Concurrent Signals Research Articles

Cancer-associated fibroblasts confer ALK inhibitor resistance in EML4-ALK -driven lung cancer via concurrent integrin and MET signaling.

Cancer-associated fibroblasts (CAFs) are associated with tumor progression and modulate drug sensitivity of cancer cells. However, the underlying mechanisms are often incompletely understood and crosstalk between tumor cells and CAFs involves soluble secreted as well as adhesion proteins. Interrogating a panel of non-small cell lung cancer (NSCLC) cell lines driven by EML4-ALK fusions, we observed substantial CAF-mediated drug resistance to clinical ALK tyrosine kinase inhibitors (TKIs). Array-based cytokine profiling of fibroblast-derived conditioned- media identified HGF-MET signaling as a major contributor to CAF-mediated paracrine resistance that can be overcome by MET TKIs. However, 'Cell Type specific labeling using Amino acid Precursors' (CTAP)-based expression and phosphoproteomics in direct coculture also highlighted a critical role for the fibronectin-integrin pathway. Flow cytometry analysis confirmed activation of integrin β1 (ITGB1) in lung cancer cells by CAF coculture. Treatment with pharmacological inhibitors, cancer cell-specific silencing or CRISPR-Cas9-mediated knockout of ITGB1 overcame adhesion protein-mediated resistance. Concurrent targeting of MET and integrin signaling effectively abrogated CAF-mediated resistance of EML4-ALK -driven NSCLC cells to ALK TKIs in vitro . Consistently, combination of the ALK TKI alectinib with the MET TKI capmatinib and/or the integrin inhibitor cilengitide was significantly more efficacious than single agent treatment in suppressing tumor growth using an in vivo EML4-ALK -dependent allograft mouse model of NSCLC. In summary, these findings emphasize the complexity of resistance-associated crosstalk between CAFs and cancer cells, which can involve multiple concurrent signaling pathways, and illustrate how comprehensive elucidation of paracrine and juxtacrine resistance mechanisms can inform on more effective therapeutic approaches.

Distributed optimization for multi-commodity urban traffic control

A distributed method for concurrent traffic signal and routing control of traffic networks is proposed. The method is based on the multi-commodity store-and-forward model, in which the destinations are the commodities. The system benefits from the communication between vehicles and infrastructure, providing optimal signal timings to intersections and routes to vehicles on a link-by-link basis. Using the augmented Lagrangian to model the constraints into the objective, the baseline centralized problem is decomposed into a set of objective-coupled subproblems, one for each intersection, enabling the solution to be computed by a distributed-gradient projection algorithm. The intersection agents only need to communicate and coordinate with neighboring intersections to ensure convergence to the optimal solution while tolerating suboptimal iterations that offer more flexibility, unlike other distributed approaches. Through microsimulation, we demonstrate the effectiveness of the proposed algorithm in traffic networks with time-varying demand. Computational analysis shows that the distributed problem is suitable for real-time applications. A robustness analysis show that the distributed formulation enables a graceful degradation of the system in case of failure.

Validation of inertial measurement units based on waveform similarity assessment against a photogrammetry system for gait kinematic analysis.

