Path Following for Autonomous Mobile Robots with Deep Reinforcement Learning.

Autonomous mobile robots have become integral to daily life, providing crucial services across diverse domains. This paper focuses on path following, a fundamental technology and critical element in achieving autonomous mobility. Existing methods predominantly address tracking through steering control, neglecting velocity control or relying on path-specific reference velocities, thereby constraining their generality. In this paper, we propose a novel approach that integrates the conventional pure pursuit algorithm with deep reinforcement learning for a nonholonomic mobile robot. Our methodology employs pure pursuit for steering control and utilizes the soft actor-critic algorithm to train a velocity control strategy within randomly generated path environments. Through simulation and experimental validation, our approach exhibits notable advancements in path convergence and adaptive velocity adjustments to accommodate paths with varying curvatures. Furthermore, this method holds the potential for broader applicability to vehicles adhering to nonholonomic constraints beyond the specific model examined in this paper. In summary, our study contributes to the progression of autonomous mobility by harmonizing conventional algorithms with cutting-edge deep reinforcement learning techniques, enhancing the robustness of path following.

Cost-benefit and discriminant validity of a stepwise dementia case-finding approach in an Asian older adult community.

Background: Case-finding is a recommended approach for dementia early detection in the community. Aims: To investigate the discriminant validity and cost-effectiveness of a stepwise dementia case-finding approach in a Singaporean older adult community. Methods: The two-phase study was conducted in the community from 2009 to 2015 in Singapore. A total of 3780 participants (age ≥60 years) completed phase I (a brief cognitive screening); 918 completed phase II and were included in the final analysis. In phase I, all participants were administered the Abbreviated Mental Test (AMT) and the Progressive Forgetfulness Question (PFQ). Those who screened positive on either test were invited to phase II, whereby the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery were administered, followed by the research diagnosis of no cognitive impairment, cognitive impairment no dementia (CIND)-Mild (≤2 impaired cognitive domains), CIND-Moderate (>2 impaired domains) or dementia. Receiver operating characteristic curve analyses were conducted for the different cognitive instruments. All discriminant indices were calculated, including sensitivity, specificity, positive and negative predictive values (NPV) and accuracy. Cost-effectiveness analysis was conducted by estimating the amount of screening time needed and the number of older adults requiring re-evaluation in two case-finding scenarios, ie, with or without preselection by the PFQ. Results: The stepwise case-finding approach (preselection by the PFQ, then MMSE or MoCA or AMT) showed an excellent NPV (>99%) and accuracy (>86%) for excluding dementia-free cases. Without preselection by the PFQ, screening time for the three cognitive tools were 317.5, 317.5 and 254 hours, with 159, 302 and 175 screen-positive older adults involved in further evaluation. By adopting the stepwise case-finding approach, total screening time were 156.5, 156.5 and 126.2 hours, which decreased by 50.7%, 50.7% and 50.3% as compared with those without preselection. Furthermore, after preselection, only 98, 167 and 145 screen-positive older adults required further evaluation, corresponding to a reduction of 38.4%, 44.7% and 17.1% in the numbers compared with those without preselection. Conclusions: A stepwise approach for dementia case-finding should be implemented in the community to minimise the time and resources needed for large-scale early detection of dementia.

Comparison of Efficacy and Psychology of Breast-Conserving Surgery and Modified Radical Mastectomy on Patients with Early Breast Cancer under Graded Nursing.

Objective: To compare the efficacy and psychology of breast-conserving surgery and modified radical mastectomy in patients with early breast cancer (BC) under graded nursing. Methods: Forty-one early breast-conserving surgery BC patients admitted to our hospital from April 2020 to March 2022 were regarded as group A, and 52 with modified radical surgery were seen as group B. The operating time, intraoperative bleeding, postoperative drainage, and hospital stay were compared, and the postoperative adverse effects were counted. In addition, patients' psychology and quality of life were assessed using the HAMD, HAMA, and QLSBC rating scales. At the time of discharge, a treatment satisfaction survey was conducted. Results: The operative time, intraoperative bleeding, postoperative drainage, and hospital stay of patients in group A were lower than those in group B (P < 0.05). After treatment, the HAMD and HAMA scores were lower in group A than in group B, while the QLSBC scores and treatment satisfaction were higher (P < 0.05). Conclusion: Breast-conserving surgery under graded nursing is less damaging to early BC patients. It can effectively shorten the postoperative recovery process and improve the psychology and quality of life, so it has higher clinical applicability.

