A Hybrid Algorithm of LSTM and Factor Graph for Improving Combined GNSS/INS Positioning Accuracy during GNSS Interruptions.

In urban road environments, global navigation satellite system (GNSS) signals may be interrupted due to occlusion by buildings and obstacles, resulting in reduced accuracy and discontinuity of combined GNSS/inertial navigation system (INS) positioning. Improving the accuracy and robustness of combined GNSS/INS positioning systems for land vehicles in the presence of GNSS interruptions is a challenging task. The main objective of this paper is to develop a method for predicting GNSS information during GNSS outages based on a long short-term memory (LSTM) neural network to assist in factor graph-based combined GNSS/INS localization, which can provide a reliable combined localization solution during GNSS signal outages. In an environment with good GNSS signals, a factor graph fusion algorithm is used for data fusion of the combined positioning system, and an LSTM neural network prediction model is trained, and model parameters are determined using the INS velocity, inertial measurement unit (IMU) output, and GNSS position incremental data. In an environment with interrupted GNSS signals, the LSTM model is used to predict the GNSS positional increments and generate the pseudo-GNSS information and the solved results of INS for combined localization. In order to verify the performance and effectiveness of the proposed method, we conducted real-world road test experiments on land vehicles installed with GNSS receivers and inertial sensors. The experimental results show that, compared with the traditional combined GNSS/INS factor graph localization method, the proposed method can provide more accurate and robust localization results even in environments with frequent GNSS signal loss.

Discovery of flavonoid-containing compound Lupalbigenin as anti-NSCLC cancer agents via suppression of EGFR and ERK1/2 pathway.

Epidermal growth factor receptor exon 20 insertions (EGFR Ex20ins) driver mutations in non-small cell lung cancer (NSCLC) is insensitive to EGFR tyrosine kinase inhibitors (TKIs). Therefore, it is necessary to develop more novel strategy to address the limitations of existing therapies targeting EGFR-mutated NSCLC. Lupalbigenin (LB), a flavonoid compound extracted from Derris scandens, has shown preclinical activity in lung cancer. However, the activity of LB in Ex20ins-driven tumors has not yet been elucidated. In this study, a series of stable BaF/3 cell-line that contains a high proportion (>90 %) of EGFR-eGFP Ex20ins were generated using an IL3-deprivation method. Ba/F3 cell models harboring dissimilar Ex20ins were used to characterize the antineoplastic mechanism of LB. Molecular docking confirmed that the LB could effectively bind to key target EGFR. The in vitro anticancer activity of LB was investigated in engineered Ba/F3 cells bearing diverse uncommon EGFR mutations. LB was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines. Mechanistic studies disclosed that LB repressed EGFR phosphorylation and downstream survival pathways in Ba/F3 cells expressing EGFR Ex20ins, resulting in caspase activation by activating the intrinsic apoptotic pathway. Further analyses showed that LB significantly induced G0/G1 cell cycle arrest and apoptosis in cells. LB also reduced the protein expression levels of CDK4, CDK6, CDK8, cyclin D1, cyclin A2, and Bcl2 and promoted the expression of cytochrome C, p27, and p53. In summary, we explored the possible potential targets of LB through network pharmacology and verified the target using in vitro experiments. Furthermore, our results demonstrated that LB showed potential anti-Ex20ins cancer activity through suppression of the EGFR and ERK1/2 signaling pathway in Ba/F3 cells bearing two to three amino acid insertion mutations. These findings suggested that LB might be valuable for further investigation as a potential candidate in the treatment of associated diseases.

Steroid pulse therapy in idiopathic nephrotic syndrome in the era of modern immunosuppressive treatment-still up to date?