When assessing gait analysis outcomes for clinical use, it is indispensable to use an accurate system ensuring a minimal measurement error. Inertial Measurement Units (IMUs) are a versatile motion capture system to evaluate gait kinematics during out-of-lab activities and technology-assisted rehabilitation therapies. However, IMUs are susceptible to distortions, offset and drifting. Therefore, it is important to have a validated instrumentation and recording protocol to ensure the reliability of the measurements, to differentiate therapy effects from system-induced errors. A protocol was carried out to validate the accuracy of gait kinematic assessment with IMUs based on the similarity of the waveform of concurrent signals captured by this system and by a photogrammetry reference system. A gait database of 32 healthy subjects was registered synchronously with both devices. The validation process involved two steps: 1) a preliminary similarity assessment using the Pearson correlation coefficient, and 2) a similarity assessment in terms of correlation, displacement and gain by estimating the offset between signals, the difference between the registered range of motion (∆ROM), the root mean square error (RMSE) and the interprotocol coefficient of multiple correlation (CMCP). Besides, the CMCP was recomputed after removing the offset between signals (CMCPoff). The correlation was strong (r > 0.75) for both limbs for hip flexion/extension, hip adduction/abduction, knee flexion/extension and ankle dorsal/plantar flexion. These joint movements were studied in the second part of the analysis. The ∆ROM values obtained were smaller than 6°, being negligible relative to the minimally clinically important difference (MCID) estimated for unaffected limbs, and the RMSE values were under 10°. The offset for hips and ankles in the sagittal plane reached -9° and -8°, respectively, whereas hips adduction/abduction and knees flexion/extension were around 1°. According to the CMCP, the kinematic pattern of hip flexion/extension (CMCP > 0.90) and adduction/abduction (CMCP > 0.75), knee flexion/extension (CMCP > 0.95) and ankle dorsi/plantar flexion (CMCP > 0.90) were equivalent when captured by each system synchronously. However, after offset correction, only hip flexion/extension (CMCPoff = 1), hip adduction/abduction (CMCPoff > 0.85) and knee flexion/extension (CMCPoff > 0.95) satisfied the conditions to be considered similar.

Understanding coaxial photodiode-based multispectral pyrometer measurements at the overhang regions in laser powder bed fusion for part qualification

Coaxial photodiode monitoring sensors provide a digital signature at the melt pool level in laser powder bed fusion (L-PBF), facilitating faster part qualification. However, current signatures are plagued by significant noise and signal variation and show counterintuitive trends such as a decrease in measured temperature near overhang surfaces. This paper investigates the behavior of coaxial photodiode-based melt pool monitoring (PD-MPM) thermal measurements at overhang regions by conducting a combination of experiments and multiphysics simulations. High-speed in situ synchrotron X-ray imaging is coupled with a coaxial photodiode system to enable comparison of the observed melt pool phenomena and monitoring signals during double-track AlSi10Mg experiments. A multiphysics model is developed to simulate the melt pool dynamics and concurrent sensor signals throughout the process. We propose a surrogate model that clarifies the correlation between sensor signals and melt pool temperature. Both experimental and simulation results emphasize the significant impacts of laser energy and keyhole formation on solid-liquid interface discontinuities and PD-MPM signals. Results reveal that a boiling region with a relatively smaller projected area, as near an overhang, can lead to a decrease in the measured melt pool temperature, even when the true peak temperature remains constant, meaning that PD-MPM temperature measurements cannot be used to estimate absolute melt pool temperature. Consequently, in overhang regions, interaction between the melt pool and underlying powder results in an abruptly deforming melt pool and a pronounced decrease in both individual photodiode intensities and overall measured melt pool temperature. This work illustrates how to correctly interpret the coaxial photodiode monitoring signals in L-PBF by uncovering the intricate dynamics within the melt pool, particularly in challenging overhang regions, and pave the foundation for data-driven part qualification.

Shared and redundant proteins coordinate signal cross-talk between MAPK pathways in yeast.

All cells must detect, interpret, and adapt to multiple and concurrent stimuli. While signaling pathways are highly specialized, different pathways often share components or have components with overlapping functions. In the yeast Saccharomyces cerevisiae, the high osmolarity glycerol (HOG) pathway has two seemingly redundant branches, mediated by Sln1 and Sho1. Both branches are activated by osmotic pressure, leading to phosphorylation of the MAPKs Hog1 and Kss1. The mating pathway is activated by pheromone, leading to phosphorylation of the MAPKs Fus3 and Kss1. Given that Kss1 is shared by the two pathways, we investigated its role in signal coordination. We activated both pathways with a combination of salt and pheromone, in cells lacking the shared MAPK and in cells lacking either of the redundant branches of the HOG pathway. By systematically evaluating MAPK activation, translocation, and transcription programs, we determined that Sho1 mediates cross talk between the HOG and mating pathways and does so through Kss1. Further, we show that Kss1 initiates a transcriptional program that is distinct from that induced by Hog1 and Fus3. Our findings reveal how redundant and shared components coordinate concurrent signals and thereby adapt to sudden environmental changes.

