A Randomized Trial Utilizing EEG Brain Computer Interface to Improve Facial Emotion Recognition in Autistic Adults.

PURPOSE: Many individuals with autism spectrum disorder (ASD) experience challenges with facial emotion recognition (FER), which may exacerbate social difficulties in ASD. Few studies have examined whether FER can be experimentally manipulated and improved for autistic people. This study utilized a randomized controlled trial design to examine acceptability and preliminary clinical impact of a novel mixed reality-based neurofeedback program, FER Assistant, using EEG brain computer interface (BCI)-assisted technology to improve FER for autistic adolescents and adults. METHODS: Twenty-seven autistic male participants (M age: 21.12 years; M IQ: 105.78; 85% white) were randomized to the active condition to receive FER Assistant (n = 17) or waitlist control (n = 10). FER Assistant participants received ten sessions utilizing BCI-assisted neurofeedback training in FER. All participants, regardless of randomization, completed a computerized FER task at baseline and endpoint. RESULTS: Results partially indicated that FER Assistant was acceptable to participants. Regression analyses demonstrated that participation in FER Assistant led to group differences in FER at endpoint, compared to a waitlist control. However, analyses examining reliable change in FER indicated no reliable improvement or decline for FER Assistant participants, whereas two waitlist participants demonstrated reliable decline. CONCLUSION: Given the preliminary nature of this work, results collectively suggest that FER Assistant may be an acceptable intervention. Results also suggest that FER may be a potential mechanism that is amenable to intervention for autistic individuals, although additional trials using larger sample sizes are warranted.

Meningioma originating from the superior petrosal vein without dural attachment: A case report.

BACKGROUND: Meningioma in the cerebellopontine angle (CPA) without dural attachment is extremely rare. We report a unique case of meningioma derived from the superior petrosal vein without dural attachment. CASE SUMMARY: A 44-year-old right-handed woman presented with a two-month history of headache and tinnitus. Brain magnetic resonance imaging showed a well-defined contrast-enhancing lesion in the right CPA without a dural tail sign. Tumor resection was performed using a right retro sigmoid approach. A dural attachment was not seen at the tentorium or posterior surface of the petrous pyramid. The tumor was firmly adherent to the superior petrosal vein. The origin site was cauterized and resected with the preservation of the superior petrosal vein. A diagnosis of meningothelial meningioma was made. The patient's headache and tinnitus gradually disappeared, and a recurrence was not observed five years after the surgery. CONCLUSION: The rare occurrence of meningioma without dural attachment makes it difficult to determine dural attachment before surgery. The absence of dural attachment makes it easy to completely resect such tumors. Vessels related to tumors should be removed carefully, considering the possible presence of tumor stem cells in the microvessels.

The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.

Nodal negatively regulates osteoclast differentiation by inducing STAT1 phosphorylation.

Several members of the transforming growth factor beta (TGF-ß) superfamily regulate the proliferation, differentiation, and function of bone-forming osteoblasts and bone-resorbing osteoclasts. However, it is still unknown whether Nodal, a member of the TGF-ß superfamily, serves a function in bone cells. In this study, we found that Nodal did not have any function in osteoblasts but instead negatively regulated osteoclast differentiation. Nodal inhibited RANKL-induced osteoclast differentiation by downregulating the expression of pro-osteoclastogenic genes, including c-fos, Nfatc1, and Blimp1, and upregulating the expression of antiosteoclastogenic genes, including Bcl6 and Irf8. Nodal activated STAT1 in osteoclast precursor cells, and STAT1 downregulation significantly reduced the inhibitory effect of Nodal on osteoclast differentiation. These findings indicate that Nodal activates STAT1 to downregulate or upregulate the expression of pro-osteoclastogenic or antiosteoclastogenic genes, respectively, leading to the inhibition of osteoclast differentiation. Moreover, the inhibitory effect of Nodal on osteoclast differentiation contributed to the reduction of RANKL-induced bone loss in vivo.

