Trideuteromethylthiolation through Reaction of Arynes, S-Methyl-d3 Sulfonothioate with Sulfonamides or Amides: Access to Trideuteromethylated Sulfilimines.

A direct and practical three-component tandem reaction of arynes, S-methyl-d3 sulfonothioate with sulfonamides or amides is developed. The reaction is highly efficient and chemoselective, which allows mild synthesis of trideuteromethylated sulfilimines with broad substrate scope and good functional group compatibility, giving the products in good to excellent yields with 92%-99% deuterium incorporation. Mechanism studies disclosed sulfenamide that generated in situ is the key intermediate for the reaction. This protocol provides potential method for introduction of -SCD3 moiety for deuteration of marked drugs and drug candidates containing sulfilimine skeleton.

Multimodal MRI-based deep-radiomics model predicts response in cervical cancer treated with neoadjuvant chemoradiotherapy.

Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative treatment approach for cervical cancer (CC) in stage Ib2-IIb, who had a strong desire to be treated with surgery. Our study aims to develop a model based on multimodal MRI by using radiomics and deep learning to predict the treatment response in CC patients treated with neoadjuvant chemoradiotherapy (NACRT). From August 2009 to June 2013, CC patients in stage Ib2-IIb (FIGO 2008) who received NACRT at Fujian Cancer Hospital were enrolled in our study. Clinical information, contrast-enhanced T1-weighted imaging (CE-T1WI), and T2-weighted imaging (T2WI) data were respectively collected. Radiomic features and deep abstract features were extracted from the images using radiomics and deep learning models, respectively. Then, ElasticNet and SVM-RFE were employed for feature selection to construct four single-sequence feature sets. Early fusion of two multi-sequence feature sets and one hybrid feature set were performed, followed by classification prediction using four machine learning classifiers. Subsequently, the performance of the models in predicting the response to NACRT was evaluated by separating patients into training and validation sets. Additionally, overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier survival curves. Among the four machine learning models, SVM exhibited the best predictive performance (AUC=0.86). Among the seven feature sets, the hybrid feature set achieved the highest values for AUC (0.86), ACC (0.75), Recall (0.75), Precision (0.81), and F1-score (0.75) in the validation set, outperforming other feature sets. Furthermore, the predicted outcomes of the model were closely associated with patient OS and DFS (p = 0.0044; p = 0.0039). A model based on MRI images with features from multiple sequences and different methods could precisely predict the response to NACRT in CC patients. This model could assist clinicians in devising personalized treatment plans and predicting patient survival outcomes.

Synthesis of Sulfilimines via Multicomponent Reaction of Arynes, Sulfamides, and Thiosulfonates.

In this work, a facile and efficient method for the synthesis of sulfilimines through multicomponent reaction of arynes, sulfamides, and thiosulfonates was developed. A variety of structurally diverse substrates and functional groups were very compatible in the reaction, giving the corresponding sulfilimines in good to high yields. This protocol could be conducted on a gram scale, and the product was easily converted to sulfide and sulfoximine. Mechanism studies revealed that sulfenamide generated in situ is the key intermediate for the reaction.

Study on chest injury and bulletproof vest protection under the combined action of blast wave and fragments.

Using a simulation based method, this paper analysis the damage effect of blast wave and fragments on human body and the protective effect of bulletproof vest. The results show that compared with the single blast shock wave, the chest injury is more serious under the combined action of blast shock wave and fragments. The peak stress of sternum, costal cartilage and rib increases by 334.34%, 170.23% and 39.72%, respectively. The peak stress on the side of the lung decreases by 3.95%, with little change. The peak stress on the front and back of the lung increases by 83.58% and 409.09% respectively. Overall, the lung injury is aggravated. With the addition of the bulletproof vest, the damage caused by fragments is reduced, and the peak stress of the sternum and the costal cartilage decreases by 48.77% and 69.78%, respectively. Due to the interaction of the blast wave with the vest and the chest, the damage caused by blast wave is aggravated. The peak stress of rib increases by 13.55%, and the peak stress of lung front, side and back increases by 1.22%, 6.51% and 3.57%, respectively.

Experimental and numerical analysis of biomechanical effects in cervical spine positioning rotation manipulation.

