Deep learning prediction of esophageal squamous cell carcinoma invasion depth from arterial phase enhanced CT images: a binary classification approach.

BACKGROUND: Precise prediction of esophageal squamous cell carcinoma (ESCC) invasion depth is crucial not only for optimizing treatment plans but also for reducing the need for invasive procedures, consequently lowering complications and costs. Despite this, current techniques, which can be invasive and costly, struggle with achieving the necessary precision, highlighting a pressing need for more effective, non-invasive alternatives. METHOD: We developed ResoLSTM-Depth, a deep learning model to distinguish ESCC stages T1-T2 from T3-T4. It integrates ResNet-18 and Long Short-Term Memory (LSTM) networks, leveraging their strengths in spatial and sequential data processing. This method uses arterial phase CT scans from ESCC patients. The dataset was meticulously segmented by an experienced radiologist for effective training and validation. RESULTS: Upon performing five-fold cross-validation, the ResoLSTM-Depth model exhibited commendable performance with an accuracy of 0.857, an AUC of 0.901, a sensitivity of 0.884, and a specificity of 0.828. These results were superior to the ResNet-18 model alone, where the average accuracy is 0.824 and the AUC is 0.879. Attention maps further highlighted influential features for depth prediction, enhancing model interpretability. CONCLUSION: ResoLSTM-Depth is a promising tool for ESCC invasion depth prediction. It offers potential for improvement in the staging and therapeutic planning of ESCC.

Using Vision Transformer for high robustness and generalization in predicting EGFR mutation status in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a common cause of cancer-related deaths worldwide, and accurate EGFR genotyping is crucial for optimal treatment outcomes. Conventional methods for identifying the EGFR genotype have several limitations. Therefore, we proposed a deep learning model using non-invasive CT images to predict EGFR mutation status with robustness and generalizability. METHODS: A total of 525 patients were enrolled at the local hospital to serve as the internal data set for model training and validation. In addition, a cohort of 30 patients from the publicly available Cancer Imaging Archive Data Set was selected for external testing. All patients underwent plain chest CT, and their EGFR mutation status labels were categorized as either mutant or wild type. The CT images were analyzed using a self-attention-based ViT-B/16 model to predict the EGFR mutation status, and the model's performance was evaluated. To produce an attention map indicating the suspicious locations of EGFR mutations, Grad-CAM was utilized. RESULTS: The ViT deep learning model achieved impressive results, with an accuracy of 0.848, an AUC of 0.868, a sensitivity of 0.924, and a specificity of 0.718 on the validation cohort. Furthermore, in the external test cohort, the model achieved comparable performances, with an accuracy of 0.833, an AUC of 0.885, a sensitivity of 0.900, and a specificity of 0.800. CONCLUSIONS: The ViT model demonstrates a high level of accuracy in predicting the EGFR mutation status of lung adenocarcinoma patients. Moreover, with the aid of attention maps, the model can assist clinicians in making informed clinical decisions.

Deglacial volcanism and reoxygenation in the aftermath of the Sturtian Snowball Earth.

The Cryogenian Sturtian and Marinoan Snowball Earth glaciations bracket a nonglacial interval during which Demosponge and green-algal biomarkers first appear. To understand the relationships between environmental perturbations and early animal evolution, we measured sulfur and mercury isotopes from the Datangpo Formation from South China. Hg enrichment with positive Δ199Hg excursion suggests enhanced volcanism, potentially due to depressurization of terrestrial magma chambers during deglaciation. A thick stratigraphic interval of negative Δ33Spy indicates that the nonglacial interlude was characterized by low but rising sulfate levels. Model results reveal a mechanism to produce the Δ33S anomalies down to -0.284‰ through Rayleigh distillation. We propose that extreme temperatures and anoxia contributed to the apparent delay in green algal production in the aftermath of the Sturtian glaciation and the subsequent reoxygenation of the iron-rich and sulfate-depleted ocean paved the way for evolution of animals.