Comparative analysis of salivary cortisol measurements using different assay methods in relation to serum-free cortisol measurement.

Objectives: Salivary cortisol reflects the biologically active form of serum cortisol, offering a noninvasive evaluation method for the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) is known for its specificity, immunoassays (IA) are commonly used because of their simplicity. This study aimed to assess the performance of salivary cortisol measurement using both IA and LC-MS/MS in comparison to serum-free cortisol measurement. Methods: Assay results for 188 saliva and 94 serum samples from 47 participants were analyzed. Salivary samples collected at different time points were analyzed using IA and LC-MS/MS. Serum samples were analyzed for cortisol, cortisol-binding globulin, and free cortisol. The statistical analyses included correlations and method comparisons. Results: The diurnal salivary cortisol profiles exhibited a comparable circadian rhythm pattern; however, the concentrations measured using IA were consistently higher than those measured using LC-MS/MS. The correlation analysis revealed robust associations among salivary cortisol (IA), salivary cortisol (LC-MS/MS), and serum-free cortisol levels (LC-MS/MS). However, the method comparison revealed a systematic bias between IA and LC-MS/MS in salivary cortisol measurement. Conclusions: This study contributes to the ongoing debate on assay techniques by affirming the suitability of IA and LC-MS/MS for salivary cortisol measurement to assess dynamic changes in HPA axis activity. The identified systematic bias emphasizes the importance of selecting methods based on specific research or clinical requirements.

Exploratory Clinical Trial of a Depression Diagnostic Software That Integrates Stress Biomarkers and Composite Psychometrics.

OBJECTIVE: This study evaluated the clinical effectiveness of Minds.NAVI, a depression screening kit combining psychometric measures and stress hormone biomarkers, in a prospective clinical trial. The objective was to assess its potential as a depression screening tool and investigate the associations between psychological assessments, salivary hormone staging, and depression severity. METHODS: Thirty-five participants with major depressive disorder and 12 healthy controls (HCs) were included. The Minds.NAVI software, utilizing the PROtective and Vulnerable factors battEry Test (PROVE) and salivary cortisol/dehydroepiandrosterone (DHEA) analysis, was employed. The PROVE test is a comprehensive self-report questionnaire that assesses depressive symptoms, suicide risk, attachment style, adverse childhood experiences, mentalization capacity, and resilience. In addition, salivary cortisol and DHEA levels were measured to evaluate the functional stage of the hypothalamic-pituitary-adrenal (HPA) axis. RESULTS: Minds.NAVI exhibited 100% sensitivity, 91.7% specificity, and 97.9% accuracy in distinguishing depression from HCs within an exploratory small group. Salivary stress hormone phases showed changes with depression stage (p=0.030), and the proportion of patients with "adrenal exhaustion stage" was higher in the moderate/severe depression group (p=0.038). Protective/vulnerable factors differed significantly between controls and depressed groups (p<0.001). Cortisol awakening response inversely correlated with depressive symptom severity (r=-0.31, p=0.034). CONCLUSION: This study suggested possible clinical effectiveness of Minds.NAVI, a depression screening tool that integrates psychometric measures and stress hormone biomarkers. The findings support the potential association between depression, chronic stress, and HPA axis hyporesponsiveness.

Multiple transcription factors of Arabidopsis thaliana that are activated by LEAFY COTYLEDON 2 regulate triacylglycerol biosynthesis.

