Tumor microenvironment (TME) has been reported to exhibit a crucial effect in lung cancer. Therefore, this study was aimed to investigate the genes associated with TME and develop a risk score to ...predict the overall survival (OS) of patients with lung adenocarcinoma (LUAD) based on these genes. The immune and stromal scores were generated by the ESTIMATE algorithm for LUAD patients in The Cancer Genome Atlas (TCGA) database. Differentially expressed gene and weighted gene co-expression network analyses were used to derive immune- and stromal-related genes. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression was applied for further selection and the selected genes were inputted into stepwise regression to develop TME-related risk score (TMErisk) which was further validated in Gene Expression Omnibus (GEO) datasets. TMErisk-related biological phenotypes were analyzed in function enrichment, tumor immune signature, and tumor mutation signature. The patient's response to immunotherapy was inferred by the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS). According to our results, TMErisk was developed based on SERPINE1, CX3CR1, CD200R1, GBP1, IRF1, STAP1, LOX, and OR7E47P. Furthermore, high TMErisk was identified as a poor factor for OS in TCGA and GEO datasets, as well as in subgroup analysis with different gender, smoking status, age, race, anatomic site, therapies, and tumor-node-metastasis (TNM) stages. Higher TMErisk is also associated negatively with the abundance of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and other stromal or immune cells. Several genes of the human leukocyte antigen (HLA) family and immune checkpoints were less expressed in the high-TMErisk group. Mutations of 19 genes occurred more frequently in the high-TMErisk group. These mutations may be associated with TME change and indicate patients' response to immunotherapy. According to our analyses, a lower TMErisk score may indicate better response and OS outcome of immunotherapy.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This paper introduces a novel cable-driven robotic platform that enables six degrees-of-freedom (DoF) natural head-neck movements. Poor postural control of the head-neck can be a debilitating symptom ...of neurological disorders such as amyotrophic lateral sclerosis and cerebral palsy. Current treatments using static neck collars are inadequate, and there is a need to develop new devices to empower movements and facilitate physical rehabilitation of the head-neck. State-of-the-art neck exoskeletons using lower DoF mechanisms with rigid linkages are limited by their hard motion constraints imposed on head-neck movements. By contrast, the cable-driven robot presented in this paper does not constrain motion and enables wide-range, 6-DoF control of the head-neck. We present the mechatronic design, validation, and control implementations of this robot, as well as a human experiment to demonstrate a potential use case of this versatile robot for rehabilitation. Participants were engaged in a target reaching task while the robot applied both assistive and resistive moments on the head during the task. Our results show that neck muscle activation increased by 19% when moving the head against resistance and decreased by 28-43% when assisted by the robot. Overall, these results provide a scientific justification for further research in enabling movement and identifying personalized rehabilitation for motor training. Beyond rehabilitation, other applications such as applying force perturbations on the head to study sensory integration and applying traction to achieve pain relief may benefit from the innovation of this robotic platform which is capable of applying controlled 6-DoF forces/moments on the head.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neck muscle weakness due to amyotrophic lateral sclerosis (ALS) can result in dropped head syndrome, adversely impacting the quality of life of those affected. Static neck collars are currently ...prescribed to hold the head in a fixed upright position. However, these braces are uncomfortable and do not allow any voluntary head-neck movements. By contrast, powered neck exoskeletons have the potential to enable head-neck movements. Our group has recently improved the mechanical structure of a state-of-the-art neck exoskeleton through a weighted optimization. To evaluate the effect of the structural changes, we conducted an experiment in which patients with ALS were asked to perform head-neck tracking tasks while using the two versions of the neck exoskeleton. We found that the neck muscle activation was significantly reduced when assisted by the structurally enhanced design compared to no assistance provided. The improved structure also improved kinematics tracking performance, allowing users to better achieve the desired head poses. In comparison, the previous design did not help reduce the muscle effort required to perform these tasks and even slightly worsened the kinematic tracking performance. It was also found that biomechanical benefits gained from using the structurally improved design were consistent across participants with both mild and severe neck weakness. Furthermore, we observed that participants preferred to use the powered neck exoskeletons to voluntarily move their heads and make eye contact during a conversation task rather than remain in a fixed upright position. Each of these findings highlights the importance of the structural design of neck exoskeletons in achieving desired biomechanical benefits and suggests that neck exoskeletons can be a viable method to improve the daily life of patients with ALS.