The utility of Vision Transformer in preoperatively predicting microvascular invasion status of hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) is a risk factor for early recurrence and poor prognosis of hepatocellular carcinoma (HCC). Preoperative assessment of MVI status is beneficial for clinical therapy and prognosis evaluation. METHODS: A total of 305 surgically resected patients were included retrospectively. All recruited patients underwent plain and contrast-enhanced abdominal CT. They were then randomly divided into training and validation sets in a ratio of 8:2. Self-attention-based ViT-B/16 and ResNet-50 analyzed CT images to predict MVI status preoperatively. Then, Grad-CAM was used to generate an attention map showing the high-risk MVI patches. Using five-fold cross validation, the performance of each model was evaluated. RESULTS: Among 305 HCC patients, 99 patients were pathologically MVI-positive and 206 were MVI-negative. ViT-B/16 with fusion phase predicted the MVI status with an AUC of 0.882 and an accuracy of 86.8% in the validation set, which is similar to ResNet-50 with an AUC of 0.875 and an accuracy of 87.2%. The fusion phase improved performance a bit as compared to the single phase used for MVI prediction. The influence of peritumoral tissue on predictive ability was limited. A color visualization of the suspicious patches where microvascular has invaded was presented by attention maps. CONCLUSION: ViT-B/16 model can predict preoperative MVI status in CT images of HCC patients. Assisted by attention maps, it can assist patients in making tailored treatment decisions.

Melittin-Carrying Nanoparticle Suppress T Cell-Driven Immunity in a Murine Allergic Dermatitis Model.

Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are the most common human skin disorders. Although corticosteroids have been widely used to treat ACD and AD, the side effects of corticosteroids encourage researchers to explore new immunoregulatory treatments. Here, an immunomodulatory approach based on lipid nanoparticles carrying α-helical configurational melittin (α-melittin-NP) is developed to overcome T cell-mediated inflammatory reactions in an oxazolone (OXA)-induced contact hypersensitivity mouse model and OXA-induced AD-like mouse model. Intradermal injection of low-dose α-melittin-NPs prevents the skin damage caused by melittin administration alone and efficiently targeted lymph nodes. Importantly, melittin and α-melittin-NPs restrain RelB activity in dendritic cells (DCs) and further suppresses dendritic cell activation and maturation in lymph nodes. Furthermore, low-dose α-melittin-NPs leads to relief of antigen recognition-induced effector T cell arrest in the dermis and inhibited allergen-specific T cell proliferation and activation. Significantly, this approach successfully controls Th1-type cytokine release in the ACD model and restricts Th2-type cytokine and IgE release in the AD-like model. Overall, intradermal delivery of low-dose α-melittin-NPs efficiently elicits immunosuppression against T cell-mediated immune reactions, providing a promising therapeutic strategy for treating skin disorders not restricted to the lesion region.

Intravital molecular imaging reveals that ROS-caspase-3-GSDME-induced cell punching enhances humoral immunotherapy targeting intracellular tumor antigens.

Tumor antigens (TAs)-induced humoral immune responses or TAs-specific antibodies have great application prospects for tumor therapy. However, more than half of TAs are intracellular antigens (intra-Ags) that are hardly recognized by antibodies. It is worthy to develop immunotherapeutic strategies for targeting intra-Ags. Methods: We used the far-red fluorescent protein tfRFP as an intracellular antigen to immunize mice and generated a liver metastasis model by injecting tfRFP-expressing B16 melanoma cells (tfRFP-B16) via the spleen. Intravital molecular imaging and atomic force microscopy were performed to visualize the formation of tfRFP antigen-antibody complexes (also known as immune complexes) and punched holes in cell membranes. Results: The results showed that the tfRFP-elicited immune responses inhibited the metastasis of tfRFP-expressing melanoma cells in the liver. In the circulating tfRFP-B16 tumor cells, elevated reactive oxygen species (ROS) induced slight caspase-3 activation, a probable key factor in the cleavage of gasdermin E (GSDME) proteins and punching of holes in the tumor cell membrane. Increased tumor cell membrane permeability led to the release of intra-Ag tfRFP and binding with anti-tfRFP antibodies. The formation of tfRFP antigen-antibody complexes on the membranes of tfRFP-B16 cells activated complement components to form membrane attack complexes to further destroy the cell membrane. Neutrophils were rapidly recruited, and F4/80+ macrophages phagocytized the dying tumor cells. Conclusion: The process of circulating tumor cell elimination in the tfRFP-immunized mice was triggered through the ROS-caspase-3-GSDME pathway to form intra-Ag-antibody immune complexes, which were involved in the activation of the complement system, as well as the recruitment of neutrophils and F4/80+ macrophages. An intra-Ag-elicited humoral immune response is a potent strategy for eliminating liver metastasis, which is unaffected by the liver immune tolerogenic status.