Physical exercise as part of the rehabilitation in primary osteoporosis: insights into the signal transduction bone formation pathways

Primary osteoporosis, a geriatric bone metabolic condition affecting both the mineral density and the microarchitecture, comes with a complex burden. Bone turnover markers tidily reflect the changes of skeleton status that are part of the physiological process or theyhighlight the abnormal status including in osteoporosis in addition to other biomolecules evaluation such as hormones, inflammatory markers, myokines and adipokines. In this narrative review, we aimed to highlight several aspects regarding osteoporosis-related rehabilitation amid mitigating the role of physical exercise as bone formation booster. Bone turnover markers assays, by capturing the essence of the bone remodelling, registered a great progress during latest years, thus show-ing an enhanced index of applicability in daily practice (despite being known and studied for more than three decades). Irisin, a novel player in the muscle-bone-metabolism cross-talk, represents a muscle-derivate hormone that is expected to highlight the interplay between physical exercise and bone formation. Other concurrent signal transduction pathways include recently described biomarkers such as preptin or the spectrum associated with serotonin-LRP5-Wnt/beta catenin canonical and non-canonical loops. Current pitfalls of the topic include the personalized recommendation of physical activity due to severe co-morbidities, the lack of homogenous studies to measure the intervention and the consecutive bone health and great variations of using the bone turnover markers amid daily practice in different centers. To conclude, part of the monitoring protocol in osteoporotic patients under specific medication against osteoporosis or during bisphosphonates drug holiday, bone turnover markers assays stands for a practical insight in every day practice. The contributing role of physical exercise to boost bone formation as reflected by these biomolecules is well understood across a multitude of signal transduction pathways. However, a current gap in practical use and surveillance of the prescription of physical activity, mechanical load and rehabilitation programs in these patients is confirmed so far. Keywords: osteoporosis, bone, fracture, rehabilitation, physical exercise, bone turnover markers, osteocalcin.

Relugolix prescribing practices and clinical experiences at an urban academic center.

e17008 Background: Relugolix is a novel oral GnRH antagonist that is now an alternative option for patients with prostate cancer (PC) who require androgen deprivation therapy (ADT). The potential benefits of relugolix include rapid testosterone decline and recovery, oral administration, and a possible cardiovascular (CV) benefit compared to traditional GnRH agonists. This study examines real-world data on relugolix prescribing practices and clinical experiences at a large, urban academic center. Methods: We conducted a retrospective, single-center cohort study of patients with PC prescribed relugolix from March 2021 through December 2023 at Beth Israel Deaconess Medical Center. We collected patient-related and clinical factors including demographics, comorbidities, CV risk factors, treatment history, reasons for relugolix prescription over GnRH agonists, medication compliance, adverse effects, and treatment outcomes. Descriptive statistics were used to characterize the cohort. Results: Among 267 patients who received a relugolix prescription, median age was 70 years old, 186 patients (69.6%) were Non-Hispanic White, 37 (13.9%) Non-Hispanic Black, 13 (4.9%) Asian, and 6 (2.2%) Hispanic of any race. Across all patients, 228 (85.3%) initiated relugolix with a median therapy duration of 181 days (range: 10 - 807). At the time of prescription, 88 patients (32.9%) were prescribed concurrent androgen receptor signal inhibitors (ARSI) and 186 (69.6%) had localized disease. Median CV risk factors per patient was 2 (range 0 - 7), and 4 patients (1.5%) developed major adverse CV events (MACE), including acute heart failure decompensation, sick sinus syndrome, ventricular tachycardia, and death during treatment. Among physician prescribers, the most common reasons for prescribing relugolix included concern for CV risk (90 prescriptions, 33.3%) and patient preference for oral administration (55 prescriptions, 20.4%). Forty-nine patients (18.3%) were switched from a GnRH agonist, mainly due to physician concern for CV risk (13, 4.9%) or patient preference (17, 6.4%). Conclusions: We describe real-world use of relugolix for PC in a large, diverse single center cohort. The most frequent reasons for choosing relugolix over a GnRH agonist were physician concern for CV risk and patient preference for a tablet over injection. Investigations of treatment initiation and adherence in relation to insurance coverage, adverse effects, and socioeconomic factors require further investigation.