BACKGROUND: Intravenous steroid pulses (SP) are successfully used for the treatment of patients with idiopathic nephrotic syndrome (INS) resistant to oral prednisone. METHODS: We performed a retrospective analysis of all patients in the three pediatric nephrology centers of the Paris region from 2002 to 2022 who were resistant to a 30-day course of oral prednisone and who received SP for their first INS flare and analyzed their disease course over 4 years. RESULTS: Forty-seven patients (17 girls), median age 3.4 years, were analyzed. Of them, 68% reached remission within 7 days of SP. No significant short-term side effects were noted. Half of the patients started immunosuppressive treatment immediately after their first remission and 62% of them relapsed at least once, whereas all the patients who did not receive immunosuppressive treatment since their first remission relapsed. Among the SP-sensitive patients, 75% needed calcineurin inhibitor (CNI) or B-cell depletion during their disease course to achieve stable remission. Forty-two percent of the whole cohort received B-cell-depleting agents. Among the 15 SP-resistant patients, all received CNI. Twelve/fifteen patients reached remission. After 4 years, 68% among the SP-sensitive patients and 87% of SP-resistant patients still had an active disease. CONCLUSIONS: SP are helpful to obtain rapid remission in pediatric INS patients resistant to oral steroids. However, as most SP-sensitive patients need immunosuppressive drugs, mainly CNI and B-cell-depleting agents it could be interesting to discuss the possibility to start CNI directly after the 30-day course of prednisone instead of SP.

Decimeter-Level Accuracy for Smartphone Real-Time Kinematic Positioning Implementing a Robust Kalman Filter Approach and Inertial Navigation System Infusion in Complex Urban Environments.

New smartphones provide real-time access to GNSS pseudorange, Doppler, or carrier-phase measurement data at 1 Hz. Simultaneously, they can receive corrections broadcast by GNSS reference stations to perform real-time kinematic (RTK) positioning. This study aims at the real-time positioning capabilities of smartphones using raw GNSS measurements as a conventional method and proposes an improvement to the positioning through the integration of Inertial Navigation System (INS) measurements. A U-Blox GNSS receiver, model ZED-F9R, was used as a benchmark for comparison. We propose an enhanced ambiguity resolution algorithm that integrates the traditional LAMBDA method with an adaptive thresholding mechanism based on real-time quality metrics. The RTK/INS fusion method integrates RTK and INS measurements using an extended Kalman filter (EKF), where the state vector x includes the position, velocity, orientation, and their respective biases. The innovation here is the inclusion of a real-time weighting scheme that adjusts the contribution of the RTK and INS measurements based on their current estimated accuracy. Also, we use the tightly coupled (TC) RTK/INS fusion framework. By leveraging INS data, the system can maintain accurate positioning even when the GNSS data are unreliable, allowing for the detection and exclusion of abnormal GNSS measurements. However, in complex urban areas such as Qazvin City in Iran, the fusion method achieved positioning accuracies of approximately 0.380 m and 0.415 m for the Xiaomi Mi 8 and Samsung Galaxy S21 Ultra smartphones, respectively. The subsequent detailed analysis across different urban streets emphasized the significance of choosing the right positioning method based on the environmental conditions. In most cases, RTK positioning outperformed Single-Point Positioning (SPP), offering decimeter-level precision, while the fusion method bridged the gap between the two, showcasing improved stability accuracy. The comparative performance between the Samsung Galaxy S21 Ultra and Xiaomi Mi 8 revealed minor differences, likely attributed to variations in the hardware design and software algorithms. The fusion method emerged as a valuable alternative when the RTK signals were unavailable or impractical. This demonstrates the potential of integrating RTK and INS measurements for enhanced real-time smartphone positioning, particularly in challenging urban environments.

The Zero-Velocity Correction Method for Pipe Jacking Automatic Guidance System Based on Fiber Optic Gyroscope.

