Evaluation of modified clear Twin Block aligner in treating adolescents with skeletal class II malocclusion: A two-centre cephalometric study.

INTRODUCTION: The purpose of this study was to evaluate the therapeutic effect of modified clear Twin Block (CTB) aligner and traditional twin block (TB) appliance from skeletal, dentoalveolar and soft tissue changes in adolescents with skeletal class II malocclusion. METHODS: A total of 80 adolescents, included in this study from two medical centres, were distributed into CTB group, TB group and control group based on the treatment they received. Lateral cephalograms at pre-treatment (T1) and post-treatment (T2) were measured by modified Pancherz's cephalometric analysis, and dentoskeletal and soft tissue changes were analysed by independent-sample t-test, paired-sample t-test, ANOVA test and Scheffe's Post Hoc test. RESULTS: Seventy-five adolescents completed the study, including 32 in the CTB group, 32 in the TB group and 11 in the control group. Both CTB and TB treatment showed significant differences in most dentoskeletal and soft tissue measurements. Compared with the control group, improvements were observed in class II molar relationship through significant different in S Vert/Ms-S Vert/Mi in the CTB group (P < .01) and the TB group (P < .001), as well as deep overjet through significant different in S Vert/Is-S Vert/Ii in the CTB group (P < .001) and the TB group (P < .001). Besides, the CTB group also showed less protrusion of lower incisors and resulted in a more significant improvement in profile with fewer adverse effects on speaking, eating and social activities. CONCLUSIONS: For adolescents with skeletal class II malocclusion, CTB appliance was as effective as TB on improving dentoskeletal and soft tissue measurements, featuring more reliable teeth control and patient acceptance.

Evaluation of optimal anterior-posterior position of upper incisors through ANS point: a retrospective study on a Chinese sample.

OBJECTIVES: This study was designed to determine the optimal anterior-posterior (AP) position of upper incisors through Anterior Nasal Spine (ANS) point. MATERIALS AND METHODS: Lateral cephalometric radiographic images of 690 patients were collected and divided into a derivation group and a validation group, and the former were subdivided into a proper AP position (PAP) group and an improper AP position (iPAP) group. The distance from facia-axis (FA) point of upper incisors to the line perpendicular to Frankfort horizontal (FH) plane through ANS (FA-ANS) was measured, and the relationship between FA-ANS and several cephalometric indices were studied through Pearson correlation analysis. Receiver operating characteristic (ROC) curves for different clinical indices were analyzed to evaluate the diagnostic efficiency of optimal AP position of upper incisors. RESULTS: The average value of FA-ANS in PAP group was 0.57±1.99, which was significantly different from FA-ANS in iPAP group. Cephalometric indices such as U1-NA, U1-SN, AB-NPo, UL-TVL, Wits, and ANB were found to be correlated with FA-ANS. The receiver operating characteristic (ROC) curves represented a greater diagnostic efficiency of FA-ANS compared with other clinical indices. CONCLUSIONS: ANS point, as a stable skeletal landmark, could be used to access an optimal AP position of upper incisors, providing aids to clinical diagnosis and treatment goal determination for clinical practice. CLINICAL RELEVANCE: A new index FA-ANS, together with other traditional indices, could help determine the optimal position of upper incisors and provide a personalized therapeutic plan.

Signal Suppression in LC-ESI-MS/MS from Concomitant Medications and Its Impact on Quantitative Studies: An Example Using Metformin and Glyburide.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been widely used in the quantitative analysis of drugs. The ubiquitous concomitant drug scenario in the clinic has spawned a large number of co-analyses based on this technique. However, signal suppression caused by concomitant drugs during electrospray ionization may affect the quantification accuracy of analytes, which has not received enough attention. In this study, metformin (MET) and glyburide (GLY) were co-eluted by the conventional optimization of chromatographic conditions to illustrate the effect of signal suppression caused by the combined drugs on the quantitative analysis. The response of MET was not affected by GLY over the investigated concentration range. However, the GLY signal could be suppressed by about 30% in the presence of MET, affecting its pharmacokinetic analysis in simulated samples. As an attempt to solve the suppression of GLY by co-eluting MET, dilution can alleviate the suppression. However, this method still has limitations due to the sacrifice of sensitivity. The stable isotope-labeled internal standard could play a role in correction and improve the quantitative accuracy of GLY, which was further confirmed in the pharmacokinetic study of simulated samples. This study provided an example model to illustrate the possible effect of clinical drug combination on LC-MS/MS drug quantitative analysis and investigated the effective methods to solve this problem.

