Administration mode matters for 5-fluorouracil therapy: Physiologically based pharmacokinetic evidence for avoidance of myelotoxicity by continuous infusion but not intravenous bolus.

AIMS: Pre-emptive prediction to avoid myelosuppression and harmful sequelae is difficult given the complex interplay among patients, drugs and treatment protocols. This study aimed to model plasma and bone marrow concentrations and the likelihood of myelotoxicity following administration of 5-fluorouracil (5-FU) by diverse intravenous (IV) bolus or continuous infusion (cIF) regimens. METHODS: Using physicochemical, in vitro and clinical data obtained from the literature consisting of various regimens and patient cohorts, a 5-FU physiologically based pharmacokinetic (PBPK) model was developed. The predicted and observed PK values were compared to assess model performance prior to examining myelotoxicity potential of IV bolus vs. cIF and DPYD wild type vs. genetic variant. RESULTS: The established model was verified by utilizing 5-FU concentration-time profiles of adequate heterogeneity contributed by 36 regimens from 15 studies. The study provided corroborative evidence to explain why cIF (vs. IV bolus) had lower myelotoxicity risk despite much higher total doses. The PBPK model was used to estimate the optimal dosage in patients heterozygous for the DPYD c.1905 + 1G > A allele and suggested that a dose reduction of at least 25% was needed (compared to the dose in wild-type subjects). CONCLUSION: A verified PBPK model was used to explain the lower myelotoxicity risk of cIF vs. IV bolus administration of 5-FU and to estimate the dose reduction needed in carriers of a DPYD variant. With appropriate data, expertise and resources, PBPK models have many potential uses in precision medicine application of oncology drugs.

Two-stage deep-learning-based colonoscopy polyp detection incorporating fisheye and reflection correction.

BACKGROUND AND AIM: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection. METHODS: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection. RESULTS: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94. CONCLUSION: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy.

Anticonvulsant effect of equilibrative nucleoside transporters 1 inhibitor in a mouse model of Dravet syndrome.

There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1aE1099X/+ mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1aE1099X/+ mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post-synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia-induced seizures in Scn1aE1099X/+ mice. This effect possibly acts on presynaptic A1R-mediated signaling modulation in granule cells.

Physiologically based mechanistic insight into differential risk of valproate hepatotoxicity between children and adults: A focus on ontogeny impact.

The anticonvulsant valproic acid (VPA) despite complex pharmacokinetics has been in clinical use for nearly 6 decades. Previous reports indicated neonates, infants, and toddlers/preschoolers had higher risk of valproate hepatotoxicity than adults. However, dosing recommendations for those less than 10 years of age are lacking. To decipher clinical puzzles, physiologically-based pharmacokinetic (PBPK) models of VPA and its hepatotoxic metabolite 4-ene-VPA were constructed and simulated with particularly integrated information of drug-metabolizing enzyme ontogeny. Adult and pediatric PK data of VPA (n = 143 subjects) and 4-ene-VPA (n = 8 subjects) collected from previous reports were used for model development and validation. Sensitivity analyses were performed to characterize ontogeny impacts of CYP2C9 and UGT2B7 on dispositions of VPA and 4-ene-VPA across age groups. Optimal VPA dosing for each pediatric age group was also predicted and objectively judged by ensuring VPA efficacy and avoiding 4-ene-VPA hepatotoxicity. The study revealed UGT2B7 ontogeny was quite influential on VPA clearance even in neonates and small children. Intrinsic clearance of CYP2C9 was the most prominent determinant for areas under the concentration-time curve of VPA and 4-ene-VPA in infants, and toddlers/preschoolers, reflecting higher hepatotoxicity risk due to noxious 4-ene-VPA accumulation in these groups. The ontogeny-based PBPK approach complements conventional allometric methods in dosing estimation for the young by providing more mechanistic insight of the processes changing with age. The established ontogeny-based PBPK approach for VPA therapy deserves further corroboration by real-world therapeutic data to affirm its clinical applicability.

The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion.