The pipe jacking guidance system based on a fiber optic gyroscope (FOG) has gained extensive attention due to its high degree of safety and autonomy. However, all inertial guidance systems have accumulative errors over time. The zero-velocity update (ZUPT) algorithm is an effective error compensation method, but accurately distinguishing between moving and stationary states in slow pipe jacking operations is a major challenge. To address this challenge, a "MV + ARE + SHOE" three-conditional zero-velocity detection (TCZVD) algorithm for the fiber optic gyroscope inertial navigation system (FOG-INS) is designed. Firstly, a Kalman filter model based on ZUPT is established. Secondly, the TCZVD algorithm, which combines the moving variance of acceleration (MV), angular rate energy (ARE), and stance hypothesis optimal estimation (SHOE), is proposed. Finally, experiments are conducted, and the results indicate that the proposed algorithm achieves a zero-velocity detection accuracy of 99.18% and can reduce positioning error to less than 2% of the total distance. Furthermore, the applicability of the proposed algorithm in the practical working environment is confirmed through on-site experiments. The results demonstrate that this method can effectively suppress the accumulated error of the inertial guidance system and improve the positioning accuracy of pipe jacking. It provides a robust and reliable solution for practical engineering challenges. Therefore, this study will contribute to the development of pipe jacking automatic guidance technology.

Identification of a novel cryptic variant chromosomal rearrangement involving 9q34, 22q11.2, and 5q22 resulting in ins(9;22) and t(5;22) in chronic myeloid leukemia: a case report.

Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic stem cells characterized by the aberrant production and uncontrolled proliferation of mature granulocytes with normal cell differentiation. The Philadelphia (Ph) chromosome resulting from reciprocal translocation between chromosomes 9 and 22 is the main genetic molecular hallmark of CML seen in more than 90% of the patients. However, about 5-10% of CML patients show a variant genetic rearrangement, involving one or more chromosomes in addition to 9 and 22. Herein, we describe the results of hematological, cytogenetic, fluorescence in situ hybridization (FISH), and high-end molecular analysis in a 77-year-old man diagnosed with CML. The combination of conventional cytogenetic analysis along with metaphase FISH and whole chromosomal paint revealed a novel cryptic variant chromosomal rearrangement involving 9q34, 22q11.2, and 5q22, resulting in ins(9;22) and t(5;22). At the molecular level, using PCR, myeloid NGS panels, and whole transcriptome analyses, we showed that this complex rearrangement indeed resulted in the formation of the BCR::ABL1 e13a2 major fusion transcript. No additional somatic mutations or kinase domain mutations were identified, thereby suggesting that the current case is indeed genetically homogeneous. This study provided strong evidence to support the idea that insertion-derived BCR::ABL1 fusions often involve complex chromosomal abnormalities that are overlooked by conventional cytogenetics but can be identified by a combination of conventional, molecular cytogenetics, and high-end NGS studies.

Effects of two-person synchronized cycling exercise on interpersonal cooperation: A near-infrared spectroscopy hyperscanning study.

Objective: Although psychological research indicating the synchronous activities can promote interpersonal cooperation, thus far there is no direct evidence that two-person synchronous exercise effectively enhances interpersonal cooperative behaviors in Physical exercise field. This suggests that, although synchronization phenomenon is widespread in sports and is considered a potential tool for enhancing teamwork, its specific effects and functioning mechanisms still need to be clarified by further scientific research. This study intends to use two-person synchronized cycling exercise to investigate the synchronized exercise effect on interpersonal cooperative behavior and its underlying neural mechanisms. Methods: Eighty college students without regular exercise habits will be randomly assigned to the experimental group (10 male dyads and 10 female dyads) and the control group (10 male dyads and 10 female dyads). During the experiment, dyads in the experimental group performed a 30-minute synchronized cycling exercise with synchronized pedaling movements; dyads in the control group rested sedentary in the same environment for 30 minutes. Interpersonal cooperative behavior was assessed with the Prisoner's Dilemma task, and the interpersonal neural synchronization(INS) data were collected in the prefrontal cortex using near-infrared hyperscanning. Results: This study compared behavior and brain activity before and after synchronous exercise. Behavioral results revealed that, compared to pre-exercise, dyads in the post-exercise had higher average cooperation rates, higher cooperation efficiency and shorter cooperation response times. Compared to post-sedentary, dyads in the post-exercise had shorter cooperation response times and higher cooperation efficiency. Furthermore, brain data showed that,compared to pre-exercise, dyads in the post-exercise had stronger INS in the dorsolateral prefrontal cortex(DLPFC), whereas the dyads in the post-exercise had stronge INS in the DLPFC compared to post-sedentary. After controlling for dyads' anxiety and mood states, this study also found a marginally significant negative correlation between INS differences in the left DLPFC and cooperation response time differences. Conclusions: This research confirms, from both behavioral and neuroscience perspectives, that one synchronization cycle can significantly enhance interpersonal cooperative behavior, and this positive effect is closely associated with increased INS in the left DLPFC. This study provides new insights into understanding how positive interactive exercises promote interpersonal cooperation through specific neural mechanisms.