Long-term neurobehavioral correlates of brain cortical microinfarcts in a memory clinic cohort in Singapore.

BACKGROUND: Cortical cerebral microinfarcts are a small vessel disease biomarker underlying cognitive impairment and dementia. However, it is unknown whether cortical cerebral microinfarcts are associated with neuropsychiatric disturbances, and whether its effects are independent of conventional small vessel disease markers. AIMS: We investigated the associations of cortical cerebral microinfarcts burden with incidence and progression of neuropsychiatric subsyndromes in a memory clinic cohort of elderly in Singapore. METHODS: In this prospective cohort, 496 subjects underwent detailed neuropsychological and clinical assessments, 3T brain MRI, and Neuropsychiatric Inventory assessment at baseline and two years later. Cortical cerebral microinfarcts and other small vessel disease markers, including white matter hyperintensities, lacunes, and microbleeds, were graded according to established criteria. Neuropsychiatric symptoms (NPS) were clustered into subsyndromes of hyperactivity, psychosis, affective, and apathy following prior findings. Functional decline was determined using the clinical dementia rating (CDR) scale. RESULTS: The presence of multiple cortical cerebral microinfarcts (≥2) was associated with higher total NPS scores (ß = 4.19, 95% CI = 2.81-5.58, p < 0.001), particularly hyperactivity (ß = 2.01, 95% CI = 1.30-2.71, p < 0.01) and apathy (ß = 1.42, 95% CI = 0.65-2.18, p < 0.01) at baseline. Between baseline and year-2, multiple cortical cerebral microinfarcts were associated with accelerated progression in total NPS scores (ß = 0.29, 95% CI = 0.06-0.53, p = 0.015), driven by hyperactivity (ß = 0.45, 95% CI = 0.17-0.72, p < 0.01). Subjects with multiple cortical cerebral microinfarcts also had a faster functional decline, as measured with the CDR-sum-of-boxes scores, when accompanied with progression (ß = 0.31, 95% CI = 0.11-0.51, p < 0.01) or hyperactivity in total NPS (ß = 0.34, 95% CI = 0.13-0.56, p < 0.01). CONCLUSION: Cortical cerebral microinfarcts are associated with incidence and progression of geriatric neurobehavioral disturbances, independent of conventional small vessel disease markers. The impact of incident cortical cerebral microinfarcts on neurocognitive and neuropsychiatric trajectories warrants further investigations.

RBM38 is negatively regulated by miR-320b and enhances Adriamycin resistance in breast cancer cells.

Breast cancer (BC) is a common type of malignant tumor that is frequently accompanied by drug resistance, which is a significant challenge in the treatment of BC. Adriamycin (ADM) is a commonly used drug for the treatment of BC. The aim of the present study was to demonstrate the association between RNA binding motif protein 38 (RBM38) and ADM resistance in BC. The results revealed that the expression levels of RBM38 were significantly upregulated in ADM-resistant BC tissues and the ADM-resistant cell line, MCF-7/A, as demonstrated using reverse transcription-quantitative PCR and western blotting. In addition, the results of the MTT assay revealed that the overexpression of RBM38 enhanced the resistance of MCF-7/A cells to ADM, promoted invasiveness, as determined using a Transwell assay, inhibited the apoptosis of resistant cells, as determined using flow cytometry, and accelerated cell cycle progression from the G0 to the S phase. The results of the dual luciferase reporter assay demonstrated the binding relationship between microRNA (miR)-320b and RBM38, and the expression levels of miR-320b were significantly downregulated in ADM-resistant BC tissues and MCF-7/A cells. Overexpression of miR-320b reversed ADM resistance, suppressed invasiveness, promoted apoptosis and arrested MCF-7/A cells in the G0 phase. In addition, RBM38 was discovered to be negatively regulated by miR-320b, which was able to restore the sensitivity of BC cells to ADM by downregulating RBM38. Further exploration of the underlying regulatory mechanism revealed that the miR-320b/RBM38 signaling axis mediated the development of ADM resistance in BC by altering the expression of cell cycle-, drug resistance- and PI3K/AKT signaling pathway-related proteins. In conclusion, the results of the present study suggested that RBM38 may be negatively regulated by miR-320b, which accelerates drug resistance in BC.

