Assessing Axillary Lymph Node Burden and Prognosis in cT1-T2 Stage Breast Cancer Using Machine Learning Methods: A Retrospective Dual-Institutional MRI Study.

BACKGROUND: Pathological axillary lymph node (pALN) burden is an important factor for treatment decision-making in clinical T1-T2 (cT1-T2) stage breast cancer. Preoperative assessment of the pALN burden and prognosis aids in the individualized selection of therapeutic approaches. PURPOSE: To develop and validate a machine learning (ML) model based on clinicopathological and MRI characteristics for assessing pALN burden and survival in patients with cT1-T2 stage breast cancer. STUDY TYPE: Retrospective. POPULATION: A total of 506 females (range: 24-83 years) with cT1-T2 stage breast cancer from two institutions, forming the training (N = 340), internal validation (N = 85), and external validation cohorts (N = 81), respectively. FIELD STRENGTH/SEQUENCE: This study used 1.5-T, axial fat-suppressed T2-weighted turbo spin-echo sequence and axial three-dimensional dynamic contrast-enhanced fat-suppressed T1-weighted gradient echo sequence. ASSESSMENT: Four ML methods (eXtreme Gradient Boosting [XGBoost], Support Vector Machine, k-Nearest Neighbor, Classification and Regression Tree) were employed to develop models based on clinicopathological and MRI characteristics. The performance of these models was evaluated by their discriminative ability. The best-performing model was further analyzed to establish interpretability and used to calculate the pALN score. The relationships between the pALN score and disease-free survival (DFS) were examined. STATISTICAL TESTS: Chi-squared test, Fisher's exact test, univariable logistic regression, area under the curve (AUC), Delong test, net reclassification improvement, integrated discrimination improvement, Hosmer-Lemeshow test, log-rank, Cox regression analyses, and intraclass correlation coefficient were performed. A P-value <0.05 was considered statistically significant. RESULTS: The XGB II model, developed based on the XGBoost algorithm, outperformed the other models with AUCs of 0.805, 0.803, and 0.818 in the three cohorts. The Shapley additive explanation plot indicated that the top variable in the XGB II model was the Node Reporting and Data System score. In multivariable Cox regression analysis, the pALN score was significantly associated with DFS (hazard ratio: 4.013, 95% confidence interval: 1.059-15.207). DATA CONCLUSION: The XGB II model may allow to evaluate pALN burden and could provide prognostic information in cT1-T2 stage breast cancer patients. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Ecobehavioural analysis of academic engagement of children with intellectual disabilities in Chinese mainstream schools.

This study examined teacher behaviours, students' academic engagement, and classroom ecology in mainstream classrooms including children with intellectual disabilities, and examined the differences in academic engagement for students with and without intellectual disabilities. A mixed-method research methodology was employed. The study demonstrated that children with intellectual disabilities exhibited high level of engagement in the following situations: the classroom layout used grouping, the classroom organisation combined groups and independent learning, the learning tasks included reading aloud, copying, watching videos, and doing homework, and teachers paid attention to all students or to children with intellectual disabilities individually and walked around the classroom during lesson time. English was the discipline with most active engagement among children with intellectual disabilities, followed by music, art, science, Chinese, sports, social studies, and mathematics. Finally, academic engagement of children with and without intellectual disabilities was mostly passive. We discuss the factors related to academic engagement of children with intellectual disabilities and provide suggestions for improving their self-management skills and classroom organisation.

Much more than just being present: participation of children with intellectual disabilities in mainstream schools.

Although school engagement is crucial to child development, research on children with intellectual disabilities in mainstream schools is scant. This sequential, explanatory mixed-methods study examined the ways in and extent to which children with intellectual disabilities participate in mainstream school activities, as well the personal and environmental factors that affect their participation. A total of 101 general teachers provided quantitative data, while eight children with intellectual impairments and their teachers and peers provided qualitative data. In the quantitative survey, no significant differences were observed between children with and those without intellectual disabilities regarding school absence, but a low similarity existed in their extent of participation. Children with intellectual disabilities engaged most frequently in life-skills and after-school activities and least frequently in social and volunteer activities. School participation was affected by the degree of disability and environmental variables. We derived two themes from qualitative research: (1) school participation of children with intellectual disabilities; and (2) factors associated with school participation of children with intellectual disabilities. The results suggest strategies that may promote the participation of children with intellectual disabilities in mainstream schools.

One-pot conversion of xylose to 1,2-pentanediol catalyzed by an organic acid-assisted Pt/NC in aqueous phase.

