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关键词： basal insulin   body mass index   CSII   growth   type 1 diabetes  

摘要： Background Available basal insulin regimes differ in pharmacokinetic profiles, which may be related to subsequent changes in anthropometry in patients with type 1 diabetes. This analysis elucidates the standardized height and body mass index development (height and BMI standard deviation score [height-SDS and BMI-SDS]) in pediatric type 1 diabetes patients depending on the choice of basal insulin. Methods Longitudinal data of 10 338 German/Austrian patients from the Diabetes Prospective Follow-up (DPV, Diabetes Patienten Verlaufsdokumentation) database were analyzed. Patients aged 5.0 to 16.9 years were treated exclusively with neutral protamine Hagedorn (NPH), insulin detemir (IDet), insulin glargine (IGla), or continuous subcutaneous insulin infusion (CSII) for at least 3 years. Population-based German reference data were used to calculate height-SDS and BMI-SDS. Multiple linear regression was conducted. Results BMI-SDS increased significantly in all regimes (NPH P = .0365;IDet P = .0003;IGla P < .0001;and CSII P < .0001). Direct comparison of the therapies revealed a favorable association only for NPH vs IGla. A rise in BMI-SDS was observed for all insulins in females, but only for IGla in males. BMI-SDS increment was not observed before 8 years of age. Initially and at the end of the observation period, mean height was above the 50th percentile of the reference population. Across the cohort, height-SDS declined during the observation period, except for CSII. Apart from the 5.0- to 7.9-year-old subgroup, long-acting insulin analogues were associated with a significant loss of height-SDS. Conclusions Choice of basal insulin regimen might influence height development. CSII appeared to have a favorable effect on growth trajectories. All therapies were associated with an increase of BMI-SDS, most evident in females.

关键词： Non-small-cell lung cancer   Medicine/Public Health   general   Pathology   Laboratory Medicine  

摘要： For neoadjuvant therapy in patients with non-small cell lung cancer, the major pathologic response of primary tumors may be an assessable and reliable surrogate measure of survival. Few studies have examined the pathologic evaluation of metastatic lymph node responses and their prognostic significance. This retrospective study enrolled 336 patients with non-small cell lung cancer (squamous cell carcinoma, n = 216;adenocarcinoma, n = 120) treated with neoadjuvant therapy including chemotherapy (n = 316) and targeted therapy (adenocarcinoma, n = 20). The treatment response of the primary tumor and lymph node metastases (LNM) were pathologically assessed according to the multidisciplinary recommendations of the International Association for the Study of Lung Cancer. The relationship of overall survival (OS) and disease-free survival (DFS) with the responses of the primary tumor or LNM was analyzed. The optimal cutoff value of the residual viable tumor (%RVT) of the primary tumor was 12% for both OS (P < 0.001) and DFS (P < 0.001). The pathologic assessment identified LNM in 208 patients. The optimal %RVT cutoff value in LNM was 8% for both OS (P = 0.003) and DFS (P < 0.001). The Spearman's rank correlation coefficient between primary tumors and corresponding LNM was 0.487 for %RVT (P < 0.001), which indicated a positive correlation. On multivariable analysis, an RVT of the primary tumor <= 12% was an independent prognostic factor for improved OS (P = 0.024), whereas an RVT of LNM <= 8% was an independent prognostic factor for increased DFS (P = 0.018). Furthermore, in the neoadjuvant chemotherapy group, the optimal %RVT cutoff values for OS in patients with squamous cell carcinoma and adenocarcinoma in the primary tumor were 12% and 58%, respectively. Considering its convenience and operability in clinical application, a 10% threshold RVT value can be used for prognostic evaluation of LNM and primary tumors of squamous cell carcinoma histology;further studies are neede

关键词： adjuvant   cetuximab   head and neck squamous cell carcinoma   prospective studies   radiotherapy  

摘要： Background Cutaneous squamous cell carcinoma of the head/neck (CSCCHN) is common due to chronic sun exposure. As CSCCHN highly expresses EGFR, we prospectively studied postoperative concurrent cetuximab with radiotherapy for locally advanced CSCCHN (LA-CSCCHN). Materials and methods Single-institutional phase II trial of LA-CSCCHN (NCT XXXX). Adjuvant radiation was given with concurrent cetuximab. Primary endpoint of 2-year LRC and secondary objectives of 2-year disease-free survival (DFS) and 2-year OS were assessed by Kaplan-Meier analysis. Results Twenty-four patients ages 47-88 (median 71 years) were treated from 2014 to 2017. Fourteen patients had T3/4 disease, 5 had N1 disease, and 7 were N2/3. At median follow-up of 42 months, median OS and DFS was not reached and 64 months. Two-year OS was 75%, 2-year DFS was 70.8%. LRC was 91.1% at 2 years. All grade 3 adverse events were related to skin toxicity (12.5% radiation-related dermatitis, 16.7% cetuximab-related rash). Conclusions LRC compares favorably to historical data examining postoperative radiation alone but requires further investigation.

摘要： Background Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood. Objectives To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma. Methods Single-cell RNA sequencing (scRNA-seq) was performed and combined with T-cell and B-cell receptor sequencing. Results We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behaviour. Conclusions These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.

