Mask structure optimization for beyond EUV lithography.

Beyond extreme ultraviolet (BEUV) lithography with a 6 × nm wavelength is regarded as a future technique to continue the pattern shirking in integrated circuit (IC) manufacturing. This work proposes an optimization method for the mask structure to improve the imaging quality of BEUV lithography. Firstly, the structure of mask multilayers is optimized to maximize its reflection coefficient. Then, a mask diffraction near-field (DNF) model is established based on the Born series algorithm, and the aerial image of BEUV lithography system can be further calculated. Additionally, the mask absorber structure is inversely designed using the particle swarm optimization (PSO) algorithm. Simulation results show a significant improvement of the BEUV lithography imaging obtained by the proposed optimization methods. The proposed workflow can also be expanded to areas of EUV and soft x ray imaging.

Developing a nomogram-based scoring model to estimate the risk of pulmonary embolism in respiratory department patients suspected of pulmonary embolisms.

Objective: Pulmonary embolisms (PE) are clinically challenging because of their high morbidity and mortality. This study aimed to create a nomogram to accurately predict the risk of PE in respiratory department patients in order to enhance their medical treatment and management. Methods: This study utilized a retrospective method to collect information on medical history, complications, specific clinical characteristics, and laboratory biomarker results of suspected PE patients who were admitted to the respiratory department at Affiliated Dongyang Hospital of Wenzhou Medical University between January 2012 and December 2021. This study involved a total of 3,511 patients who were randomly divided into a training group (six parts) and a validation group (four parts) based on a 6:4 ratio. The LASSO regression and multivariate logistic regression were used to develop a scoring model using a nomogram. The performance of the model was evaluated using receiver operating characteristic curve (AUC), calibration curve, and clinical decision curve. Results: Our research included more than 50 features from 3,511 patients. The nomogram-based scoring model was established using six predictive features including age, smoke, temperature, systolic pressure, D-dimer, and fibrinogen, which achieved AUC values of 0.746 in the training cohort (95% CI 0.720-0.765) and 0.724 in the validation cohort (95% CI 0.695-0.753). The results of the calibration curve revealed a strong consistency between probability predicted by the nomogram and actual probability. The decision curve analysis (DCA) also demonstrated that the nomogram-based scoring model produced a favorable net clinical benefit. Conclusion: In this study, we successfully developed a novel numerical model that can predict the risk of PE in respiratory department patients suspected of PE, which can not only appropriately select PE prevention strategies but also decrease unnecessary computed tomographic pulmonary angiography (CTPA) scans and their adverse effects.

A nomogram for predicting the risk of pulmonary embolism in neurology department suspected PE patients: A 10-year retrospective analysis.

Objective: The purpose of this retrospective study was to establish a numerical model for predicting the risk of pulmonary embolism (PE) in neurology department patients. Methods: A total of 1,578 subjects with suspected PE at the neurology department from January 2012 to December 2021 were considered for enrollment in our retrospective study. The patients were randomly divided into the training cohort and the validation cohort in the ratio of 7:3. The least absolute shrinkage and selection operator regression were used to select the optimal predictive features. Multivariate logistic regression was used to establish the numerical model, and this model was visualized by a nomogram. The model performance was assessed and validated by discrimination, calibration, and clinical utility. Results: Our predictive model indicated that eight variables, namely, age, pulse, systolic pressure, hemoglobin, neutrophil count, low-density lipoprotein, D-dimer, and partial pressure of oxygen, were associated with PE. The area under the receiver operating characteristic curve of the model was 0.750 [95% confidence interval (CI): 0.721-0.783] in the training cohort and 0.742 (95% CI: 0.689-0.787) in the validation cohort, indicating that the model showed a good differential performance. A good consistency between the prediction and the real observation was presented in the training and validation cohorts. The decision curve analysis in the training and validation cohorts showed that the numerical model had a good net clinical benefit. Conclusion: We established a novel numerical model to predict the risk factors for PE in neurology department suspected PE patients. Our findings may help doctors to develop individualized treatment plans and PE prevention strategies.

GRP/GRPR signaling pathway aggravates hyperuricemia-induced renal inflammation and fibrosis via ABCG2-dependent mechanisms.