The influence of alloying on slip intermittency and the implications for dwell fatigue in titanium.

Dwell fatigue, the reduction in fatigue life experienced by titanium alloys due to holds at stresses as low as 60% of yield, has been implicated in several uncontained jet engine failures. Dislocation slip has long been observed to be an intermittent, scale-bridging phenomenon, similar to that seen in earthquakes but at the nanoscale, leading to the speculation that large stress bursts might promote the initial opening of a crack. Here we observe such stress bursts at the scale of individual grains in situ, using high energy X-ray diffraction microscopy in Ti-7Al-O alloys. This shows that the detrimental effect of precipitation of ordered Ti3Al is to increase the magnitude of rare pri〈a〉 and bas〈a〉 slip bursts associated with slip localisation. By contrast, the addition of trace O interstitials is beneficial, reducing the magnitude of slip bursts and promoting a higher frequency of smaller events. This is further evidence that the formation of long paths for easy basal plane slip localisation should be avoided when engineering titanium alloys against dwell fatigue.

Integration of clinical and transcriptomics reveals programming of the lipid metabolism in gastric cancer.

Lipid metabolism has a profound impact on gastric cancer (GC) progression and is a newly targetable vulnerability for cancer therapy. Given the importance of lipids in cancer cellular processes, in this study we employed lipidomic clinical and transcriptomic data to connect the variations of lipid metabolism changes of GC. We constructed a clinical nomogram based on the lipid factors and other clinical items. Then by using multi-omics techniques, we established a lipid-related gene signature for individualized prognosis prediction in patients with GC. Moreover, a total of 1357 GC cases were then applied to evaluate the robustness of this model. WGCNA was used to identify co-expression modules and enriched genes associated with GC lipid metabolism. The role of key genes ACLY in GC was further investigated. The prognostic value of the lipgenesis signature was analyzed using Cox regression model, and clinical nomogram was established. Among them, we observed overexpression of ACLY significantly increased the levels of intracellular free fatty acid and triglyceride, and activated AKT/mTOR pathway to promote cancer development. In conclusion, our findings revealed that GC exhibited a reprogramming of lipid metabolism in association with an altered expression of associated genes. Among them, ACLY significantly promoted GC lipid metabolism and increased cancer cell proliferation, suggesting that this pathway can be targetable as a metabolic vulnerability in future GC therapy.

Using gravity model to make store closing decisions: A data driven approach.

Many studies propose methods for finding the best location for new stores and facilities, but few studies address the store closing problem. As a result of the recent COVID-19 pandemic, many companies have been facing financial issues. In this situation, one of the most common solutions to prevent loss is to downsize by closing one or more chain stores. Such decisions are usually made based on single-store performance; therefore, the under-performing stores are subject to closures. This study first proposes a multiplicative variation of the well-known Huff gravity model and introduces a new attractiveness factor to the model. Then a forward-backward approach is used to train the model and predict customer response and revenue loss after the hypothetical closure of a particular store from a chain. In this research the department stores in New York City are studied using large-scale spatial, mobility, and spending datasets. The case study results suggest that the stores recommended being closed under the proposed model may not always match the single store performance, and emphasizes the fact that the performance of a chain is a result of interaction among the stores rather than a simple sum of their performance considered as isolated and independent units. The proposed approach provides managers and decision-makers with new insights into store closing decisions and will likely reduce revenue loss due to store closures.

Effect of serum vitamin D on metabolic associated fatty liver disease: a large population-based study.

