Redundancy Reduction for Sensor Deployment in Prosthetic Socket: A Case Study.

The irregular pressure exerted by a prosthetic socket over the residual limb is one of the major factors that cause the discomfort of amputees using artificial limbs. By deploying the wearable sensors inside the socket, the interfacial pressure distribution can be studied to find the active regions and rectify the socket design. In this case study, a clustering-based analysis method is presented to evaluate the density and layout of these sensors, which aims to reduce the local redundancy of the sensor deployment. In particular, a Self-Organizing Map (SOM) and K-means algorithm are employed to find the clustering results of the sensor data, taking the pressure measurement of a predefined sensor placement as the input. Then, one suitable clustering result is selected to detect the layout redundancy from the input area. After that, the Pearson correlation coefficient (PCC) is used as a similarity metric to guide the removal of redundant sensors and generate a new sparser layout. The Jenson-Shannon Divergence (JSD) and the mean pressure are applied as posterior validation metrics that compare the pressure features before and after sensor removal. A case study of a clinical trial with two sensor strips is used to prove the utility of the clustering-based analysis method. The sensors on the posterior and medial regions are suggested to be reduced, and the main pressure features are kept. The proposed method can help sensor designers optimize sensor configurations for intra-socket measurements and thus assist the prosthetists in improving the socket fitting.

A20 Ameliorates Intracerebral Hemorrhage-Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination.

Reducing excessive inflammation is beneficial for the recovery from intracerebral hemorrhage (ICH). Here, the roles and mechanisms of A20 (TNFAIP3), an important endogenous anti-inflammatory factor, are examined in ICH. A20 expression in the PBMCs of ICH patients and an ICH mouse model was detected, and the correlation between A20 expression and neurologic deficits was analyzed. A20 expression was increased in PBMCs and was negatively related to the modified Rankin Scale score. A20 expression was also increased in mouse perihematomal tissues. A20-/- and A20-overexpressing mice were generated to further analyze A20 function. Compared with wild-type (WT) mice, A20-/- and A20-overexpressing mice showed significant increases and decreases, respectively, in hematoma volume, neurologic deficit score, mortality, neuronal degeneration, and proinflammatory factors. Moreover, WT-A20-/- parabiosis was established to explore the role of A20 in peripheral blood in ICH injury. ICH-induced damage, including brain edema, neurologic deficit score, proinflammatory factors, and neuronal apoptosis, was reduced in A20-/- parabionts compared with A20-/- mice. Finally, the interactions between TRAF6 and Ubc13 and UbcH5c were increased in A20-/- mice compared with WT mice; the opposite occurred in A20-overexpressing mice. Enhanced IκBα degradation and NF-κB activation were observed in A20-/- mice, but the results were reversed in A20-overexpressing mice. These results suggested that A20 is involved in regulating ICH-induced inflammatory injury in both the central and peripheral system and that A20 reduces ICH-induced inflammation by regulating TRAF6 polyubiquitination. Targeting A20 may thus be a promising therapeutic strategy for ICH.

Toll-Like Receptor 4/MyD88-Mediated Signaling of Hepcidin Expression Causing Brain Iron Accumulation, Oxidative Injury, and Cognitive Impairment After Intracerebral Hemorrhage.

BACKGROUND: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown. METHODS: Parabiosis and ICH models combined with in vivo and in vitro experiments were used to investigate the roles of hepcidin in brain iron metabolism after ICH. RESULTS: Increased hepcidin-25 was found in serum and primarily in astrocytes after ICH. The brain iron efflux, oxidative brain injury, and cognition impairment were improved in Hepc-/- ICH mice but aggravated by the human hepcidin-25 peptide in C57BL/6 ICH mice. Data obtained in in vitro studies showed that increased hepcidin inhibited the intracellular iron efflux of brain microvascular endothelial cells but was rescued by a hepcidin antagonist, fursultiamine. Using parabiosis ICH models also shows that increased serum hepcidin prevents brain iron efflux. In addition, Toll-like receptor 4 (TLR4)/MyD88 signaling pathway increased hepcidin expression by promoting interleukin-6 expression and signal transducer and activator of transcription 3 phosphorylation. TLR4-/- and MyD88-/- mice exhibited improvement in brain iron efflux at 7, 14, and 28 days after ICH, and the TLR4 antagonist (6R)-6-[N-(2-chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate significantly decreased brain iron levels at days 14 and 28 after ICH and improved cognition impairment at day 28. CONCLUSIONS: The results presented here show that increased hepcidin expression caused by inflammation prevents brain iron efflux via inhibition of the intracellular iron efflux of brain microvascular endothelial cells entering into circulation and aggravating oxidative brain injury and cognition impairment, which identifies a mechanistic target for muting inflammation to promote brain iron efflux and to attenuate oxidative brain injury after ICH.