The gastrin-releasing peptide receptor (GRPR) binds to ligands such as gastrin-releasing peptide (GRP) and plays a variety of biological roles. In this study, we investigated the therapeutic effect of a novel gastrin-releasing peptide receptor antagonist RH-1402 in hyperuricemia-induced kidney fibrosis and its underlying mechanisms. We conducted enzyme linked immunosorbent assay (ELISA) and immunohistochemical analyses and found that proGRP and GRPR expression levels were significantly increased in patients with hyperuricemic nephropathy (HN) and HN mice. GRPR knockdown significantly attenuated inflammatory and fibrotic responses in adenosine-treated human proximal tubule epithelial cells. GRPR knockout or GRPR conditional knockout in renal tubular epithelial cells significantly alleviated the decline in renal function and fibrosis in HN mice in vivo. RNA-seq and String database analysis revealed that GRP/GRPR promoted HN by suppressing the ABCG2/PDZK1 and increasing TGF-ß/Smad3 levels by activating the NF-κB pathway. Overexpression of GRPR increased TGF-ß/Smad3 levels, where as it reduced ABCG2/PDZK1 levels in adenosine-treated HK2 cells, which was reversed by the NF-κB inhibitor. Furthermore, we evaluated the therapeutic effects of the novel GRPR inhibitor RH-1402 on hyperuricaemia-induced renal injury and evaluated the inflammatory and fibrosis responses in vivo and in vitro. Pre-treatment with RH-1402 attenuated hyperuricaemia-induced renal injury, restored renal function, and suppressed renal inflammation and fibrosis. Taken together, GRPR enhances hyperuricaemia-induced tubular injury, inflammation, and renal fibrosis via ABCG2-dependent mechanisms and may serve as a promising therapeutic target for HN treatment.

Genetic and Phenotype Analysis of a Chinese Cohort of Infants and Children With Epilepsy.

Background: Epilepsy in childhood is a common and diverse neurological disorder. We conducted a genetic and phenotype analysis of a Chinese cohort of infants and children with epilepsy. Methods: We conducted a pedigree analysis of 260 Chinese patients with epilepsy onset during infancy or childhood by whole exome sequencing (WES). Results: Of the 260 probands analyzed, a genetic diagnosis was established in 135 patients. One-hundred eighty-eight phenotypes were detected in those 135 positive/likely positive patients, 106 patients had more than two phenotypes, and 67 patients had more than three phenotypes. A total of 142 variants of 81 genes were detected among the positive/likely positive patients. Among these 142 variants, of which 87 of 66 genes were novel. Conclusion: Our findings extend the variant spectrum of genes related to epilepsy. Our results will be useful for genetic testing and counseling for patients with epilepsy.

A randomized, parallel control and multicenter clinical trial of evidence-based traditional Chinese medicine massage treatment VS External Diclofenac Diethylamine Emulgel for the treatment of knee osteoarthritis.

BACKGROUND: Both massage and topically administered NSAIDs are safe and effective treatments for knee osteoarthritis (KOA); however, different massage technique sects in China caused assessment difficulties for the treatment of KOA. In order to standardize the massage techniques and procedures, we organized multi-disciplinary experts in China to acquire an evidence-based traditional Chinese medicine massage treatment of knee osteoarthritis. The purposes of this study will be to provide clinicians a complementary and alternative therapy for patients and to evaluate the efficacy and safety of evidence-based traditional Chinese medicine massage treatment of KOA compared to External Diclofenac Diethylamine Emulgel. METHODS AND DESIGN: A randomized controlled trial in which 300 participants diagnosed with KOA will be recruited and randomly allocated to either the experimental group or the control group in a ratio of 2:1. Two hundred participants will receive evidence-based traditional Chinese medicine massage 2 sessions per week for 10 weeks as the experimental group, and 100 participants will receive External Diclofenac Diethylamine Emulgel 3-4 times per day for 10 weeks as the control group. The patients in the two groups will receive follow-up at two time points at 5 weeks and 10 weeks from the beginning of treatment, respectively. The MRI scans and X-ray will be performed at baseline and at the end of the intervention. The primary outcome will be the changes in the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Secondary outcomes will be measured by the PRO scale for knee osteoarthritis based on the concept of traditional Chinese medicine (Chinese scale for knee osteoarthritis (CSKO)), X-ray evaluation, and MRI scan evaluation. The data of WOMAC and CSKO will be analyzed at the baseline, 5 weeks, and 10 weeks from the beginning of treatment. The data from MRI scans and X-rays will be analyzed at baseline and at the end of the intervention. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session. DISCUSSION: This study will provide clinicians with much-needed knowledge for the treatment of KOA through a controlled trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800014400 . Registered on 10 January 2018.

An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells.

Although prostate cancer (CaP) is the most frequently diagnosed malignant tumor and the second leading cause of cancer deaths in American men, the mechanisms explaining the development and progression of CaP remain largely unknown. Recent studies have shown that some aberrantly expressed microRNAs (miRNAs) are involved in tumorigenesis. Although aberrant expression of certain miRNAs has been discovered in CaP, their function in this disease has not yet been defined. In this study, we found differential expression of miR-125b in androgen-dependent and independent CaP cells, as well as in benign and malignant prostate tissues. Furthermore, androgen signaling was able to up-regulate the expression of miR-125b. In addition, transfection of synthetic miR-125b stimulated androgen-independent growth of CaP cells and down-regulated the expression of Bak1. Our results suggest that miR-125b acts as an oncogene, contributing to the pathogenesis of CaP.