Nondestructive monitoring of annealing and chemical-mechanical planarization behavior using ellipsometry and deep learning.

The Cu-filling process in through-silicon via (TSV-Cu) is a key technology for chip stacking and three-dimensional vertical packaging. During this process, defects resulting from chemical-mechanical planarization (CMP) and annealing severely affect the reliability of the chips. Traditional methods of defect characterization are destructive and cumbersome. In this study, a new defect inspection method was developed using Mueller matrix spectroscopic ellipsometry. TSV-Cu with a 3-µm-diameter and 8-µm-deep Cu filling showed three typical types of characteristics: overdishing (defect-OD), protrusion (defect-P), and defect-free. The process dimension for each defect was 13 nm. First, the three typical defects caused by CMP and annealing were investigated. With single-channel deep learning and a Mueller matrix element (MME), the TSV-Cu defect types could be distinguished with an accuracy rate of 99.94%. Next, seven effective MMEs were used as independent channels in the artificial neural network to quantify the height variation in the Cu filling in the z-direction. The accuracy rate was 98.92% after training, and the recognition accuracy reached 1 nm. The proposed approach rapidly and nondestructively evaluates the annealing bonding performance of CMP processes, which can improve the reliability of high-density integration.

Immunological classification of glioblastoma and its prognostic implications.

OBJECTIVES: The progress of immunotherapy for glioblastoma (GBM) is currently slow. To improve immunotherapy, we need a deeper understanding of the immune microenvironment of GBM. Here, we aimed to establish a classification system based on immune expression profile in GBM. METHODS: Immune gene expression profiles of 152 patients with GBM from The Cancer Genome Atlas (TCGA) were used to identify subtypes by consensus clustering, and the classification system was reproduced in the two validation datasets (CGGA and GSE16011). Clinical information, molecular characteristics, immune infiltration, and genomic variation were integrated to characterize the subtypes. RESULTS: Two distinct immune subtypes in GBM were successfully identified and validated. The Im2 subtype was closely related to IDH-wildtype and combined +7/-10, while the Im1 subtype was associated with IDH mutation. Survival curve analysis showed that the Im2 subtype was associated with significantly shorter survival than the Im1 subtype. Im2 showed a high immune score and stromal score, low tumor purity, enrichment of macrophages, and high immune checkpoint and HLA gene expression. Im1 was characterized by low immune score and stromal score, high tumor purity, enrichment of lymphocytes, and low immune checkpoint and HLA gene expression. Finally, we developed an immune-related signature in GBM with better prognosis prediction. CONCLUSIONS: Our study confirmed the immune heterogeneity of GBM and might provide valuable classification for immunotherapy.

Prognostic Factors and Treatments Efficacy in Spontaneous Spinal Epidural Hematoma: A Multicenter Retrospective Study.

BACKGROUND AND OBJECTIVES: Spontaneous spinal epidural hematoma (SSEH) is an uncommon but serious condition with a high morbidity rate. Although SSEH is related to numerous risk factors, its etiology remains unclear. There is a paucity of data on its prognostic factors. We aim to evaluate prognostic factors for SSEH in this study. METHOD: A retrospective study was performed on patients who were admitted for SSEH in 3 academic neurosurgical centers from January 2010 to June 2021. Clinical parameters, including clinical condition on admission, anticoagulants use, imaging modality, the timing and type of surgery performed, and outcomes, were collected. Prognostic factors were analyzed. The Frankel scale was used to assess the clinical condition. RESULTS: A total of 105 patients with SSEH were retrieved from medical records, with a mean age of 51.3 years. Eighty-three patients (79%) complained of acute onset of severe neck or back pain. Eighty-two patients (78%) suffered from moderate to severe neurologic deficits (Frankel scale A-C). Anticoagulation usage was found in 20% of cases. Lower thoracic spine (p = 0.046), use of anticoagulants (p = 0.019), sphincter function disfunction (p = 0.008), severe neurologic deficits at admission (p < 0.001), and rapid deterioration (<1 hour, p = 0.004) were found to be associated with poor outcomes. Surgical decompression was performed in 74 (70%) cases. The univariate and multivariate analysis revealed that preoperative severe neurologic deficits (p = 0.005) and extended paraplegia time (>12 hours, p = 0.004) were independent adverse prognostic factors. The univariate analysis revealed that lower thoracic spine location (p = 0.08) and rapid progression (<6 hours, p = 0.005) were correlated with poor prognosis, but the multivariate analysis failed to identify them as independent prognostic factors. DISCUSSION: Adverse prognostic factors for SSEH might include thoracic segment location, use of anticoagulation, severe neurologic deficits on admission, sphincter dysfunction, and rapid progression. Preoperative neurologic deficit and extended paraplegia time were strongly correlated with the prognosis in the subset of patients who underwent surgical decompression. Timely surgical decompression is recommended for patients with moderate/severe neurologic deficits or progressive neurologic deterioration.