BACKGROUND: Several studies have revealed that serum vitamin D is an important factor for metabolic associated fatty liver disease (MAFLD), but there had been no consistent conclusion. METHODS: Of 427,507 subjects who underwent health examination, 83,625 who met the inclusion criteria were included in a cross-sectional analysis. Clinical and laboratory data were collected for analysis. MAFLD was diagnosed by abdominal imaging. RESULTS: Multivariate linear regression models discovered a negative association between serum vitamin D and MAFLD (OR: 0.92, 95% CI: 0.90 to 0.94, p = .001), after adjusting for other well-identified risk factors. The same result was found when serum vitamin D was handled as a categorical variable (quartile, Q1-Q4) (Q4 vs. Q1, OR: 0.82, 95% CI: 0.77 to 0.87, p < .001), and a significant linear trend was observed (p for trend <.001). After analysis, a nonlinear relationship was detected between serum vitamin D and MAFLD, with an inflection point of 2.23 (44.6 nmol/L or 17.84 ng/mL). The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.16 (1.06 to 1.28) and 0.89 (0.86 to 0.91), respectively. All interactions with MAFLD were not significant for age, sex, diabetes, hypertension, smoking and body mass index (p for interaction = .110, .558, .335, .195, .616 and .401, respectively). CONCLUSIONS: There was a nonlinear relationship between serum vitamin D and MAFLD. When the serum vitamin D level was ≥44.6 nmol/L (17.84 ng/mL), a negative correlation between serum vitamin D and MAFLD was detected. Below this level, serum vitamin D might promote the progression of MAFLD.

On the Origin of Plastic Deformation and Surface Evolution in Nano-Fretting: A Discrete Dislocation Plasticity Analysis.

Discrete dislocation plasticity (DDP) calculations were carried out to investigate a single-crystal response when subjected to nano-fretting loading conditions in its interaction with a rigid sinusoidal asperity. The effects of the contact size and preceding indentation on the surface stress and profile evolution due to nano-fretting were extensively investigated, with the aim to unravel the deformation mechanisms governing the response of materials subjected to nano-motion. The mechanistic drivers for the material's permanent deformations and surface modifications were shown to be the dislocations' collective motion and piling up underneath the contact. The analysis of surface and subsurface stresses and the profile evolution during sliding provides useful insight into damage and failure mechanisms of crystalline materials subject to nano-fretting; this can lead to improved strategies for the optimisation of material properties for better surface resistance under micro- and nano-scale contacts.

Integrative Radiogenomics Approach for Risk Assessment of Postoperative and Adjuvant Chemotherapy Benefits for Gastric Cancer Patients.

Gastric cancer (GC) is a typical heterogeneous malignant tumor, whose insensitivity to chemotherapy is a common cause of tumor recurrence and metastasis. There is no doubt regarding the effectiveness of adjuvant chemotherapy (ACT) for GC, but the population for whom it is indicated and the selection of specific options remain the focus of present research. The conventional pathological TNM prediction focuses on cancer cells to predict prognosis, while they do not provide sufficient prediction. Enhanced computed tomography (CT) scanning is a validated tool that assesses the involvement of careful identification of the tumor, lymph node involvement, and metastatic spread. Using the radiomics approach, we selected the least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for predicting the overall survival (OS) and disease-free survival (DFS) of patients with complete postoperative gastric cancer and further identifying candidate benefits from ACT. The radiomics trait-associated genes captured clinically relevant molecular pathways and potential chemotherapeutic drug metabolism mechanisms. Our results of precise surrogates using radiogenomics can lead to additional benefit from adjuvant chemotherapy and then survival prediction in postoperative GC patients.

Radio frequency mixing modules for superconducting qubit room temperature control systems.