Learning From Alarms: A Robust Learning Approach for Accurate Photoplethysmography-Based Atrial Fibrillation Detection Using Eight Million Samples Labeled With Imprecise Arrhythmia Alarms.

Atrial fibrillation (AF) is a common cardiac arrhythmia with serious health consequences if not detected and treated early. Detecting AF using wearable devices with photoplethysmography (PPG) sensors and deep neural networks has demonstrated some success using proprietary algorithms in commercial solutions. However, to improve continuous AF detection in ambulatory settings towards a population-wide screening use case, we face several challenges, one of which is the lack of large-scale labeled training data. To address this challenge, we propose to leverage AF alarms from bedside patient monitors to label concurrent PPG signals, resulting in the largest PPG-AF dataset so far (8.5 M 30-second records from 24,100 patients) and demonstrating a practical approach to build large labeled PPG datasets. Furthermore, we recognize that the AF labels thus obtained contain errors because of false AF alarms generated from imperfect built-in algorithms from bedside monitors. Dealing with label noise with unknown distribution characteristics in this case requires advanced algorithms. We, therefore, introduce and open-source a novel loss design, the cluster membership consistency (CMC) loss, to mitigate label errors. By comparing CMC with state-of-the-art methods selected from a noisy label competition, we demonstrate its superiority in handling label noise in PPG data, resilience to poor-quality signals, and computational efficiency.

Optimized piezoelectric bone regeneration through inhibiting sympathetic nerve-bone interaction

Electrical cues are crucial for osteogenesis. To tackle critical-sized bone defects, piezoelectric materials non-invasively generate electrical stimuli via ultrasonic excitation, imitating natural bone's piezoelectricity. Two-dimensional piezoelectric nanomaterials, with their flexibility and cellular interactions, effectively improve osteogenic outcomes. Yet, the concurrent electrical and injury signals may overly activate sympathetic nerves, causing excessive norepinephrine release, which hinders osteogenic differentiation by targeting mesenchymal stem cells' β2-receptors. Addressing this, we developed a sophisticated drug carrier, encapsulating piezoelectric zinc sulfide (ZnS) in a polydopamine (PDA) coating with the β blocker propranolol (PRO), creating ZnS@PDA-PRO. This nanocarrier generates electrical signals and releases Zn2+ to promote osteogenic differentiation, while PRO mitigates sympathetic nerve inhibition, enhancing the regeneration of critical-sized bone defects.

Comparison of Concurrent and Asynchronous Running Kinematics and Kinetics From Marker-Based and Markerless Motion Capture Under Varying Clothing Conditions.

As markerless motion capture is increasingly used to measure 3-dimensional human pose, it is important to understand how markerless results can be interpreted alongside historical marker-based data and how they are impacted by clothing. We compared concurrent running kinematics and kinetics between marker-based and markerless motion capture, and between 2 markerless clothing conditions. Thirty adults ran on an instrumented treadmill wearing motion capture clothing while concurrent marker-based and markerless data were recorded, and ran a second time wearing athletic clothing (shorts and t-shirt) while markerless data were recorded. Differences calculated between the concurrent signals from both systems, and also between each participant's mean signals from both asynchronous clothing conditions were summarized across all participants using root mean square differences. Most kinematic and kinetic signals were visually consistent between systems and markerless clothing conditions. Between systems, joint center positions differed by 3cm or less, sagittal plane joint angles differed by 5° or less, and frontal and transverse plane angles differed by 5° to 10°. Joint moments differed by 0.3N·m/kg or less between systems. Differences were sensitive to segment coordinate system definitions, highlighting the effects of these definitions when comparing against historical data or other motion capture modalities.