The direct synthesis of 1,2-pentanediol (1,2-PeD) from renewable xylose and its derivatives derived from hemicellulose is appealing yet challenging due to its low selectivity for the target product. In this study, one-pot catalytic conversion of xylose to 1,2-PeD was performed by using nitrogen-doped carbon (NC) supported Pt catalysts with the assistance of organic acids. A remarkable yield of 49.3% for 1,2-PeD was achieved by reacting 0.1869 g xylose in 30 mL water at 200 °C under a hydrogen pressure of 3 MPa for 8 h in the presence of 0.1 g of 2.5Pt/NC600 catalyst and 0.1869 g propanoic acid co-catalyst. The presence of vicinal Pt-acid pair sites on the surface of the 2.5Pt/NC600 catalyst exhibited a synergistic effect in promoting the hydrogenation of furfural to furfuryl alcohol intermediate and subsequent hydrogenation and ring-opening reactions leading to the formation of 1,2-PeD. The addition of organic acids, may serve as both acid catalyst for dehydration of xylose and hydrogen donor for hydrogenation of furfural and furfuryl alcohol, thereby promoting the one-pot conversion of xylose to 1,2-PeD. Remarkably, the 2.5Pt/NC600 catalyst demonstrated outstanding catalytic performance and good reusability over five consecutive cycles without significant deactivation.

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .

Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, EGFR-mutated, advanced non-small cell lung cancer: data from a randomized phase III trial (AENEAS).

BACKGROUND: The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. METHODS: Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS). RESULTS: Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. CONCLUSIONS: These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03849768.

Development and validation of machine learning models for predicting HER2-zero and HER2-low breast cancers.

OBJECTIVES: To develop and validate machine learning models for human epidermal growth factor receptor 2 (HER2)-zero and HER2-low using MRI features pre-neoadjuvant therapy (NAT). METHODS: Five hundred and sixteen breast cancer patients post-NAT surgery were randomly divided into training (n = 362) and internal validation sets (n = 154) for model building and evaluation. MRI features (tumour diameter, enhancement type, background parenchymal enhancement, enhancement pattern, percentage of enhancement, signal enhancement ratio, breast oedema, and apparent diffusion coefficient) were reviewed. Logistic regression (LR), support vector machine (SVM), k-nearest neighbour (KNN), and extreme gradient boosting (XGBoost) models utilized MRI characteristics for HER2 status assessment in training and validation datasets. The best-performing model generated a HER2 score, which was subsequently correlated with pathological complete response (pCR) and disease-free survival (DFS). RESULTS: The XGBoost model outperformed LR, SVM, and KNN, achieving an area under the receiver operating characteristic curve (AUC) of 0.783 (95% CI, 0.733-0.833) and 0.787 (95% CI, 0.709-0.865) in the validation dataset. Its HER2 score for predicting pCR had an AUC of 0.708 in the training datasets and 0.695 in the validation dataset. Additionally, the low HER2 score was significantly associated with shorter DFS in the validation dataset (hazard ratio: 2.748, 95% CI, 1.016-7.432, P = .037). CONCLUSIONS: The XGBoost model could help distinguish HER2-zero and HER2-low breast cancers and has the potential to predict pCR and prognosis in breast cancer patients undergoing NAT. ADVANCES IN KNOWLEDGE: HER2-low-expressing breast cancer can benefit from the HER2-targeted therapy. Prediction of HER2-low expression is crucial for appropriate management. MRI features offer a solution to this clinical issue.

Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer.

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Magnesium alleviates growth inhibition under low potassium by enhancing photosynthesis and carbon-nitrogen metabolism in apple plants.

Potassium (K) and magnesium (Mg) play analogous roles in regulating plant photosynthesis and carbon and nitrogen (C-N) metabolism. Based on this consensus, we hypothesize that appropriate Mg supplementation may alleviate growth inhibition under low K stress. We monitored morphological, physiological, and molecular changes in G935 apple plants under different K (0.1 and 6 mmol L-1) and Mg supply (3 and 6 mmol L-1) conditions. Low K stress caused changes in root and leaf structure, inhibited photosynthesis, and limited the root growth of the apple rootstock. Further study on Mg supplementation showed that it could promote the uptake of K+ and NO3- by upregulating the expression of K+ transporter proteins such as Arabidopsis K+ transporter 1 (MdAKT1), high-affinity K+ transporter 1 (MdHKT1), and potassium transporter 5 (MdPT5) and nitrate transporters such as nitrate transporter 1.1/1.2/2.1/2.4 (MdNRT 1.1/1.2/2.1/2.4). Mg promoted the translocation of 15N from roots to leaves and enhanced photosynthetic N utilization efficiency (PNUE) by increasing the proportion of photosynthetic N and alleviating photosynthetic restrictions. Furthermore, Mg supplementation improved the synthesis of photosynthates by enhancing the activities of sugar-metabolizing enzymes (Rubisco, SS, SPS, S6PDH). Mg also facilitated the transport of sucrose and sorbitol from leaves to roots by upregulating the expression of sucrose transporter 1.1/1.2/4.1/4.2 (MdSUT 1.1/1.2/4.1/4.2) and sorbitol transporter 1.1/1.2 (MdSOT 1.1/1.2). Overall, Mg effectively alleviated growth inhibition in apple rootstock plants under low K stress by facilitating the uptake of N and K uptake, optimizing nitrogen partitioning, enhancing nitrogen use efficiency (NUE) and PNUE, and promoting the photosynthate synthesis and translocation.