Plant triacylglycerols (TAG) are used in food and various industrial feedstocks. LEAFY COTYLEDON 2 (LEC2), a master positive regulator of TAG biosynthesis, regulates a complex network of transcription factors (TFs) during seed development. Aside from WRINKLED1 (WRI1), the TFs regulated by LEC2 related to TAG biosynthesis have not yet been identified. Previously, we identified 25 seed-expressing TFs that were upregulated in Arabidopsis leaves that overexpressed senescence-induced LEC2. In this study, each of the 25 TFs was transiently expressed in the leaves of Nicotiana benthamiana to identify unknown TFs that regulate TAG biosynthesis. The TAG content of the transformed leaves was analyzed using thin layer chromatography and gas chromatography. We observed that five TFs, ARABIDOPSIS RESPONSIVE REGULATOR 21 (ARR21), AINTEGUMENTA-LIKE 6 (AIL6), APETALA2/ETHYLENE RESPONSIVE FACTOR 55 (ERF55), WRKY DNA-BINDING PROTEIN 8 (WRKY8), and ARABIDOPSIS NAC DOMAIN CONTAINING PROTEIN 38 (ANAC038) increased TAG synthesis in the leaves. Among these, the promoters of AIL6, ERF55, WRKY8, and ANAC038 contain RY motifs, which are LEC2-binding sites activated by LEC2. AIL6 overexpression in Arabidopsis increased the total fatty acid (FA) content in seeds and altered the FA composition, with increases in 16:0, 18:1, and 18:2 and decreases in 18:0, 18:3, and 20:1 compared with those in the wild type (WT). AIL6 overexpression activates several FA and TAG biosynthesis genes. Therefore, our study successfully identified several new TFs regulated by LEC2 in TAG biosynthesis and showed that AIL6 increased the TAG content in seeds.

Diagnostic Performance of Pointwise Encoding Time Reduction with Radial Acquisition Subtraction-based MR Angiography in the Follow-up of Intracranial Aneurysms after Clipping.

PURPOSE: While follow-up assessment of clipped aneurysms (CAs) using magnetic resonance angiography (MRA) can be challenging due to susceptibility artifacts, a novel MRA sequence pointwise encoding time reduction with radial acquisition (PETRA) subtraction-based MRA, has been developed to reduce these artifacts. The aim of the study was to validate the diagnostic performance of PETRA-MRA by comparing it with digital subtraction angiography (DSA) as a reference for follow-up of CAs using a 3T MR scanner. METHODS: Patients with clipping who underwent both PETRA-MRA and DSA between September 2019 and December 2021 were retrospectively included. Two neuroradiologists independently reviewed with the reconstructed images of PETRA-MRA to assess the visibility of the arteries around the clips and aneurysm recurrence or remnants of CA using a 3-point scale. The diagnostic accuracy of PETRA-MRA was evaluated in comparison to DSA. RESULTS: The study included 34 patients (28 females, mean age 59 ± 9.6 years) with 48 CAs. The PETRA-MRA allowed visualization of the parent vessels around the clips in 98% of cases, compared to 39% with time-of-flight (TOF) MRA (p < 0.0001). The DSA confirmed 14 (29.2%) residual or recurrent aneurysms. The PETRA-MRA demonstrated a high accuracy, specificity, positive predictive value, and negative predictive value of 99.2%, 100%, 100%, and 97.8%, respectively, while the sensitivity was 66.7%. CONCLUSION: This retrospective study demonstrates that PETRA-MRA provides excellent visibility of adjacent vessels near clips and has a high diagnostic accuracy in detecting aneurysm remnants or recurrences in CAs. Further prospective studies are warranted to establish its utility as a reliable alternative for follow-up after clipping.

Gamma knife radiosurgery as primary management for intracranial meningioma identified as growing on serial imaging.