Diagnostic performance evaluation of adult Chiari malformation type I based on convolutional neural networks.

PURPOSE: This study aimed to evaluate the diagnostic performance of convolutional neural network (CNN) models in Chiari malformation type I (CMI) and to verify whether CNNs can identify the morphological features of the craniocervical junction region between patients with CMI and healthy controls (HCs). To date, numerous indicators based on manual measurements are used for the diagnosis of CMI. However, the corresponding postoperative efficacy and prognostic evaluations have remained inconsistent. From a diagnostic perspective, CNN models may be used to explore the relationship between the clinical features and image morphological parameters. METHODS: This study included a total of 148 patients diagnosed with CMI at our institution and 205 HCs were included. T1-weighted sagittal magnetic resonance imaging (MRI) images were used for the analysis. A total of 220 and 355 slices were acquired from 98 patients with CMI and 155 HCs, respectively, to train and validate the CNN models. In addition, median sagittal images obtained from 50 patients with CMI and 50 HCs were selected to test the models. We applied original cervical MRI images (CI) and images of posterior cranial fossa and craniocervical junction area (CVI) to train the CI- and CVI-based CNN models. Transfer learning and data augmentation were used for model construction and each model was retrained 10 times. RESULTS: Both the CI- and CVI-based CNN models achieved high diagnostic accuracy. In the validation dataset, the models had diagnostic accuracy of 100% and 97% (p = 0.005), sensitivity of 100% and 98% (p = 0.016), and specificity of 100% (p = 0.929), respectively. In the test dataset, the accuracy was 97% and 96% (p = 0.25), sensitivity was 97% and 92% (p = 0.109), and specificity was 100% (p = 0.123), respectively. For patients with cerebellar subungual herniation less than 5 mm, three out of the 10 CVI-based retrained models reached 100% sensitivity. CONCLUSIONS: Our results revealed that the CNN models demonstrated excellent diagnostic performance for CMI. The models had higher sensitivity than the application of cerebellar tonsillar herniation alone and could identify features in the posterior cranial fossa and craniocervical junction area of patients. Our preliminary experiments provided a feasible method for the diagnosis and study of CMI using CNN models. However, further studies are needed to identify the morphologic characteristics of patients with different clinical outcomes, as well as patients who may benefit from surgery.

Identification and Fine Mapping of the Recessive Gene BK-5, Which Affects Cell Wall Biosynthesis and Plant Brittleness in Maize.

