18-2 and SZ15 were identified in case 1 and case 2, respectively.ConclusionsPatients infected with different strains of C. psittaci may own different clinical manifestations. C. psittaci infection should be suspected when pneumonia appears, accompanied by digestive symptoms and multiple organ dysfunction, especially under the exposure of specific birds.

ObjectiveTo evaluate the performance and validate the diagnostic value of a nucleotide matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) with the analysis process optimized in identification of mycobacterium species.MethodsThe optimized analysis process was used for mycobacterial identification in the nucleic MALDI-TOF-MS. 108 samples were used for assessing the performance of nucleic MALDI-TOF-MS, including 25 reference standards, 37 clinical isolates, 37 BALF, and 9 plasmids. The BALF of 38 patients suspected of pulmonary mycobacterial infection was collected for validation. Clinical etiological diagnosis was used as the gold standard to evaluate the diagnostic value of nucleotide MALDI-TOF-MS.ResultsThe sensitivity, specificity, and accuracy of the nucleotide MALDI-TOF-MS in mycobacterial identification were 96.91%, 100% and 97.22%, respectively, and the limit of detection for mycobacterium tuberculosis (MTB) was 50 bacteria/mL. Among 38 patients suspected of pulmonary mycobacterial infection, 33 were diagnosed with pulmonary tuberculosis infection, and 5 with non-mycobacterial infection. In clinical validation, the positive rates of MALDI-TOF-MS, Xpert MTB/RIF, culture and AFS in BALF of patients diagnosed with tuberculosis infection were 72.7%, 63.6%, 54.5% and 27.3%, respectively. The sensitivity/specificity of MALDI-TOF-MS, Xpert, culture and AFS in diagnosing MTB were 72.7%/100%, 63.6%/100%, 54.5%/100%, 27.3%/100%, with the areas under the curve of 0.864, 0.818, 0.773, and 0.636, respectively.ConclusionOptimized nucleotide MALDI-TOF-MS has satisfactory sensitivity, specificity and low LOD in the identification of mycobacteria, which may serve as a potential assay for mycobacterial identification.

At present, metagenomic next-generation sequencing (mNGS) based on Illumina platform has been widely reported for pathogen detection. There are few studies on the diagnosis of major pathogens and treatment regulation using mNGS based on Illumina versus Nanopore. We aim to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) by Illumina and Nanopore for the detection of pathogens in bronchoalveolar lavage fluid (BALF) in suspected community-acquired pneumonia (CAP) patients. BALF samples collected from 66 suspected CAP patients within 48 hours of hospitalization were divided into two parts, one for conventional culture and the other for mNGS by two platforms (Illumina and Nanopore). The clinical value based on infection diagnosis, diagnostic performance for main pathogens and treatment guidance were assessed. More types of species were detected by Nanopore than Illumina, especially in viruses, fungus and mycobacterium. Illumina and Nanopore showed similar detectability in bacterium except for mycobacterium tuberculosis complex/nontuberculosis mycobacteria. Pathogenic infection was established or excluded in 53 of 66 patients. There was little difference in the coincidence rate between Illumina and Nanopore with the clinical diagnosis, but both were superior to the culture (57.81%, 59.38%, 25%, respectively). Compared with Illumina, the diagnostic area under the curve of Nanopore was higher in fungi, but lower in bacteria and Chlamydia psittaci. There was no statistically significant difference between Illumina and Nanopore in guiding drug treatment (56.1% vs. 50%, p=0.43), but both were superior to the culture (56.1% vs. 28.8%, p=0.01; 50% vs. 28.8%, p=0.01). Single inflammatory indicators could not be used to determine whether the patients with culture-negative BALF were established or excluded from infection. The species detected at 1 h and 4 h by Nanopore were consistent to some extent, and its turn-around time (TAT) was significantly shorter than Illumina (p