A concurrent fault diagnosis method for electric isolation valves in nuclear power plants based on rule-based reasoning and data-driven methods

In order to improve the fault diagnosis ability of electric isolation valves in nuclear power plants, especially for the diagnosis of concurrent faults, a novel concurrent fault diagnosis method based on rule reasoning and data-driven methods is proposed in this study. The concurrent fault diagnosis method is divided into two layers: the rule-based reasoning layer and data-driven layer. In order to realize the diagnosis of most concurrent faults, the rule-based reasoning layer is established by a rule inference model according to the failure mode and effects analysis (FMEA) of the electric isolation valve. In order to diagnose concurrent faults with mutual interference of fault features that cannot be diagnosed by rule-based reasoning layer, the data-driven layer is established by variational mode decomposition (VMD) and fast independent component analysis (Fast-ICA) method to separate concurrent fault signals and gate recurrent unit (GRU) method to identify fault patterns. After testing on the electric valve test bench and simulation data, multiple concurrent faults of the electric isolation valve are diagnosed accurately by the proposed concurrent fault diagnosis framework, including complex concurrent faults such as internal leakage and external leakage, and the framework can also work in a single fault diagnosis scenario without changing models. Compared with the concurrent fault diagnosis based on multi-label support vector machine, the accuracy of concurrent fault diagnosis is improved by about 25.3%. The research can provide a new idea for the concurrent fault diagnosis of electric isolation valves and other equipment.

Concurrent M-QAM transmission performance assessment in a combined four SOA-MZIs arrangement

In this paper, the utilization of four semiconductor optical amplifier Mach-Zehnder interferometers (SOA-MZIs) is explored to achieve concurrent M-QAM (M-ary Quadrature Amplitude Modulation) transmission. Utilizing an actively mode-locked laser, we generate pulses with a duration of 0.5 ps at a repetition rate of 20 GHz, serving as our sampling source. The incoming M-QAM signals, spanning various frequencies, undergo down-mixing at the SOA-MZIs combined exit, resulting in diverse output frequencies by respecting the bandpass sampling procedures. The unparalleled simultaneous M-QAM transmission is assessed through critical metrics such as error vector magnitude (EVM) and bit error rate (BER). The SOA-MZI conversion efficiency (CE) exhibits a notable transition, ranging from 90 % at 76 GHz to 68 % at 84 GHz based on 1024-QAM data. The concurrent down-mixed signals showcase EVM values of 3, 2, 1, and 0.25 % for 16-, 64-, 256-, and 1024-QAM, respectively, at the first range of output frequencies. Besides, an exceptional BER value of 93×10−6 is attained at a symbol rate of 0.25 GSymb/s at 84 GHz for the 1024-QAM replica. A comparative analysis reveals that under identical parameter settings, the proposed Gaussian filter expounds lower EVM values compared to the root raised cosine (RRC) filter. These results highlight the success of the novel experimental approach employing SOA-MZIs for simultaneous down-mixing of four M-QAM carriers with varying levels, showcasing outstanding performance outcomes.

3D dual-mode tactile sensor with decoupled temperature and pressure sensing: Toward biological skins for wearable devices and smart robotics

The potential of wearable devices and smart robotics stands to be greatly enhanced by the development of dual-mode sensors emulating human skin functionality. However, challenges in their realization and the mitigation of crosstalk issues from concurrent signals persist. We present a pressure-temperature-tactile sensor (PTTS) built upon a 3D porous structure and conductive nanocomposites encompassing graphene, multi-walled carbon nanotubes, silicone rubber, and polyaniline. The PTTS showcases a pressure detection range from 0 to 110 kPa, pressure sensitivity at 0.3488 kPa−1, a low-pressure detection threshold of 186 Pa, and temperature sensitivity up to 21.5 μV/K. Crucially, the PTTS effectively untangles the dual functions of pressure and temperature sensing, thus mitigating crosstalk. It achieves computer communication through Morse code, enabling efficient demonstrations of human-computer interaction. Furthermore, the sensor accurately captures human motion while concurrently gauging ambient temperature without signal interference. Our device introduces an innovative avenue for non-contact sensing and human-computer interaction across applications, underscoring its potential to revolutionize wearable devices and smart robotics, consequently impacting diverse industries.

Killer instincts: natural killer cells as multifactorial cancer immunotherapy.