BACKGROUND: Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion. METHODS: Cerebral ischemia-reperfusion injury was examined in mice with transient middle cerebral artery occlusion (tMCAO) for 90 minutes, followed by 24-hour reperfusion. Infarct volume, brain edema, neuroinflammation, microvascular structure, regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), and the production of reactive oxygen species (ROS) were examined following the reperfusion. RESULTS: Ent2 deletion reduced the infarct volume, brain edema, and neuroinflammation in mice with cerebral ischemia-reperfusion. tMCAO-induced disruption of brain microvessels was ameliorated in Ent2-/- mice, with a reduced expression of matrix metalloproteinases-9 and aquaporin-4 proteins. Following the reperfusion, the rCBF of the wild-type (WT) mice was quickly restored to the baseline, whereas, in Ent2-/- mice, rCBF was slowly recovered initially, but was then higher than that in the WT mice at the later phase of reperfusion. The improved CMRO2 and reduced ROS level support the beneficial effects caused by the changes in the rCBF of Ent2-/- mice. Further studies showed that the protective effects of Ent2 deletion in mice with tMCAO involve adenosine receptor A2AR. CONCLUSIONS: Ent2 plays a critical role in modulating cerebral collateral circulation and ameliorating pathological events of brain ischemia and reperfusion injury.

Mechanistic Insights into Harmine-Mediated Inhibition of Human DNA Methyltransferases and Prostate Cancer Cell Growth.

Mammalian DNA methyltransferases (DNMTs), including DNMT1, DNMT3A, and DNMT3B, are key DNA methylation enzymes and play important roles in gene expression regulation. Dysregulation of DNMTs is linked to various diseases and carcinogenesis, and therefore except for the two approved anticancer azanucleoside drugs, various non-nucleoside DNMT inhibitors have been identified and reported. However, the underlying mechanisms for the inhibitory activity of these non-nucleoside inhibitors still remain largely unknown. Here, we systematically tested and compared the inhibition activities of five non-nucleoside inhibitors toward the three human DNMTs. We found that harmine and nanaomycin A blocked the methyltransferase activity of DNMT3A and DNMT3B more efficiently than resveratrol, EGCG, and RG108. We further determined the crystal structure of harmine in complex with the catalytic domain of the DNMT3B-DNMT3L tetramer revealing that harmine binds at the adenine cavity of the SAM-binding pocket in DNMT3B. Our kinetics assays confirm that harmine competes with SAM to competitively inhibit DNMT3B-3L activity with a Ki of 6.6 µM. Cell-based studies further show that harmine treatment inhibits castration-resistant prostate cancer cell (CRPC) proliferation with an IC50 of ∼14 µM. The CPRC cells treated with harmine resulted in reactivating silenced hypermethylated genes compared to the untreated cells, and harmine cooperated with an androgen antagonist, bicalutamide, to effectively inhibit the proliferation of CRPC cells. Our study thus reveals, for the first time, the inhibitory mechanism of harmine on DNMTs and highlights new strategies for developing novel DNMT inhibitors for cancer treatment.

Using wound cartoon visual education to enhance nurses' knowledge of wound care.

Cartoon education methods have been used effectively as a teaching tool and were considered potentially useful to improve nurses' knowledge and professional skills to ensure quality patient care. Therefore, this study aimed to enhance nurses' knowledge of wound care using the cartoon visual education program. After the 4 weeks, nurses were given questionnaires about knowledge of wound care, self-efficacy, situation anxiety, and trait anxiety to understand the nurse's situation before and after the teaching program analysis. Significant differences were observed in their education level, rank, marital status, and whether or not they had children, and received wound education. Linear regression results show significant differences in wound care knowledge and situational anxiety. The study indicates that cartoon visual education is enhancing nursing staff's knowledge of wound care and mitigating situational anxiety and thus can improve the quality of wound care by nursing staff and is used to standardise wound care education, resulting in better wound care services.