The cellulose of the plant cell wall indirectly affects the cell shape and straw stiffness of the plant. Here, the novel brittleness mutant brittle stalk-5 (bk-5) of the maize inbred line RP125 was characterized. We found that the mutant displayed brittleness of the stalk and even the whole plant, and that the brittleness phenotype existed during the whole growth period from germination to senescence. The compressive strength was reduced, the cell wall was thinner, and the cellulose content was decreased compared to that of the wild type. Genetic analysis and map-based cloning indicated that bk-5 was controlled by a single recessive nuclear gene and that it was located in a 90.2-Kb region on chromosome 3 that covers three open reading frames (ORFs). Sequence analysis revealed a single non-synonymous missense mutation, T-to-A, in the last exon of Zm00001d043477 (B73: version 4, named BK-5) that caused the 951th amino acid to go from leucine to histidine. BK-5 encodes a cellulose synthase catalytic subunit (CesA), which is involved with cellulose synthesis. We found that BK-5 was constitutively expressed in all tissues of the germinating stage and silking stage, and highly expressed in the leaf, auricula, and root of the silking stage and the 2-cm root and bud of the germinating stage. We found that BK-5 mainly localized to the Golgi apparatus, suggesting that the protein might move to the plasma membrane with the aid of Golgi in maize. According to RNA-seq data, bk-5 had more downregulated genes than upregulated genes, and many of the downregulated genes were enzymes and transcription factors related to cellulose, hemicellulose, and lignin biosynthesis of the secondary cell wall. The other differentially expressed genes were related to metabolic and cellular processes, and were significantly enriched in hormone signal transduction, starch and sucrose metabolism, and the plant-pathogen interaction pathway. Taken together, we propose that the mutation of gene BK-5 causes the brittle stalk phenotype and provides important insights into the regulatory mechanism of cellulose biosynthesis and cell wall development in maize.

Multi-View Laser Point Cloud Global Registration for a Single Object.

Global registration is an important step in the three-dimensional reconstruction of multi-view laser point clouds for moving objects, but the severe noise, density variation, and overlap ratio between multi-view laser point clouds present significant challenges to global registration. In this paper, a multi-view laser point cloud global registration method based on low-rank sparse decomposition is proposed. Firstly, the spatial distribution features of point clouds were extracted by spatial rasterization to realize loop-closure detection, and the corresponding weight matrix was established according to the similarities of spatial distribution features. The accuracy of adjacent registration transformation was evaluated, and the robustness of low-rank sparse matrix decomposition was enhanced. Then, the objective function that satisfies the global optimization condition was constructed, which prevented the solution space compression generated by the column-orthogonal hypothesis of the matrix. The objective function was solved by the Augmented Lagrange method, and the iterative termination condition was designed according to the prior conditions of single-object global registration. The simulation analysis shows that the proposed method was robust with a wide range of parameters, and the accuracy of loop-closure detection was over 90%. When the pairwise registration error was below 0.1 rad, the proposed method performed better than the three compared methods, and the global registration accuracy was better than 0.05 rad. Finally, the global registration results of real point cloud experiments further proved the validity and stability of the proposed method.

Real-time ultrasound-MRI fusion image virtual navigation for locating intraspinal tumour in a pregnant woman.

BACKGROUND: Standard fluoroscopic guidance (C-arm fluoroscopy) has been routinely used for intraoperative localization of spinal level for surgical removal of intraspinal tumour, while it is not suitable for selected patients, e.g. pregnant women, who need to avoid radiation exposure. Fusion imaging of real-time ultrasound (US) and magnetic resonance imaging (MRI) is a radiation-free technique which has been reported to have good localization accuracy in managing several conditions. CLINICAL PRESENTATION: A 37-year-old pregnant patient, presented with a progressively aggravating lower back pain for 20 days and was incapable of lying supine with lower extremities swelling for 1 week, was referred to our hospital in her 18th week of gestation. Lumbar MRI identified an L1 level intraspinal lesion, and surgery was planned. To avoid the ionizing radiation generated by fluoroscopy, volume navigation technique (VNT) based fusion imaging of US and MRI was used to localize the intraspinal lesion, which was removed entirely via minimally invasive interlaminar approach. Pathological examination confirmed the diagnosis of ependymoma of the conus medullaris. Her symptoms were largely relieved after the operation, and a healthy baby was delivered at the 40th week of pregnancy. CONCLUSION: We presented the first case of using VNT based fusion imaging of real-time US/MRI to guide the surgical resection of an intraspinal tumour. Future study with larger patient number is needed to validate this technique as an alternative to fluoroscopy in patients who need to avoid radiation exposure.