Natural killer (NK) cells integrate heterogeneous signals for activation and inhibition using germline-encoded receptors. These receptors are stochastically co-expressed, and their concurrent engagement and signaling can adjust the sensitivity of individual cells to putative targets. Against cancers, which mutate and evolve under therapeutic and immunologic pressure, the diversity for recognition provided by NK cells may be key to comprehensive cancer control. NK cells are already being trialled as adoptive cell therapy and targets for immunotherapeutic agents. However, strategies to leverage their naturally occurring diversity and agility have not yet been developed. In this review, we discuss the receptors and signaling pathways through which signals for activation or inhibition are generated in NK cells, focusing on their roles in cancer and potential as targets for immunotherapies. Finally, we consider the impacts of receptor co-expression and the potential to engage multiple pathways of NK cell reactivity to maximize the scope and strength of antitumor activities.

A synaptic corollary discharge signal suppresses midbrain visual processing during saccade-like locomotion

In motor control, the brain not only sends motor commands to the periphery, but also generates concurrent internal signals known as corollary discharge (CD) that influence sensory information processing around the time of movement. CD signals are important for identifying sensory input arising from self-motion and to compensate for it, but the underlying mechanisms remain unclear. Using whole-cell patch clamp recordings from neurons in the zebrafish optic tectum, we discovered an inhibitory synaptic signal, temporally locked to spontaneous and visually driven locomotion. This motor-related inhibition was appropriately timed to counteract visually driven excitatory input arising from the fish’s own motion, and transiently suppressed tectal spiking activity. High-resolution calcium imaging revealed localized motor-related signals in the tectal neuropil and the upstream torus longitudinalis, suggesting that CD enters the tectum via this pathway. Together, our results show how visual processing is suppressed during self-motion by motor-related phasic inhibition. This may help explain perceptual saccadic suppression observed in many species.

Hyperglycemia-induced miR182-5p drives glycolytic and angiogenic response in Proliferative Diabetic Retinopathy and RPE cells via depleting FoxO1

PurposeDiabetic Retinopathy (DR) is associated with metabolic dysfunction in cells such as retinal pigmented epithelium (RPE). Small molecular weight microRNAs can simultaneously regulate multiple gene products thus having pivotal roles in disease pathogenesis. Since miR182-5p is involved in regulating glycolysis and angiogenesis, two pathologic processes of DR, we investigated its status in DR eyes and in high glucose model in vitro. Methodology: Total RNA was extracted from vitreous humor of PDR (n = 48) and macular hole (n = 22) subjects followed by quantification of miR182-5p and its target genes. ARPE-19 cells, cultured in DMEM under differential glucose conditions (5 mM and 25 mM) were used for metabolic and biochemical assays. Cells were transfected with miRNA182 mimic or antagomir to evaluate the gain and loss of function effects. ResultsPDR patient eyes had high levels of miR182-5p levels (p < 0.05). RPE cells under high glucose stress elevated miR182-5p expression with altered glycolytic pathway drivers such as HK2, PFKP and PKM2 over extended durations. Additionally, RPE cells under high glucose conditions exhibited reduced FoxO1 and enhanced Akt activation. RPE cells transfected with miR182-5p mimic phenocopied the enhanced basal and compensatory glycolytic rates observed under high glucose conditions with increased VEGF secretion. Conversely, inhibiting miR182-5p reduced Akt activation, glycolytic pathway proteins, and VEGF while stabilizing FoxO1. ConclusionGlycolysis-associated proteins downstream of the FoxO1-Akt axis were regulated by miR182-5p. Further, miR182-5p increased expression of VEGFR2 and VEGF levels, likely via inhibition of ZNF24. Thus, the FoxO1-Akt-glycolysis/VEGF pathway driving metabolic dysfunction with concurrent angiogenic signaling in PDR may be potentially targeted for treatment via miR182-5p modulation.