Safety evaluation of curdlan as a food additive.

The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion on the safety of curdlan as a new food additive used as firming and gelling agent, stabiliser, thickener. Curdlan is a high molecular weight polysaccharide consisting of ß-1,3-linked glucose units, produced by fermentation from Rhizobium radiobacter biovar 1 strain NTK-u. The toxicological dataset consisted of sub-chronic, chronic and carcinogenicity, reproductive and developmental toxicity studies as well as genotoxicity. In vivo data showed that curdlan is not absorbed as such but is extensively metabolised by the gut microbiota into CO2 and other innocuous compounds. Curdlan was not genotoxic and was well-tolerated with no overt organ-specific toxicity. Effects observed at very high doses of curdlan, such as decreased growth and increased cecum weight, are common for indigestible bulking compounds and therefore considered physiological responses. In a combined three-generation reproductive and developmental toxicity study, decreased pup weight was observed during lactation at 7500 mg curdlan/kg body weight (bw) per day, the highest dose tested. The Panel considered the observed effects as treatment-related and adverse, although likely secondary to nutritional imbalance and identified a conservative no observed adverse effect level (NOAEL) of 2500 mg/kg bw per day. Despite the limitations noted in the dataset, the Panel was able to conclude applying the margin of exposure (MOE) approach. Given that curdlan and its break-down products are not absorbed and that the identified adverse effect is neither systemic nor local, no adjustment factor was deemed necessary. Thus, an MOE of at least 1 was considered sufficient. The highest exposure estimate was 1441 mg/kg bw per day in toddlers at the 95th percentile of the proposed maximum use level exposure assessment scenario. The Panel concluded that there is no safety concern for the use of curdlan as a food additive at the proposed uses and use levels.

An INSULIN and IAPP dual reporter enables tracking of functional maturation of stem cell-derived insulin producing cells.

OBJECTIVE: Human embryonic stem cell (hESC; SC)-derived pancreatic ß cells can be used to study diabetes pathologies and develop cell replacement therapies. Although current differentiation protocols yield SCß cells with varying degrees of maturation, these cells still differ from deceased donor human ß cells in several respects. We sought to develop a reporter cell line that could be used to dynamically track SCß cell functional maturation. METHODS: To monitor SCß cell maturation in vitro, we created an IAPP-2A-mScar and INSULIN-2A-EGFP dual fluorescent reporter (INS2A-EGFP/+;IAPP2A-mScarlet/+) hESC line using CRISPR/Cas9. Pluripotent SC were then differentiated using a 7-stage protocol to islet-like cells. Immunohistochemistry, flow cytometry, qPCR, GSIS and electrophysiology were used to characterise resulting cell populations. RESULTS: We observed robust expression of EGFP and mScarlet fluorescent proteins in insulin- and IAPP-expressing cells without any compromise to their differentiation. We show that the proportion of insulin-producing cells expressing IAPP increases over a 4-week maturation period, and that a subset of insulin-expressing cells remain IAPP-free. Compared to this IAPP-free population, we show these insulin- and IAPP-expressing cells are less polyhormonal, more glucose-sensitive, and exhibit decreased action potential firing in low (2.8 mM) glucose. CONCLUSIONS: The INS2A-EGFP/+;IAPP2A-mScarlet/+ hESC line provides a useful tool for tracking populations of maturing hESC-derived ß cells in vitro. This tool has already been shared with 3 groups and is freely available to all.

