A precision medicine approach for psychiatric disease based on repeated symptom scores

For psychiatric diseases, rich information exists in the serial measurement of mental health symptom scores. We present a precision medicine framework for using the trajectories of multiple symptoms to make personalized predictions about future symptoms and related psychiatric events. Our approach fits a Bayesian hierarchical model that estimates a population-average trajectory for all symptoms and individual deviations from the average trajectory, then fits a second model that uses individual symptom trajectories to estimate the risk of experiencing an event. The fitted models are used to make clinically relevant predictions for new individuals. We demonstrate this approach on data from a study of antipsychotic therapy for schizophrenia, predicting future scores for positive, negative, and general symptoms, and the risk of treatment failure in 522 schizophrenic patients with observations over 8 weeks. While precision medicine has focused largely on genetic and molecular data, the complementary approach we present illustrates that innovative analytic methods for existing data can extend its reach more broadly. The systematic use of repeated measurements of psychiatric symptoms offers the promise of precision medicine in the field of mental health.     

人工智能在血吸虫病防控中的应用现状与前景

血吸虫病是一种严重危害人类健康、影响社会经济发展的寄生虫病。人工智能技术已广泛应用于肿瘤筛查、心电图、影像学与病理学分析等临床医学领域,并有望实现血吸虫病精准防控。目前,人工智能技术已应用于血吸虫病肝纤维化、异位血吸虫病临床评估,晚期血吸虫病预后预测,钉螺、虫卵、毛蚴自动检测,血吸虫病流行病学监测和药物发现等方面。本文对近年来人工智能技术在血吸虫病防控领域的应用进展与前景进行综述。     

Evaluating the accuracy (trueness and precision) of interim crowns manufactured using digital light processing according to post-curing time: An in vitro study

PURPOSEThis study aimed to compare the accuracy (trueness and precision) of interim crowns fabricated using DLP (digital light processing) according to post-curing time.MATERIALS AND METHODSA virtual stone study die of the upper right first molar was created using a dental laboratory scanner. After designing interim crowns on the virtual study die and saving them as Standard Triangulated Language files, 30 interim crowns were fabricated using a DLP-type 3D printer. Additively manufactured interim crowns were post-cured using three different time conditions-10-minute post-curing interim crown (10-MPCI), 20-minute post-curing interim crown (20-MPCI), and 30-minute post-curing interim crown (30-MPCI) (n = 10 per group). The scan data of the external and intaglio surfaces were overlapped with reference crown data, and trueness was measured using the best-fit alignment method. In the external and intaglio surface groups (n = 45 per group), precision was measured using a combination formula exclusive to scan data (₁₀C₂). Significant differences in accuracy (trueness and precision) data were analyzed using the Kruskal-Wallis H test, and post hoc analysis was performed using the Mann-Whitney U test with Bonferroni correction (α=.05).RESULTSIn the 10-MPCI, 20-MPCI, and 30-MPCI groups, there was a statistically significant difference in the accuracy of the external and intaglio surfaces (P <.05). On the external and intaglio surfaces, the root mean square (RMS) values of trueness and precision were the lowest in the 10-MPCI group.CONCLUSIONInterim crowns with 10-minute post-curing showed high accuracy.     

Segment-embedded frame definition affects the hip joint centre precision during walking

Due to marker-specific soft tissue artefacts, the choice of the markers defining the segment-embedded frame affects the functional joint centre location, with subsequent error propagation to joint kinematics and kinetics in gait analysis. Our aim was to assess the effect of the number and placement of markers on the precision of the hip joint centre (HJC) location during walking.Twelve markers (2 x 6) were attached to the pelvis and left thigh of 15 young male subjects. Set-up movements were collected to locate an optimised functional HJC. For all permutations of three from six markers, a HJC was located and subsequently reconstructed in a static trial and during walking. Precision measures with two different definitions of the origin, namely a single maker or their mean-point, and using three, four, five and six were calculated. Finally, marker triads that reduced the variability of the HJC location were determined. Both the number of markers and method for defining the origin significantly affected the HJC precision during static and walking trials. For walking, precision of 39 mm using three markers improved to 5 mm using redundant markers and the mean marker position as the segment origin. Markers placed close to the joint gave more consistent results.     