Deletion of equilibrative nucleoside transporter 2 disturbs energy metabolism and exacerbates disease progression in an experimental model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease, characterized by motor dysfunction and abnormal energy metabolism. Equilibrative nucleoside transporter 1 (ENT1) and ENT2 are the major nucleoside transporters in cellular plasma membrane of the brain. Yet, unlike ENT1 whose function has been better investigated in HD, the role of ENT2 in HD remains unclear. The present study aimed to investigate the impacts of ENT2 deletion on HD using a well-characterized mouse model (R6/2). Microarray analysis, quantitative real-time polymerase chain reaction, and immunostaining of ENT2 in postmortem human brain tissues were conducted. R6/2 mice with or without genetic deletion of ENT2 were generated. Motor functions, including rotarod performance and limb-clasping test, were examined at the age of 7 to 12 weeks. Biochemical changes were evaluated by immunofluorescence staining and immunoblotting at the age of 12 to 13 weeks. In regard to energy metabolism, levels of striatal metabolites were determined by liquid chromatography coupled with the fluorescence detector or quadrupole time-of-flight mass spectrometer. Mitochondrial bioenergetics was assessed by the Seahorse assay. The results showed that ENT2 protein was detected in the neurons and astrocytes of human brains and the levels in the postmortem brain tended to be higher in patients with HD. In mice, ENT2 deletion did not alter the phenotype of the non-HD controls. Yet, ENT2 deletion deteriorated motor function and increased the number of aggregated mutant huntingtin in the striatum of R6/2 mice. Notably, disturbed energy metabolism with decreased ATP level and increased AMP/ ATP ratio was observed in R6/2-Ent2-/- mice, compared with R6/2-Ent2+/+ mice, resulting in the activation of AMPK in the late disease stage. Furthermore, ENT2 deletion reduced the NAD+/NADH ratio and impaired mitochondrial respiration in the striatum of R6/2 mice. Taken together, these findings indicate the crucial role of ENT2 in energy homeostasis, in which ENT2 deletion further impairs mitochondrial bioenergetics and deteriorates motor function in R6/2 mice.

Equilibrative Nucleoside Transporter 1 is a Target to Modulate Neuroinflammation and Improve Functional Recovery in Mice with Spinal Cord Injury.

Neuroinflammation plays a critical role in the neurological recovery of spinal cord injury (SCI). Adenosine can modulate neuroinflammation, whose uptake is mediated by nucleoside transporters. This study aimed to investigate the roles of equilibrative nucleoside transporter 1 (Ent1) in the inflammatory responses and functional recovery of SCI. Spinal cord contusion at the T10 dorsal portion was induced in mice to cause partial paralysis of the hindlimbs. Genetic deletion and pharmacological inhibition of Ent1 were used to evaluate the role of Ent1 in SCI. The outcomes were evaluated in terms of the Basso Mouse Scale (BMS), gait analysis, astrogliosis, microgliosis, and cytokine levels on day 14 post-injury. As a result, Ent1 deletion reduced neuroinflammation and improved the BMS score (4.88 ± 0.35 in Ent1-/- vs. 3.78 ± 1.09 in Ent1+/+) and stride length (3.74 ± 0.48 cm in Ent1-/- vs. 2.82 ± 0.78 cm in Ent1+/+) of mice with SCI. Along with the reduced lesion size, more preserved neurons were identified in the perilesional area of mice with Ent1 deletion (102 ± 23 in Ent1-/- vs. 73 ± 10 in Ent1+/+). The results of pharmacological inhibition were consistent with the findings of genetic deletion. Moreover, Ent1 inhibition decreased the protein level of complement 3 (an A1 marker), but increased the levels of S100 calcium-binding protein a10 (an A2 marker) and transforming growth factor-ß, without changing the levels of inducible nitric oxide synthase (a M1 marker) and arginase 1 (a M2 marker) at the injured site. These findings indicate the important role of Ent1 in the pathogenesis and treatment of SCI.

Albumin-Bilirubin Grade as a Novel Predictor of the Development and Short-Term Survival of Post-Banding Ulcer Bleeding Following Endoscopic Variceal Ligation in Cirrhotic Patients.