关键词： B-cell subsets   dengue fever   flow cytometry   follicular helper T cells  

摘要： Background Humoral immunity is thought to play a central role in mediating the immunopathogenesis of dengue virus (DENV) infection;however, the B-cell responses elicited by primary DENV2 infection are incompletely understood. Follicular helper T cells (Tfh) are important to promote B-cell activation and differentiation. Methods The present study analyzed the detailed dynamic changes of circulating B-cell subsets and Tfh (cTfh) using flow cytometry to explore their responses to DENV2 infection. Results Thirty-six patients with DENV2 and 21 healthy individuals were included. The results showed that CD27(+)CD38(+) plasmablasts emerged after DENV2 infection, and correlated with CXCR5(+)PD-1(+) or CXCR5(+)ICOS(+)PD-1(+) cTfh, which increased after DENV2 infection, and correlated with DENV2 RNA viral loads. Significantly low levels of CD27(-) naive B cells, and CD24(hi)CD27(hi) and CD24(hi)CD38(hi) regulatory B cells (Breg) were observed after DENV2 infection, which correlated negatively with CXCR5(+)PD-1(+) or CXCR5(+)ICOS(+)PD-1(+) cTfh cells. Conclusion Overall, these results provide insights into the DENV2-elicited B-cell response and revealed previously unidentified CD24(hi)CD27(hi) and CD24(hi)CD38(hi) Breg responses to DENV2 infection.

关键词： Stage IA   Prognostic   predictive risk stratification   Surgery   Lung adenocarcinoma   Plainum-doublet chemotherapy  

摘要： Following surgical resection, 250 stage I-IIA NSCLC patients underwent molecular risk stratification with a clinically-certified 14-gene prognostic assay. Molecular high-risk patients were prospectively advised to undergo adjuvant platinum-based chemotherapy (AC). Molecular risk was independent of EGFR mutation status and there was significantly better freedom from recurrence among high-risk patients who were treated with AC (97%) than untreated high-risk patients (72%). Background: A clinically-certified gene expression profile improved survival in a cohort of stage I-IIA NSCLC patients by identifying those likely to benefit from adjuvant intervention. EGFR mutation status has not provided this type of predictive risk discrimination in stage IA NSCLC, and overtreatment of low-risk stage IB patients may have limited the overall benefit seen recently in the adjuvant application of a third-generation TKI. We compared EGFR mutation data to molecular risk stratification in a prospective, early-stage cohort. Materials and Methods: Two hundred fifty eligible stage I-IIA non-squamous NSCLC patients underwent prospective molecular risk stratification by the 14-gene prognostic assay. Platinum doublet adjuvant chemotherapy (AC) was recommended for molecular high-risk (MHR). Differences in freedom from recurrence (FFR) and disease-free survival (DFS) were evaluated. Results: At 29 months, prospective molecular testing yielded an estimated FFR of 94.6% and 72.4% in low-risk and untreated MHR patients, respectively, and 97.0% among MHR patients receiving AC ( P < .001). In contrast, there was no association between EGFR status and recurrence, while molecular risk predicted survival and response to AC within both the EGFR mutation( + ) and mutation(-) populations. Sixty-seven percent of EGFR( + ) and 49% of EGFR(-) patients were molecular low-risk. Conclusion: This prospective study demonstrates the utility of the 14-gene assay independent of EGFR mutation. Basing adjuvant interv

关键词： Quantum machine learning   Image classification   Deep learning   Hybrid model  

摘要： Deep learning algorithms gained prominence in analyzing images for real-time applications such as detection of objects, segmentation of instances, semantic segmentation, and classification of image scenes. However, deep learning models for image classification, such as convolutional neural networks, require extensive computational facilities. Also, training such models with multiple layers becomes complex as many trainable parameters are to be optimized. Quantum computing emerged as a research area to handle complex problems using quantum-mechanical properties for computation on a quantum computer. In this work, we primarily focus on designing a hybrid quantum-classical deep learning model for image scene classification. We propose a novel hybrid architecture that uses quantum computation for feature extraction and classical computation for scene classification. In the hybrid architecture, we use quantum measurement-based features to obtain the quantum representations of images. The obtained quantum representations of images are used to train and build a classical deep learning model for image scene classification. Our experiments performed on ibm_santiago quantum computer show that the proposed model is suitable for implementation on noisy intermediate scaled quantum computers. Our experimental results show that the proposed model can classify data efficiently using trainable parameters approximate to 27-30% less than the state-of-the-art models on satellite image datasets. Hence, the complexity of training the deep learning models reduces as the number of parameters to be optimized reduces. Using the proposed architecture, the deep learning model can classify data with an overall accuracy of 95.89%, 86.13%, and 79.32% on UC Merced Land-Use, AID, and NWPU-RESISC45 datasets, respectively, for image scene classification.

关键词： Disease genetics   Macroautophagy   Neural ageing   Neurological disorders   Proteases  

摘要： A Correction to this paper has been published: https://***/10.1038/s41418-021-00783-2

关键词： cell therapy   mesenchymal stromal   stem cells   MSCs   myocardial infarction   regenerative medicine   umbilical cord   Wharton's jelly  

摘要： Although biologically appealing, the concept of tissue regeneration underlying first- and second-generation cell therapies has failed to translate into consistent results in clinical trials. Several types of cells from different origins have been tested in pre-clinical models and in patients with acute myocardial infarction (AMI). Mesenchymal stromal cells (MSCs) have gained attention because of their potential for immune modulation and ability to promote endogenous tissue repair, mainly through their secretome. MSCs can be easily obtained from several human tissues, the umbilical cord being the most abundant source, and further expanded in culture, making them attractive as an allogeneic "of-the-shelf" cell product, suitable for the AMI setting. The available evidence concerning umbilical cord-derived MSCs in AMI is reviewed, focusing on large animal pre-clinical studies and early human trials. Molecular and cellular mechanisms as well as current limitations and possible translational solutions are also discussed. (c) 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.