Safety and Efficacy of Wingspan Stenting for Severe Symptomatic Atherosclerotic Stenosis of the Middle Cerebral Artery: Analysis of 278 Continuous Cases.

OBJECTIVE: Our objective is to investigate the safety and long-term efficacy of the Wingspan stent (Boston Scientific, Natick, MA, USA) for treating severe atherosclerotic stenosis of the middle cerebral artery (MCA). METHODS: A total of 278 consecutive patients from our stroke database with clinical symptoms within the prior 90 days and intracranial atherosclerotic stenosis of 70% or above of the MCA were enrolled in this study between September 2012 and November 2014, and these patients were followed until the end of June 2015. The endpoint events included any stroke or death within 30 days after stenting and any subsequent ipsilateral ischemic stroke. RESULTS: Among the 278 enrolled patients, 277 patients (99.6%) successfully underwent stenting. The mean rate of stenosis decreased from 82.5 ± 7.9% to 9.0 ± 3.2% following treatment. Within 30 days after stenting, 12 patients (4.3%) experienced endpoint events, including 8 cases (2.9%) of hemorrhagic stroke and 4 cases (1.4%) of ischemic stroke; 2 perioperative deaths occurred. During 8-33 months of follow-up, 19 patients developed endpoint events. The 1- and 2-year endpoint event rates were 5.8% (95% confidence interval [CI], 5.0%-15.7%) and 7.2% (95% CI, 4.3%-10.1%), respectively. CONCLUSIONS: From this study, we can conclude that the treatment of severe symptomatic atherosclerotic stenosis of the MCA using the Wingspan stent was safe and effective and that the long-term stroke recurrence rate after stenting was low.

Serum hepcidin concentrations correlate with serum iron level and outcome in patients with intracerebral hemorrhage.

Iron plays a detrimental role in the intracerebral hemorrhage (ICH)-induced brain damage, while hepcidin is the most important iron-regulated hormone. Here, we investigate the association between serum hepcidin and serum iron, outcome in patients with ICH. Serum samples of 81 cases with ICH were obtained on consecutive days to detect the levels of hepcidin, iron, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The National Institutes of Health Stroke Scale score (NIHSS) was measured at admission and on days 7 and 30, and the modified Rankin Scale (mRS) score was evaluated at 3 months after ICH. Additionally, the correlations of serum hepcidin with serum iron and the mRS score were analyzed by a generalized linear model. Higher serum hepcidin levels were detected in patients with poor outcomes (P < 0.001), and the mRS score increased by a mean of 1.135 points (95% CI 1.021-1.247, P < 0.001) for every serum hepcidin quartile after adjusting for other prognostic variables. Pearson correlation analysis showed that serum hepcidin was negatively correlated with serum iron (r = -0.5301, P < 0.001), and a significantly lower concentration of serum iron was found in patients with poor outcomes (P = 0.007). Additionally, serum hepcidin was independently correlated with mRS scores of ICH patients (OR 1.115, 95% CI 0.995-1.249, P = 0.021). Our results suggest that serum hepcidin is closely related to the outcome of patients with ICH and may be a biological marker for outcome prediction.

Recent antitumor therapy does not increase Omicron COVID-19 severity in cancer patients: a two-center retrospective study in China.

Background: The impact of anticancer therapy and related clinical factors on the severity of COVID-19 in cancer patients during the Omicron pandemic has not been established. The recent outbreak in China caused predominantly by the BA.5.2 and BF.7 strains of Omicron provided us with the opportunity to observe objectively the impact of this strain in oncology patients. We initiated this two-center retrospective study in China to determine the impact of anti-cancer treatment, other clinical factors, and cancer characteristics on COVID-19 severity in cancer patients infected with coronavirus during the SARS-CoV-2 Omicron variant pandemic in China. Methods: We retrospectively included 554 cancer patients infected with COVID-19 from two medical centers. Data on their anticancer treatment prior to COVID-19 infection and general clinical characteristics (sex, age, past medical history, etc.) were collected. Univariate statistical analysis was performed to identify the factors associated with the severity of COVID-19. Results: Among 554 cancer patients infected with COVID-19, there were 15 (2.7%) severe/critical cases, 86 (15.5%) cases with medium severity, and 453 (81.8%) cases with mild severity. Univariate analysis revealed that advanced age, male sex, worse ECOG score, unvaccinated status, and previous liver, kidney, and brain diseases were associated with more severe COVID-19. However, recent antitumor therapy, including cytotoxic chemotherapy within two weeks did not have a significant correlation with the severity of COVID-19 caused by the Omicron variant. Conclusion: The severity of COVID-19 caused by the Omicron variant is not exacerbated by recent anticancer therapy in cancer patients. Therefore, anticancer therapy should not be discontinued in such cases, especially those with mild severity.