Background and Objectives: Endoscopic variceal ligation (EVL) is the primary and secondary treatment for acute esophageal variceal bleeding. Post-banding ulcer bleeding (PBUB) may lead to bleeding episodes following EVL, increasing mortality. The aim of this study was to evaluate the risk factors for PBUB and predict the 6-week mortality risk after PBUB. Materials and Methods: We retrospectively analyzed the data collected from cirrhotic patients with EVL from 2015 to 2017. The incidence of PBUB and the 6-week mortality rate were evaluated. Risk factors for PBUB and predictive factors for mortality after PBUB were analyzed. Results: A total of 713 patients were enrolled in this study. Among the studied subjects, the incidence of PBUB was 5.8% (N = 41). The 6-week mortality rate was 63.4% (26/41). In multivariate analysis, MELD score ≥20 (OR: 3.77, 95% CI: 1.94−7.33, p < 0.001), ALBI score of 3 (OR: 2.67, 95% CI: 1.34−5.3, p = 0.005) and the presence of gastric varices (OR: 2.1, 95% CI: 1.06−4.16, p = 0.03) were associated with the development of PBUB. Patients with ALBI grade 3 (OR: 4.8, 95% CI: 1.18−19.6, p = 0.029) and Child-Pugh scores B and C (OR: 16.67, 95% CI: 1.75−158.1, p = 0.014) were associated with 6-week mortality after PBUB. Conclusions: PBUB is a complication with low incidence but increased mortality following EVL. The ALBI grade is a useful score to predict not only the development of PBUB but also the 6-week mortality after PBUB.

Ibuprofen treatment ameliorates memory deficits in rats with collagen-induced arthritis by normalizing aberrant MAPK/NF-κB and glutamatergic pathways.

Many studies have indicated that the risk of cognitive impairment is higher in patients with rheumatoid arthritis (RA). Additionally, patients with RA may have a lower incidence of cognitive impairment with long-term use of ibuprofen. This study was aimed at investigating the impacts of RA on memory function and the mechanisms that ibuprofen may exhibit to improve memory function in rats with collagen-induced arthritis (CIA). Ibuprofen (30 mg/kg) was given twice daily to CIA rats for two weeks starting from Day 18 following the first immunization. Memory function was measured by the Morris water maze (MWM) test and long-term potentiation (LTP). The proinflammatory cytokine levels and downstream signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB), were examined. Furthermore, the glutamatergic system, including glutamate transporters/receptors and brain extracellular levels of glutamate, was investigated. The results showed that the impaired learning memory in CIA rats, examined by the MWM test and LTP, can be ameliorated by ibuprofen treatment. Along with the improvement in memory deficits, ibuprofen attenuated both neuroinflammation and the associated elevated levels of phosphorylated p38, JNK, and p65 in the hippocampus of CIA rats. In addition, the decreased excitatory amino acid transporter 2 level, the increased extracellular glutamate, and the upregulated hippocampal NMDA receptor 2B of CIA rats were all normalized by ibuprofen treatment. These findings suggest that the effect of ibuprofen on the memory improvement in CIA rats is associated with the normalization of the activated MAPK and NF-κB pathways and the aberrant glutamatergic system.

Prognostic Significance of Perineural Invasion in Patients with Stage II/III Gastric Cancer Undergoing Radical Surgery.

The prognostic significance of perineural invasion in patients with gastric cancer (GC) is controversial. This study aimed to determine the prognostic value of perineural invasion in patients with stage II/III GC undergoing radical surgery. A total of 1913 patients with stage II/III GC who underwent curative resection between 1994 and 2015 were recruited. Clinicopathological factors, tumor recurrence patterns, disease-free survival, and cancer-specific survival were compared in terms of perineural invasion. The prognostic factors of disease-free survival and cancer-specific survival were determined using univariate and multivariate analyses. Perineural invasion was found in 57.1% of the patients. Age of <65 years, female sex, large tumor size, upper tumor location, total gastrectomy, advanced tumor invasion depth and nodal involvement, greater metastatic to examined lymph node ratio, undifferentiated tumor, and presence of lymphatic or vascular invasion were significantly associated with perineural invasion. The patients with perineural invasion had higher locoregional/peritoneal recurrence rates than those without. Perineural invasion was independently associated with disease-free survival and cancer-specific survival. In conclusion, perineural invasion positivity is associated with aggressive tumor behaviors and higher locoregional/peritoneal recurrence rates in patients with stage II/III GC undergoing curative surgery. It is an independent unfavorable prognostic factor of disease recurrence and cancer-specific survival.