Gamma knife radiosurgery (GKRS) has emerged as a highly effective therapeutic modality for the management of intracranial meningiomas. However, the role of GKRS in treating growing meningiomas detected during active surveillance remains unclear. This study seeks to investigate the long-term outcomes of GKRS treatment for growing meningiomas. A retrospective analysis was conducted on patients who underwent GKRS as the primary treatment for growing meningiomas between 2004 and 2021. Growing meningiomas were defined as those exhibiting a > 10% increase in tumor volume (TV) compared to the previous imaging. Fifty-nine patients who received GKRS as their initial treatment were included, with a minimum follow-up period of 12 months. Comprehensive clinical, radiological, and procedural data were analyzed. Serial TV assessments were performed for all tumors before and after GKRS. Tumor progression and regression were defined as a > 10% increase or decrease in TV, respectively, compared to the pretreatment image. At a median follow-up of 41 months (range 15-197 months), TV was unchanged in 16 patients (27.1%), decreased in 41 patients (69.5%), and increased in 2 patients (3.4%). Multivariate analysis revealed that both TV (cm3) (hazard ratio [HR], 1.107; 95% confidence interval [CI], 1.002-1.222; P = .045) and volume growing rate (%/yr) (HR, 1.013; 95% CI, 1.000-1.025; P = .04) significantly correlated with tumor progression. Eleven patients (18.6%) experienced new or worsening symptoms. In multivariate analysis, factor predicting new or worsening neurological function was preexisting calcification (HR, 5.297; 95% CI, 1.328-21.124; P = .018). GKRS demonstrates a promising level of tumor control with minimal risk of neurological deterioration when applied to growing meningiomas. These findings provide compelling support for considering GKRS as a valuable therapeutic option following an initial period of active surveillance for these tumors.

Central Nervous System Dissemination of Solitary Sporadic Supratentorial Hemangioblastoma: A Case Report and Literature Review.

We report a patient with whole neuroaxis dissemination of a sporadic supratentorial hemangioblastoma (HB) for more than 15 years. A 68-year-old female patient presented with severe radiating pain in the right leg. Gadolinium-enhanced lumbar spine MRI showed an intradural mass (2.5 cm in diameter) at the L4 level. The patient had been severely disabled for 22 years after a previous intraventricular brain tumor resection. At that time, the diagnosis was angioblastic meningioma, which was thought to be incorrect. At 14 years after the brain surgery, gamma knife radiosurgery was performed three times for newly developed or recurred supratentorial and infratentorial tumors in the cerebrospinal fluid pathway. The patient underwent lumbar spinal surgery, and a gross total removal of the mass was performed, which confirmed the histopathological diagnosis of HB. We reexamined the old histopathological specimen of the intraventricular tumor from 20 years ago and changed the diagnosis from angioblastic meningioma to supratentorial HB. Six months after spinal surgery, the patient underwent a second spinal surgery and brain surgery, and the histopathological diagnosis was HB following both surgeries, which was the same following the first spinal surgery. Here, we report a sporadic supratentorial HB patient who showed cranial and spinal disseminations for more than two decades along with a literature review.

MCP-5 suppresses osteoclast differentiation through Ccr5 upregulation.

Human monocyte chemoattractant protein-1 (MCP-1) in mice has two orthologs, MCP-1 and MCP-5. MCP-1, which is highly expressed in osteoclasts rather than in osteoclast precursor cells, is an important factor in osteoclast differentiation. However, the roles of MCP-5 in osteoclasts are completely unknown. In this study, contrary to MCP-1, MCP-5 was downregulated during receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation and was considered an inhibitory factor in osteoclast differentiation. The inhibitory role of MCP-5 in osteoclast differentiation was closely related to the increase in Ccr5 expression and the inhibition of IκB degradation by RANKL. Transgenic mice expressing MCP-5 controlled by Mx-1 promoter exhibited an increased bone mass because of a decrease in osteoclasts. This result strongly supported that MCP-5 negatively regulated osteoclast differentiation. MCP-5 also prevented severe bone loss caused by RANKL.

DEEPOMICS FFPE, a deep neural network model, identifies DNA sequencing artifacts from formalin fixed paraffin embedded tissue with high accuracy.