The performance of Cd, Ni, and Cu release from river sediment at different pH was investigated by a leaching test using deionised water and river water as leachants. Visual MINTEQ geochemical ...software was used to model the experimental results to predict heavy metal release from sediments. The distribution and speciation of heavy metals in the sediments after leaching test were analyzed by Tessier sequential extraction. Leaching test results showed that the release amounts of Cd, Ni, and Cu are in the range of 10.2–27.3 mg·kg−1, 80.5–140.1 mg·kg−1, and 6.1–30.8 mg·kg−1, respectively, with deionised water as leachant at different pH. As far as the river water was used as the leaching solution in the test, the results show similar metal leaching contents and tendencies to that of the deionised water as leaching solution. The results of Tessier sequential extraction indicate that Cd of residual fraction easily forms obvious precipitate under the acidic condition, especially in the range of pH 0–4 with the residual of Cd over 50% of the total Cd in the sediment. The exchangeable content of Ni decreases with the increase of pH under the range of 0–5. The Fe-Mn oxide fraction of Cu in the sediments changes significantly from pH 0 to pH 9. Based on the effect of pH on the leaching of Cd, Ni, and Cu from the polluted sediment in the tests, more accurate information could be obtained to assess the risk related to metal release from sediments once it is exposed to the changed acid/alkali water conditions.
Full text
Available for:
FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Head drop is a symptom commonly seen in patients with amyotrophic lateral sclerosis. These patients usually experience neck pain and have difficulty in swallowing and breathing. Static neck braces ...are used in current treatment. These braces, however, immobilize the head in a single configuration, which causes muscle atrophy. This letter presents the design of a dynamic neck brace for the first time in the literature, which can both measure and potentially assist in the head motion of the human user. This letter introduces the brace design method and validates its capability to perform measurements. The brace is designed based on kinematics data collected from a healthy individual via a motion capture system. A pilot study was conducted to evaluate the wearability of the brace and the accuracy of measurements with the brace. This study recruited ten participants who performed a series of head motions. The results of this human study indicate that the brace is wearable by individuals who vary in size, the brace allows nearly 70% of the overall range of head rotations, and the sensors on the brace give accurate motion of the head with an error of under 5° when compared to a motion capture system. We believe that this neck brace can be a valid and accurate measurement tool for human head motion. This brace will be a big improvement in the available technologies to measure head motion as these are currently done in the clinic using hand-held protractors in two orthogonal planes.
Immunotherapy has moved to the forefront of modern oncologic treatment in the past few decades. Various forms of immunotherapy currently are emerging, including oncolytic viruses. In this therapy, ...viruses are engineered to selectively propagate in tumor cells and reduce toxicity for non-neoplastic tissues. Adenovirus is one of the most frequently employed oncolytic viruses because of its capacity in tumor cell lysis and immune response stimulation. Upregulation of immunostimulatory signals induced by oncolytic adenoviruses (OAds) might significantly remove local immune suppression and amplify antitumor immune responses. Existing genetic engineering technology allows us to design OAds with increasingly better tumor tropism, selectivity, and antitumor efficacy. Several promising strategies to modify the genome of OAds have been applied: capsid modifications, small deletions in the pivotal viral genes, insertion of tumor-specific promoters, and addition of immunostimulatory transgenes. OAds armed with tumor-associated antigen (TAA) transgenes as cancer vaccines provide additional therapeutic strategies to trigger tumor-specific immunity. Furthermore, the combination of OAds and immune checkpoint inhibitors (ICIs) increases clinical benefit as evidence shown in completed and ongoing clinical trials, especially in the combination of OAds with antiprogrammed death 1/programed death ligand 1 (PD-1/PD-L1) therapy. Despite remarkable antitumor potency, oncolytic adenovirus immunotherapy is confronted with tough challenges such as antiviral immune response and obstruction of tumor microenvironment (TME). In this review, we focus on genomic modification strategies of oncolytic adenoviruses and applications of OAds in cancer immunotherapy.
The optimization of a broach surface is of great significance to improve the cutting performance of the tool. However, the traditional optimization method (surface texture, coating, etc.) destroys ...the stress distribution of the tool and reduces the service life of the tool. To avoid these problems, four kinds of flocking surfaces (FB1, FB2, FB3, and FB4), imitating the biological structure of Daphniphyllum calycinum Benth (DCB), were fabricated on the rake face of the broach by electrostatic flocking. The broaching experiment, wettability, and spreading experiment were then conducted. Moreover, the mathematical model of the friction coefficient of the bionic broach was built. The effect of broaches with different flocking surfaces on the broaching force, chip morphology, and surface quality of workpieces was studied. The results indicate that the flocked broaches (FB) with good lubricity and capacity of microchips removal (CMR) present a smaller cutting force (
) and positive pressure (
) compared to the unflocked broach (NB), and reduce the friction coefficient (COF). The chip curl was decreased, and the shear angle was increased by FB, which were attributed to the function of absorbing lubricant, storing, and sweeping microchips. Its vibration suppression effect enhanced the stability in the broaching process and improved the surface quality of the workpiece. More importantly, the FB2 with the most reasonable fluff area and spacing exhibited the best cutting performance. The experimental conclusions and methods of this paper can provide a new research idea for functional structure tools.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
YG8 is a common cemented carbide material with excellent mechanical properties and mechanical properties, so it is widely used in the actual industry. However, due to the active chemical properties ...and strong affinity of tungsten alloy steel, it is easy to produce bonding and peeling in application, resulting in an unstable process and short service life. In order to control and reduce the surface wear of YG8 cemented carbide, groove-textured surface (GS) and flocking surface (FS) were prepared on smooth surface (SS). The friction characteristics of the samples were studied under different applied load conditions. The results show that the average friction coefficient of SS, GS and FS is inversely proportional to the load in dry/oil environment. Compared with SS, FS exhibits the lowest friction coefficient, which is reduced by 30.78% (dry friction) and 13.13% (oil lubrication). FS effectively improves the tooth jump phenomenon of the sample and the amplitude of the friction coefficient, friction force and load, and has the best anti-friction characteristics. At the same time, the FS with the fastest contact angle drop at any time also showed excellent wetting ability, and the wear rate decreased by an order of magnitude. The implantation of fibers in the groove inhibits the spalling and furrow of wear track, which is attributed to the effect of fibers on damage repair. In the friction process, FS increases the content of the O element and induces the formation of oxides. The friction mechanism is mainly chemical wear. The excellent tribological properties of FS have a good guiding significance and theoretical support for improving the tribological properties of high hardness material surfaces.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The in situ immobilization performances of Zn, Mn, Pb, and Cd in the contaminated sediments using additives hydroxyapatite (HAP), CaO, MgO, and HAP + CaO/MgO were investigated by European Community ...Bureau of Reference (BCR) extraction test, toxicity characteristic leaching procedure (TCLP), and heavy metal releasing test. The results of immobilization test showed that 40.70% of Zn, 47.47% of Mn, 70.40% of Pb, and 61.86% of Cd were immobilized in forms of the oxidizable and residual speciation in the sediments applied by composite additives (HAP + CaO or MgO) with each additive’s dosage of 10% of the sediment. The results of TCLP indicated that, compared to the blank samples, nearly 80% of Zn, Pb, Cd, and 50% of Mn were reduced in the leaching solutions using the composite additives. In addition, the heavy metal releasing experiment demonstrated that the releasing amounts of heavy metals in the immobilized sediments were much lower than those in raw sediments, and the equilibrium of metal releasing cost 24–31 days. The results of this work demonstrated that 10% HAP coupled with 10% CaO or 10% MgO is feasible in immobilizing heavy metals and decreasing the releasing risk of heavy metals in sediments.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aiming at the problems of small sample size and large feature dimension in the identification of ipsilateral supraclavicular lymph node metastasis status in breast cancer using ultrasound radiomics, ...an optimized feature combination search algorithm is proposed to construct linear classification models with high interpretability. The genetic algorithm (GA) is used to search for feature combinations within the feature subspace using least absolute shrinkage and selection operator (LASSO) regression. The search is optimized by applying a high penalty to the L1 norm of LASSO to retain excellent features in the crossover operation of the GA. The experimental results show that the linear model constructed using this method outperforms those using the conventional LASSO regression and standard GA. Therefore, this method can be used to build linear models with higher classification performance and more robustness.
PDF