Rational Design on Chemical Regulation of Interfacial Microstress Engineering by Matching Young's Modulus in a CsPbBr3 Perovskite Film with Mechanical Compatibility toward Enhanced Photoelectric Conversion Efficiency.

Thermodynamically induced tensile stress in the perovskite film will lead to the formation of atomic vacancies, seriously destroying the photovoltaic efficiency stability of the perovskite solar cells (PSCs). Among them, cations and halide anions vacancies are unavoidable; these point vacancies are considered to be a major source of the ionic migration and perovskite degradation at the crystal boundary and surface of the perovskite films. Here, we use choline bromide to modify the perovskite film by occupying the atomic defects in the CsPbBr3 perovskite film. The results show that the zwitterion quaternary ammonium ions and bromide ions in choline bromide can simultaneously occupy the Cs+ cation and Br- anions vacancies in the perovskite film by the ionic bonding effect, for which the defect-state density on the surface of the perovskite film can be significantly reduced, leading to the effective enhancement of carrier lifetime. In addition, the residual stress at the crystal boundary can be effectively reduced by lowering the Young's modulus in the CsPbBr3 perovskite film. As a result, the optimized device achieves a photoelectric conversion efficiency (PCE) of 9.06% with an increase of 41.1% compared to the control device with a PCE of 6.42%. Most importantly, the newborn thermal stress due to thermal expansion during heat working conditions can be transferred from the polycrystalline perovskite to the carbon layer by the matched Young's modulus, thus resulting in improved stability perovskite film under environmental conditions. The work provides new insights for preparing high-quality perovskite films with low defect-state density and residual stress.

Intercalation of Zinc Monochloride Cations by Deep Eutectic Solvents for High-Performance Rechargeable Non-aqueous Zinc Ion Batteries.

Zinc ion batteries have been extensively studied with an aqueous electrolyte system. However, the batteries suffer from a limited potential window, gas evolution, cathode dissolution, and dendrite formation on the anode. Considering these limitations, we developed an alternative electrolyte system based on deep eutectic solvents (DESs) because of their low cost, high stability, biodegradability, and non-flammability, making them optimal candidates for sustainable batteries. The DES electrolyte enables reversible Zn plating/stripping and effectively suppresses zinc dendrite formation. Furthermore, in-depth characterizations reveal that the energy storage mechanism can be attributed to [ZnCl]+ ion intercalation and the intermediate complex ion plays a pivotal role in electrochemical reactions, which deliver a high reversible capacity of 310 mAh g-1 at 0.1 A g-1and long-term stability (167 mAh g-1 at a current density of 0.3 A g-1 after 300 cycles, Coulombic efficiency: ∼98%). Overall, this work represents our new finding in rechargeable batteries with the DES electrolyte.

Correction: Huang et al. High-Uniform and High-Efficient Color Conversion Nanoporous GaN-Based Micro-LED Display with Embedded Quantum Dots. Nanomaterials 2021, 11, 2696.

The authors wish to make following corrections in this paper [...].

High-Uniform and High-Efficient Color Conversion Nanoporous GaN-Based Micro-LED Display with Embedded Quantum Dots.

Quantum dot (QD)-based RGB micro-LED technology is seen as one of the most promising approaches towards full color micro-LED displays. In this work, we present a novel nanoporous GaN (NP-GaN) structure that can scatter light and host QDs, as well as a new type of micro-LED array based on an NP-GaN embedded with QDs. Compared to typical QD films, this structure can significantly enhance the light absorption and stability of QDs. As a result, the green and red QDs exhibited light conversion efficiencies of 90.3% and 96.1% respectively, leading to improvements to the luminous uniformity of the green and red subpixels by 90.7% and 91.2% respectively. This study provides a viable pathway to develop high-uniform and high-efficient color conversion micro-LED displays.