Formalin-fixed, paraffin-embedded (FFPE) tissue specimens are routinely used in pathological diagnosis, but their large number of artifactual mutations complicate the evaluation of companion diagnostics and analysis of next-generation sequencing data. Identification of variants with low allele frequencies is challenging because existing FFPE filtering tools label all low-frequency variants as artifacts. To address this problem, we aimed to develop DEEPOMICS FFPE, an AI model that can classify a true variant from an artifact. Paired whole exome sequencing data from fresh frozen and FFPE samples from 24 tumors were obtained from public sources and used as training and validation sets at a ratio of 7:3. A deep neural network model with three hidden layers was trained with input features using outputs of the MuTect2 caller. Contributing features were identified using the SHapley Additive exPlanations algorithm and optimized based on training results. The performance of the final model (DEEPOMICS FFPE) was compared with those of existing models (MuTect filter, FFPolish, and SOBDetector) by using well-defined test datasets. We found 41 discriminating properties for FFPE artifacts. Optimization of property quantification improved the model performance. DEEPOMICS FFPE removed 99.6% of artifacts while maintaining 87.1% of true variants, with an F1-score of 88.3 in the entire dataset not used for training, which is significantly higher than those of existing tools. Its performance was maintained even for low-allele-fraction variants with a specificity of 0.995, suggesting that it can be used to identify subclonal variants. Different from existing methods, DEEPOMICS FFPE identified most of the sequencing artifacts in the FFPE samples while retaining more of true variants, including those of low allele frequencies. The newly developed tool DEEPOMICS FFPE may be useful in designing capture panels for personalized circulating tumor DNA assay and identifying candidate neoepitopes for personalized vaccine design. DEEPOMICS FFPE is freely available on the web ( http://deepomics.co.kr/ffpe ) for research.

Leksell Frame-Based Stereotactic Biopsy for Infratentorial Tumor : Practical Tips and Considerations.

The Leksell frame-based transcerebellar approach was proposed with the arc support frame attached upside down to the Z coordinate. This study presented practical tips and considerations for obtaining adequate tissue samples for deep-seated cerebellar lesions or lower brainstem lesions specifically those accessible via the cerebellar peduncle. For practical insights, the Leksell coordinate frame G was fixed to prevent the anterior screw implantation within the temporalis muscle, to avoid interference with the magnetic resonance (MR)-adapter, and taking into account the magnetic field of MR in close proximity to the tentorium. After mounting of indicator box, the MR imaging evaluation should cover both the indicator box and the infratentorial region that deviated from it. The coordinates [X, Y, Za, Arc0, Ringa0] obtained from Leksell SurgiPlan® software (Elekta, Stockholm, Sweden) with arc 00 located on the patient's right side were converted to [X, Y, Zb=360-Za, Arc0, Ringb0=Ringa0-1800]. The operation was performed in the prone position under general anesthesia in four patients with deep cerebellar (n=3) and brainstem (n=1) tumors. The biopsy results showed two cases of diffuse large B-cell lymphoma, one metastatic braintumor and one glioblastoma. One patient required frame repositioning as a complication. Drawing upon the methodology outlined in existing literature, we anticipate that imparting supplementary expertise could render the stereotactic biopsy of infratentorial tumors more consistent and manageable for the practitioner, thereby facilitating adequate tissue samples and minimizing patient complications.

Sestrin2 inhibits RANKL-induced osteoclastogenesis through AMPK activation and ROS inhibition.

Sestrins are stress-responsive proteins with antioxidant properties. They participate in cellular redox balance and protect against oxidative damage. This study investigated the effects of Sestrin2 (Sesn2) on osteoclast differentiation and function. Overexpressing Sesn2 in osteoclast precursor cells significantly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis. This was assessed as reduced expression of various osteoclast markers, including c-Fos, nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor, tartrate-resistant acid phosphatase, and cathepsin K. Conversely, downregulation of Sesn2 produced the opposite effect. Mechanistically, Sesn2 overexpression enhanced AMPK activation and the nuclear translocation of nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2), promoting antioxidant enzymes. Moreover, azithromycin (Azm) induced Sesn2 expression, which suppressed RANKL-induced osteoclast differentiation. Specifically, Azm treatment reduced RANKL-induced production of reactive oxygen species in osteoclasts. Furthermore, intraperitoneal administration of Azm ameliorated RANKL-induced bone loss by reducing osteoclast activity in mice. Taken together, our results suggested that Azm-induced Sesn2 act as a negative regulator of RANKL-induced osteoclast differentiation through the AMPK/NFATc1 signaling pathway. Concisely, targeting Sesn2 can be a potential pharmacological intervention in osteoporosis.