Unlocking the biomechanical effects of cervical spine positioning rotation manipulation in the treatment of patients with neck pain. In this paper, the safety of the cervical positioning rotation manipulation is analyzed by experimentally obtaining head kinematic data, importing them into a finite element model that has been developed and validated, and calculating and analyzing the angular displacements, disc pressures, and articular surface contact forces in the normal and pathological models. The results show that the cervical spine positioning rotation technique is more effective in adjusting the position and applying force to the cervical spine C5-C6 "tendon out of the groove and bone misalignment" pathological model. Also, the cervical positioning rotation manipulation is applied with less variation in disc nucleus pulposus pressure than in the non-positioning situation. Thus, in patients with disc degeneration, cervical positioning rotational manipulation has a more direct mechanical effect and is safer than non-positioning rotational manipulation. The cervical spine positioning rotation manipulation is a safe method that can effectively treat patients with neck pain. It has been well demonstrated in the computational analysis of the pathological model.

Study on protective performance and gradient optimization of helmet foam liner under bullet impact.

Protective equipment in war plays a vital role in the safety of soldiers, the threat to soldiers from brain damage caused by deformation at the back of the helmet cannot be ignored, so research on reduce blunt post-cranial injury has great significance and value. This study first conducted gunshot experiments, used rifle bullets impact bulletproof plate and different density liner foam to record the incident process and internal response of craniocerebral model. After verifying the accuracy of finite element model through experimental data, optimization model is established based on response surface method to optimize the structure of gradient foam, analyze the cranial strain and energy absorption to select the best density and thickness distribution of each foam layer. Optimization results show that liner foam which designed to have lower density and thicker thickness for impact and brace layers, higher density and thinner thickness for middle layer can significantly improve the energy absorption efficiency. Compared to the 40.65 J of energy absorption before optimization, the optimized gradient foam can absorb 109.3 J of energy, with a 169% increase in the absorption ratio. The skull strain in the craniocerebral model was reduced from 1.260 × 10-2 to 1.034 × 10-2, with a reduction of about 22%. This study provides references for the design and development of protective equipment and plays an important role in ensuring the safety of soldiers in the battlefield environment.

Experimental Study on Intracranial Pressure and Biomechanical Response in Rats under the Blast Wave.

Explosion overpressure propagates extracranially and causes craniocerebral injury after being transmitted into the brain. Studies on the extent of skull to reduce impact overpressure are still lacking. Therefore, it is necessary to study the relationship between intracranial pressure (ICP) and external field pressure and the situation of craniocerebral injury under the blast wave. Pressure sensor of ϕ 1.2 mm was disposed 3 mm posterior to the bregma of rat skull, and type I biological shock tube (BST-I) was used as the source of injury while a side-on air pressure sensor was installed at the horizontal position of the ICP sensor. Eleven groups of blast experiments with peak air overpressure ranging from 167 kPa to 482 kPa were performed to obtain the variation law of ICP and injury of rats. Data measured by sensors show that the peak pressure formed in the rat brain are lower than the external air overpressure; the differential pressure between the inside and outside of the brain is 27-231 kPa. When side-on air overpressure is ≤363 kPa, ICP is ≤132 kPa, and the hemorrhage area of the rat's brain is <15%, the injury is minor. When side-on air overpressure is 363 kPa-401 kPa, ICP range is from 132 kPa to 248 kPa, hemorrhage area is about 15%-20%, and the injury increases. When side-on air overpressure is 401 kPa-435 kPa, ICP range from 248 kPa to 348 kPa, the hemorrhage area is about 20%-24%, and the injury is serious. When side-on air overpressure ≥482 kPa, the peak ICP surged to 455 kPa and the peak negative ICP reached -84 kPa, the hemorrhage area exceeded 26%. When the external blast wave is weak, skull can absorb the blast wave better, reducing the pressure by 81.4%, when the external shockwave is strong, skull only reduces the pressure by 5.6%, but both can play certain protective role. The fitting curve of air overpressure and ICP can be used to predict the changes of ICP under different external blast overpressure. Analysis of cranial injury showed that the area of cranial hemorrhage with extremely severe injury increased by 107.9% compared with mild injury, increased by 53.3% compared with moderate injury, and increased by 21.6% compared with severe injury. This work may provide references for the dynamic response of biological cranial and brain injury mechanism under the effect of blast wave.

The organocatalytic synthesis of perfluorophenylsulfides via the thiolation of trimethyl(perfluorophenyl)silanes and thiosulfonates.

The organic superbase t-Bu-P4-catalyzed direct thiolation of trimethyl(perfluorophenyl)silanes and thiosulfonates was developed. Yields of perfluorophenylsulfides of up to 97% under catalysis of 5 mol% t-Bu-P4 were achieved. This method was shown to provide an efficient way to construct the perfluorophenyl-sulfur bond under mild metal-free reaction conditions.

Whole-body hyperthermia combined with chemotherapy and intensity-modulated radiotherapy for treatment of advanced nasopharyngeal carcinoma: a retrospective study with propensity score matching.