Simple and Reliable Method for Gastric Subepithelial Tumor Localization Using Endoscopic Tattooing before Totally Laparoscopic Resection.

BACKGROUND: Totally laparoscopic surgery for early gastric cancer and subepithelial tumors has been popularized worldwide, yet localization of early or small-sized tumors is a persistent challenge due to difficulty being identified with the lack of manual tactile sensation. Thus, accurate localization with tattooing before the surgery would help improve efficiency during surgery. There are multiple methods to localize tumors before laparoscopy, each with varying advantages and disadvantages. The use of endoscopic tattooing with dye has been carried out for several decades due to its safety, lower cost, and convenience. However, there is a lack of studies on endoscopic tattooing before totally laparoscopic resection. AIMS: To evaluate the effect of endoscopic tattooing with dye for gastric subepithelial tumors localization before laparoscopic resection and to evaluate the tattooing effect on different locations of tumors in stomach. METHOD: We retrospectively collected data of patients with gastric subepithelial tumors who underwent endoscopic tattooing before totally laparoscopic resection from 2017 to 2020 in a university affiliated medical center. All patients were analyzed for preoperative characteristics and then categorized into two groups based on tumor locations concerning the difficulty of laparoscopic surgery. The independent t test and Chi-square test were performed to compare perioperative outcome and complications between these two groups. RESULT: A total of 19 patients were included retrospectively at our center. The individuals were 5 male and 14 female patients with a mean age of 58.2 years old. Most patients had no symptoms, and the tumors were found incidentally in 12 patients (63%). All tumors were identified clearly during laparoscopic resection. The mean tumor size was 2.3 cm. The surgeries took an average of 111 min and a mean of 7 mL blood loss was found. All tumors had negative resection margins with no recurrence during follow-up. Gastrointestinal stromal tumor was the major pathologic diagnosis, found in 12 patients (63%), followed by the leiomyoma in 5 patients (26%). Only three patients had mild adverse effects after surgery and the symptoms were self-limited. Our analysis found no significant difference in preoperative patient characteristics and perioperative outcomes between patients with differing tumor locations. CONCLUSION: This study is the first and largest report on endoscopic tattooing with dye before laparoscopic resection of gastric subepithelial tumor resection. Our results emphasize that endoscopic tattooing with dye is a safe and reliable method for localizing subepithelial tumors in the stomach prior to totally laparoscopic resection, with no correlation to where the tumor is located.

RTLIO: Real-Time LiDAR-Inertial Odometry and Mapping for UAVs.

Most UAVs rely on GPS for localization in an outdoor environment. However, in GPS-denied environment, other sources of localization are required for UAVs to conduct feedback control and navigation. LiDAR has been used for indoor localization, but the sampling rate is usually too low for feedback control of UAVs. To compensate this drawback, IMU sensors are usually fused to generate high-frequency odometry, with only few extra computation resources. To achieve this goal, a real-time LiDAR inertial odometer system (RTLIO) is developed in this work to generate high-precision and high-frequency odometry for the feedback control of UAVs in an indoor environment, and this is achieved by solving cost functions that consist of the LiDAR and IMU residuals. Compared to the traditional LIO approach, the initialization process of the developed RTLIO can be achieved, even when the device is stationary. To further reduce the accumulated pose errors, loop closure and pose-graph optimization are also developed in RTLIO. To demonstrate the efficacy of the developed RTLIO, experiments with long-range trajectory are conducted, and the results indicate that the RTLIO can outperform LIO with a smaller drift. Experiments with odometry benchmark dataset (i.e., KITTI) are also conducted to compare the performance with other methods, and the results show that the RTLIO can outperform ALOAM and LOAM in terms of exhibiting a smaller time delay and greater position accuracy.