EphA8 inhibits cell apoptosis via AKT signaling and is associated with poor prognosis in breast cancer.

Erythropoietin­producing hepatocellular receptors (Ephs) comprise the largest subfamily of receptor tyrosine kinases and have been reported to be involved in a variety of biological cellular processes, including tumorigenesis and cancer progression. The present study aimed to determine the expression levels and clinicopathological significance of EphA8 in breast cancer (BC) using immunohistochemistry analysis of tissue microarrays. The results of the present study revealed that EphA8 expression levels were upregulated in BC tissue and were associated with tumor size and TNM stage. In addition, upregulated expression levels of EphA8 were identified to be a poor prognostic biomarker for patients with BC. The knockdown of EphA8 expression using short hairpin RNA resulted in increased levels of apoptosis as well as decreased proliferation, migration and invasion of BC cells both in vivo and in vitro. The knockdown of EphA8 also decreased the phosphorylation of AKT, which was accompanied by downregulation of Bcl­2 expression levels and upregulation of p53, Caspase­3 and Bax expression levels. Moreover, knockdown of EphA8 expression increased the chemosensitivity of BC cells to paclitaxel. In conclusion, the results of the present study indicated that EphA8 may be a useful prognostic marker in BC and that knockdown of EphA8 may represent a novel strategy in adjuvant chemotherapy for the treatment of BC.

The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-ß Signaling Pathway.

BACKGROUND: Long non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. Herein, we explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC. METHODS: Next-generation sequencing was conducted to compare the expression of different lncRNAs in TNBC tumor and paracancerous tissues, after which ADAMTS9-AS2differential expression in these tumor tissues was evaluated via qPCR. The functional role of this lncRNA was assessed by overexpressing it in vitro and in vivo. FISH and PCR were used to assess the localization of ADAMTS9-AS2within cells. Downstream targets of ADAMTS9-AS2 signaling were identified via RNA pulldown assays and transcriptomic sequencing. RESULTS: The expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size. Overexpressing ADAMTS9-AS2 promoted the apoptotic death and cell cycle arrest of tumor cells in vitro and inhibited tumor growth in vivo. From a mechanistic perspective, ADAMTS9-AS2 was found to control the expression of RPL22 and to thereby modulate TGF-ß signaling to control TNBC progression. CONCLUSION: ADAMTS9-AS2 controls the expression of RPL22 and thereby regulates TNBC malignancy via the TGF-ß signaling pathway.

Elevated Expression of RIOK1 Is Correlated with Breast Cancer Hormone Receptor Status and Promotes Cancer Progression.

PURPOSE: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers-such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. MATERIALS AND METHODS: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. RESULTS: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)-negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. CONCLUSION: These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

High methionyl-tRNA synthetase expression predicts poor prognosis in patients with breast cancer.

