Clinically relevant immune subtypes based on alternative splicing landscape of immune-related genes for lung cancer advanced PPPM approach.

Background: Alternative splicing (AS) occurs in the process of gene post-transcriptional process, which is very important for the correct synthesis and function of protein. The change of AS pattern may lead to the change of expression level or function of lung cancer-related genes, and then affect the occurrence and development of lung cancers. The specific AS pattern might be used as a biomarker for early warning and prognostic assessment of a cancer in the framework of predictive, preventive, and personalized medicine (PPPM; 3PM). AS events of immune-related genes (IRGs) were closely associated with tumor progression and immunotherapy. We hypothesize that IRG-AS events are significantly different in lung adenocarcinomas (LUADs) vs. controls or in lung squamous cell carcinomas (LUSCs) vs. controls. IRG-AS alteration profiling was identified to construct IRG-differentially expressed AS (IRG-DEAS) signature models. Study on the selective AS events of specific IRGs in lung cancer patients might be of great significance for further exploring the pathogenesis of lung cancer, realizing early detection and effective monitoring of lung cancer, finding new therapeutic targets, overcoming drug resistance, and developing more effective therapeutic strategies, and better used for the prediction, diagnosis, prevention, and personalized medicine of lung cancer. Methods: The transcriptomic, clinical, and AS data of LUADs and LUSCs were downloaded from TCGA and its SpliceSeq databases. IRG-DEAS events were identified in LUAD and LUSC, followed by their functional characteristics, and overall survival (OS) analyses. OS-related IRG-DEAS prognostic models were constructed for LUAD and LUSC with Lasso regression, which were used to classify LUADs and LUSCs into low- and high-risk score groups. Furthermore, the immune cell distribution, immune-related scores, drug sensitivity, mutation status, and GSEA/GSVA status were analyzed between low- and high-risk score groups. Also, low- and high-immunity clusters and AS factor (SF)-OS-related-AS co-expression network and verification of cell function of CELF6 were analyzed in LUAD and LUSC. Results: Comprehensive analysis of transcriptomic, clinical, and AS data of LUADs and LUSCs identified IRG-AS events in LUAD (n = 1607) and LUSC (n = 1656), including OS-related IRG-AS events in LUAD (n = 127) and LUSC (n = 105). A total of 66 IRG-DEAS events in LUAD and 89 IRG-DEAS events in LUSC were identified compared to controls. The overlapping analysis between IRG-DEASs and OS-related IRG-AS events revealed 14 OS-related IRG-DEAS events for LUAD and 16 OS-related IRG-DEAS events for LUSC, which were used to identify and optimize a 12-OS-related-IRG-DEAS signature prognostic model for LUAD and an 11-OS-related-IRG-DEAS signature prognostic model for LUSC. These two prognostic models effectively divided LUAD or LUSC samples into low- and high-risk score groups that were closely associated with OS, clinical characteristics, and tumor immune microenvironment, with significant gene sets and pathways enriched in the two groups. Moreover, weighted gene co-expression network (WGCNA) and nonnegative matrix factorization method (NMF) analyses identified four OS-relevant subtypes of LUAD and six OS-relevant subtypes of LUSC, and ssGSEA identified five immunity-relevant subtypes of LUAD and five immunity-relevant subtypes of LUSC. Interestingly, splicing factors-OS-related-AS network revealed hub molecule CELF6 was significantly related to the malignant phenotype in lung cancer cells. Conclusions: This study established two reliable IRG-DEAS signature prognostic models and constructed interesting splicing factor-splicing event networks in LUAD and LUSC, which can be used to construct clinically relevant immune subtypes, patient stratification, prognostic prediction, and personalized medical services in the PPPM practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00366-4.

Expediting Ethylbenzene Oxidation via a Bimetallic Cobalt-Manganese Spinel Structure with a Modulated Electronic Environment.

The catalytic oxidation of ethylbenzene (EB) into acetophenone (AP) is a vibrant area, with a growing number of researchers paying attention to this thematic investigation. Herein, we demonstrate that spinel-type (Co,Mn)(Co,Mn)2O4 can function as an efficient catalyst for the solvent-free oxidation of EB with molecular oxygen. The incorporation of Mn into the Co3O4 network can break the local structural symmetry of Co-O-Co linkages due to the bond competition, inducing the formation of an asymmetrical Co-O-Mn configuration with an electron local exchange interaction. The Co-O-Mn sites can facilitate the perturbation of nonpolar O2 and thus contribute to the generation of abundant •O2- species for initiating the oxidation of EB. We envision that this study not only provides a promising catalyst for EB oxidation but also affords a new insight into the design of advanced spinel oxides for selective oxidation reactions.

Treatment of hospital wastewater by electron beam technology: Removal of COD, pathogenic bacteria and viruses.

The effective treatment of hospital sewage is crucial to human health and eco-environment, especially during the pandemic of COVID-19. In this study, a demonstration project of actual hospital sewage using electron beam technology was established as advanced treatment process during the outbreak of COVID-19 pandemic in Hubei, China in July 2020. The results indicated that electron beam radiation could effectively remove COD, pathogenic bacteria and viruses in hospital sewage. The continuous monitoring date showed that the effluent COD concentration after electron beam treatment was stably below 30 mg/L, and the concentration of fecal Escherichia coli was below 50 MPN/L, when the absorbed dose was 4 kGy. Electron beam radiation was also an effective method for inactivating viruses. Compared to the inactivation of fecal Escherichia coli, higher absorbed dose was required for the inactivation of virus. Absorbed dose had different effect on the removal of virus. When the absorbed dose ranged from 30 to 50 kGy, Hepatitis A virus (HAV) and Astrovirus (ASV) could be completely removed by electron beam treatment. For Rotavirus (RV) and Enterovirus (EV) virus, the removal efficiency firstly increased and then decreased. The maximum removal efficiency of RV and EV was 98.90% and 88.49%, respectively. For the Norovirus (NVLII) virus, the maximum removal efficiency was 81.58%. This study firstly reported the performance of electron beam in the removal of COD, fecal Escherichia coli and virus in the actual hospital sewage, which would provide useful information for the application of electron beam technology in the treatment of hospital sewage.

Current developments of robotic hip exoskeleton toward sensing, decision, and actuation: A review.

The aging population is now a global challenge, and impaired walking ability is a common feature in the elderly. In addition, some occupations such as military and relief workers require extra physical help to perform tasks efficiently. Robotic hip exoskeletons can support ambulatory functions in the elderly and augment human performance in healthy people during normal walking and loaded walking by providing assistive torque. In this review, the current development of robotic hip exoskeletons is presented. In addition, the framework of actuation joints and the high-level control strategy (including the sensors and data collection, the way to recognize gait phase, the algorithms to generate the assist torque) are described. The exoskeleton prototypes proposed by researchers in recent years are organized to benefit the related fields realizing the limitations of the available robotic hip exoskeletons, therefore, this work tends to be an influential factor with a better understanding of the development and state-of-the-art technology.

Neck circumference and waist circumference associated with cardiovascular events in type 2 diabetes (Beijing Community Diabetes Study 23).

Obesity increases the risk of developing cardiovascular disease and other metabolic diseases. We intended to compare three different anthropometric indicators of obesity, in predicting the incidence of cardiovascular events in Chinese type 2 diabetes. Beijing Community Diabetes Study was a prospective multi-center study conducted in Beijing community health centers. Type 2 diabetes patients from fourteen community health centers were enrolled at baseline. The primary endpoint was cardiovascular events. The upper quartile of neck circumference (NC) was set as greater NC. A total of 3299 diabetes patients were enrolled. In which, 941 (28.52%) had cardiovascular disease at baseline. Logistic analysis showed that central obesity (waist circumference (WC) above 90 cm in men and 85 cm in women) and greater NC were all related to baseline cardiovascular disease (adjusted OR = 1.49, and 1.55). After 10-year follow-up, 340 (10.31%) had cardiovascular events. Compared with patients without cardiovascular events, those having cardiovascular events had higher BMI, larger WC and NC. Cox regression analysis showed that greater WC and NC were all associated with the occurrence of cardiovascular events (adjusted HR = 1.41, and 1.38). A higher NC and WC might increase the risk of cardiovascular events by about 40% in type 2 diabetes patients in Beijing communities.

A data-driven respiratory motion estimation approach for PET based on time-of-flight weighted positron emission particle tracking.