Introduction: Due to the use of different detection reagents and methods, coagulation analyzers can produce different results. Therefore, detection instruments, reagents and methods are important factors affecting the results of coagulation test. Therefore, this paper aims to establish reference intervals applicable to our laboratory for the Roche Cobas t 711 for routine coagulation assays.Methods:We completed a preliminary evaluation of the analytical performance of the cobas t 711 before any experiment. Healthy volunteer recruitment and ostensibly healthy patients via physical examination were performed to collect individual reference samples. Data were grouped and compared according to age, and the Z test was used to determine whether there was a statistically significant difference between the mean values after grouping. Results: The self-established PT, APTT and TT reference intervals were 8.4–10.2s, 26.8–42.3s and 14.5–17.1s, respectively. The reference ranges of FIB, AT and DD for people aged 50 years or below were 1.85–3.78 (g/l), 83.9–113.2 (%) and 0–0.45 (mg/l), respectively, and those for people older than 50 years were 2.22–3.86 (g/l), 76.0–112.0 (%) and 0–0.52 (mg/l), respectively. Conclusion: The self-built reference intervals for the Roche t 711 were basically consistent with those in the instructions, except the APTT ranges were slightly wider. Laboratories should establish applicable reference intervals according to their own conditions to provide guidance for the diagnosis, monitoring and prognosis of clinically related diseases.

Welding defect constitute a great danger to the safe usage of petroleum pipelines. In addition, manual welding defect detection has numerous deficiencies, such as subjectivity and inaccurate estimation of geometric parameters. Thus, we proposed an automatic welding defect detection system for X-ray images. In the system, five typical defects (cracks, lack of penetration, lack of fusion, round defects, and stripy defects) and non-defects were chosen for recognition. There are three stages in the system: defect extraction, defect detection, and defect recognition. In the first stage, background subtraction with an adaptive thresholding method was adopted to identify the potential defects. In the second stage, to extract real defects from the massive number of potential defects, the adaptive cascade boosting (AdaBoost) algorithm was employed for binary classification. Grayscale features and geometric properties of the defects were extracted for the classification. In the third stage, the AdaBoost algorithm was extended for multi-classification. In the process of distinguishing defects from non-defects, a high detection rate is necessary. To ensure the high true positive rate (TPR) and the low false positive rate (FPR), we proposed the cascade AdaBoost algorithm with penalty term. The accuracy of the defect detection was 85.5%, and the TPR was 91.66%. Moreover, three comparison tests of support vector machine (SVM), k-nearest neighbor (KNN), and random forest (RF) were employed to validate the superiority of AdaBoost. The experimental results indicate that the proposed detection system can be effective for defect detection.

In recent years, electric powered wheelchairs have become indispensable in long-term care. Up so far, many electrically powered wheelchairs have been developed to reduce the burden of caregivers, in which omnidirectional electrically powered wheelchairs attracted researchers’ attentions because these types of EPWs can be used without stress in narrow and/or crowded spaces. In this research, we have developed an omnidirectional wheelchair typed mobile assistive robot with power assistance. In addition, traditional electric powered wheelchairs use a joystick or a force sensor as the operation interface. Joysticks cannot be used by the elderly or disabled, and force sensors are too expensive to be used for wheelchairs. In this study, we have developed a new type of Human Machine Interface (HMI) using a mechanism that can detect force at low cost by using linear potentiometers and compression coil springs instead of a force sensor. The accuracy of the developed HMI is verified, and its effectiveness is confirmed in practical use. Further, we conducted power assisted experiments in forward/backward and lateral directions and turn on the spot using an admittance control with the developed HMI attached to our omnidirectional wheelchair robot. From the experimental results, the developed HMI control accurately measures the forces applied on the wheelchair by the user. Finally, a power-assisted experiment was conducted in the straight direction on a 5-degree slope. These experiments proved that our HMI-based power assist system is effective for omnidirectional wheelchairs.

Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. To elucidate molecular mechanism(s) associated with IDH1/2 mutations, we established mouse embryonic fibroblasts (MEF) cells and human colorectal cancer cells stably expressing cancer-associated IDH1R132C or IDH2R172S, and analyzed the change in metabolic characteristics of the these cells. We found that IDH1/2 mutants induced intracellular 2-HG accumulation and inhibited cell proliferation. Expression profile analysis by RNA-seq unveiled that glucose transporter 1 (Glut1) was induced by the IDH1/2 mutants or treatment with 2-HG in the MEF cells. Consistently, glucose uptake and lactate production were increased by the mutants, suggesting the deregulation of glucose metabolism. Furthermore, PI3K/Akt/mTOR pathway and Hif1α expression were involved in the up-regulation of Glut1. Together, these results suggest that Glut1 is a potential target regulated by cancer-associated IDH1/2 mutations.

To expand the knowledge on the tempo-spatial patterns of zooplankton and the key modulated factors in urban aquatic ecosystem, we investigated zooplankton and water quality from April 2018 to January 2019 in the hinterland of the Three Gorges Reservoir area, Wanzhou City of China. The results indicated that water quality indicated by the trophic state index (TSI) reached a state of mesotrophication to light eutrophication in the Yangtze River, and a state of moderate- to hyper- eutrophication in its tributaries. Based on the biomass of zooplanktons, Asplanchna priodonta was the most common specie in April; Encentrum sp., Filinia cornuta and Epiphanes senta were the most noticeable species in summer; Cyclopoida Copepodid, Sinocalanus dorrii and Philodina erythrophthalma became the dominant species in winter. Generally, rotifers prevailed in April and August, and copepods became the most popular in January. According to canonical correspondence analysis, nitrate, temperature (T), ammonia, water level and permanganate index (CODMn) significantly influenced the community structure of zooplankton (p < 0.05). The dominant species shifts of zooplankton were partly associated with nutrient level (nitrate and ammonia) under periodic water level fluctuations. Rotifers and protozoans were characterized as high T adapted and CODMn-tolerant species comparing with cladocerans and copepods. The ratio of microzooplankton to mesozooplankton (Pmicro/meso) has presented a strongly positive relationship with T (p < 0.001), as well as Pmicro/meso and CODMn (p < 0.001). It implied that zooplankton tended to miniaturize individual size via species shift under high T and/or CODMn conditions induced by global warming and human activities. The information hints us that climate change and human activities are likely to produce fundamental changes in urban aquatic ecosystem by reorganizing biomass structure of the food web in future.

Abstract Parkinson’s disease (PD) and Parkinsonism are common neurodegenerative disorders with continuously increasing prevalence, causing high global burdens. However, data concerning the comorbidity burden of patients with PD or Parkinsonism in China are lacking. To investigate the health condition and comorbidity burden, a total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary hospitals in seven cities across China from 2003 to 2012. Their comorbidity burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and Parkinsonism patients. Compared with PD patients, Parkinsonism patients were older (69.8 ± 11.5 vs. 67.9 ± 11.4, P

Electroencephalography neurofeedback (EEG-NFB) training can induce changes in the power of targeted EEG bands. The objective of this study is to enhance and evaluate the specific changes of EEG power spectral density that the brain-machine interface (BMI) users can reliably generate for power augmentation through EEG-NFB training. First, we constructed an EEG-NFB training system for power augmentation. Then, three subjects were assigned to three NFB training stages, based on a 6-day consecutive training session as one stage. The subjects received real-time feedback from their EEG signals by a robotic arm while conducting flexion and extension movement with their elbow and shoulder joints, respectively. EEG signals were compared with each NFB training stage. The training results showed that EEG beta (12–40 Hz) power increased after the NFB training for both the elbow and the shoulder joints’ movements. EEG beta power showed sustained improvements during the 3-stage training, which revealed that even the short-term training could improve EEG signals significantly. Moreover, the training effect of the shoulder joints was more obvious than that of the elbow joints. These results suggest that NFB training can improve EEG signals and clarify the specific EEG changes during the movement. Our results may even provide insights into how the neural effects of NFB can be better applied to the BMI power augmentation system and improve the performance of healthy individuals.