Detecting representative characteristics of different genders using intraoral photographs: a deep learning model with interpretation of gradient-weighted class activation mapping.

BACKGROUND: Sexual dimorphism is obvious not only in the overall architecture of human body, but also in intraoral details. Many studies have found a correlation between gender and morphometric features of teeth, such as mesio-distal diameter, buccal-lingual diameter and height. However, it's still difficult to detect gender through the observation of intraoral photographs, with accuracy around 50%. The purpose of this study was to explore the possibility of automatically telling gender from intraoral photographs by deep neural network, and to provide a novel angle for individual oral treatment. METHODS: A deep learning model based on R-net was proposed, using the largest dataset (10,000 intraoral images) to support the automatic detection of gender. In order to reverse analyze the classification basis of neural network, Gradient-weighted Class Activation Mapping (Grad-CAM) was used in the second step, exploring anatomical factors associated with gender recognizability. The simulated modification of images based on features suggested was then conducted to verify the importance of characteristics between two genders. Precision (specificity), recall (sensitivity) and receiver operating characteristic (ROC) curves were used to evaluate the performance of our network. Chi-square test was used to evaluate intergroup difference. A value of p < 0.05 was considered statistically significant. RESULTS: The deep learning model showed a strong ability to learn features from intraoral images compared with human experts, with an accuracy of 86.5% and 82.5% in uncropped image data group and cropped image data group respectively. Compared with hard tissue exposed in the mouth, gender difference in areas covered by soft tissue was easier to identify, and more significant in mandibular region than in maxillary region. For photographs with simulated removal of lips and basal bone along with overlapping gingiva, mandibular anterior teeth had similar importance for sex determination as maxillary anterior teeth. CONCLUSIONS: Deep learning method could detect gender from intraoral photographs with high efficiency and accuracy. With assistance of Grad-CAM, the classification basis of neural network was deciphered, which provided a more precise entry point for individualization of prosthodontic, periodontal and orthodontic treatments.

Nicotine Delivery and Pharmacokinetics of an Electronic Cigarette Compared With Conventional Cigarettes in Chinese Adult Smokers: A Randomized Open-Label Crossover Clinical Study.

INTRODUCTION: To evaluate the nicotine pharmacokinetics of a commercial electronic cigarette (e-cigarette) relative to conventional cigarettes in Chinese adult smokers. AIMS AND METHODS: A randomized, open-label, crossover clinical study was conducted on 23 healthy adult Chinese smokers. In two sessions, subjects used either the e-cigarettes with 30 mg/g nicotine in e-liquid or conventional cigarettes of a given brand, at one puff every 30 seconds for a total of 10 puffs. Blood samples were collected at specified time points for 4 hours after the first puff. Subjective effects on desire-to-smoke and physiological parameters such as heart rate and oxyhemoglobin saturation levels were also examined before and after using the two products. RESULTS: The baseline-adjusted maximum nicotine concentration (Cmax-BL), time-to-peak nicotine concentration (Tmax), and nicotine absorption rate (Cmax-BL divided by Tmax) were found to be similar for the e-cigarette versus those of conventional cigarettes (p > .05). Total nicotine exposure measured as the area-under-curve (AUC0-t-BL) was significantly lower for the e-cigarette relative to that of conventional cigarettes. In addition, the subjects found that e-cigarettes were well tolerated under controlled puffing conditions. CONCLUSIONS: The test e-cigarettes achieved similar nicotine delivery and pharmacokinetic profiles to those of the comparator cigarettes, indicating that this e-cigarette could be a potential alternative to conventional cigarettes for those adult smokers. IMPLICATIONS: There are no data in the published literature on the nicotine pharmacokinetics of e-cigarettes in Chinese smokers. To the best of our knowledge, this is the first study to evaluate the nicotine delivery and pharmacokinetic profile of a commercial e-cigarette brand compared with conventional cigarettes in Chinese adult smokers. After the use of test e-cigarettes, nicotine delivery and pharmacokinetic profile were similar to those of conventional cigarettes in Chinese adult smokers.

Development, validation and application of a UHPLC-MS/MS method for quantification of the adiponectin-derived active peptide ADP355 in rat plasma.