BACKGROUND: Several studies have reported the combination of intracavity or cervical lymph node hyperthermia with chemoradiotherapy (CRT) to improve clinical outcomes in nasopharyngeal carcinoma (NPC), but the combination with whole-body hyperthermia (WBH) for treating NPC is unexplored. We aimed to assess the efficacy of the combination of radiotherapy, chemotherapy and WBH in patients with locoregionally advanced NPC. METHODS: Between July 2008 and November 2012, 239 newly diagnosed NPC patients were enrolled in a pre-propensity score-matched cohort, including 193 patients who received CRT (CRT group) and 46 who underwent CRT with WBH (HCRT group). The feasibility and clinical outcomes of both groups were evaluated and toxicities assessed. Survival rates were assessed using the Kaplan-Meier method, log-rank test and Cox regression. RESULTS: Following propensity score matching, 46 patients from each group were included. The 5-year overall survival (OS) rates were 65.2% in the CRT group and 80.3% in the HCRT group (p=.027). In contrast, the other survival outcomes at 5 years were similar between the groups: locoregional recurrence-free survival (LRRFS), 74.7% vs. 87.6% (p=.152); distant metastasis-free survival (DMFS), 67.4% vs. 77.9% (p=.125); and progression-free survival (PFS), 53.1% vs. 69.2% (p=.115). In the multivariate analyses, the only two independent predictors of OS were clinical stage and HCRT. CONCLUSIONS: These results suggest that WBH, when combined with CRT, can improve the OS of patients with advanced NPC.

Craniocerebral Dynamic Response and Cumulative Effect of Damage Under Repetitive Blast.

Soldiers suffer from multiple explosions in complex battlefield environment resulting in aggravated brain injuries. At present, researches mostly focus on the damage to human body caused by single explosion. In the repetitive impact study, small animals are mainly used for related experiments to study brain nerve damage. No in-depth research has been conducted on the dynamic response and damage of human brain under repetitive explosion shock waves. Therefore, this study use the Euler-Lagrange coupling method to construct an explosion shock wave-head fluid-structure coupling model, and numerically simulated the brain dynamic response subjected to single and repetitive blast waves, obtained flow field pressure, skull stress, skull displacement, intracranial pressure to analyze the brain damage. The simulation results of 100 g equivalent of TNT exploding at 1 m in front of the craniocerebral show that repetitive blast increase skull stress, intracranial pressure, skull displacement, and the damage of brain tissue changes from moderate to severe. Repetitive blasts show a certain cumulative damage effect, the severity of damage caused by double blast is 122.5% of single shock, and the severity of damage caused by triple blast is 105.9% of double blast and 131.5% of single blast. The data above shows that it is necessary to reduce soldiers' exposure from repetitive blast waves.

Direct Assembly of Polysubstituted Naphthalenes via a Tandem Reaction of Benzynes and α-Cyano-ß-methylenones.

A mild and transition-metal-free benzannulation reaction for the construction of the naphthalene skeleton has been described. Benzynes react with α-cyano-ß-alkylenones through a tandem nucleophilic addition/cyclization/aromatization process to afford polysubstituted naphthalenes in 50-94% yields.

A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a dismal long-term outcome. We aimed to construct a multi-gene model for prognosis prediction to inform HCC management. The cancer-specific differentially expressed genes (DEGs) were identified using RNA-seq data of paired tumor and normal tissue. A prognostic signature was built by LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to further understand the underlying molecular mechanisms. A 10-gene signature was constructed to stratify the TCGA and ICGC cohorts into high- and low-risk groups where prognosis was significantly worse in the high-risk group across cohorts (P < 0.001 for all). The 10-gene signature outperformed all previously reported models for both C-index and the AUCs for 1-, 3-, 5-year survival prediction (C-index, 0.84 vs 0.67 to 0.73; AUCs for 1-, 3- and 5-year OS, 0.84 vs 0.68 to 0.79, 0.81 to 0.68 to 0.80, and 0.85 vs 0.67 to 0.78, respectively). Multivariate Cox regression analysis revealed risk group and tumor stage to be independent predictors of survival in HCC. A nomogram incorporating tumor stage and signature-based risk group showed better performance for 1- and 3-year survival than for 5-year survival. GSEA revealed enrichment of pathways related to cell cycle regulation among high-risk samples and metabolic processes in the low-risk group. Our 10-gene model is robust for prognosis prediction and may help inform clinical management of HCC.