As the number of qubits in nascent quantum processing units increases, the connectorized RF (radio frequency) analog circuits used in first generation experiments become exceedingly complex. The physical size, cost, and electrical failure rate all become limiting factors in the extensibility of control systems. We have developed a series of compact RF mixing boards to address this challenge by integrating I/Q quadrature mixing, intermediate frequency/LO (local oscillator)/RF power level adjustments, and direct current bias fine tuning on a 40 × 80 mm2 four-layer printed circuit board with electromagnetic interference shielding. The RF mixing module is designed to work with RF and LO frequencies between 2.5 and 8.5 GHz. The typical image rejection and adjacent channel isolation are measured to be ∼27 dBc and ∼50 dB. By scanning the drive phase in a loopback test, the module short-term amplitude and phase linearity are typically measured to be 5 ×10-4 (Vpp/Vmean) and 1 ×10-3 radian (pk-pk). The operation of the RF mixing board was validated by integrating it into the room temperature control system of a superconducting quantum processor and executing randomized benchmarking characterization of single and two qubit gates. We measured a single-qubit process infidelity of 9.3(3) × 10-4 and a two-qubit process infidelity of 2.7(1) × 10-2.

Ergonomic considerations when slotting piece-pick operations in distribution centers.

Many warehouse slotting algorithms have overlooked worker ergonomics. This research aimed to develop ergonomics slotting guidelines based upon the back and shoulder postures and electromyographic (EMG) responses of the deltoid and erector spinae muscles when individual items are picked from, or full cases replenished to, different shelf heights In the first study of two studies, participants lifted small items representative of piece-pick tasks from seven shelf heights. In the second study, participants performed a simulated full case replenishment task in which they lifted boxes weighing between 2.7 and 10.9 kg from a cart into a flow rack. Shelf height significantly affected all postural and EMG variables and there was a trade-off between back and shoulder muscle activity across the varying shelf heights. Together, these studies were used to develop some general ergonomic slotting guidelines that could be implemented to reduce biomechanical load exposures experienced by distribution center workers.

Identification of novel hepatitis B virus therapeutic vaccine candidates derived from polymerase protein.

Hepatitis B virus (HBV) infection is a worldwide health problem with high morbidity and mortality rates. The therapeutic vaccine is a promising method of treatment, and HBV polymerase plays a vital role in viral replication. Therefore, a therapeutic vaccine that binds to HBV DNA polymerase may control HBV infection. We predicted and selected epitopes of polymerase using online databases and analysis software. We then performed molecular docking and peptide binding assays to evaluate the binding energies and affinities between polymerase epitopes and the HLA-A0201 molecule. Finally, we induced T cells from the peripheral blood mononuclear cells (PBMCs) of healthy donors using each epitope and quantified the functions of epitope-specific T cells by IFN-γELISPOT assay, T2 cell cytotoxicity assay, HepG2.2.15 cell cytotoxicity assay and HBV gene expression assays. Four epitopes (RVTGGVFLV, GLLGFAAPF, LLDDEAGPL and YMDDVVLGA) had low binding energy and two epitopes (RVTGGVFLV and GLLGFAAPF) had a high binding affinity. The T cells stimulated by two epitopes (GLLGFAAPF and HLYSHPIIL) had a greater ability to induce immune response and suppress HBV. The HBV DNA polymerase epitopes identified in this study are promising targets for designing an epitope-based therapeutic vaccine against HBV.

Nickel isotopes link Siberian Traps aerosol particles to the end-Permian mass extinction.

The end-Permian mass extinction (EPME) was the most severe extinction event in the past 540 million years, and the Siberian Traps large igneous province (STLIP) is widely hypothesized to have been the primary trigger for the environmental catastrophe. The killing mechanisms depend critically on the nature of volatiles ejected during STLIP eruptions, initiating about 300 kyr before the extinction event, because the atmosphere is the primary interface between magmatism and extinction. Here we report Ni isotopes for Permian-Triassic sedimentary rocks from Arctic Canada. The δ60Ni data range from -1.09‰ to 0.35‰, and exhibit the lightest δ60Ni compositions ever reported for sedimentary rocks. Our results provide strong evidence for global dispersion and loading of Ni-rich aerosol particles into the Panthalassic Ocean. Our data demonstrate that environmental degradation had begun well before the extinction event and provide a link between global dispersion of Ni-rich aerosols, ocean chemistry changes, and the EPME.