Hyb_SEnc: An Antituberculosis Peptide Predictor Based on a Hybrid Feature Vector and Stacked Ensemble Learning.

Tuberculosis has plagued mankind since ancient times, and the struggle between humans and tuberculosis continues. Mycobacterium tuberculosis is the leading cause of tuberculosis, infecting nearly one-third of the world's population. The rise of peptide drugs has created a new direction in the treatment of tuberculosis. Therefore, for the treatment of tuberculosis, the prediction of anti-tuberculosis peptides is crucial.This paper proposes an anti-tuberculosis peptide prediction method based on hybrid features and stacked ensemble learning. First, a random forest (RF) and extremely randomized tree (ERT) are selected as first-level learning of stacked ensembles. Then, the five best-performing feature encoding methods are selected to obtain the hybrid feature vector, and then the decision tree and recursive feature elimination (DT-RFE) are used to refine the hybrid feature vector. After selection, the optimal feature subset is used as the input of the stacked ensemble model. At the same time, logistic regression (LR) is used as a stacked ensemble secondary learner to build the final stacked ensemble model Hyb_SEnc. The prediction accuracy of Hyb_SEnc achieved 94.68% and 95.74% on the independent test sets of AntiTb_MD and AntiTb_RD, respectively. In addition, we provide a user-friendly Web server (http://www.bioailab. com/Hyb_SEnc). The source code is freely available at https://github.com/fxh1001/Hyb_SEnc.

Telehealth With Comprehensive Live-Fed Real-World Data as a Patient Care Platform for Lung Cancer: Implementation and Evaluation Study.

BACKGROUND: Telehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. OBJECTIVE: The primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician's perspective. METHODS: A telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform's registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. RESULTS: Over a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. CONCLUSIONS: This study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.

YY1/circCTNNB1/miR-186-5p/YY1 positive loop aggravates lung cancer progression through the Wnt pathway.

Lung cancer is one familiar cancer that threatens the lives of humans. circCTNNB1 has been disclosed to have regulatory functions in some diseases. However, the functions and related regulatory mechanisms of circCTNNB1 in lung cancer remain largely indistinct. The mRNA and protein expression levels were examined through real-time polymerase chain reaction (RT-qPCR) and western blot. The cell proliferation was tested through CCK-8 assay. The cell migration and invasion were confirmed through Transwell assays. The cell senescence was evaluated through SA-ß-gal assay. The binding ability between miR-186-5p and circCTNNB1 (or YY1) was verified through luciferase reporter and RIP assays. In this study, the higher expression of circCTNNB1 was discovered in lung cancer tissues and cell lines and resulted in poor prognosis. In addition, circCTNNB1 facilitated lung cancer cell proliferation, migration, invasion, and suppressed cell senescence. Knockdown of circCTNNB1 retarded the Wnt pathway. Mechanism-related experiments revealed that circCTNNB1 combined with miR-186-5p to target YY1. Through rescue assays, YY1 overexpression could rescue decreased cell proliferation, migration, invasion, increased cell senescence, and retarded Wnt pathway mediated by circCTNNB1 suppression. Furthermore, YY1 acts as a transcription factor that can transcriptionally activate circCTNNB1 to form YY1/circCTNNB1/miR-186-5p/YY1 positive loop. Through in vivo assays, circCTNNB1 accelerated tumour growth in vivo. All findings revealed that a positive loop YY1/circCTNNB1/miR-186-5p/YY1 aggravated lung cancer progression by modulating the Wnt pathway.

Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous EGFR-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial.

PURPOSE: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC. METHODS: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review. RESULTS: In total, 172 patients with nonsquamous EGFR-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%). CONCLUSION: Teliso-V was associated with durable responses in c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

Supramolecular salicylic acid combined with niacinamide in chloasma: A randomized controlled trial.

BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma. METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%]. RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group. CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.