Brain–Machine Interfaces (BMIs) have attracted much attention in recent decades, mainly for their applications involving severely disabled people. Recently, research has been directed at enhancing the ability of healthy people by connecting their brains to external devices. However, there are currently no successful research reports focused on robotic power augmentation using electroencephalography (EEG) signals for the shoulder joint. In this study, a method is proposed to estimate the shoulder’s electromyography (EMG) signals from EEG signals based on the concept of a virtual flexor–extensor muscle. In addition, the EMG signal of the deltoid muscle is used as the virtual EMG signal to establish the EMG estimation model and evaluate the experimental results. Thus, the shoulder’s power can be augmented by estimated virtual EMG signals for the people wearing an EMG-based power augmentation exoskeleton robot. The estimated EMG signal is expressed via a linear combination of the features of EEG signals extracted by Independent Component Analysis, Short-time Fourier Transform, and Principal Component Analysis. The proposed method was verified experimentally, and the average of the estimation correlation coefficient across different subjects was 0.78 (±0.037). These results demonstrate the feasibility and potential of using EEG signals to provide power augmentation through BMI technology.

A power-assisted exoskeleton should be capable of reducing the burden on the wearer’s body or rendering his or her work improved and efficient. More specifically, the exoskeleton should be easy to wear, be simple to use, and provide power assistance without hindering the wearer’s movement. Therefore, it is necessary to evaluate the backdrivability, range of motion, and power-assist capability of such an exoskeleton. This evaluation identifies the pros and cons of the exoskeleton, and it serves as the basis for its subsequent development. In this study, a lightweight upper-limb power-assisted exoskeleton with high backdrivability was developed. Moreover, a motion capture system was adopted to measure and analyze the workspace of the wearer’s upper limb after the exoskeleton was worn. The results were used to evaluate the exoskeleton’s ability to support the wearer’s movement. Furthermore, a small and compact three-axis force sensor was used for power assistance, and the effect of the power assistance was evaluated by means of measuring the wearer’s surface electromyography, force, and joint angle signals. Overall, the study showed that the exoskeleton could achieve power assistance and did not affect the wearer’s movements.

In this paper, aiming to estimate force/torque information from brain activity to help and support the daily lives of human beings, we estimate the human muscular activity from EEG (Electroencephalogram) by PCA (Principal Component Analysis) and RLS (Recursive Least Squares). EEG and EMG (Electromyogram) are measured when a subject is flexing and extending his arm, and their linear model is established by PCA. Then, this linear model between EEG and EMG is updated by the angle, the angular velocity and the angular acceleration of the robot arm. Finally, EMG is estimated from EEG using the updated model. The results show that the estimation of EMG from EEG is possible, and using EEG support human's activities has a great potential.

Brain-Machine Interface (BMI) has been considered as an effective way to help and support both the disabled rehabilitation and healthy individuals’ daily lives to use their brain activity information instead of their bodies. In order to reduce costs and control exoskeleton robots better, we aim to estimate the necessary torque information for a subject from his/her electroencephalography (EEG) signals when using an exoskeleton robot to perform the power assistance of the upper limb without using external torque sensors nor electromyography (EMG) sensors. In this paper, we focus on extracting the motion-relevant EEG signals’ features of the shoulder joint, which is the most complex joint in the human’s body, to construct a power assistance system using wearable upper limb exoskeleton robots with BMI technology. We extract the characteristic EEG signals when the shoulder joint is doing flexion and extension movement freely which are the main motions of the shoulder joint needed to be assisted. Independent component analysis (ICA) is used to extract the source information of neural components, and then the average method is used to extract the characteristic signals that are fundamental to achieve the control. The proposed approach has been experimentally verified. The results show that EEG signals begin to increase at 300–400 ms before the motion and then decrease at the beginning of the generation of EMG signals, and the peaks appear at about one second after the motion. At the same time, we also confirmed the relationship between the change of EMG signals and the EEG signals on the time dimension, and these results also provide a theoretical basis for the delay parameter in the linear model which will be used to estimate the necessary torque information in future. Our results suggest that the estimation of torque information based on EEG signals is feasible, and demonstrate the potential of using EEG signals via the control of brain-machine interface to support human activities continuously.