A UHPLC-MS/MS method for the quantification of ADP355, an adiponectin-derived active peptide, was developed and validated. The extraction method employed simple protein precipitation using methanol and chromatographic separation was achieved on anAccucore™ RP-MS C18 column (100 × 2.1 mm, 2.6 µm, 80 Å), using 0.1% formic acid in both water and acetonitrile with gradient elution at the flow rate of 400 µl/min within 4.0 min. Detections were performed under positive ion mode with multiple reaction monitoring ion transitions m/z 1109.2 → 309.8 and 871.4 → 310.1 for ADP355 and Jt003 respectively at unit resolution. The linearity range of the calibration curve was 2-1,000 ng/ml with a lower limit detection of 0.5 ng/ml. The selectivity, linearity, precision, accuracy, recovery, matrix effect and stability were validated, and all items met the requirement of US Food and Drug Administration guidance. This method was successfully applied to an intravenous pharmacokinetic study of ADP355 in rats and the in-vitro stability in rat serum, plasma and whole blood was also assessed.

Effects of biophysical cues of 3D hydrogels on mesenchymal stem cells differentiation.

For stem cell research, three-dimensional (3D) hydrogels are increasingly recognized as more physiological systems than two-dimensional culture plates due to bidirectional and 3D interaction of stem cells and surrounding matrix. Among various stem cells, mesenchymal stem cells (MSCs) are one of the most widely applied from bench to bedside. In 3D hydrogels, MSCs are allowed to actively remodel the surrounding matrix through proteolytic degradation and cell-exerted force, which highly resembles in vivo situation. Notably, factors affecting hydrogel modifiability including matrix viscoelasticity and matrix degradability have been found to regulate adhesion, morphology, and fate decision of MSCs. In addition, MSCs within 3D hydrogels have been found to employ multiple mechanotransduction mechanisms including not only the classic integrin-actomyosin cytoskeleton system but also ion channels, microtubule cytoskeleton, and self-secreted proteinaceous matrix. This review summarizes the effects of biophysical cues on MSCs differentiation in 3D hydrogels and underlying mechanobiology in a hope to update our readers' understanding of stem cell biology and guide tissue engineering.

Signal Drift in Liquid Chromatography Tandem Mass Spectrometry and Its Internal Standard Calibration Strategy for Quantitative Analysis.

The present project studied the signal drift in liquid chromatography tandem mass spectrometry (LC-MS/MS) and proposed a strategy for compensating such drift. In the study, four 4-component groups were repeatedly run on different LC-MS/MS systems for over 12 h to investigate the dependence of signal drift on time and hardware systems. The 4-component groups each consisted of (1) an analyte, (2) a stable isotope labeled analyte, (3) a compound with similar structure to the analyte, and (4) a compound with dissimilar structure. All of the species showed significant signal drift, generally more than 25% over 12 h. The analyte and its stable isotope labeled analog always have the same drifting pattern including the trends and direction from one LC-MS/MS system to another. Signal drift was also found to be concentration dependent. Our experiments further proved that a conventional stable isotope labeled internal standard in LC-MS/MS quantification would not compensate the variations caused by concentration-dependent signal drift. An ideal internal standard for LC-MS/MS has both identical structure and similar concentration to the analyte. For that, we proposed a new internal standard strategy, pseudo internal standard (Pseudo IS), for LC-MS/MS quantification. Pseudo IS could effectively compensate signal drift in spite of its significant time, system, and concentration dependencies.

The role of nervous system in adaptive response of bone to mechanical loading.

Bone tissue is remodeled through the catabolic function of the osteoclasts and the anabolic function of the osteoblasts. The process of bone homeostasis and metabolism has been identified to be co-ordinated with several local and systemic factors, of which mechanical stimulation acts as an important regulator. Very recent studies have shown a mutual effect between bone and other organs, which means bone influences the activity of other organs and is also influenced by other organs and systems of the body, especially the nervous system. With the discovery of neuropeptide (calcitonin gene-related peptide, vasoactive intestinal peptide, substance P, and neuropeptide Y) and neurotransmitter in bone and the adrenergic receptor observed in osteoclasts and osteoblasts, the function of peripheral nervous system including sympathetic and sensor nerves in bone resorption and its reaction to on osteoclasts and osteoblasts under mechanical stimulus cannot be ignored. Taken together, bone tissue is not only the mechanical transmitter, but as well the receptor of neural system under mechanical loading. This review aims to summarize the relationship among bone, nervous system, and mechanotransduction.

Perspective into the regulation of cell-generated forces toward stem cell migration and differentiation.