Therapeutic effect of oral insulin-chitosan nanobeads pectin-dextrin shell on streptozotocin-diabetic male albino rats.

The current study inspects the therapeutic effects of orally ingested insulin-loaded chitosan nanobeads (INS-CsNBs) with a pectin-dextrin (PD) coating on streptozotocin (STZ)-induced diabetes in Wistar rats. The study also assessed antioxidant effects in pancreatic tissue homogenate, insulin, C-peptide, and inflammatory markers interleukin-1 beta and interleukin-6 (IL-1ß and IL-6) in serum. Additionally, histopathological and immunohistochemical examination of insulin granules, oxidative stress, nuclear factor kappa B (NF-κB P65), and sirtuin-1 (SIRT-1) protein detection, as well as gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl2), and Bcl-2-associated X protein (Bax) in pancreatic tissue were investigated. After induction of diabetes with STZ, rats were allocated into 6 groups: the normal control (C), the diabetic control (D), and the diabetic groups treated with INS-CsNBs coated with PD shell (50 IU/kg) (NF), free oral insulin (10 IU/kg) (FO), CsNBs-PD shell (50 IU/kg) (NB), and subcutaneous insulin (10 IU/kg) (Sc). The rats were treated daily for four weeks. Treatment of diabetic rats with INS-CsNBs coated with PD shell resulted in a significant improvement in blood glucose levels, elevated antioxidant activities, decreased NF-κB P65, IL-1ß, and IL-6 levels, upregulated Nrf-2 and HO-1, in addition to a marked improvement in the histological architecture and integrity compared to the diabetic group. The effects of oral INS-CsNBs administration were comparable to those of subcutaneous insulin. In conclusion, oral administration of INS-loaded Cs-NBs with a pectin-dextrin shell demonstrated an ameliorative effect on STZ-induced diabetes, avoiding the drawbacks of subcutaneous insulin.

[Chinese Expert Consensus on the Standardized Diagnosis and Treatment of 
Non­small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations (2024 Edition)].

The standard clinical practice of managing the non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations was elaborated in Chinese expert consensus on non­small cell lung cancer with EGFR exon 20 insertion mutations (2023 edition), and this rare subset has gradually attracted attention recently. With the deepening of treatment area exploration and the approval of new targeted drugs, there are more options for the diagnosis and treatment of EGFR ex20ins positive NSCLC patients. Therefore, based on the previous version of consensus, the expert panel has updated this consensus on the standardized clinical diagnosis and treatment of EGFR ex20ins mutation NSCLC through reference to literature and clinical data, and combined with the experts' own clinical experience. The updated recommendations includes disease congnition, testing methods, therapy and recent relevant clinical trials for NSCLC patients with EGFR ex20ins mutation, in order to provide better medication reference for clinical physicians.
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Current clinical practice and physicians' insights on Chinese patients with advanced non-small cell lung cancer habouring epidermal growth factor receptor 20 insertion mutation.