Mussel-Mimetic Hydrogel Coating with Anticoagulant and Antiinflammatory Properties on a Poly(lactic acid) Vascular Stent.

Biodegradable stents are the most promising alternatives for the treatment of cardiovascular disease nowadays, and the strategy of preparing functional coatings on the surface is highly anticipated for addressing adverse effects such as in-stent restenosis and stent thrombosis. Yet, inadequate mechanical stability and biomultifunctionality limit their clinical application. In this study, we developed a multicross-linking hydrogel on the polylactic acid substrates by dip coating that boasts impressive antithrombotic ability, antibacterial capability, mechanical stability, and self-healing ability. Gelatin methacryloyl, carboxymethyl chitosan, and oxidized sodium alginate construct a double-cross-linking hydrogel through the dynamic Schiff base chemical and in situ blue initiation reaction. Inspired by the adhesion mechanism employed by mussels, a triple-cross-linked hydrogel is formed with the addition of tannic acid to increase the adhesion and antibiofouling properties. The strength and hydrophilicity of hydrogel coating are regulated by changing the composition ratio and cross-linking degree. It has been demonstrated in tests in vitro that the hydrogel coating significantly reduces the adhesion of proteins, MC3T3-E1 cells, platelets, and bacteria by 85% and minimizes the formation of blood clots. The hydrogel coating also exhibits excellent antimicrobial in vitro and antiinflammatory properties in vivo, indicating its potential value in vascular intervention and other biomedical fields.

Nitrogen-potassium balance improves leaf photosynthetic capacity by regulating leaf nitrogen allocation in apple.

Nitrogen (N) and potassium (K) are two important mineral nutrients in regulating leaf photosynthesis. However, the influence of N and K interaction on photosynthesis is still not fully understood. Using a hydroponics approach, we studied the effects of different N and K conditions on the physiological characteristics, N allocation and photosynthetic capacity of apple rootstock M9T337. The results showed that high N and low K conditions significantly reduced K content in roots and leaves, resulting in N/K imbalance, and allocated more N in leaves to non-photosynthetic N. Low K conditions increased biochemical limitation (BL), mesophyll limitation (MCL), and stomatal limitation (SL). By setting different N supplies, lowering N levels under low K conditions increased the proportion of water-soluble protein N (Nw) and sodium dodecyl sulfate-soluble proteins (Ns) by balancing N/K and increased the proportion of carboxylation N and electron transfer N. This increased the maximum carboxylation rate and mesophyll conductance, which reduced MCL and BL and alleviated the low K limitation of photosynthesis in apple rootstocks. In general, our results provide new insights into the regulation of photosynthetic capacity by N/K balance, which is conducive to the coordinated supply of N and K nutrients.

PSAC-6mA: 6mA site identifier using self-attention capsule network based on sequence-positioning.

DNA N6-methyladenine (6mA) modifications play a pivotal role in the regulation of growth, development, and diseases in organisms. As a significant epigenetic marker, 6mA modifications extensively participate in the intricate regulatory networks of the genome. Hence, gaining a profound understanding of how 6mA is intricately involved in these biological processes is imperative for deciphering the gene regulatory networks within organisms. In this study, we propose PSAC-6mA (Position-self-attention Capsule-6mA), a sequence-location-based self-attention capsule network. The positional layer in the model enables positional relationship extraction and independent parameter setting for each base position, avoiding parameter sharing inherent in convolutional approaches. Simultaneously, the self-attention capsule network enhances dimensionality, capturing correlation information between capsules and achieving exceptional results in feature extraction across multiple spatial dimensions within the model. Experimental results demonstrate the superior performance of PSAC-6mA in recognizing 6mA motifs across various species.

Examination of the adoption intention of new energy vehicles from the perspective of functional attributes and media richness.

Drawing on the theory of media richness, this paper aims to explore the impact of media richness on consumers' adoption intention through their perception of new energy vehicle (NEV) function attributes, and assess the moderation roles of brand familiarity and locus of control. A structural equation model is applied to analyze the data collected from 427 respondents. Empirical results demonstrate that consumers' perception of an electric attribute (i.e., charging efficiency) and two intelligent attributes (i.e., car networking and self-driving) are determinants of their adoption intention of NEVs. The other electric attribute (range) is trivial in consumers' perception. We also find that low, medium, and high-richness media significantly affect consumers' perception of NEVs' functional attributes. Compared to the high-richness, medium-richness correlates significantly with two types of NEV functional attributes. Regarding moderating effects, consumer familiarity with NEV's brand negatively impacts the relationship between media richness and adoption intention. Furthermore, low and medium-richness media effectively stimulate individuals with external control to adopt NEV, while high-richness media adversely influence individuals with internal control.