Font Design Optimization Model for New Media Short Video Based on Virtual Reality Digital Processing Technology.

Time is not a static idea, but neither is the evolution of the media and design industries. Our creative tools and the media have seen a significant transformation in the last 20 years. Digital technology will shape the media and design industries in the future. Until the next major technological revolution, digitalization will have a lasting effect on the media and design industries. The development and liberation of many designers' ideas and perspectives thanks to modern digital processing technology for virtual reality has sparked an unprecedented "boom" in design. People's senses of sight, sound, and touch will be completely satisfied thanks to the incorporation of such technologies in the design process. A vast history and rich cultural heritage can be found in the field of font design. It has continuously played a crucial role in the advancement of science and technology. The creation of a new media short video typeface based on digital processing technology for virtual reality is suggested in this study. After mastering the font style, the new media short video font is extracted using virtual reality digital processing technology, and the identification system is built utilising virtual three-dimensional technology. The simulation test and analysis are done last. The proposed approach has an accuracy that is 9.34% greater than the conventional technique, according to simulation findings. This outcome demonstrates in detail how font design becomes more humanized when virtual reality digital processing technology is used. It demonstrates how people and information interact and genuinely stress the importance of human participation and dominance. Ethics and aesthetics are combined in font design. The fashion and aesthetic ideas of the new century are reflected in it like a mirror. As a result, font design is now being pursued in a new way, and its new application concept unquestionably has a significant impact on the design sector today.

Alternative Perspective on Rapid Wine Oxidation through Changes in Gas-Phase Volatile Concentrations, Highlighted by Matrix Component Effects.

A new perspective is presented to investigate the sensorially relevant gas-phase concentrations of volatile compounds in wine. This is achieved by measuring the partition coefficients and matrix-phase concentrations of volatiles using static headspace-gas chromatography-ion mobility spectrometry. Physicochemical properties that can contribute to the partition behaviors of 10 volatile esters, such as hydrophobicity and matrix temperature, are also discussed. Partition coefficients are then linked to quantitative measurements to obtain partial pressures, which describe the availability of volatile compounds in the gas phase. The concept of partition coefficients and partial pressure has then been applied to a time series of aroma changes due to oxidation in commercial wines. As a follow-up study, a full factorial design was devised to inspect the impact of three common wine matrix components, namely, copper, polyphenols, and ascorbic acid, on the partial pressure changes after 30-day oxidation treatment in either full-alcohol or low-alcohol simulated wine matrices. Interesting interactive effects between antioxidant behaviors and alcohol levels were elucidated, especially around the controversial use of ascorbic acid in winemaking. These results can guide winemakers who wish to minimize oxidative damage to wine aroma during wine storage or bulk transport, where ullage may be present or continual oxygen ingress may be occurring.

Volatile-Based Prediction of Sauvignon Blanc Quality Gradings with Static Headspace-Gas Chromatography-Ion Mobility Spectrometry (SHS-GC-IMS) and Interpretable Machine Learning Techniques.

The analytical scope of static headspace-gas chromatography-ion mobility spectrometry (SHS-GC-IMS) was applied to wine aroma analysis for the first time. The method parameters were first fine-tuned to achieve optimal analytical results, before the method stability was demonstrated, in terms of repeatability and reproducibility. Succinct qualitative identification of compounds was also realized, with the identification of several volatiles that have seldom been described previously in Sauvignon Blanc wine, such as methyl acetate, ethyl formate, and amyl acetate. Using the SHS-GC-IMS data in an untargeted approach, computer modeling of large datasets was applied to link aroma chemistry via prediction models to wine sensory quality gradings. Six machine learning models were compared, and artificial neural network (ANN) returned the most promising performance with a prediction accuracy of 95.4%. Despite its inherent complexity, the ANN model offered intriguing insights on the influential volatiles that correlated well with higher and lower sensory gradings. These findings could, in the future, guide winemakers in establishing wine quality, particularly during blending operations prior to bottling.

Validation Study on the Simultaneous Quantitation of Multiple Wine Aroma Compounds with Static Headspace-Gas Chromatography-Ion Mobility Spectrometry.