Two-Day Fraction Gamma Knife Radiosurgery for Large Brain Metastasis.

Objective: We investigated how treating large brain metastasis (LBM) using two-day fraction gamma knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for two consecutive days, with a biologically effective dose (BED) equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Methods: Between November 2017 and December 2021, 42 patients (mean age: 68.3 years, range: 50-84 years, male: 29 [69.1%], female: 13 [30.9%]) with 44 tumors underwent two-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (NSCLC, N=16), small cell lung cancer (SCLC, N=7), colorectal cancer (N=7), breast cancer (N=3), gastric cancer (N=2), and other cancers (N=7). Twenty-one (50.0%) patients had a single LBM, nineteen (46.3%) had a single LBM and other metastasi(e)s, and two had two (4.7%) large brain metastases. At the time of the two-day fraction GKRS, the tumors had a mean volume of 23.1 cc (range: 12.5-67.4). on each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. Results: We obtained clinical and magnetic resonance imaging (MRI) follow-up data for 34 patients (81%) with 35 tumors, who had undergone two-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (P = 0.019) and lung cancer origin (P = 0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat SRS ranged from 15-878 days (median: 263±38 days, mean: 174±43) after the two-day fraction GKRS. Eight patients (18.2%) were still alive. Conclusion: Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS.

Strategy for dealing with unfamiliar and thick vessels during microvascular decompression: A first case report of hemifacial spasm caused by a persistent primitive trigeminal artery.

RATIONALE: A persistent primitive trigeminal artery (PPTA) is a rare embryonic cerebrovascular anomaly. Hemifacial spasm (HFS) refers to involuntary contractions of facial muscles caused by the compression of blood vessels against the root exit zone of the facial nerve. There have been no reported cases of PPTA causing neurovascular contact and HFS. Microvascular decompression surgery effectively treats HFS, but operating on strong PPTA vessels poses challenges. We aim to introduce a more efficient approach for overcomes these difficulties and facilitates surgery. PATIENT CONCERNS: A 44-year-old male patient without any underlying medical conditions presented to our hospital with involuntary movements of the left side of his face accompanied by numbness in the left maxilla (V2 area). DIAGNOSIS: Brain magnetic resonance imaging and magnetic resonance angiography showed that PPTA was in contact with the left facial nerve. INTERVENTIONS AND OUTCOMES: Following a retro-sigmoid craniotomy, we attempted to interpose the facial nerve and the PPTA as an offender vessel, but the decompression was not sufficient. However, after transposing the vessel using the proximal Teflon transposition with interposition technique, the strength of the involuntary movements was reduced. Following surgery, there was no more lateral spreading response, and the patient symptoms improved. LESSIONS: In cases where the vessel causing HFS is particularly strong and thick, the proximal Teflon transposition with interposition technique for transposition may be advantageous. This method could simplify and enhance the efficacy of microvascular decompression, without compromising the quality of surgical outcomes.

Method of Evaluating Multiple Scenarios in a Single Simulation Run for Automated Vehicle Assessment.

With advances in the technology applied to automated driving systems (ADSs), active efforts have been made to evaluate the safety of ADS in various complex situations using simulations. In accordance with these efforts, numerous institutions have developed single-scenario pools that reflect a variety of road and traffic characteristics and ADS performances. However, a single scenario has limitations in comprehensively evaluating the performance of complex ADS. Therefore, this study proposed a methodology that combines and transforms single scenarios into multiple scenarios. This aided in continuously evaluating the ADS performance over entire road segments and implemented this methodology in the simulations.

Glioma Single-Cell Biomechanical Analysis by Cyclic Conical Constricted Microfluidics.

