Objectives
To develop and evaluate machine learning models using baseline and restaging computed tomography (CT) for predicting and early detecting pathological downstaging (pDS) with neoadjuvant ...chemotherapy in advanced gastric cancer (AGC).
Methods
We collected 292 AGC patients who received neoadjuvant chemotherapy. They were classified into (a) primary cohort (206 patients with 3–4 cycles chemotherapy) for model development and internal validation, (b) testing cohort I (46 patients with 3–4 cycles chemotherapy) for evaluating models’ predictive ability before and after the complete course, and (c) testing cohort II (
n
= 40) for model evaluation on its performance at early treatment. We extracted 1,231 radiomics features from venous phase CT at baseline and restaging. We selected radiomics models based on 28 cross-combination models and measured the areas under the curve (AUC). Our prediction radiomics (PR) model is designed to predict pDS outcomes using baseline CT. Detection radiomics (DR) model is applied to restaging CT for early pDS detection.
Results
PR model achieved promising outcomes in two testing cohorts (AUC 0.750,
p
= .009 and AUC 0.889,
p
= .000). DR model also showed a good predictive ability (AUC 0.922,
p
= .000 and AUC 0.850,
p
= .000), outperforming the commonly used RECIST method (NRI 39.5% and NRI 35.4%). Furthermore, the improved DR model with averaging outcome scores of PR and DR models showed boosted results in two testing cohorts (AUC 0.961,
p
= .000 and AUC 0.921,
p
= .000).
Conclusions
CT-based radiomics models perform well on prediction and early detection tasks of pDS and can potentially assist surgical decision-making in AGC patients.
Key Points
• Baseline contrast-enhanced computed tomography (CECT)-based radiomics features were predictive of pathological downstaging, allowing accurate identification of non-responders before therapy.
• Restaging CECT-based radiomics features were predictive to achieve pDS after and even at an early stage of neoadjuvant chemotherapy.
• Combination of baseline and restaging CECT-based radiomics features was promising for early detection and preoperative evaluation of pathological downstaging of AGC.
Carbon nanotube (CNT) fibers are renowned for their exceptional axial tensile strength and modulus. However, in yarn form, they frequently encounter transverse loading in practical applications, ...which exposes their suboptimal mechanical attributes rooted in inadequate inter-tube interactions and yarn surface defects. Efforts to mitigate micro-slippage among CNTs have encompassed gap-filling methodologies with varied materials, yet the outcomes have fallen short of expectations. This work aimed to enhance the mechanical properties of CNT yarns via infiltration with polyacrylonitrile (PAN) under supercritical carbon dioxide (sc-CO2) conditions. PAN was strategically chosen for its capability to undergo pre-oxidation and subsequent carbonization, leading to robust graphitic reinforcement. Leveraging sc-CO2’s swelling and high permeability properties, the infiltration process effectively plugged interstitial spaces, elevating the yarn’s tensile strength to 277.50 MPa and Young’s modulus to 5094.05 MPa. Additional enhancements were realized after pre-oxidation, conferring a dense, reinforced shell structure that augmented tensile strength by 96.93% and Young’s modulus by 298.80%. Scanning electron microscopy (SEM) analyses revealed a homogeneous PAN distribution within the yarn matrix, corroborated by X-ray photoelectron spectroscopy (XPS) evidence of C-N bonding, indicative of a successfully interlaced network. Consequently, this investigation introduces a novel strategy to tackle micro-slippage in CNT yarns, thereby achieving substantial improvements in their mechanical resilience.
Intervertebral disc degeneration was characterized with aberrant intervertebral disc nucleus pulposus cells apoptosis. MiR-532 was reported to be up-regulated in the patients with intervertebral disc ...degeneration. However, the role of miR-532 in intervertebral disc degeneration remains unclear. Thus, current study aim to investigate the effects of miR-532 on human intervertebral disc nucleus pulposus cells.
Quantitative PCR was firstly used to evaluate the level of miR-532 expression in intervertebral disc nucleus pulposus cells. Then, luciferase reporter assays was used to confirm the target genes of miR-532. The effects of miR-532 on cell proliferation were assayed using EdU transfection. Next, apoptosis level was examined by flow cytometry utilizing Annexin V-FITC/PI double staining, and the protein expression in cells was detected with Western blotting. Finally, The expression of β-catenin protein was demonstrated by fluorescence confocal microscopy and the interaction between β-catenin and Bcl-9 was detected by co-immunoprecipitation.
MiR-532 was significantly upregulated in patient with intervertebral disc degeneration. In addition, intervertebral disc nucleus pulposus cells apoptosis was significantly increased in miR-532 mimics treated group. Moreover, Bcl-9 was confirmed to be a direct target of miR-532 via luciferase reporter assays and western blot assays.
MiR-532 downregulation of the Wnt/β-catenin signaling via targeting Bcl-9 and induced human intervertebral disc nucleus pulposus cells apoptosis.