The efficacy of a lifting strap as an ergonomic intervention for EMS providers: Does it make it easier to raise a supine patient to an upright sitting posture?

Patient handling related musculoskeletal injuries are prevalent among Emergency Medical Service (EMS) providers. The first step in many patient handling situations is where a supine patient on the floor is brought to a sitting position. This study investigated whether a strap, placed under the patient's torso and long enough that EMS providers can perform the patient raising task in a standing posture, reduced muscular effort. Fifteen participants raised a simulated patient, with the help of an assistant, using the strap method and a traditional method (grasping the shoulders) in an open area, a restricted space, and in a bathtub. Torso postures improved in all location conditions when using the strap. The muscle activation data showed mixed results. While EMG responses from the latissimus dorsi muscles were reduced, EMG activity of the erector spinae muscles increased when the strap was used. Perceived effort assessments supported the use of the strap.

Development and validation of a noninvasive clinical scoring system to predict significant fibrosis in patients with nonalcoholic fatty liver disease.

BACKGROUND: The aims of this study were to identify risk factors for significant fibrosis (SF) by assessing physical and laboratory parameters and develop and validate a clinical score and nomogram for the prediction of SF in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: This retrospective study included 225 patients with histologically confirmed NAFLD who were divided into two cohorts using 10-fold cross validation for model training and validation. The clinical score and nomogram were used to predict the NAFLD outcome. RESULTS: The model for predicting SF (stage ≥ 2) including the free T4/free T3 ratio, low-density lipoprotein cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), percentage of appendicular skeletal muscle mass and aspartate aminotransferase (AST) level in the training and validation cohorts yielded an area under the receiver operator characteristic curve (AUROC) of 0.79 and 0.78, respectively. The AUROC of the combined clinical score for the prediction of SF was 0.82 (95% CI, 0.75-0.89) at a cutoff value of 3 points, with a sensitivity (SE) of 77.19%, specificity (SP) of 82.88%, positive predictive value (PPV) of 63.77%, and negative predictive value (NPV) of 90.30%. The nomogram had good performance in quantitatively predicting the risk probability of SF. CONCLUSION: Our study showed that a noninvasive clinical scoring system using easily available physical and laboratory variables can identify patients with NAFLD with or without SF with a high degree of accuracy. Application of this system may decrease the need for staging liver biopsy specimens and allow early identification and intervention in these high-risk patients.

Simulation and Optimization of FEV Limit Discharge's Heat Dissipation Based on Orthogonal Experiments.

The temperature difference between batteries has effects on the performance of the battery packs of electric vehicles (EVs). Therefore, it is necessary to design a battery cooling management system. In order to reduce the maximum temperature difference of the cooling system of the Formula Electric Vehicle (FEV) automobile, the orthogonal experimental design method was adopted in this paper, and the temperature field of the FEV air-cooled cooling system structure under a short-time high-current discharge condition was simulated for many times. The maximum temperature difference after simulating optimization was about 7 K, and the overall optimization degree was close to 40%. The research results showed that the gap between the single battery and the battery pack was very important to heat dissipation.

Application of a drift compensation low-level radio frequency system based on time-multiplexing pick-up/reference signals.

The high accuracy, low drift low-level radio frequency (LLRF) system is essential for the long-term stability of the accelerator RF and the acquirement of low emittance, high intensity electron beams. A time-multiplexing pick-up/reference signal based LLRF system is proposed to deal with the component temperature related phase drift and has been deployed and applied at the Xi'an Gamma-ray Light Source (XGLS) injector. The long term dual-receiver out-of-loop stability experiments with a continuous wave laser based phase reference distribution system (PRDS) show that the LLRF system can achieve ∼40 fs Root-Mean-Square (rms) phase accuracy and 51 fs/52 fs peak-peak drift (in 7 days/17 h with the high power RF system, respectively) while the reference phase varies both ∼30 ps. An ∼4 h beam-based experiment has also been conducted to evaluate the overall performance of the whole XGLS timing and synchronization system, which shows that the PRDS, LLRF system, high power RF system, and laser oscillator laser-RF synchronization system can keep long-term phase stability.