At present, metagenomic next-generation sequencing (mNGS) based on Illumina platform has been widely reported for pathogen detection. There are few studies on the diagnosis of major pathogens and treatment regulation using mNGS based on Illumina versus Nanopore. We aim to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) by Illumina and Nanopore for the detection of pathogens in bronchoalveolar lavage fluid (BALF) in suspected community-acquired pneumonia (CAP) patients. BALF samples collected from 66 suspected CAP patients within 48 hours of hospitalization were divided into two parts, one for conventional culture and the other for mNGS by two platforms (Illumina and Nanopore). The clinical value based on infection diagnosis, diagnostic performance for main pathogens and treatment guidance were assessed. More types of species were detected by Nanopore than Illumina, especially in viruses, fungus and mycobacterium. Illumina and Nanopore showed similar detectability in bacterium except for mycobacterium tuberculosis complex/nontuberculosis mycobacteria. Pathogenic infection was established or excluded in 53 of 66 patients. There was little difference in the coincidence rate between Illumina and Nanopore with the clinical diagnosis, but both were superior to the culture (57.81%, 59.38%, 25%, respectively). Compared with Illumina, the diagnostic area under the curve of Nanopore was higher in fungi, but lower in bacteria and Chlamydia psittaci. There was no statistically significant difference between Illumina and Nanopore in guiding drug treatment (56.1% vs. 50%, p=0.43), but both were superior to the culture (56.1% vs. 28.8%, p=0.01; 50% vs. 28.8%, p=0.01). Single inflammatory indicators could not be used to determine whether the patients with culture-negative BALF were established or excluded from infection. The species detected at 1 h and 4 h by Nanopore were consistent to some extent, and its turn-around time (TAT) was significantly shorter than Illumina (p<0.01). Illumina and Nanopore both have its own advantages in pathogenic diagnosis and play similar roles in infection diagnosis and guiding clinical treatment. Nanopore has a relatively short TAT, which may be promising in rapid etiological diagnosis of acute and critically ill patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Methods: Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Results: Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/ 42) based on pathogen diagnosis. Conclusion: Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection. [ABSTRACT FROM AUTHOR]

In this paper, we present an analytic solution for pulse wave propagation in a flexible arterial model with tapering, physiological boundary conditions and variable wall properties (wall elasticity and thickness). The change of wall properties follows a profile that is proportional to rα, where r represents the lumen radius and α is a material coefficient. The cross-sectionally averaged velocity and pressure are obtained by solving a hyperbolic system derived from the mass and momentum conservations, and they are expressed in Bessel functions of order (4 - α)/(3 - α) and 1/(3 - α), respectively. The solution is successfully validated by comparing it with numerical results from three-dimensional (3-D) fluid--structure interaction simulations. Subsequently, the solution is employed to study pulse wave propagation in an arterial model, revealing that the wall properties and the physiological outlet boundary conditions, such as the resistor--capacitor--resistor (RCR) model, play a crucial role in characterizing the input impedance and reflection coefficient. At low-frequency range, the input impedance is found to be insensitive to the wall properties and is primarily determined by the RCR parameters. At high-frequency range, the input impedance oscillates around the local characteristic impedance, and the oscillation amplitude varies non-monotonically with α. Expressions for the input impedance at both low-frequency and high-frequency limits are presented. This analytic solution is also successfully applied to model flow inside a patient-specific arterial tree, with the maximum relative errors in pressure and flow rate never exceeding 1.6% and 9.0% when compared with results from 3-D numerical simulations. [ABSTRACT FROM AUTHOR]