AIMS: Methionyl-tRNA synthetase (MARS) is known to play a critical role in initiating translation and protection against cellular damages in vivo. The aim of this study was to clarify the role of MARS in breast cancer (BC) progression. METHODS: The expressions of MARS messenger RNA (mRNA) and protein in human BC tissues and adjacent non-cancerous tissues were detected by quantitative real-time PCR, western blot and immunohistochemistry. The prognostic potential of MARS in patients with BC was assessed by univariate and multivariate survival analyses. The association between the MARS expression and BC progression was further evaluated by the bioinformatics database of UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Database of Normal and Tumor Tissues (GENT). The role of MARS in the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of human breast cancer cell line (MCF-7 cells) was investigated after siRNA transfection. RESULTS: The expression level of MARS mRNA in the fresh BC tissues was significantly higher than that in the adjacent tissues. Immunohistochemistry showed that the expression level of MARS was closely associated with the clinicopathologial parameters of patients with BC, including the HER-2 status, Ki-67 status, molecular classification, tumour grade, N stage and tumour, node, metastasis (TNM) stage, and this finding was further confirmed by UALCAN database. The Kaplan-Meier analysis showed that high MARS expression and TNM stage were predictors of poor prognosis of patients with BC. The proliferation, migration and EMT capabilities of MCF-7 cells were significantly suppressed after MARS knockdown. An overview of UALCAN, GEPIA and GENT results suggested that MARS may be an oncogene of BC, as well as a potential therapeutic target of this malignant tumour. CONCLUSIONS: High expression level of MARS in the human BC tissues was significantly associated with the unfavourable prognosis of patients with BC, suggesting that MARS may serve as a potential prognostic marker for the clinical diagnosis and prognostic prediction of BC.

miR-448 inhibits the epithelial-mesenchymal transition in breast cancer cells by directly targeting the E-cadherin repressor ZEB1/2.

Recently, accumulating evidence provides that dysregulation of microRNAs (miRNAs) is considered to play vital roles in tumor progression. Based on microRNA arrays, we found that microRNA-448 (miR-448) was significantly downregulated in breast cancer tissue specimens. In our study, we were in an effort to clarify the function, the direct target gene, and the molecular mechanisms of miR-448 in breast cancer. By quantitative RT-PCR, we analyzed the expression of miR-448 in 16 patients with BC. Overexpression of miR-448 was established by transfecting miR-448-mimics into MDA-MB-231 and MCF-7 cells, methyl thiazolyl- tetrazolium and colony formation assays were performed to evaluate its effects on cell proliferation. We also performed cell migration and invasion assays in breast cells overexpressing miRNA-448. All the results indicated that overexpression of miR-448 in breast cancer cells markedly suppressed cell proliferation, migration, and invasion. Through the quantitative RT-PCR and Western Blots, we also evaluated epithelial-mesenchymal transition. We found that overexpression of miR-448 also downregulated the expression of vimentin, a well-known mesenchymal marker. Meanwhile, the epithelial marker E-cadherin was unregulated, suggesting that miR-448 inhibited epithelial-mesenchymal transition . Bioinformatics assay coupled with Western Blot and luciferase assays revealed that miR-448 directly binds to the 3'UTR of E-cadherin repressor ZEB1/2, resulting in suppression of epithelial-mesenchymal transition in breast cancer cells. Impact statement In our study, we revealed that miR-448 played a vital role in breast cancer development and we also uncovered the mechanisms of it. Following is the short description of the main findings: miR-448 is downregulated in BC. miR-448 regulates cell proliferation, migration, and invasion in BC. miR-448 specifically regulates ZEB1/2 through binding to the 3'UTR in BC cells. miR-448 inhibits cell migration, invasion, and EMT by targeting to the 3'UTR of ZEB1/2.