PURPOSE: Respiratory motion of patients during positron emission tomography (PET)/computed tomography (CT) imaging affects both image quality and quantitative accuracy. Hardware-based motion estimation, which is the current clinical standard, requires initial setup, maintenance, and calibration of the equipment, and can be associated with patient discomfort. Data-driven techniques are an active area of research with limited exploration into lesion-specific motion estimation. This paper introduces a time-of-flight (TOF)-weighted positron emission particle tracking (PEPT) algorithm that facilitates lesion-specific respiratory motion estimation from raw listmode PET data. METHODS: The TOF-PEPT algorithm was implemented and investigated under different scenarios: (a) a phantom study with a point source and an Anzai band for respiratory motion tracking; (b) a phantom study with a point source only, no Anzai band; (c) two clinical studies with point sources and the Anzai band; (d) two clinical studies with point sources only, no Anzai band; and (e) two clinical studies using lesions/internal regions instead of point sources and no Anzai band. For studies with radioactive point sources, they were placed on patients during PET/CT imaging. The motion tracking was performed using a preselected region of interest (ROI), manually drawn around point sources or lesions on reconstructed images. The extracted motion signals were compared with the Anzai band when applicable. For the purposes of additional comparison, a center-of-mass (COM) algorithm was implemented both with and without the use of TOF information. Using the motion estimate from each method, amplitude-based gating was applied, and gated images were reconstructed. RESULTS: The TOF-PEPT algorithm is shown to successfully determine the respiratory motion for both phantom and clinical studies. The derived motion signals correlated well with the Anzai band; correlation coefficients of 0.99 and 0.94-0.97 were obtained for the phantom study and the clinical studies, respectively. TOF-PEPT was found to be 13-38% better correlated with the Anzai results than the COM methods. Maximum Standardized Uptake Values (SUVs) were used to quantitatively compare the reconstructed-gated images. In comparison with the ungated image, a 14-39% increase in the max SUV across several lesion areas and an 8.7% increase in the max SUV on the tracked lesion area were observed in the gated images based on TOF-PEPT. The distinct presence of lesions with reduced blurring effect and generally sharper images were readily apparent in all clinical studies. In addition, max SUVs were found to be 4-10% higher in the TOF-PEPT-based gated images than in those based on Anzai and COM methods. CONCLUSION: A PEPT- based algorithm has been presented for determining movement due to respiratory motion during PET/CT imaging. Gating based on the motion estimate is shown to quantifiably improve the image quality in both a controlled point source phantom study and in clinical data patient studies. The algorithm has the potential to facilitate true motion correction where the reconstruction algorithm can use all data available.

Catalytic ozonation of norfloxacin using Co3O4/C composite derived from ZIF-67 as catalyst.

In this study, Co3O4-carbon composite was synthesized by calcined metal organic framework (MOF) ZIF-67 and used as efficient catalysts for ozonation of norfloxacin (NOF). The MOF-derived Co3O4-C composite remained similar polyhedrons structure of ZIF-67, suggesting that Co3O4 was well-dispersed in Co3O4-C composite. Furthermore, a larger amount of surface carbon-oxygen functional groups were distributed on Co3O4-C composite, which resulted in the diversification of active sites for catalytic ozonation reaction. NOF degradation and mineralization could be effectively enhanced in Co3O4-C/O3 process. Moreover, NOF mineralization by catalytic ozonation strongly depended on the solution pH, while other operational conditions, such as O3 concentration and catalyst dosage had not obvious influence on it. Co3O4-C composite could significantly accelerate O3 decomposition to produce active free radicals (such as •OH), which enhanced the mineralization of NOF. The possible catalytic mechanism of Co3O4-C composite was proposed. Additionally, after five consecutive use of Co3O4-C composite in catalytic ozonation process, there was no obvious decrease in TOC removal efficiency, indicating a stable performance of Co3O4-C composite, which was suitable for the catalytic ozonation for wastewater treatment.

Correlation of serum meteorin-like concentrations with diabetic nephropathy.

OBJECTIVE: Meteorin-like (Metrnl), a secreted myokine, is induced in white adipose tissue during cold exposure and in muscle after exercise. The present investigation aims to determine the hypothesis that serum Metrnl concentrations are correlated with diabetic nephropathy (DN). METHODS: The investigation was performed in a population of 221 patients with type 2 diabetes mellitus (T2DM) and 74 healthy subjects. T2DM patients were divided into three groups: normoalbuminuria (n = 100), microalbuminuria (n = 86), and macroalbuminuria (n = 35) subgroups based on urine albumin to creatinine ratio (ACR). RESULTS: All the three T2DM subgroups showed lower serum Metrnl concentrations compared with the controls. Serum Metrnl concentrations were significantly decreased in T2DM patients with macroalbuminuria group than in the other T2DM subgroups. In addition, T2DM patients with microalbuminuria group had decreased serum Metrnl concentrations compared with those with normoalbuminuria; however, the difference was not significant. Logistic regression analysis demonstrated a correlation between serum Metrnl and a decreased risk of T2DM and DN (OR: 0.954, 95% CI: 0.935-0.973, P < 0.001 and OR: 0.981, 95% CI: 0.971-0.997, P = 0.014, respectively). Simply linear regression analysis indicated a negative association between serum Metrnl and duration of disease, body mass index (BMI), HbA1c, blood urea nitrogen, creatinine, uricacid, ACR, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers treatment. BMI, HbA1c, and ACR were still correlated with the serum Metrnl after a multiple linear regression analysis. CONCLUSION: Serum Metrnl concentrations are inversely correlated with renal function and DN.

Pavement Crack Detection from Mobile Laser Scanning Point Clouds Using a Time Grid.