Clinical Features and Therapeutic Evaluation of Central Nervous System Involvement in Pediatric Anaplastic Large Cell Lymphoma

Objective：To analyze the clinical features of central nervous system involvement (CNS3) in pediatric anaplastic large cell lymphoma (ALCL) and evaluate the efficacy of CNCL-ALCL-2017 protocol for the treatment of CNS3. Methods：The clinical data of 215 pediatric ALCL patients ≤18 years old enrolled in the Chinese Children's Cancer Group (CNCL) between April 2017 and March 2023 were collected sequentially. All enrolled patients staging and CNS layering were according to the IPNHLSS staging system and treated with CNCL-ALCL-2017 protocol (modified BFM-ALCL99 protocol). The clinical features at diagnosis and treatment outcomes of CNS3 patients were analyzed. All patients were followed up until June 30, 2023. Data were collected using a unified information platform. Associations between patient characteristics were analyzed with Chi-squared or Fisher's exact tests. Eventfree survival (EFS) and overall survival (OS) curves were estimated according to the KaplanMeier method and compared by Logrank test. Furthermore, statistical analysis was performed using SPSS 22.0 software. P&amp;lt;0.05 was considered statistically significant. Results: Among the 215 ALCL pediatric patients, 17 (7.9%) had CNS3, including 13 males and 4 females with median age of 8.0 (range 1.0-14.0) years. In this patients, brain parenchyma and spinal cord involvement were found in 58.8% (10/17) patients on imaging, with space-occupying lesions in 7 cases and abnormal signals on MRI in 4 cases. Concurrent space-occupying lesions and abnormal signals on MRI was detected in 1 case. Cerebrospinal fluid (CSF) positivity was detected in 35.3% (6/17) patients, including 2 cases with positive ALK gene and 5 cases with positive flow cytometry, with 1 case positive for both. Cranial nerve deficits such as facial nerve palsy, visual or hearing impairment were observed in 23.5% (4/17) patients. Concurrent CSF, imaging and cranial nerve abnormalities were present in 5.9% (1/17), while two of this were present in 29.4% (5/17). Isolated CSF positivity without other abnormalities was detected in 23.5% (4/17). Pathological subtypes included common type (76.5%, 13/17), histiocyte-rich variant (5.9%, 1/17), small cell variant (5.9%, 1/17), others (11.8%, 2/17). Immunohistochemistry showed ALK + in 94.1% (16/17) and CD3 + in 76.5% (13/17). Concurrent ALK gene positivity in both peripheral blood and bone marrow was detected in 64.7% (11/17), with 58.8% (10/17) positive in both samples. The median follow-up of all patients was 35.4 months (range 0.5-74.9). All CNS3 patients had stage IV disease and were treated with regimen D (with 5 g/m 2 methotrexate). The 3-year OS was 94.3%, 98.2% and 93.3% for CNS1 (144, 67.0%), CNS2 (54, 25.1%) and CNS3 (17, 7.9%) patients, respectively; the 3-year EFS was 85.6%, 90.3% and 86.7%, respectively. No significant differences were found among the three groups. The 3-year OS and EFS for the whole cohort were 95.1% and 84.7%, respectively, also with no significant differences from the CNS3 group. Of the CNS3 patients, 1 was lost to follow-up after the first course, 1 died during treatment, and the interim CR rate was 75.0% (12/16). CSF conversion was achieved in 3/6 (50%) CSF-positive patients. 6.25% (1/16) patient had CSF ALK gene re-positivity during maintenance and persistent positivity despite additional ALK inhibitor alectinib and intrathecal therapy. In the CNS1 group, 2 cases were lost to follow-up and 4 cases died. The relapse rate was 11.4% (16/140), and the rate of central nervous system relapse was 2.1% (3/140). Additionally, the rate of CNS1 relapse was slightly higher but not statistically significantly different for CNS2. Conclusions: CNS involvement is relatively rare in pediatric ALCL. Detection rate of CNS3 can be improved by CSF flow cytometry and gene screening. The prognosis of CNS3 was significantly improved with CNCL-ALCL-2017 protocol, which may be related to the increased dose of methotrexate in the protocol. The short follow-up time and the small number of cases in this group may affect the results. Furthermore, CNS relapse rate of CNS2 was not markedly higher compared to CNS1. Keywords: Anaplastic large cell lymphoma; Pediatric; Central nervous system; Clinical features; Prognosis