BACKGROUND: The present study aimed to investigate physicians' perspectives on the diagnosis and treatment decisions for patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutations in a real-world setting in China using an online questionnaire. METHODS: This study was performed via the CAPTRA-Lung collaboration between December 9, 2022 and March 6, 2023. The questionnaire was distributed digitally to physicians around China and was comprised of three sections: basic characteristics of surveyed physicians, diagnosis and treatment status of NSCLC patients with the EGFR exon20ins-mutation, and physicians' perspectives on treatment options. Physicians who treat more than 10 patients with advanced NSCLC every month and who have treated patients with advanced EGFR exon20ins-mutant NSCLC in the past six months were involved in this study. RESULTS: A total of 53,729 questionnaires were distributed and 390 valid ones were collected. The EGFR mutation test was performed in 80.9% and 59.9% of patients receiving first-line or second-line therapy and beyond (hereinafter "second-line")therapy, respectively. In terms of treatment options, chemotherapy plus antiangiogenic therapy was the most common treatment option (30.0% of patients in first-line settings; 25.0% of patients in second-line settings), and a certain proportion of patients received novel EGFR exon20ins-targeted agents (including tyrosine kinase inhibitors [TKIs] and bispecific antibodies) in first- or second-line settings, which accounted for 11.9% and 15.7% of all treated patients, respectively. Additionally, physicians reported the highest satisfaction score for the efficacy and safety of targeted agents. Most physicians believed that EGFR exon20ins-targeted TKIs represented the most promising treatment option (80.2% in first-line treatment and 73.3% in second-line treatment). Among several novel agents under study, sunvozertinib has received the highest recognition for efficacy and safety. CONCLUSIONS: This study investigated the current diagnosis and treatment status and physicians' perspective, of patients with EGFR exon20ins-mutant NSCLC. The results highlight significant unmet clinical needs in this subgroup of patients. EGFR exon20ins-targeted TKIs were recognized as the most promising treatment regimen and may benefit more patients considering their awareness and acceptance of targeted therapy.

Wearable Multi-Sensor Positioning Prototype for Rowing Technique Evaluation.

The goal of this study is to determine the feasibility of a wearable multi-sensor positioning prototype to be used as a training tool to evaluate rowing technique and to determine the positioning accuracy using multiple mathematical models and estimation methods. The wearable device consists of an inertial measurement unit (IMU), an ultra-wideband (UWB) transceiver, and a global navigation satellite system (GNSS) receiver. An experiment on a rowing shell was conducted to evaluate the performance of the system on a rower's wrist, against a centimeter-level GNSS reference trajectory. This experiment analyzed the rowing motion in multiple navigation frames and with various positioning methods. The results show that the wearable device prototype is a viable option for rowing technique analysis; the system was able to provide the position, velocity, and attitude of a rower's wrist, with a positioning accuracy ranging between ±0.185 m and ±1.656 m depending on the estimation method.

Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure. METHODS: Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing. RESULTS: Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group. CONCLUSIONS: Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.

A brief report on stable disease among amivantamab-treated patients with post-platinum epidermal growth factor receptor exon 20 insertion-mutated non-small cell lung cancer: A response-based analysis from the CHRYSALIS study.

BACKGROUND: Amivantamab, an EGFR-MET bispecific antibody, is the first approved targeted therapy for patients with EGFR Ex20ins NSCLC after prior platinum-based chemotherapy-a population with historically poor outcomes before amivantamab approval. As antitumor activity in single-arm studies typically focuses on responders, the evaluation of outcomes in patients with stable disease (SD) as best response is of clinical interest. PATIENTS AND METHODS: Among 114 patients with post-platinum EGFR Ex20ins NSCLC in CHRYSALIS (NCT02609776; data cutoff: March 30, 2021), response was assessed by blinded independent central review via RECIST v1.1. Patients alive and receiving therapy at 12 weeks were grouped by response at this landmark: partial or complete response (PR+), SD, or progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) by response cohort were determined using the Kaplan-Meier method; hazard ratios (HRs) and 95% confidence intervals (CIs) between response cohorts were calculated using Cox proportional hazards regression. RESULTS: Among patients alive and receiving therapy at 12 weeks (n=107), 42 (39%) had PR+, 52 (49%) had SD, and 13 (12%) had PD. Among patients with PR+ and SD, median PFS was 12.2 and 7.0 months, respectively. A corresponding improvement in OS was observed in patients achieving PR+ (median: not reached; HR vs PD=0.21 [95% CI: 0.08-0.54]) and SD (median: 23.0 months; HR vs PD=0.33 [95% CI: 0.14-0.77]), relative to those with PD (median: 14.0 months). CONCLUSION: SD was observed in 49% of patients receiving amivantamab, with corresponding increases in OS that dramatically improved the prognoses of this patient population.