This paper presents a novel algorithm for detecting pavement cracks from mobile laser scanning (MLS) data. The algorithm losslessly transforms MLS data into a regular grid structure to adopt the proven image-based methods of crack extraction. To address the problem of lacking topology, this study assigns a two-dimensional index for each laser point depending on its scanning angle or acquisition time. Next, crack candidates are identified by integrating the differential intensity and height changes from their neighbors. Then, morphology filtering, a thinning algorithm, and the Freeman codes serve for the extraction of the edge and skeleton of the crack curves. Further than the other studies, this work quantitatively evaluates crack shape parameters: crack direction, width, length, and area, from the extracted crack points. The F1 scores of the quantity of the transverse, longitudinal, and oblique cracks correctly extracted from the test data reached 96.55%, 87.09%, and 81.48%, respectively. In addition, the average accuracy of the crack width and length exceeded 0.812 and 0.897. Experimental results demonstrate that the proposed approach is robust for detecting pavement cracks in a complex road surface status. The proposed method is also promising in serving the extraction of other on-road objects.

Association between Neck Circumference and the Occurrence of Cardiovascular Events in Type 2 Diabetes: Beijing Community Diabetes Study 20 (BCDS-20).

BACKGROUND: Neck circumference (NC) was found to be related to the risk factors of cardiovascular disease. However, the effects of NC on cardiovascular disease are still controversial. A prospective study of Chinese patients with type 2 diabetes was performed to evaluate the relationship between NC and cardiovascular disease. METHODS: A multicenter prospective study with eight-year follow-up was conducted in Beijing communities. Cardiovascular events were defined as myocardial infarction, unstable angina pectoris, hospitalization for heart failure, coronary revascularization, cardiac death, stroke, transient ischemic attack, and cerebral hemorrhage. RESULTS: A total of 3,009 diabetic patients were recruited. Following an eight-year follow-up, 211 patients with cardiovascular events (105 in men and 106 in women) were identified. All patients were categorized into two groups according to the upper quartile of NC (43 cm in men and 39 cm in women). The prevalence of cardiovascular events in men with an NC >43 cm (16.48%) was higher than that in the group with an NC <43 cm (8.16%, p=0.007). The prevalence of cardiovascular events in women with the NC >39 cm (10.67%) was higher compared to the group with NC <39 cm (5.31%, p=0.004). The longitudinal prevalence of cardiovascular events in groups with different NC increased with the increasing duration of follow-up (p < 0.001). Cox regression analysis showed that higher NC was associated with the occurrence of cardiovascular events after adjusting for confounding variables (adjusted HR = 2.305 (1.535-3.460)). CONCLUSIONS: NC was associated with the occurrence of cardiovascular events in type 2 diabetes in Chinese communities, and greater NC may increase the risk of cardiovascular events by about 2.3-fold.

Respiratory Motion Correction Using A Novel Positron Emission Particle Tracking Technique: A Framework Towards Individual Lesion-Based Motion Correction.

Respiratory motion during PET/CT imaging is a matter of concern due to degraded image quality and reduced quantitative accuracy caused by motion artifacts. One class of motion correction methods relies on hardware-based respiratory motion tracking systems in order to use respiratory cycles for correcting motion artifacts. Another class of hardware-free methods extract motion information from the reconstructed images or sinograms. Hardware-based methods, however, are limited by calibration requirement, patient discomfort, lack of adaptability during scanning, presence of electronic drift during respiratory monitoring etc. Extracting motion information from reconstructed images is also limited by the fact that the original raw information requires significant processing before it can be used. Hence the motivation behind this work is to introduce a software-based approach that can be applied on raw 64-bit listmode data. The basic design of the proposed method is based on the fundamentals of Positron Emission Particle Tracking (PEPT) with additional incorporation of Time of Flight (TOF) information. Respiratory motion of patients has been extracted from the raw PET data by tracking a point source attached to the patient in areas on and near the chest. The key objective of this work is to describe a new process by which this particle tracking based motion correction system can eventually be lesion specific and correct the motion for a particular lesion within the patient. This work thus serves as a framework for lesion specific motion correction.

An isocenter estimation tool for proton gantry alignment.

A novel tool has been developed to automate the process of locating the isocenter, center of rotation, and sphere of confusion of a proton therapy gantry. The tool uses a Radian laser tracker to estimate how the coordinate frame of the front-end beam-line components changes as the gantry rotates. The coordinate frames serve as an empirical model of gantry flexing. Using this model, the alignment of the front and back-end beam-line components can be chosen to minimize the sphere of confusion, improving the overall beam positioning accuracy of the gantry. This alignment can be performed without the beam active, improving the efficiency of installing new systems at customer sites.