Stem cells are promising candidates for cell-based therapies in diverse conditions including regenerating damaged tissues, treating inflammation in virtue of sepsis, acute renal failure, and cardiovascular disease. Advancement of these therapies relies on the ability to guide stem cells to migrate directly and differentiate towards specific cell phenotypes. During the past decade, many researchers have demonstrated that exogenous applied forces could significantly affect the migration and lineage differentiation of stem cells. Besides, recent advances have highlighted the critical role of internal forces due to cell-matrix interaction in the function of stem cells. Stem cells can generate contractile forces to sense the mechanical properties of cell-generated force microenvironment, and thereby perceive mechanical information that directs broad aspects of stem cell functions, including migration and lineage commitment. In the review, we recount the cell-generated force microenvironment of stem cells and discuss the interactions between cell-generated forces with migration and differentiation of stem cells. We also summarize key experimental evidence of a tight linkage between migration and lineage differentiation of stem cells and pose important unanswered questions in this field.

Development, Validation, and Application of a New Method To Correct the Nonlinearity Problem in LC-MS/MS Quantification Using Stable Isotope-Labeled Internal Standards.

Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has become an indispensable tool for bioanalysis. To quantify a small molecule with LC-MS/MS, a stable isotope-labeled analyte is routinely used as the internal standard. However, cross signal contributions between the analyte and its stable isotope labeled internal standard (SIL-IS) could cause problems when the signal response of the LC-MS/MS system is nonlinear. In the present work, we try to illustrate how the "cross talk" between the analyte and its SIL-IS may cause problems for a nonlinear system. We assume that the instrumental responses toward the analyte and its SIL-IS are the same. When the calibration curve is nonlinear, the addition of a SIL-IS would practically move the response of the analyte up along the parabolic line causing a change in the signal strength of the analyte (usually decrease). The more the SIL-IS is added, the larger change the analyte signal would become. Such a problem would only be corrected by making the calibration curve linear. To this end, we proposed a component equation (CE) as the calibration for nonlinearity correction. In this study, we contrasted the accuracy of CE with the common quantitative method using two drugs whose mass spectrometric responses are linear and nonlinear, respectively. The acceptable accuracy results demonstrated that the CE calibration was comparable with the regular quantitative SIL-IS method with a proper weighting factor and much better than that without weighting. Therefore, CE calibration may provide another reliable way for LC-MS/MS quantification.

Nucleoskeletal stiffness regulates stem cell migration and differentiation through lamin A/C.

Stem cell-based tissue engineering provides a prospective strategy to bone tissue repair. Bone tissue repair begins at the recruitment and directional movement of stem cells, and ultimately achieved on the directional differentiation of stem cells. The migration and differentiation of stem cells are regulated by nucleoskeletal stiffness. Mechanical properties of lamin A/C contribute to the nucleoskeletal stiffness and consequently to the regulation of cell migration and differentiation. Nuclear lamin A/C determines cell migration through the regulation of nucleoskeletal stiffness and rigidity and involve in nuclear-cytoskeletal coupling. Moreover, lamin A/C is the essential core module regulating stem cell differentiation. The cells with higher migration ability tend to have enhanced differentiation potential, while the optimum amount of lamin A/C in migration and differentiation of MSCs is in conflict. This contrary phenomenon may be the result of mechanical microenvironment modulation.

A validated LC-MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay.

An accurate and sensitive LC-MS/MS method for determining thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in human plasma was developed and validated using umbelliferone as an internal standard. The analytes were extracted from plasma (100 µL) by liquid-liquid extraction with ethyl acetate and then separated on a BETASIL C18 column (4.6 × 150 mm, 5 µm) with mobile phase composed of methanol-water containing 0.1% formic acid (70:30, v/v) in isocratic mode at a flow rate of 0.5 mL/min. The detection was performed using an API triple quadrupole mass spectrometer in atmospheric pressure chemical ionization mode. The precursor-to-product ion transitions m/z 259.1 → 186.1 for thalidomide, m/z 273.2 → 161.3 for 5-hydroxy thalidomide, m/z 273.2 → 146.1 for 5'-hydroxy thalidomide and m/z 163.1 → 107.1 for umbelliferone (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentrations of 10.0-2000.0 ng/mL for thalidomide, 0.2-50.0 ng/mL for 5-hydroxy thalidomide and 1.0-200.0 ng/mL for 5'-hydroxy thalidomide. The method was validated with respect to linear, within- and between-batch precision and accuracy, extraction recovery, matrix effect and stability. Then it was successfully applied to estimate the concentration of thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in plasma samples collected from Crohn's disease patients after a single oral administration of thalidomide 100 mg.

Hot Workability of the Multi-Size SiC Particle-Reinforced 6013 Aluminum Matrix Composites.