REST and RCOR genes display distinct expression profiles in neurons and astrocytes using 2D and 3D human pluripotent stem cell models.

Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor involved in neurodevelopment and neuroprotection. REST forms a complex with the REST corepressors, CoREST1, CoREST2, or CoREST3 (encoded by RCOR1, RCOR2, and RCOR3, respectively). Emerging evidence suggests that the CoREST family can target unique genes independently of REST, in various neural and glial cell types during different developmental stages. However, there is limited knowledge regarding the expression and function of the CoREST family in human neurodevelopment. To address this gap, we employed 2D and 3D human pluripotent stem cell (hPSC) models to investigate REST and RCOR gene expression levels. Our study revealed a significant increase in RCOR3 expression in glutamatergic cortical and GABAergic ventral forebrain neurons, as well as mature functional NGN2-induced neurons. Additionally, a simplified astrocyte transdifferentiation protocol resulted in a significant decrease in RCOR2 expression following differentiation. REST expression was notably reduced in mature neurons and cerebral organoids. In summary, our findings provide the first insights into the cell-type-specific expression patterns of RCOR genes in human neuronal and glial differentiation. Specifically, RCOR3 expression increases in neurons, while RCOR2 levels decrease in astrocytes. The dynamic expression patterns of REST and RCOR genes during hPSC neuronal and glial differentiation underscore the potential distinct roles played by REST and CoREST proteins in regulating the development of these cell types in humans.

Association of HLA-G 3'UTR polymorphisms with hepatitis B virus infection in Tunisian population.

Hepatitis B virus (HBV) infection is a major public health burden. The mechanisms of immune evasion during chronic HBV (CHB) infection are poorly understood. Human leukocyte antigen (HLA)-G, an immune checkpoint molecule, plays a crucial role in the tolerance mechanisms of various infectious diseases. The 3' untranslated region (3'UTR), including the HLA-G + 3142 C > G polymorphism (rs1063320) and the 14-pb Ins/Del (rs66554220) has been strongly suggested to influence HLA-G expression. This study conducted a case-control analysis to evaluate the potential correlation between the HLA-G + 3142 C > G polymorphism and HBV infection outcome in a Tunisian cohort. The HLA-G + 3142 C > G polymorphism was analysed by PCR-RFLP in 242 patients with chronic HBV infection (116 males and 126 females), 241 healthy controls (116 males and 125 females), and 100 spontaneously resolved subjects (52 males and 48 females). Patients with chronic HBV infection showed a higher frequency of the + 3142G allele compared to healthy controls and spontaneously resolved subjects (p = 0.001 and p = 0.002, respectively). An association between the + 3142G allele and high HBV DNA levels was observed when HBV patients were stratified based on their HBV DNA levels (p = 0.016). Furthermore, the dominant model (GG + GC vs CC) was associated with liver function parameters, including AST, ALT, and high HBV DNA levels (p = 0.04, p < 0.001 and p = 0.002, respectively). However, there was no significant association found between this polymorphism and the fibrosis stage (p = 0.32). The haplotype analysis, using a subset of previously published data on the HLA-G 14-pb Ins/Del polymorphism, revealed an association between the Ins/G haplotype and chronic HBV infection (H1: InsG, p < 0.001). Our findings suggest that the + 3142G allele is a risk factor for the persistence and progression of HBV infection, while the + 3142C allele serves as a protective allele associated with the spontaneous resolution of the infection. Additionally, the HLA-G 3'UTR haplotype Ins/G is associated with chronic HBV infection in the Tunisian population.