Determining the grade of glioma is a critical step in choosing patients' treatment plans in clinical practices. The pathological diagnosis of patient's glioma samples requires extensive staining and imaging procedures, which are expensive and time-consuming. Current advanced uniform-width-constriction-channel-based microfluidics have proven to be effective in distinguishing cancer cells from normal tissues, such as breast cancer, ovarian cancer, prostate cancer, etc. However, the uniform-width-constriction channels can result in low yields on glioma cells with irregular morphologies and high heterogeneity. In this research, we presented an innovative cyclic conical constricted (CCC) microfluidic device to better differentiate glioma cells from normal glial cells. Compared with the widely used uniform-width-constriction microchannels, the new CCC configuration forces single cells to deform gradually and obtains the biophysical attributes from each deformation. The human-derived glioma cell lines U-87 and U-251, as well as the human-derived normal glial astrocyte cell line HA-1800 were selected as the proof of concept. The results showed that CCC channels can effectively obtain the biomechanical characteristics of different 12-25 µm glial cell lines. The patient glioma samples with WHO grades II, III, and IV were tested by CCC channels and compared between Elastic Net (ENet) and Lasso analysis. The results demonstrated that CCC channels and the ENet can successfully select critical biomechanical parameters to differentiate the grades of single-glioma cells. This CCC device can be potentially further applied to the extensive family of brain tumors at the single-cell level.

Machine learning approach to monitor inkjet jetting status based on the piezo self-sensing.

One of the advantages of inkjet printing in digital manufacturing is the ability to use multiple nozzles simultaneously to improve the productivity of the processes. However, the use of multiple nozzles makes inkjet status monitoring more difficult. The jetting nozzles must be carefully selected to ensure the quality of printed products, which is challenging for most inkjet processes that use multi-nozzles. In this article, we improved inkjet print head monitoring based on self-sensing signals by using machine learning algorithms. Specifically, supervised machine learning models were used to classify nozzle jetting conditions. For this purpose, the self-sensing signals were acquired, and the feature information was extracted for training. A vision algorithm was developed to label the nozzle status for classification. The trained models showed that the classification accuracy is higher than 99.6% when self-sensing signals are used for monitoring. We also proposed a so-called hybrid monitoring method using trained machine learning models, which divides the feature space into three regions based on predicted jetting probability: certain jetting, certain non-jetting, and doubt regions. Then, the nozzles with uncertain status in the doubt region can be verified by jet visualization to improve the accuracy and efficiency of the monitoring process.

Joint semiparametric kernel network regression.

Variable selection and graphical modeling play essential roles in highly correlated and high-dimensional (HCHD) data analysis. Variable selection methods have been developed under both parametric and nonparametric model settings. However, variable selection for nonadditive, nonparametric regression with high-dimensional variables is challenging due to complications in modeling unknown dependence structures among HCHD variables. Gaussian graphical models are a popular and useful tool for investigating the conditional dependence between variables via estimating sparse precision matrices. For a given class of interest, the estimated precision matrices can be mapped onto networks for visualization. However, the limitation of Gaussian graphical models is that they are only applicable to discretized response variables and for the case when p log ( p ) ≪ n $$ p\log (p)\ll n $$ , where p $$ p $$ is the number of variables and n $$ n $$ is the sample size. They are necessary to develop a joint method for variable selection and graphical modeling. To the best of our knowledge, the methods for simultaneously selecting variable selection and estimating networks among variables in the semiparametric regression settings are quite limited. Hence, in this paper, we develop a joint semiparametric kernel network regression method to solve this limitation and to provide a connection between them. Our approach is a unified and integrated method that can simultaneously identify important variables and build a network among those variables. We developed our approach under a semiparametric kernel machine regression framework, which can allow for nonlinear or nonadditive associations and complicated interactions among the variables. The advantages of our approach are that it can (1) simultaneously select variables and build a network among HCHD variables under a regression setting; (2) model unknown and complicated interactions among the variables and estimate the network among these variables; (3) allow for any form of semiparametric model, including non-additive, nonparametric model; and (4) provide an interpretable network that considers important variables and a response variable. We demonstrate our approach using a simulation study and real application on genetic pathway-based analysis.