Multicomponent Reaction of Phosphines, Benzynes, and CO2: Facile Synthesis of Stable Zwitterionic Phosphonium Inner Salts.

The first synthesis of benzyne-derived stable zwitterions is reported. Benzynes generated in situ from 2-(trimethylsilyl)aryl triflates undergo a multicomponent reaction with phosphines and CO2 to produce the stable 1,5-zwitterionic species in moderate to excellent isolated yields, which provides a novel method for the preparation of phosphonium inner salts under mild and transition-metal-free conditions.

Study on Behind Helmet Blunt Trauma Caused by High-Speed Bullet.

The mechanism of Behind Helmet Blunt Trauma (BHBT) caused by a high-speed bullet is difficult to understand. At present, there is still a lack of corresponding parameters and test methods to evaluate this damage effectively. The purpose of the current study is therefore to investigate the response of the human skull and brain tissue under the loading of a bullet impacting a bullet-proof helmet, with the effects of impact direction, impact speed, and impactor structure being considered. A human brain finite element model which can accurately reconstruct the anatomical structures of the scalp, skull, brain tissue, etc., and can realistically reflect the biomechanical response of the brain under high impact speed was employed in this study. The responses of Back Face Deformation (BFD), brain displacement, skull stress, and dura mater pressure were extracted from simulations as the parameters reflecting BHBT risk, and the relationships between BHBT and bullet-proof equipment structure and performance were also investigated. The simulation results show that the frontal impact of the skull produces the largest amount of BFD, and when the impact directions are from the side, the skull stress is about twice higher than other directions. As the impact velocity increases, BFD, brain displacement, skull stress, and dura mater pressure increase. The brain damage caused by different structural bullet bodies is different under the condition of the same kinetic energy. The skull stress caused by the handgun bullet is the largest. The findings indicate that when a bullet impacts on the bullet-proof helmet, it has a higher probability of causing brain displacement and intracranial high pressure. The research results can provide a reference value for helmet optimization design and antielasticity evaluation and provide the theoretical basis for protection and rescue.

Sparse Feature Learning of Hyperspectral Imagery via Multiobjective-Based Extreme Learning Machine.

Hyperspectral image (HSI) consists of hundreds of narrow spectral band components with rich spectral and spatial information. Extreme Learning Machine (ELM) has been widely used for HSI analysis. However, the classical ELM is difficult to use for sparse feature leaning due to its randomly generated hidden layer. In this paper, we propose a novel unsupervised sparse feature learning approach, called Evolutionary Multiobjective-based ELM (EMO-ELM), and apply it to HSI feature extraction. Specifically, we represent the task of constructing the ELM Autoencoder (ELM-AE) as a multiobjective optimization problem that takes the sparsity of hidden layer outputs and the reconstruction error as two conflicting objectives. Then, we adopt an Evolutionary Multiobjective Optimization (EMO) method to solve the two objectives, simultaneously. To find the best solution from the Pareto solution set and construct the best trade-off feature extractor, a curvature-based method is proposed to focus on the knee area of the Pareto solutions. Benefited from the EMO, the proposed EMO-ELM is less prone to fall into a local minimum and has fewer trainable parameters than gradient-based AEs. Experiments on two real HSIs demonstrate that the features learned by EMO-ELM not only preserve better sparsity but also achieve superior separability than many existing feature learning methods.

Effect of osteoporosis on internal fixation after spinal osteotomy: A finite element analysis.

BACKGROUND: Severe kyphotic deformity can affect the quality of life of the elderly and is commonly treated by an osteotomy. Considering that the elderly often suffer from osteoporosis, the safety and efficacy of internal fixation are particularly important. The aim of this study was to analyse the effect of osteoporosis on internal fixation after spinal osteotomy. METHODS: One patient with a thoracolumbar kyphotic deformity who underwent spinal osteotomy was included. The CT images of the entire spine were used to construct a finite element model of the spine internal fixation after osteotomy. Material parameters were assigned to osteoporosis and normal bone groups, and the loads were used to simulate different working conditions, including axial compression, flexion, extension and lateral bending. FINDINGS: Compared with normal bone mass, the pressure on osteotomized vertebrae was reduced by 8.32%, 1.92%, 36.79% and 79.80% in mild osteoporosis model during axial compression, flexion, extension and lateral bending, respectively. The pressure on screws and rods was increased in an osteoporosis model under axial compression. During flexion and lateral bending, the pressure on screws was increased but was decreased on rods. The opposite result was found during extension. With the degree of osteoporosis increases, the change of stress is more obvious. INTERPRETATION: Under different bone mass conditions, the distribution patterns of stress in vertebrae, screws and rods were relatively similar. Collectively, the stress levels of vertebral bone were decreased and the stress levels of the screw/rod system were increased in an osteoporosis model compared to a normal bone model. Hence, osteoporosis may increase the risk of fracture and internal fixation failure.