In this study, coupled hemodynamic–acoustic simulations are employed to study the generation and propagation of murmurs associated with aortic stenoses where the aorta with a stenosed aortic valve is modeled as a curved pipe with a constriction near the inlet. The hemodynamics of the poststenotic flow is investigated in detail in our previous numerical study (Zhu et al., 2018, “Computational Modelling and Analysis of Haemodynamics in a Simple Model of Aortic Stenosis,” J. Fluid Mech., 851, pp. 23–49). The temporal history of the pressure on the aortic lumen is recorded during the hemodynamic study and used as the murmur source in the acoustic simulations. The thorax is modeled as an elliptic cylinder and the thoracic tissue is assumed to be homogeneous, linear and viscoelastic. A previously developed high-order numerical method that is capable of dealing with immersed bodies is applied in the acoustic simulations. To mimic the clinical practice of auscultation, the sound signals from the epidermal surface are collected. The simulations show that the source of the aortic stenosis murmur is located at the proximal end of the aortic arch and that the sound intensity pattern on the epidermal surface can predict the source location of the murmurs reasonably well. Spectral analysis of the murmur reveals the disconnect between the break frequency obtained from the flow and from the murmur signal. Finally, it is also demonstrated that the source locations can also be predicted by solving an inverse problem using the free-space Green's function. The implications of these results for cardiac auscultation are discussed. [ABSTRACT FROM AUTHOR]

Brain-Machine Interface (BMI) has been considered as an effective way to help and support both the disabled rehabilitation and healthy individuals' daily lives to use their brain activity information instead of their bodies. In order to reduce costs and control exoskeleton robots better, we aim to estimate the necessary torque information for a subject from his/her electroencephalography (EEG) signals when using an exoskeleton robot to perform the power assistance of the upper limb without using external torque sensors nor electromyography (EMG) sensors. In this paper, we focus on extracting the motion-relevant EEG signals' features of the shoulder joint, which is the most complex joint in the human's body, to construct a power assistance system using wearable upper limb exoskeleton robots with BMI technology. We extract the characteristic EEG signals when the shoulder joint is doing flexion and extension movement freely which are the main motions of the shoulder joint needed to be assisted. Independent component analysis (ICA) is used to extract the source information of neural components, and then the average method is used to extract the characteristic signals that are fundamental to achieve the control. The proposed approach has been experimentally verified. The results show that EEG signals begin to increase at 300-400 ms before the motion and then decrease at the beginning of the generation of EMG signals, and the peaks appear at about one second after the motion. At the same time, we also confirmed the relationship between the change of EMG signals and the EEG signals on the time dimension, and these results also provide a theoretical basis for the delay parameter in the linear model which will be used to estimate the necessary torque information in future. Our results suggest that the estimation of torque information based on EEG signals is feasible, and demonstrate the potential of using EEG signals via the control of brain-machine interface to support human activities continuously. [ABSTRACT FROM AUTHOR]

In a study motivated by considerations associated with heart murmurs and cardiac auscultation, numerical simulations are used to analyse the haemodynamics in a simple model of an aorta with an aortic stenosis. The aorta is modelled as a curved pipe with a 180° turn, and three different stenoses with area reductions of 50 %, 62.5 % and 75 % are examined. A uniform steady inlet velocity with a Reynolds number of 2000 is used for all of the cases and direct numerical simulation is employed to resolve the dynamics of the flow. The poststenotic flow is dominated by the jet that originates from the stenosis as well as the secondary flow induced by the curvature, and both contribute significantly to the flow turbulence. On the anterior surface of the modelled aorta, the location with maximum pressure fluctuation, which may be considered as the source location for the murmurs, is found to be located around 60° along the aortic arch, and this location is relatively insensitive to the severity of the stenosis. For all three cases, this high-intensity wall pressure fluctuation includes contributions from both the jet and the secondary flow. Spectral analysis shows that for all three stenoses, the Strouhal number of the vortex shedding of the jet shear layer is close to 0.93, which is higher than the shedding frequency of a corresponding free jet or a jet confined in a straight pipe. This frequency also appears in the pressure spectra at the location postulated as the source of the murmurs, in the form of a 'break frequency.' The implications of these findings for cardiac auscultation-based diagnosis of aortic stenosis are also discussed. [ABSTRACT FROM AUTHOR]