A new quantitative method based on static headspace-gas chromatography-ion mobility spectrometry (SHS-GC-IMS) is proposed, which enables the simultaneous quantitation of multiple aroma compounds in wine. The method was first evaluated for its stability and the necessity of using internal standards as a quality control measure. The two major hurdles in applying GC-IMS in quantitation studies, namely, nonlinearity and multiple ion species, were also investigated using the Boltzmann function and generalized additive model (GAM) as potential solutions. Metrics characterizing the model performance, including root mean squared error, bias, limit of detection, limit of quantitation, repeatability, reproducibility, and recovery, were investigated. Both nonlinear fitting methods, Boltzmann function and GAM, were able to return desirable analytical outcomes with an acceptable range of error. Potential pitfalls that would cause inaccurate quantitation, that is, effects of ethanol content and competitive ionization, were also discussed. The performance of the SHS-GC-IMS method was subsequently compared against that of a currently established method, namely, GC-MS, using commercial wine samples. These findings provide an initial validation of a GC-IMS-based quantitation method, as well as a starting point for further enhancing the analytical scope of GC-IMS.

Factors Affecting the Response to First-Line Treatments in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BACKGROUND AND PURPOSE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study aimed to explore the possible factors affecting the response to first-line treatments in patients with anti-NMDAR encephalitis. METHODS: We enrolled 29 patients who were diagnosed as anti-NMDAR encephalitis between January 1, 2015, and June 30, 2018. They were divided into the remission and nonremission groups according to their response to first-line treatments. The demographics, clinical manifestations, main ancillary examinations, follow-up treatments, and prognosis of patients were recorded. The symptoms reported on in this study occurred before treatments or during the course of first-line treatments. RESULTS: There were 18 patients (62.07%) in the remission group and 11 patients (37.93%) in the nonremission group. Compared to the remission group, a higher proportion of the patients in the nonremission group exhibited involuntary movements, decreased consciousness, central hypoventilation, lung infection, and hypoalbuminemia. The nonremission group had a high incidence of increased intracranial pressure and significant elevations of the neutrophil-to-lymphocyte ratio in peripheral blood (NLR), aspartate aminotransferase, and fibrinogen. Six patients (54.55%) in the nonremission group received second-line immunotherapy. Only one patient (3.45%) died, which was due to multiple-organ failure. CONCLUSIONS: Anti-NMDAR-encephalitis patients with more symptoms-especially involuntary movements, disturbance of consciousness, central hypoventilation, and accompanying hypoalbuminemia and pulmonary infection-may respond poorly to first-line treatments. Positive second-line immunotherapy therefore needs to be considered. Admission to an intensive-care unit, increased cerebrospinal fluid pressure, and increased NLR might be the significant factors affecting the response to first-line treatments.

18F-fluorodeoxyglucose positron emission tomography predicts lymph node responses to definitive chemoradiotherapy in esophageal squamous cell carcinoma patients.

PURPOSE: To evaluate the capability of 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG-PET/CT) to predict the clinical response of metastatic lymph node (mLN) to definitive chemoradiotherapy (dCRT) and guide personalized radiation dose in esophageal squamous cell carcinoma (ESCC) patients. PATIENTS AND METHODS: One hundred and forty-three mLNs from 59 patients with ESCC treated with dCRT and who had undergone a pretreatment 18F-FDG-PET/CT scan were included in the study. All defined mLNs were contoured by nuclear medicine radiologists. Response was evaluated by contrast-enhanced computed tomography and 18F-FDG-PET/CT. RESULTS: Sixty-nine mLNs showed complete response (CR), and 74 mLNs showed non-complete response. The 143 mLNs were divided into 4 groups (Groups 1-4) based on the quartiles of maximum standardized uptake value (SUVmax-G1, SUVmax-G2, SUVmax-G3, and SUVmax-G4) and metabolic tumor volume (MTV-G1, MTV-G2, MTV-G3, and MTV-G4). The CR rate of SUVmax-G2 was significantly higher than the other 3 groups. The escalated radiation dose improved the CR rate of lymph nodes in SUVmax-G3 (55 Gy) and SUVmax-G4 (61 Gy). The lowest CR rate was found in MTV-G4 (the group with the largest MTV). The escalated radiation dose (59.7 Gy) improved the CR rate of lymph node in MTV-Groups 3 and 4. CONCLUSION: Pretreatment metabolic parameters can predict the response of mLNs to dCRT for patients with ESCC. The parameters could also be used to guide personalized dose to mLNs.

Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia/macrophage polarization through the IL-10/GSK3ß/PTEN axis.

Inflammation mediated by the peripheral infiltration of inflammatory cells plays an important role in intracerebral hemorrhage (ICH) induced secondary injury. Previous studies have indicated that regulatory T lymphocytes (Tregs) might reduce ICH-induced inflammation, but the precise mechanisms that contribute to ICH-induced inflammatory injury remain unclear. Our results show that the number of Tregs in the brain increases after ICH. Inducing Tregs deletion using a CD25 antibody or Foxp3DTR-mice increased neurological deficient scores (NDS), the level of inflammatory factors, hematoma volumes, and neuronal degeneration. Meanwhile, boosting Tregs using a CD28 super-agonist antibody reduced the inflammatory injury. Furthermore, Tregs depletion shifted microglia/macrophage polarization toward the M1 phenotype while boosting Tregs shifted this transition toward the M2 phenotype. In vitro, a transwell co-culture model of microglia and Tregs indicated that Tregs changed the polarization of microglia, decreased the expression of MHC-II, IL-6, and TNF-α and increased CD206 expression. IL-10 originating from Tregs mediated the microglia polarization by increasing the expression of Glycogen Synthase Kinase 3 beta (GSK3ß), which phosphorylates and inactivates Phosphatase and Tensin homologue (PTEN) in microglia, TGF-ß did not participate in this conversion. Thus, Tregs ameliorated ICH-induced inflammatory injury by modulating microglia/macrophage polarization toward the M2 phenotype through the IL-10/GSK3ß/PTEN axis.

Association of CYP2C19 Polymorphisms with the Clinical Efficacy of Clopidogrel Therapy in Patients Undergoing Carotid Artery Stenting in Asia.

The CYP2C19 gene plays a detrimental role in the metabolism of clopidogrel. This study aimed to investigate the association between CYP2C19 polymorphisms and the clinical efficacy of clopidogrel therapy in patients who have undergone carotid artery stenting (CAS). CYP2C19 genotype screening was performed on 959 ischemic stroke patients. Of these patients, 241 who had undergone CAS were enrolled in the study. They were all followed up for 1 year after stent surgery, and the primary clinical end-points were ischemic events. The frequencies of the CYP2C19*2 and *3 alleles among the 959 patients were 31.80% and 5.06%, respectively. Regarding the 241 participants who had undergone CAS, multivariate Cox regression analysis showed that the CYP2C19 loss-of-function (LOF) alleles (*2 and *3) were risk factors for post-CAS prognosis. Within 1 year of follow-up, the patients carrying the CYP2C19 LOF alleles were more likely to experience ischemic events than those carrying none. The occurrence of ischemic events did not significantly differ between the *2 and *3 allele carriers. Our results suggest that CYP2C19 LOF alleles (*2 and *3) significantly impact the prognosis of patients on clopidogrel therapy after CAS and that the CYP2C19*2 and CYP2C19*3 alleles have the same effects on prognosis.

Interleukin-23 Secreted by Activated Macrophages Drives γδT Cell Production of Interleukin-17 to Aggravate Secondary Injury After Intracerebral Hemorrhage.

BACKGROUND: Neuroinflammation plays a key role in intracerebral hemorrhage (ICH)-induced secondary brain injury, but the specific roles of peripheral inflammatory cells such as macrophages and lymphocytes remain unknown. The purpose of this study was to explore the roles of macrophages, T lymphocytes, and the cytokines they secrete as potential targets for treating secondary brain injury after ICH. METHODS AND RESULTS: Our results showed that peripheral macrophages and T lymphocytes successively infiltrated the brain, with macrophage counts peaking 1 day after ICH and T-lymphocyte counts peaking after 4 days. These peaks in cellular infiltration corresponded to increases in interleukin (IL)-23 and IL-17 expression, respectively. We found that hemoglobin from the hematoma activated IL-23 secretion by infiltrating macrophages by inducing the formation of toll-like receptor (TLR) 2/4 heterodimer. This increased IL-23 expression stimulated γδT-cell production of IL-17, which increased brain edema and neurologic deficits in the model mice as a proinflammatory factor. Finally, we found that sparstolonin B (SsnB) could ameliorate brain edema and neurologic deficits in ICH model mice via inhibition of TLR2/TLR4 heterodimer formation, and notably, SsnB interacted with myeloid differentiation factor 88 Arg196. CONCLUSIONS: Together, our results reveal the importance of the IL-23/IL-17 inflammatory axis in secondary brain injury after ICH and thus provide a new therapeutic target for ICH treatment.