Multi-Objective Sparsity Maximum Mode De-Composition: A New Method for Rotating Machine Fault Diagnosis on High-Speed Train Axle Box

Signal decomposition techniques generally have two limitations. First, for adaptive correlated kurtogram (ACK) and variational mode decomposition (VMD), etc., the definition of the decomposition target has no direct relationship with the features of fault impacts, i.e., the decomposition is not guided by the health indices used to characterize bearing faults, resulting in fault impacts cannot be completely separated from vibration data. Second, it is hard to accurately determine the decomposition stop parameter (the number of final output modes), resulting in frequent over- or under-decomposition. All these are not conducive to bearing fault detection in engineering practice. In this paper, a new decomposition method, multi-objective sparse maximum mode decomposition (MOSMMD), is proposed. Firstly, by analyzing the Fourier spectrum of vibration data, MOSMMD constructs multiple finite impulse response filters covering different frequency bands to obtain initial candidate modes. Then, aiming at maximizing <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L2</i> / <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L1</i> norm of envelope spectrum (ES), the upper and lower cutoff frequencies of each filter are adjusted adaptively through iterative optimization, and the frequency bands covered by each mode are adjusted accordingly. Finally, by using that fault feature harmonics have periodic natures in ES, the redundant modes are eliminated and only the modes with obvious fault features are output. Compared with VMD and ACK, the decomposition target of MO-SMMD is directly related to the fault features, i.e., cyclostationarity of fault impacts, which makes the extraction of fault impacts more accurate. Moreover, the number of final output modes of MOSMMD is determined adaptively and does not need to be set in advance as an input parameter. Also, MOSMMD can decompose fault modes from vibration data without prior fault information, even when processing concurrent fault signals. Simulation and experiments demonstrate the superiority of the proposed MOSMMD.

Proactive suppression can be applied to multiple salient distractors in visual search.

There is a growing body of research demonstrating that the capture of attention by a single salient distractor can be prevented via proactive suppression. In real-world contexts, there are often several distracting events that compete for attention, but it is entirely unknown whether multiple objects can be suppressed concurrently. We used behavioral and electrophysiological measures to investigate the existence and time course of multiple-item suppression. We employed search displays that contained either one or two uniquely colored distractors that differed in their salience (S+ and S-), or no such distractors. Search performance improved with the number of salient distractors, indicating that the suppression of multiple items reduced the effective display set size. This was also the case when the target color was no longer fully predictable, ruling out an alternative explanation in terms of attentional guidance by target templates. In an experiment where S+ and S- always appeared together in the same display, the PD component (a marker of proactive suppression) was triggered exclusively by the more salient distractor (S+), indicative of single-item suppression. However, when displays with one or both salient distractors were intermixed, a reliable PD component was also triggered by S-, even when it was accompanied by S+ in the same display. These results show that multiple concurrent salient signals can be proactively inhibited. They demonstrate that signal suppression processes can be adaptively employed to counteract visual distraction at different locations, in order to facilitate the attentional selection of relevant objects in crowded visual environments. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Underdetermined Blind Source Separation of Bioacoustic Signals

Bioacoustic signals have been used as a modality in environmental monitoring and biodiversity research. These signals also carry species or individual information, thus allowing the recognition of species and individuals based on vocals. Nevertheless, vocal communication in a crowded social environment is a challenging problem for automated bioacoustic recogniser systems due to interference problems in concurrent signals from multiple individuals. The bioacoustics sources are separated from the mixtures of multiple individual signals using a technique known as Blind source separation (BSS) to address the abovementioned issue. In this work, we explored the BSS of an underdetermined mixture based on a two-stage sparse component analysis (SCA) approach that consisted of (1) mixing matrix estimation and (2) source estimation. The key point of our procedure was to investigate the algorithm’s robustness to noise and the effect of increasing the number of sources. Using the two-stage SCA technique, the performances of the estimated mixing matrix and the estimated source were evaluated and discussed at various signal-to-noise ratios (SNRs). The use of different sources is also validated. Given its robustness, the SCA algorithm presented a stable and reliable performance in a noisy environment with small error changes when the noise level was increased.