A computational framework consisting of a one-way coupled hemodynamic-acoustic method and a wave-decomposition based postprocessing approach is developed to investigate the biomechanics of arterial bruits. This framework is then applied for studying the effect of the shear wave on the generation and propagation of bruits from a modeled stenosed artery. The blood flow in the artery is solved by an immersed boundary method (IBM) based incompressible flow solver. The sound generation and propagation in the blood volume are modeled by the linearized perturbed compressible equations, while the sound propagation through the surrounding tissue is modeled by the linear elastic wave equation. A decomposition method is employed to separate the acoustic signal into a compression!longitudinal component (curl free) and a shear!transverse component (divergence free), and the sound signals from cases with and without the shear modulus are monitored on the epidermal surface and are analyzed to reveal the influence of the shear wave. The results show that the compression wave dominates the detected sound signal in the immediate vicinity of the stenosis, whereas the shear wave has more influence on surface signals further downstream of the stenosis. The implications of these results on cardiac auscultation are discussed. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that cardiovascular functions might play a critical role in Alzheimer's disease (AD) pathogenesis. However, the relationship among heart function, blood flow of cerebral vessels, and AD remains unclear. In the present study, AD patients (n = 34) and age- and gender-matched cognitively normal controls (n = 34) were recruited. Demographic and comorbidity information was collected. The ejection fraction was measured using echocardiography, and the mean velocity, pulsatility index (PI), and resistance index (RI) of the basilar artery (BA), left terminal internal carotid artery (LTICA), and right terminal internal carotid artery (RTICA) were measured using transcranial Doppler. The data of lacunae, white matter changes, and plaques in the aortic arch and carotid arteries were collected from brain magnetic resonance imaging and computed tomography angiography images. Compared with normal controls, AD patients had lower ejection fractions and cerebral blood flow velocities and higher RI and PI in the BA, LTICA, and RTICA, as well as more plaques in the aortic and carotid arteries. In the multivariate logistic regression analysis, the ejection fraction and the mean velocity of the BA and LTICA were independently associated with AD after adjusting for age, gender, education, vascular risk factors, arterial plaques, and brain ischemic lesions detected in the brain images. These findings suggest that heart function and vascular condition may play important roles in AD pathogenesis. Improving cardiovascular functions could be a promising approach for the prevention and treatment of AD. [ABSTRACT FROM AUTHOR]

Ammonia-oxidizing archaea (AOA) play a major role in the ammonia oxidation as the first and limiting step of nitrification. In this research the abundance of AOA in eight small lakes and reservoirs at different trophic states were investigated by amoA gene quantification. Several environmental factors,including temperature, pH, Secchi depth (SD) and total phosphorus (TP), total nitrogen (TN), ammonia nitrogen (NH4+-H) and chlorophyll a (Chl a) contents, total carbon (TC), the classical Carlson index TSI were simultaneously monitored. The results showed that amoA copies ranged from 7.80 × 104 to 1.23 × 106 per liter in water samples and from 1.62 × 105 to 1.30 × 106 per gram in sediment samples. For identify factors that regulate the abundance of AOA in these environments, correlation analysis was performed and the results revealed that the abundance of AOA showed a positive correlation with TN and NH4+-H in both water and sediment samples, while other environmental factors showed no correlation with the abundance of AOA, suggesting that nitrogen is the main factor regulating AOA abundance. [ABSTRACT FROM AUTHOR]

Numerous palaeoclimatic and modem instrumental data indicated that the climate of Yunnan-Guizhou Plateau has undergone a significant warming during the past century. In this research. biological silicon, ostracods, physicochemical proxies of Lake Lugu sediment core were analyzed to illuminate the change on the lake ecosystem and their cause analysis in the past century. The correlations between those proxies and the temperature and precipitation data of the Lijiang region during 1951-2010 AD were analyzed. The results showed that: biosilicon, ostracods and physicochemical proxies changed greatly with the depth of the sediment, especially 14.5 cm which represent for the past 70 years. The results of ostracods combination showed that since 1990, the relative abundance of cold water species reduced, such as Cyclocypris and Candona. while the relative abundance of the warm water species increased, like Eucypris and Cypris. Limnocythere was the dorminant species in the core. The absolute abundance of ostracoda increased sharply from the end of last century and reduced rapidly in recent years. The content of biological silicon maintained at a relative higher level since 1990. which indicated that the primary productivity was relatively high in Lake Lugu during this period and phytoplankton containing silicon (e.g. Diatoms) increased. Therefore climate change in this region led to the increase of primary productivity in lake Lugu over the last 20 years. [ABSTRACT FROM AUTHOR]