Analytical quaternion-based bias estimation algorithm for fast and accurate stationary gyro-compassing.

This work introduces a novel approach to Strapdown Inertial Navigation System (SINS) alignment, distinct from recursive methods like Kalman filtering. The proposed methodology expedites bias error calculations by utilizing quaternion-based analytical relationships, which bypasses the slow convergence behavior associated with recursive algorithms, particularly in azimuth angle error estimation. In addition, the proposed approach demonstrates comparable accuracy to traditional fine alignment methods. Simulations and experiments validate that in contrast to the 10-min time requirement of traditional fine alignment methods (for azimuth angle estimation in stationary conditions), the proposed approach achieves the same accuracy within 20 s. However, limitations exist as the algorithm is applicable only in stationary conditions, and necessitating a high-grade IMU capable of measuring the earth's rotation rate.

Extracellular electrophysiology on clonal human ß-cell spheroids.

Background: Pancreatic islets are important in nutrient homeostasis and improved cellular models of clonal origin may very useful especially in view of relatively scarce primary material. Close 3D contact and coupling between ß-cells are a hallmark of physiological function improving signal/noise ratios. Extracellular electrophysiology using micro-electrode arrays (MEA) is technically far more accessible than single cell patch clamp, enables dynamic monitoring of electrical activity in 3D organoids and recorded multicellular slow potentials (SP) provide unbiased insight in cell-cell coupling. Objective: We have therefore asked whether 3D spheroids enhance clonal ß-cell function such as electrical activity and hormone secretion using human EndoC-ßH1, EndoC-ßH5 and rodent INS-1 832/13 cells. Methods: Spheroids were formed either by hanging drop or proprietary devices. Extracellular electrophysiology was conducted using multi-electrode arrays with appropriate signal extraction and hormone secretion measured by ELISA. Results: EndoC-ßH1 spheroids exhibited increased signals in terms of SP frequency and especially amplitude as compared to monolayers and even single cell action potentials (AP) were quantifiable. Enhanced electrical signature in spheroids was accompanied by an increase in the glucose stimulated insulin secretion index. EndoC-ßH5 monolayers and spheroids gave electrophysiological profiles similar to EndoC-ßH1, except for a higher electrical activity at 3 mM glucose, and exhibited moreover a biphasic profile. Again, physiological concentrations of GLP-1 increased AP frequency. Spheroids also exhibited a higher secretion index. INS-1 cells did not form stable spheroids, but overexpression of connexin 36, required for cell-cell coupling, increased glucose responsiveness, dampened basal activity and consequently augmented the stimulation index. Conclusion: In conclusion, spheroid formation enhances physiological function of the human clonal ß-cell lines and these models may provide surrogates for primary islets in extracellular electrophysiology.

Experimental Research on Shipborne SINS Rapid Mooring Alignment with Variance-Constraint Kalman Filter and GNSS Position Updates.

Analytical coarse alignment and Kalman filter fine alignment based on zero-velocity are typically used to obtain initial attitude for inertial navigation systems (SINS) on a static base. However, in the shipboard mooring state, the static observation condition is corrupted. This paper presents a rapid alignment method for SINS on swaying bases. The proposed method begins with a coarse alignment technique in the inertial frame to obtain an initial rough attitude. Subsequently, a Kalman filter with position updates is employed to estimate the remaining misalignment error. To enhance the filter estimation performance, an appropriate lower boundary is set to the target states' variances according to a carefully designed relative convergence index. The variance-constraint Kalman filter (VCKF) approach is proposed in this paper, and the shipborne experiments validate its effectiveness. The results demonstrate that the VCKF approach significantly reduces the time requirement for fine alignment to achieve the same accuracy on a swaying base, from 90 min in the classic Kalman filter to 30 min. Additionally, the parameter estimation performance in the Kalman filter is also improved, particularly in situations where unpredicted external interference is involved during fine alignment.