The size and distribution of ceramic particles in aluminum matrix composites have been reported to remarkably influence their properties. For a single ceramic particle, the particle size is too small and prone to agglomeration, which makes the mechanical properties of the composites worse. When the ceramic particle size is too large, the particles and alloy at the interface are not firmly bonded, and the effect of dispersion distribution is not achieved, which will also reduce the mechanical properties of the composites. The multi-size ceramic particles are expected to improve this situation, while their effect on hot workability is less studied. In this study, the hot deformation behavior, constitutive model, processing map and SEM microstructure were investigated to evaluate the hot workability of multi-size SiC particle-reinforced 6013 aluminum matrix composites. The results showed that the increased deformation temperature and decreased strain rate could decrease flow stresses. The flow stress behaviors of the composites can be described by the sine-hyperbolic Arrhenius equation with the deformation activation energy of Q = 205.863 kJ/mol. The constitutive equation of the composites is ε ˙=3.11592×1013sinh0.024909σ4.12413exp−205863RT. Then, the hot processing map of the SiCp/6013 composites was constructed and verified by SEM observations. The rheological instability zone was in the region of a high strain rate. The optimal processing zone for composites was 450~500 °C and 0.03~0.25 s−1. In addition, the strain level was found to increase both the Q value and the area of the instability zone.

Improvement in Mechanical Properties of Al2024 Alloy Using Mechanical Working and Heat Treatment.

Extrusion speed has a significant influence on the extrusion temperature, microstructure and mechanical properties of the material in the repetitive continuous extrusion forming (RCEF) process. In this work, the mechanical properties of Al2024 were improved by adjusting the speed (with a general range of 2-10 rpm) of repetitive continuous extrusion and applying subsequent heat treatment. During the RCEF process, an increase in the extrusion speed from 4 to 8 rpm was found to increase the extrusion temperature and then enhance the solid solution function. The grain size was affected by the combined effect of deformation speed and its induced temperature. A high-strength Al2024 (ultimate tensile strength of 497.6 MPa) with good elongation (12.93%) was obtained by increasing the extrusion speed and conducting solid solution and artificial aging treatments. The main strengthening mechanisms could be attributed to finer grain size and a larger amount of S (Al2CuMg) precipitates.

Influence of Pre-Heat Treatment on the Deformation Behaviors, Microstructural Characteristics, and Mechanical Properties of a Continuously Cast Al-Cu-Mg Alloy during Continuous Extrusion Process.

The presence of a second phase in Al-Cu-MG alloys, with various sizes and supersaturation-solid-solubility, which can be changed by pre-heat-treatment, could have remarkable influence on hot workability and mechanical performance. In the present work, a continuously cast 2024 Al alloy was homogenized and then subjected to hot compression and continuous extrusion (Conform) along with the initial as-cast alloy. The results showed that the 2024 Al alloy specimen with pre-heat treatment had a higher resistance to deformation and dynamic recovery (DRV) during hot compression process compared with the as-cast sample. Meanwhile, dynamic recrystallization (DRX) was advanced in the pre-heat-treated sample. After the Conform Process, the pre-heat-treated sample also attained better mechanical properties without additional solid solution treatment. The higher supersaturation solid solubility and dispersoids generated during pre-heat treatment was proved to play a key role in restricting boundary migration, tangling dislocation motion and promoting the precipitation of S phase, which raised resistance to DRV and plastic deformation and enhanced the mechanical properties.

The interplay between the nerves and skeleton: a 30-year bibliometric analysis.

Background: The mechanisms and effects of the interplay between the nerves and skeleton remain a popular research topic. This study aimed to analyze and evaluate publications on nerve-bone interactions using bibliometrics and to identify the state of the art of current research, hotspots, and future directions. Methods: This study included 1989 articles and reviews from the Web of Science Core Collection (WoSCC) published from January 1, 1991, to June 22, 2022. The Bibliometrix package of R 4.2.0 (The R Foundation for Statistical Computing, Vienna, Austria) was used to analyze basic information about the publications, including the annual number of publications, institution analysis, author influence analysis, journal analysis, and the national cooperation network. We also used CiteSpace 5.8.R3 for bibliometric analysis, including co-occurrence, co-citation, and cluster analysis. Results: We discovered a significant increase in the number of articles on nerve-bone interactions published over the last 10 years. The most active country and institution were the United States and the University of Minnesota, respectively. In terms of journals and cocited journals, Bone was ranked highest with respect to the number of publications, while Journal of Bone and Mineral Research was ranked highest among cited journals. Wang Lei was the author with the most publications, and Bjurholm A was the most cited author. The analysis of references and keywords revealed that the impact of nerve- and neuromodulation-related factors on stem cell differentiation was a persistently hot topic. Osteoarthritis, neuropeptide Y, and osteoclastogenic process are likely to be the next era of research hotspots. The neurovascular crosstalk within bone has received great attention, especially in skeletal diseases, which may provide potential targets for future treatments. Conclusions: We used a bibliometric method to provide an efficient, objective, and comprehensive assessment of existing research about the interplay between the skeletal and nervous systems and to accurately identify hotspots and research frontiers, providing valuable information for future research.

Revealing the Influence of SiC Particle Size on the Hot Workability of SiCp/6013 Aluminum Matrix Composites.

SiC particle (SiCp) size has been found to significantly influence the hot workability of particle-reinforced aluminum matrix composites (AMC). In this work, therefore, three types of SiCp/6013 composites with different SiCp sizes (0.7, 5 and 15 µm) were prepared and then subjected to isothermal hot compression tests. In addition, constitutive analysis, processing maps and microstructural characterizations were used to reveal the influence of SiCp size on the hot workability of SiCp/6013 composite. The results showed that the values of hot deformation activation energy Q increased with decreasing SiCp size. Specifically, at lower temperatures (e.g., 350 and 400 °C), the highest peak stress was shown in the AMC with SiCp size of 0.7 µm (AMC-0.7), while in the AMC with SiCp size of 5 µm (AMC-5) at higher temperatures (e.g., 450 and 500 °C). This is because a finer SiCp size would lead to stronger dislocation pinning and grain refinement strengthening effects, and such effects would be weakened at higher temperatures. Further, dynamic softening mechanisms were found to transform from dynamic recovery to dynamic recrystallization with increasing SiCp size, and the dynamic recrystallization occurred more easily at higher temperatures and lower strain rates. Consequently, the instability zones of the composites are all mainly located in the deformation region with lower temperature and higher strain rate, and smaller SiCp results in larger instability zones.

Artificial intelligence system for automated landmark localization and analysis of cephalometry.

OBJECTIVES: Cephalometric analysis is essential for diagnosis, treatment planning and outcome assessment of orthodontics and orthognathic surgery. Utilizing artificial intelligence (AI) to achieve automated landmark localization has proved feasible and convenient. However, current systems remain insufficient for clinical application, as patients exhibit various malocclusions in cephalograms produced by different manufacturers while limited cephalograms were applied to train AI in these systems. METHODS: A robust and clinically applicable AI system was proposed for automatic cephalometric analysis. First, 9870 cephalograms taken by different radiography machines with various malocclusions of patients were collected from 20 medical institutions. Then 30 landmarks of all these cephalogram samples were manually annotated to train an AI system, composed of a two-stage convolutional neural network and a software-as-a-service system. Further, more than 100 orthodontists participated to refine the AI-output landmark localizations and retrain this system. RESULTS: The average landmark prediction error of this system was as low as 0.94 ± 0.74 mm and the system achieved an average classification accuracy of 89.33%. CONCLUSIONS: An automatic cephalometric analysis system based on convolutional neural network was proposed, which can realize automatic landmark location and cephalometric measurements classification. This system showed promise in improving diagnostic efficiency in clinical circumstances.

µPESI-MS/MS System for Screening and Quantitating Drugs in Plasma Samples.

Recently, we developed a novel microprobe electrospray ionization (µPESI) source and its coupled MS (µPESI-MS/MS) system. Here, we aimed to widely validate the µPESI-MS/MS method for quantitative analysis of drugs in plasma samples. Furthermore, the relationship between the quantitative performance of the µPESI-MS/MS method and the physicochemical properties of target drugs was analyzed. The µPESI-MS/MS methods for quantitative analysis of 5 representative drugs with a relatively wide range of molecular weight, pKa, and log P values were developed and validated. The results showed that the linearity, accuracy, and precision of these methods met the requirements of the European Medicines Agency (EMA) guidance. Then a total of 75 drugs from plasma samples were primarily detected using the µPESI-MS/MS methods, among which 48 drugs could be quantitatively measured. Logistics regression suggested that drugs with significantly greater log P and physiological charge had better quantitative performance using the µPESI-MS/MS method. Collectively, these results clearly demonstrate the practical application of the µPESI-MS/MS system as a rapid approach to the quantitative analysis of drugs in plasma samples.