This paper presents TransRepair, a fully automatic approach for testing and repairing the consistency of machine translation systems. TransRepair combines mutation with metamorphic testing to detect ...inconsistency bugs (without access to human oracles). It then adopts probability-reference or cross-reference to post-process the translations, in a grey-box or black-box manner, to repair the inconsistencies. Our evaluation on two state-of-the-art translators, Google Translate and Transformer, indicates that TransRepair has a high precision (99%) on generating input pairs with consistent translations. With these tests, using automatic consistency metrics and manual assessment, we find that Google Translate and Transformer have approximately 36% and 40% inconsistency bugs. Black-box repair fixes 28% and 19% bugs on average for Google Translate and Transformer. Grey-box repair fixes 30% bugs on average for Transformer. Manual inspection indicates that the translations repaired by our approach improve consistency in 87% of cases (degrading it in 2%), and that our repairs have better translation acceptability in 27% of the cases (worse in 8%).
Sirtuin3 (sirt3) plays a pivotal role in improving oxidative stress and mitochondrial dysfunction which directly induced neuronal apoptosis after intracerebral hemorrhage (ICH). Reactive oxygen ...species (ROS) is also a critical activator in triggering NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasomes activation which can regulate inflammatory responses in brain. Moreover, hyperglycemia can aggravate the ICH-induced damage. Hence, this study was designed to investigate the mechanisms of neuroprotection of sirt3 in hyperglycemic ICH.
ICH model was established by autologous blood injection. Hyperglycemia was induced by intraperitoneal injection with streptozotocin. Honokiol (HKL, a pharmacological agonist of sirt3) was injected intraperitoneally at doses of 2.5, 5, or 10 mg/kg. Sirt3 small interfering RNA transfection was implemented through intracerebroventricular injection. The expression of sirt3 and its downstream signaling molecules were detected using Western blotting or immunofluorescence staining. Morphological changes of mitochondria were detected by electron microscopy. SH-SY5Y cells were incubated with 10 μM oxyhemoglobin for 48 h to establish an
ICH model, and then JC-1 staining was used to determine mitochondrial membrane potential (Δψ
).
Hyperglycemia could suppress sirt3 expression after ICH when compared with non-diabetic rats. Sirt3 protein expression was decreased to the minimum at 24 h in perihematoma tissues. Electron microscope analysis indicated that hyperglycemic ICH induced extensive mitochondrial vacuolization. HKL attenuated ROS accumulation, adenosine triphosphate reduction, and Δψ
through Sirt3-superoxide dismutase 2 (SOD2) and Sirt3-NRF1-TFAM pathway. Sirt3 knockdown could exacerbate the neuronal apoptosis and reverse the positive effects of HKL. Sirt3 activation could decrease NLRP3 and interleukin-1β levels through deacetylating SOD2 and scavenging ROS.
HKL protects against hyperglycemic ICH-induced neuronal injury via a sirt3-dependent manner.
Predicting the dynamics and functions of microbiomes constructed from the bottom-up is a key challenge in exploiting them to our benefit. Current models based on ecological theory fail to capture ...complex community behaviors due to higher order interactions, do not scale well with increasing complexity and in considering multiple functions. We develop and apply a long short-term memory (LSTM) framework to advance our understanding of community assembly and health-relevant metabolite production using a synthetic human gut community. A mainstay of recurrent neural networks, the LSTM learns a high dimensional data-driven non-linear dynamical system model. We show that the LSTM model can outperform the widely used generalized Lotka-Volterra model based on ecological theory. We build methods to decipher microbe-microbe and microbe-metabolite interactions from an otherwise black-box model. These methods highlight that Actinobacteria, Firmicutes and Proteobacteria are significant drivers of metabolite production whereas
shape community dynamics. We use the LSTM model to navigate a large multidimensional functional landscape to design communities with unique health-relevant metabolite profiles and temporal behaviors. In sum, the accuracy of the LSTM model can be exploited for experimental planning and to guide the design of synthetic microbiomes with target dynamic functions.
Aging is a major risk for developing cardiac and skeletal muscle dysfunction, yet the underlying mechanism remains elusive. Here we demonstrated that the mitochondria-associated endoplasmic reticulum ...membranes (MAMs) in the rat heart and skeletal muscle were disrupted during aging. Using quantitative morphological analysis, we showed that the mitochondria-endoplasmic reticulum contacts (MERCs) were reduced by half over the lifespan with an early onset of accelerated thickening in the clefts. The ultrastructural changes were further validated by proteomic profiling of the MAM fractions. A combination of subcellular fractionation and quantitative mass spectrometry identified 1306 MAM-enriched proteins in both heart and skeletal muscle, with a catalog of proteins dysregulated with aging. Functional mapping of the MAM proteome suggested several aging signatures to be closely associated with the ER-mitochondria crosstalk, including local metabolic rewiring, calcium homeostasis imbalance, and impaired organelle dynamics and autophagy. Moreover, we identified a subset of highly interconnected proteins in an ER-mitochondria organization network, which were consistently down-regulated with aging. These decreased proteins, including VDAC1, SAMM50, MTX1 and MIC60, were considered as potential contributors to the age-related MAM dysfunction. This study highlights the perturbation in MAM integrity during the striated muscle aging process, and provides a framework for understanding aging biology from the perspective of organelle interactions.
Attitude determination based on a micro-electro-mechanical system inertial measurement unit (MEMS-IMU) has attracted extensive attention. The non-gravitational components of the MEMS-IMU have a ...significant effect on the accuracy of attitude estimation. To improve the attitude estimation of low-dynamic vehicles under uneven soil conditions or vibrations, a robust Kalman filter (RKF) was developed and tested in this paper, where the noise covariance was adaptively changed to compensate for the external acceleration of the vehicle. The state model for MEMS-IMU attitude estimation was initially constructed using a simplified direction cosine matrix. Subsequently, the variance of unmodeled external acceleration was estimated online based on filtering innovations of different window lengths, where the acceleration disturbance was addressed by tradeoffs in time-delay and prescribed computation cost. The effectiveness of the RKF was validated through experiments using a three-axis turntable, an automatic vehicle, and a tractor tillage test. The turntable experiment demonstrated that the angle result of the RKF was 0.051° in terms of root mean square error (RMSE), showing improvements of 65.5% and 29.2% over a conventional KF and MTi-300, respectively. The dynamic attitude estimation of the automatic vehicle showed that the RKF achieves smoother pitch angles than the KF when the vehicle passes over speed bumps at different speeds; the RMSE of pitch was reduced from 0.875° to 0.460° and presented a similar attitude trend to the MTi-300. The tractor tillage test indicated that the RMSE of plough pitch was improved from 0.493° with the KF to 0.259° with the RKF, an enhancement of approximately 47.5%, illustrating the superiority of the RKF in suppressing the external acceleration disturbances of IMU-based attitude estimation.
Intracerebral hemorrhage (ICH) can induce excessive accumulation of reactive oxygen species (ROS) that may subsequently cause severe white matter injury. The process of oligodendrocyte progenitor ...cell (OPC) differentiation is orchestrated by microglia and astrocytes, and ROS also drives the activation of microglia and astrocytes. In light of the potent ROS scavenging capacity of ceria nanoparticles (CeNP), we aimed to investigate whether treatment with CeNP ameliorates white matter injury by modulating ROS-induced microglial polarization and astrocyte alteration.
ICH was induced in vivo by collagenase VII injection. Mice were administered with PLX3397 for depleting microglia. Primary microglia and astrocytes were used for in vitro experiments. Transmission electron microscopy analysis and immunostaining were performed to verify the positive effects of CeNP in remyelination and OPC differentiation. Flow cytometry, real-time polymerase chain reaction, immunofluorescence and western blotting were used to detect microglia polarization, astrocyte alteration, and the underlying molecular mechanisms.
CeNP treatment strongly inhibited ROS-induced NF-κB p65 translocation in both microglia and astrocytes, and significantly decreased the expression of M1 microglia and A1 astrocyte. Furthermore, we found that CeNP treatment promoted remyelination and OPC differentiation after ICH, and such effects were alleviated after microglial depletion. Interestingly, we also found that the number of mature oligodendrocytes was moderately increased in ICH + CeNP + PLX3397-treated mice compared to the ICH + vehicle + PLX3397 group. Therefore, astrocytes might participate in the pathophysiological process. The subsequent phagocytosis assay indicated that A1 astrocyte highly expressed C3, which could bind with microglia C3aR and hinder microglial engulfment of myelin debris. This result further replenished the feedback mechanism from astrocytes to microglia.
The present study reveals a new mechanism in white matter injury after ICH: ICH induces M1 microglia and A1 astrocyte through ROS-induced NF-κB p65 translocation that hinders OPC maturation. Subsequently, A1 astrocytes inhibit microglial phagocytosis of myelin debris via an astrocytic C3-microglial C3aR axis. Polyethylene glycol-CeNP treatment inhibits this pathological process and ultimately promotes remyelination. Such findings enlighten us that astrocytes and microglia should be regarded as a functional unit in future works.
Efficient enhancement of the toughness of epoxy resins has been a bottleneck for expanding their suitability for advanced applications. Here, polysulfone (PSF) was adopted to toughen and modify the ...epoxy. The influences of PSF on the mechanical and thermal properties of the epoxy resin were systematically studied by optical microscopy, Fourier transform infrared spectrometer (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analyzer (TG), dynamic mechanical thermal analyzer (DMA), mechanical tests and scanning electron microscope (SEM). The dissolution experimental results showed that PSF presents a good compatibility with the epoxy resin and could be well dissolved under controlled conditions. The introduction of PSF was found to promote the curing reaction of the epoxy resin without participating in the curing reaction and changing the curing mechanism as revealed by the FT-IR and DSC studies. The mechanical properties of PSF/epoxy resin blends showed that the fracture toughness and impact strength were significantly improved, which could be attributed to the bicontinuous phase structure of PSF/epoxy blends. Representative phase structures resulted from the reaction induced phase separation process were clearly observed in the PSF/epoxy blends during the curing process of epoxy resin, which presented dispersed particles, bicontinuous and phase inverted structures with the increase of the PSF content. Our work further confirmed that the thermal stability of the PSF/epoxy blends was slightly increased compared to that of the pure epoxy resin, mainly due to the good heat resistance of the PSF component.
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