The regulation of the design and construction of new buildings is insufficient; controlling the energy consumption of buildings in the service stage is the key to realizing the goal of energy saving of buildings by tiered pricing for electricity consumption based on quota. Fifty families in Kunming, China were investigated through questionnaire survey and spot test; regression analysis and energy simulation were conducted to obtain the annual energy consumption of a nuclear family. The quota was finally established based on the correction of the two results according to the actual situation; annual energy consumption per capita was used as the unit, which was more reasonable than the annual energy consumption per floor area that was used by numerous scholars. The study demonstrates that the annual per capita energy consumption is significantly related with per capita floor area and annual per capita income. With the popularity of solar hot water system, natural ventilation is the main way for cooling in summer and the requirement of indoor comfort cannot be met during winter in residential buildings in Kunming. Thus, the value of energy simulation is higher than that of regression analysis. Finally, the corrected value of energy simulation was determined to be the final quota, which was 7.7% lower than the value of regression analysis, to meet the requirements of energy efficiency and indoor comfort. To sum up, both the value of regression analysis and the adjusted value of energy simulation could be determined as the quota. The study has a reference value to the prediction of the energy consumption of buildings, which also offers a guideline for the local government to establish relevant policies. [ABSTRACT FROM AUTHOR]

In this work, a high-order numerical approach based on the immersed-boundary method to simulate viscous incompressible flows involving arbitrary boundaries is described. The idea is to combine compact finite difference schemes and a high-order direct forcing approach of the sharp-interface immersed-boundary method. In this approach, a particular challenge is to solve the pressure Poisson equation using the compact stencil. This issue is addressed by introducing an efficient approach based on high-order corrections to the right-hand side of the Poisson equation (that is, the source term) while retaining the second-order short stencil for the Laplace operator. The two-dimensional implementation is described, for which third-order global convergence is achieved when an immersed boundary is present. [ABSTRACT FROM AUTHOR]

Background: Capsaicin-rich diets are common worldwide. Capsaicin has been shown to have favorable effects on various diseases including atherosclerosis, cardiovascular diseases, stroke, obesity, hypertension, cancer, and gastrointestinal and inflammatory diseases. The impact of capsaicin on Alzheimer's disease (AD), which is the most common form of dementia in the elderly, remains unknown.Objective: To investigate the correlations of capsaicin intake with cognition and blood markers of AD.Methods: A total of 338 participants aged 40 years or older were enrolled from communities. Dietary habits regarding chili pepper consumption were collected using a Food Frequency Questionnaire (FFQ). Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (MMSE). Blood amyloid-β (Aβ)40 and Aβ42 were measured with ELISA kits.Results: In univariate analysis, MMSE scores (r = 0.209, p < 0.001), serum Aβ40 levels (r = -0.149, p = 0.006), the ratio of Aβ42/Aβ40 (r = 0.11, p = 0.043) and total serum Aβ levels (r = -0.097, p = 0.075), but not serum Aβ42 levels (r = 0.17, p = 0.757), were significantly correlated with total capsaicin diet scores. In multivariate analysis, total capsaicin diet scores were positively associated with MMSE scores and inversely associated with serum Aβ40 levels, and total serum Aβ levels, but not serum Aβ42 levels and the ratio of Aβ42/Aβ40, after adjustment for age, gender, educational level, smoking history, alcohol consumption, body mass index (BMI) and comorbidities.Conclusion: These findings suggest that a capsaicin-rich diet may exert favorable effects on AD blood biomarkers and cognitive function in middle-aged and elderly adults. [ABSTRACT FROM AUTHOR]