Application value of multi-gene mutation detection in the clinical management of pediatric papillary thyroid carcinoma: a preliminary exploration

ObjectivesThyroid cancer rarely occurs in children and adolescents. Molecular markers such as BRAF, RAS, and RET/PTC have been widely used in adult PTC. It is currently unclear whether these molecular markers have equivalent potential for application in pediatric patients. This study aims to explore the potential utility of a multi-gene conjoint analysis based on next-generation targeted sequencing for pediatric papillary thyroid carcinoma (PTC).Materials and methodsThe patients diagnosed with PTC (aged 18 years or younger) in the pediatrics department of Lishui District Hospital of Traditional Chinese Medicine were retrospectively screened. A targeted enrichment and sequencing analysis of 116 genes associated with thyroid cancer was performed on paraffin-embedded tumor tissues and paired paracancerous tissue of fifteen children (average age 14.60) and nine adults (average age 49.33) PTC patients. Demographic information, clinical indicators, ultrasonic imaging information and pathological data were collected. The Kendall correlation test was used to establish a correlation between molecular variations and clinical characteristics in pediatric patients.ResultsA sample of 15 pediatric PTCs revealed a detection rate of 73.33% (11/15) for driver gene mutations BRAF V600E and RET fusion. Compared to adult PTCs, the genetic mutation landscape of pediatric PTCs was more complex. Six mutant genes overlap between the two groups, and an additional seventeen unique mutant genes were identified only in pediatric PTCs. There was only one unique mutant gene in adult PTCs. The tumor diameter of pediatric PTCs tended to be less than 4cm (p<0.001), and the number of lymph node metastases was more than five (p<0.001). Mutations in specific genes unique to pediatric PTCs may contribute to the onset and progression of the disease by adversely affecting hormone synthesis, secretion, and action mechanisms, as well as the functioning of thyroid hormone signaling pathways. But, additional experiments are required to validate this hypothesis.ConclusionBRAF V600E mutation and RET fusion are involved in the occurrence and development of adolescent PTC. For pediatric thyroid nodules that cannot be determined as benign or malignant by fine needle aspiration biopsy, multiple gene combination testing can provide a reference for personalized diagnosis and treatment by clinical physicians

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The application of the instantaneous states reduction to the orbital monitoring of pivotal arcs of the Chang'E-1 satellite

In the Chinese lunar exploration project, the Chang'E-1 (CE-1) satellite was jointly monitored by the United S-band range and Doppler and the VLBI technique. A real-time reduction of the tracking data is realized to deduce the time series of the instantaneous state vectors (ISV) (position and velocity vectors) of the CE-1 satellite, and is applied to the orbital monitoring of pivotal arcs. This paper introduces this real-time data reduction method and its application to the orbital monitoring of pivotal arcs of the CE-1 satellite in order to serve as a source of criticism and reference

Specific Sensitivity Analysis and Imitative Full Stress Method for Optimal BCCZ Lattice Structure by Additive Manufacturing

Additive manufacturing (AM) can quickly and easily obtain lattice structures with light weight and excellent mechanical properties. Body-centered cubic (BCC) lattice structure is a basic type of lattice structure. BCC with Z strut (BCCZ) lattice structure is a derivative structure of BCC lattice structure, and it has good adaptability to AM. Generally, the thickness of each pillar in the BCCZ lattice structure is uniform, which results in the uneven stress distribution of each pillar. This makes the potential of light weight and high strength of the BCCZ lattice structure not fully played, and the utilization rate of materials can be further improved. This paper designs an optimization method. Through the structural analysis of a BCCZ lattice structure, an optimization method of a BCCZ lattice structure based on parametric modeling parameters is presented. The section radius of all pillars in the BCCZ lattice is taken as a design variable, and the specific sensitivity analysis method and simulated full stress optimization idea are successively used to determine the optimal section radius of each pillar. Finally, the corresponding model is designed and samples are manufactured by LPBF technology for simulation and experimental verification. The results of simulation and experiment show that the strength limit of the optimized parts increased by 18.77% and 18.43%, respectively, compared with that before optimization

Specific Sensitivity Analysis and Imitative Full Stress Method for Optimal BCCZ Lattice Structure by Additive Manufacturing

Additive manufacturing (AM) can quickly and easily obtain lattice structures with light weight and excellent mechanical properties. Body-centered cubic (BCC) lattice structure is a basic type of lattice structure. BCC with Z strut (BCCZ) lattice structure is a derivative structure of BCC lattice structure, and it has good adaptability to AM. Generally, the thickness of each pillar in the BCCZ lattice structure is uniform, which results in the uneven stress distribution of each pillar. This makes the potential of light weight and high strength of the BCCZ lattice structure not fully played, and the utilization rate of materials can be further improved. This paper designs an optimization method. Through the structural analysis of a BCCZ lattice structure, an optimization method of a BCCZ lattice structure based on parametric modeling parameters is presented. The section radius of all pillars in the BCCZ lattice is taken as a design variable, and the specific sensitivity analysis method and simulated full stress optimization idea are successively used to determine the optimal section radius of each pillar. Finally, the corresponding model is designed and samples are manufactured by LPBF technology for simulation and experimental verification. The results of simulation and experiment show that the strength limit of the optimized parts increased by 18.77% and 18.43%, respectively, compared with that before optimization