L-Cysteine enhances nutrient absorption via a cystathionine-ß-synthase-derived H2 S pathway in rodent jejunum.

Hydrogen sulphide (H2 S) is generated endogenously from L-cysteine (L-Cys) by the enzymes cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE). In addition, L-Cys is commonly used as a precursor in the food and pharmaceutical industries. The aim of the present study is to determine whether L-Cys regulates intestinal nutrient transport. To that end, the presence of CBS and CSE in the jejunum epithelium was assessed by immunohistochemistry, Western blotting and the methylene blue assay. In addition, in vivo L-Cys (100 mg/kg, administered immediately after the glucose load) significantly increased blood glucose levels 30 min after the oral administration of glucose to mice. This effect of L-Cys was completely blocked by amino-oxyacetic acid (AOA; 50 mg/kg; administered at the same time as L-Cys) an inhibitor of CBS. Measurements of the short-circuit current (Isc) in the rat jejunum epithelium revealed that L-Cys (1 mmol/L; 6 min before the administration of L-alanine) enhances Na(+)-coupled L-alanine or glucose transport, and that this effect is inhibited by AOA (1 mmol/L;10 min before the administration of L-Cys), but not D,L-propargylglycine (PAG;1 mmol/L; 10 min before the administration of L-Cys), a CSE inhibitor. Notably, L-Cys-evoked enhancement of nutrient transport was alleviated by glibenclamide (Gli;0.1 mmol/L; 10 min before the administration of L-Cys), a K(+) channel blocker. Together, the data indicate that L-Cys enhances jejunal nutrient transport, suggesting a new approach to future treatment of nutrition-related maladies, including a range of serious health consequences linked to undernutrition.

Chloroquine stimulates Cl- secretion by Ca2+ activated Cl- channels in rat ileum.

Chloroquine (CQ), a bitter tasting drug widely used in treatment of malaria, is associated gastrointestinal side effects including nausea or diarrhea. In the present study, we investigated the effect of CQ on electrolyte transport in rat ileum using the Ussing chamber technique. The results showed that CQ evoked an increase in short circuit current (ISC) in rat ileum at lower concentration (≤5×10(-4) M) but induced a decrease at higher concentrations (≥10(-3) M). These responses were not affected by tetrodotoxin (TTX). Other bitter compounds, such as denatoniumbenzoate and quinine, exhibited similar effects. CQ-evoked increase in ISC was partly reduced by amiloride(10(-4) M), a blocker of epithelial Na(+) channels. Furosemide (10(-4) M), an inhibitor of Na(+)-K(+)-2Cl(-) co-transporter, also inhibited the increased ISC response to CQ, whereas another Cl(-) channel inhibitor, CFTR(inh)-172(10(-5) M), had no effect. Intriguingly, CQ-evoked increases were almost completely abolished by niflumic acid (10(-4) M), a relatively specific Ca(2+)-activated Cl(-) channel (CaCC) inhibitor. Furthermore, other CaCC inhibitors, such as DIDS and NPPB, also exhibited similar effects. CQ-induced increases in ISC were also abolished by thapsigargin(10(-6) M), a Ca(2+) pump inhibitor and in the absence of either Cl(-) or Ca(2+) from bathing solutions. Further studies demonstrated that T2R and CaCC-TMEM16A were colocalized in small intestinal epithelial cells and the T2R agonist CQ evoked an increase of intracelluar Ca(2+) in small intestinal epithelial cells. Taken together, these results demonstrate that CQ induces Cl(-) secretion in rat ileum through CaCC at low concentrations, suggesting a novel explanation for CQ-associated gastrointestinal side-effects during the treatment of malaria.