Development of a Three-Dimensional Finite Element Model of Thoracolumbar Kyphotic Deformity following Vertebral Column Decancellation.

BACKGROUND: Vertebral column decancellation (VCD) is a new spinal osteotomy technique to correct thoracolumbar kyphotic deformity (TLKD). Relevant biomechanical research is needed to evaluate the safety of the technique and the fixation system. We aimed to develop an accurate finite element (FE) model of the spine with TLKD following VCD and to provide a reliable model for further biomechanical analysis. METHODS: A male TLKD patient who had been treated with VCD on L2 and instrumented from T10 to L4 was a volunteer for this study. The CT scanning images of the postoperative spine were used for model development. The FE model, simulating the spine from T1 to the sacrum, includes vertebrae, intervertebral discs, spinal ligaments, pedicle screws, and rods. The model consists of 509580 nodes and 445722 hexahedrons. The ranges of motion (ROM) under different loading conditions were calculated for validation. The stresses acting on rods, screws, and vertebrae were calculated. RESULTS: The movement trend, peak stress, and ROM calculated by the current FE model are consistent with previous studies. The FE model in this study is able to simulate the mechanical response of the spine during different motions with different loading conditions. Under axial compression, the rod was the part bearing the peak stress. During flexion, the stress was concentrated on proximal pedicle screws. Under extension and lateral bending, an osteotomized L1 vertebra bore the greatest stress on the model. During tests, ligament disruption and unit deletion were not found, indicating an absence of fracture and fixation breakage. DISCUSSION: A subject-specific FE model of the spine following VCD is developed and validated. It can provide a reliable and accurate digital platform for biomechanical analysis and surgical planning.

Rhodium(I)-Catalyzed Aryl C-H Carboxylation of 2-Arylanilines with CO2.

An unprecedented Rh(I)-catalyzed, amino-group-assisted C-H carboxylation of 2-arylanilines with CO2 under redox-neutral conditions has been developed. This reaction was promoted by a phosphine ligand with t-BuOK as the base and did not require the use of additional strong organometallic reagent. It enabled an efficient direct conversion of a broad range of 2-(hetero)arylanilines including electron-deficient heteroarenes to various phenanthridinones. Possible intermediates of the reaction were also evaluated in the preliminary mechanistic studies.

An unsupervised parameter learning model for RVFL neural network.

With the direct input-output connections, a random vector functional link (RVFL) network is a simple and effective learning algorithm for single-hidden layer feedforward neural networks (SLFNs). RVFL is a universal approximator for continuous functions on compact sets with fast learning property. Owing to its simplicity and effectiveness, RVFL has attracted significant interest in numerous real-world applications. In reality, the performance of RVFL is often challenged by randomly assigned network parameters. In this paper, we propose a novel unsupervised network parameter learning method for RVFL, named sparse pre-trained random vector functional link (SP-RVFL for short) network. The proposed SP-RVFL uses a sparse autoencoder with ℓ1-norm regularization to adaptively learn superior network parameters for specific learning tasks. By doing so, the learned network parameters in SP-RVFL are embedded with the valuable information of input data, which alleviate the randomly generated parameter issue and improve the algorithmic performance. Experiments and comparisons on 16 diverse benchmarks from different domains confirm the effectiveness of the proposed SP-RVFL. The corresponding results also demonstrate that RVFL outperforms extreme learning machine (ELM).

Creating a human head finite element model using a multi-block approach for predicting skull response and brain pressure.

To better understand head injuries, human head finite element (FE) models have been reported in the literature. In scenarios where the head is directly impacted and measurements of head accelerations are not available, a high-quality skull model, as well as a high-quality brain model, is needed to predict the effect of impact on the brain through the skull. Furthermore, predicting cranial bone fractures requires comprehensively validated skull models. Lastly, high-quality meshes for both the skull and brain are needed for accurate strain/stress predictions across the entire head. Hence, we adopted a multi-block approach to develop hexahedral meshes for the brain, skull, and scalp simultaneously, a first approach in its kind. We then validated our model against experimental data of brain pressures (Nahum et al., 1977 ) and comprehensive skull responses (Yoganandan et al., 1995 , Yoganandan et al., 2004 , and Raymond et al., 2009 ). We concluded that a human head FE model was developed with capabilities to predict blunt- and ballistic-impact-induced skull fractures and pressure-related brain injuries.