High TREM2 expression correlates with poor prognosis in gastric cancer.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a member of the immunoglobulin superfamily and associates with TYRO protein tyrosine kinase-binding protein at the cell membrane to form a receptor signaling complex. Gastric cancer (GC) is one of the most common human cancers in the world. We found that TREM2 expressions in GC and adjacent tissues were significantly different. The goal of this study was to measure TREM2 protein and mRNA expression levels in GC tissues and evaluate their value as potential prognostic markers. We analyzed TREM2 mRNA and protein expression by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, in 317 samples of GC tissue, matched normal tissue, or benign gastric lesions. The associations between TREM2 level and various clinicopathologic characteristics were assessed, and the correlation between TREM2 expression and prognosis of GC patients was analyzed using Oncomine and Kaplan-Meier Plotter online resources. TREM2 mRNA and protein expression levels were both significantly higher in GC compared with normal gastric tissues (P<.0001 and P<.001, respectively). Among the clinicopathological characteristics evaluated, differentiation (P<.05), N stage (P<.001), and TNM stage (P<.001) were all significantly associated with high TREM2 expression. TREM2 levels were inversely correlated with patient prognosis. Our data suggest that TREM2 expression could be an effective prognostic biomarker for GC.

[Clinical characteristics and resistance of wound surface infections causing by Bacillus cereus in the department of orthopaedics].

OBJECTIVE: To study clinical characteristics and resistance of wound surface infections, so as to guide clinical diagnosis and rational administration. METHODS: The clinical setting and laboratory results were collected by analyzing 20 strains of Bacillus cereus isolated from clinical samples in patients from our hospital from October 2011 to June 2012, including 18 males and 2 females,ranging in age from 22 to 67 years old, averaged (47.30 +/- 11.16) years old. The courses of disease ranged from 5 to 20 days. All the patients were treated with nutrition support therapy, debridement and the corresponding antibiotic therapy. The patients had anemia, low protein hyperlipidemia and wound contamination history while Bacillus cereus infected. Thirty people were selected as normal group, including 23 males and 7 females,with an average age of (45.20 +/- 15.05) years old. Infection control condition was assessed by comparing culture for pathogens and patients wound redness or exudation cases before and after treatment. Antimicrobial susceptibility test was conducted by K-B method. RESULTS: A total of 20 stains of Bacillus cereus were isolated from wound surface infections in department of orthopedics of our hospital. Among them,the infections were correlated with the wound contamination (16/20), malnutrition (20/20), and open-fracture (20/20), operation time (15 cases > 3 h). The laboratory blood test showed that the levels of TP [(49.94 +/- 8.24) g/L], ALB [(29.54 +/- 5.45 ) g/L] and Hb [(103.20 +/- 11.79) g/L] in the infection group was lower than those of control group; in the contrast, the levels of WBC [(8.35 +/- 2.31) x 10(9)/L], NEUT [(6.98 +/- 1.99) x 10(9)/L], hs-CRP [(73.60 +/- 55.14) mg/L] and CK [(900.10 +/- 1 259.12) IU/L] were higher in the infection group than those of control group, and the differences were statistically significant (P < 0.01). The diameter of inhibition zone in penicillin, cefazolin, cefuroxime, ceftazidime, cefepime, cotrimoxazole, erythromycin were less than 15 mm, and suggested that Bacillus cereus resisted to these antibiotics. However, the diameter of inhibition zone in clindamycin, vancomycin, gentamicin, ciprofloxacin, imipenem were larger than 20 mm and this data indicated that the bacteria were highly sensitive to these antibiotics. CONCLUSION: Orthopedic patients who immunocompromised, hypoproteinemia and accompanied by open wounds and contaminated wound susceptible to infect Bacillus cereus; sensitive antimicrobial drugs should be selected on the basis of supplement albumin, symptomatic and supportive treatment.

[Surveillance of soil-transmitted nematode infections in Menghai County, Yunnan Province from 2006 to 2009].

In the national monitoring point, Menghai County, Yunnan Province, the total prevalence rate of soil-transmitted nematode infections was 88.12%, of which the rates of Ascaris lumbricoides, Trichuris trichiura, hookworm and cestode infections were 69.70%, 59.79%, 36.79%, and 1.30% respectively from 2006 to 2009. The infection intensities were slight. The Ascaris lumbricoides infection rate in soil of vegetable garden was 44.5%. In conclusion, the infection rate of soil-transmitted nematodes is high in the monitoring point.