Precision of maxillo-mandibular registration with intraoral scanners in vitro

PurposeTo compare the precision of maxillo-mandibular registration and resulting full arch occlusion produced by three intraoral scanners in vitro.MethodsSix dental models (groups A–F) were scanned five times with intraoral scanners (CEREC, TRIOS, PLANMECA), producing both full arch and two buccal maxillo-mandibular scans. Total surface area of contact points (defined as regions within 0.1 mm and all mesh penetrations) was measured, and the distances between four pairs of key points were compared, each two in the posterior and anterior.ResultsTotal surface area of contact points varied significantly among scanners across all groups. CEREC produced the smallest contact surface areas (5.7–25.3 mm²), while PLANMECA tended to produce the largest areas in each group (22.2–60.2 mm²). Precision of scanners, as measured by the 95% CI range, varied from 0.1–0.9 mm for posterior key points. For anterior key points the 95% CI range was smaller, particularly when multiple posterior teeth were still present (0.04–0.42 mm). With progressive loss of posterior units (groups D–F), differences in the anterior occlusion among scanners became significant in five out of six groups (D–F left canines and D, F right canines, p < 0.05).ConclusionsMaxillo-mandibular registrations from three intraoral scanners created significantly different surface areas of occlusal contact. Posterior occlusions revealed lower precision for all scanners than anterior. CEREC tended towards incorrect posterior open bites, whilst TRIOS was most consistent in reproducing occluding units.     

Full arch precision of six intraoral scanners in vitro

PurposeIntraoral scanners may offer an alternative to traditional impressions. That intraoral scanners produce precise scans is essential. Popular methods used to evaluate precision tend to rely on mean distance deviation between repeated scans. Mean value measurements may underestimate errors resulting in misleading conclusions and clinical decisions. This study investigated the precision of six intraoral scanners using the traditional method of measuring mean error, and a proposed method considering only the most extreme and clinically relevant aspects of a scan.MethodsAn edentulous model was scanned five times using six intraoral scanners. The repeated scans were aligned, uniformly trimmed and mean surface deviation measured across all 20 scan combinations within each scanner group. All scan combinations were then measured by arranging scan vertices from greatest to smallest unsigned distance from its compared scan and measuring the median value within the 1% of most greatly deviating points. Traditional mean deviation results and upper-bound deviations were compared.ResultsThe upper-bound deviation within a scan reported errors up to two times greater than those found when measuring global mean distances. Results revealed clinically relevant errors of more than 0.3 mm in scans produced by the Planmeca and Dentalwings scanners, findings not seen when measuring mean distance error of the complete scan.ConclusionsUpper-bound deviation of a cropped scan may provide a clinically useful metric for scanner precision. The Aadva, 3Shape, CEREC and TDS produced scans potentially appropriate for clinical use while Planmeca and Dentalwings produced deviations greater than 0.3 mm when measuring the upper-bound deviation.     

Personalized Immuno-Oncology

Cancer immunotherapy, which aims to control the immune system to eradicate cancer cells and prevent their spread, needs to be personalized because anticancer immune responses can be inhibited in several ways that vary from patient to patient. Cancer immunotherapy includes pharmaceuticals such as immune checkpoint inhibitors and monoclonal antibodies (MAbs) as well as cell therapy, immunogene therapy, and vaccines. Combination of programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) drugs with other immunotherapy drugs, for example, antibody-drug conjugates, as well as combination of PD-1/PD-L1 drugs with other therapies, for example, chemotherapy and radiation therapy, are being explored. Biomarkers are important for predicting the response to immunotherapy. Molecular diagnostics and sequencing are important technologies for guiding treatment in immuno-oncology. Genomic profiling of tumor mutational burden may enhance the predictive utility of PD-L1 expression and facilitate personalized combination immunotherapy. Optimization of personalized immuno-oncology requires integration of several technologies and selection of those best suited for an individual patient. Advances in immuno-oncology are also attributed to technologies for targeted delivery of anticancer therapeutics such as antigen-capturing nanoparticles for precision targeting and selective delivery. A breakthrough in cell therapy of cancer is a chimeric antigen receptors-T cell, which combines the antigen-binding site of a MAb with the signal activating machinery of a T cell, freeing antigen recognition from major histocompatibility complex restriction. Gene-editing tools such as clustered regularly interspaced short palindromic repeats have a promising application for removing alloreactivity and decreasing immunogenicity of third-party T cells. In conclusion, personalized immuno-oncology is one of the most promising approaches to management of cancer.     

Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy

Background/Objectives

A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount.