Exploring the role of human-following robots in supporting the mobility and wellbeing of older people.

With the ever-pressing challenges of societal ageing, robotic technologies for older people are increasingly portrayed as a solution for better independent living for longer. However, the application of human-following robots for elderly citizens has not yet been considered, and any prospective benefits offered by the technology for active ageing have previously been overlooked. This qualitative research aimed to explore older people's needs and requirements towards the human-following robot through the reflexive thematic analysis of semi-structured interview data from 17 independent older adults, supported by a video-based demonstration of the robot. The results indicate that older people believed that human-following robot has the potential to provide social benefits to an independent older adult by encouraging walking trips and prompting social interaction with others in the community. Practical limitations and cost of the robot are barriers to adoption at present. The findings indicate that there is potential for human-following robots to support active ageing, through increasing opportunities for the social participation of an older adult, but further development of the robot is needed for this potential to be realised.

Analysing the effect of gender on the human-machine interaction in level 3 automated vehicles.

The emergence of the level 3 automated vehicles (L3 AVs) can enable drivers to be completely disengaged from driving and safely perform other non-driving related tasks, but sometimes their takeover of control of the vehicle is required. The takeover of control is an important human-machine interaction in L3 AVs. However, little research has focused on investigating the effect of gender on takeover performance. In order to fill this research gap, a driving simulator study with 76 drivers (33 females and 43 males) was conducted. The participants took over control from L3 AVs, and the timing and quality of takeover were measured. The results show that although there was no significant difference in most of the measurements adopted to quantify takeover performance between female and male. Gender did affect takeover performance slightly, with women exhibited slightly better performance than men. Compared to men, women exhibited a smaller percentage of hasty takeovers and slightly faster reaction times as well as slightly more stable operation of the steering wheel. The findings highlight that it is important for both genders to recognise they can use and interact with L3 AVs well, and more hands-on experience and teaching sessions could be provided to deepen their understanding of L3 AVs. The design of the car interiors of L3 AVs should also take into account gender differences in the preferences of users for different non-driving related tasks.

IKZF1 selectively enhances homologous recombination repair by interacting with CtIP and USP7 in multiple myeloma.

Rationale: In multiple myeloma (MM), the activities of non-homologous end joining (NHEJ) and homologous recombination repair (HR) are increased compared with healthy controls. Whether and how IKZF1 as an enhancer of MM participates in the DNA repair pathway of tumor cells remains elusive. Methods: We used an endonuclease AsiSI-based system and quantitative chromatin immunoprecipitation assay (qChIP) analysis to test whether IKZF1 is involved in DNA repair. Immunopurification and mass spectrometric (MS) analysis were performed in MM1.S cells to elucidate the molecular mechanism that IKZF1 promotes DNA damage repair. The combination effect of lenalidomide or USP7 inhibitor with PARP inhibitor on cell proliferation was evaluated using MM cells in vitro and in vivo. Results: We demonstrate that IKZF1 specifically promotes homologous recombination DNA damage repair in MM cells, which is regulated by its interaction with CtIP and USP7. In this process, USP7 could regulate the stability of IKZF1 through its deubiquitinating activity. The N-terminal zinc finger domains of IKZF1 and the ubiquitin-like domain of USP7 are necessary for their interaction. Furthermore, targeted inhibition IKZF1 or USP7 could sensitize MM cells to PARP inhibitor treatment in vitro and in vivo. Conclusions: Our findings identify USP7 as a deubiquitinating enzyme for IKZF1 and uncover a new function of IKZF1 in DNA damage repair. In translational perspective, the combination inhibition of IKZF1 or USP7 with PARP inhibitor deserves further evaluation in clinical trials for the treatment of MM.

Investigating factors influencing takeout shopping demand under COVID-19: Generalized additive mixed models.

The COVID-19 pandemic severely hampered the freedom of shopping travel while increasing individuals' interest in takeout. Although many studies have examined takeout shopping, the available literature provides insufficient evidence on the factors influencing takeout shopping demand under the COVID-19. In this study, generalized additive mixed models were developed based on sampling data of takeout orders in Nanjing before, during, and post the pandemic to measure the associations between takeout shopping demand and neighborhood characteristics at the business circle scale. The results show that population density, house prices, road density, and catering all have a significant impact on takeout shopping demand, while the roles of land use (residential and company indexes) before and post the pandemic are opposite. Besides, the factors influencing the recovery of the demand before and after the pandemic were analyzed. These findings provide important insights into the development of the takeout industry in the post-pandemic era.

ZCL-082, a boron-containing compound, induces apoptosis of non-Hodgkin's lymphoma via targeting p90 ribosomal S6 kinase 1/NF-κB signaling pathway.

INTRODUCTION: Despite the rapid progress in the diagnosis and treatment, the prognosis of some types of non-Hodgkin's lymphoma (NHL), especially those with double-hit or double-expressor genotypes, remains poor. Novel targets and compounds are needed to improve the prognosis of NHL. METHODS: We investigated the effect of ZCL-082, a novel boron-containing compound with anti-proliferating activity against ovarian cancer cells, on NHL cells and human peripheral blood mononuclear cells by CCK-8 assay, Annexin V/PI double staining assay, RH123/PI double staining, Western blot, and immunohistochemistry. NF-κB pathway activity was analyzed using luciferase reporter gene assay and RT-PCR. The location of p65 was detected by immunofluorescence and nuclear/cytoplasmic fractionation assay. Immunoprecipitation and chromatin immunoprecipitation assays were used to detect the binding between p65 and p300. CETSA and molecular docking assay were carried out to test the interaction between ZCL-082 and p90 ribosomal S6 kinase 1 (RSK1). Kinase reaction was conducted to examine the inhibition of RSK1 kinase activity by ZCL-082. RESULTS: We found that ZCL-082 can induce the apoptosis of various NHL cell lines in vitro and in vivo. ZCL-082 significantly inhibits TNFα- or LPS-induced NF-κB activation without disturbing TNFα-induced IκBα degradation or the nuclear translocation and DNA-binding ability of p65. However, ZCL-082 markedly suppresses the phosphorylation of p65 on Ser536 and the interaction between p65 and p300. The overexpression of the phosphomimetic mutant of p65 at Ser536 partially abrogates ZCL-082-induced cell death. We further found that ZCL-082 directly binds to and inhibits the activity of RSK1. RSK1 can phosphorylate RelA/p65 on Ser536 and its overexpression is associated with the poor prognosis of lymphoma. The overexpression of RSK1 partially rescues ZCL-082-induced cell death. Molecular docking studies show that ZCL-082 fits well with the N-terminal kinase domain of RSK1. Furthermore, the combination of ZCL-082 and BCL-2 inhibitor ABT-199 has a synergistic apoptosis-inducing effect against double-hit lymphoma cell line OCI-Ly10. DISCUSSION: We found that ZCL-082 is a highly promising anti-lymphoma compound that targets RSK1 and interferes with the RSK1/NF-κB signaling pathway. The combination of ZCL-082 with BCL-2 inhibitor may represent a novel strategy to improve the outcome of double-hit or double-expressor lymphoma.

Achieving WHO's Goal for Reducing Cesarean Section Rate in a Chinese Hospital.

Background: To address the worldwide dramatically increased Cesarean section (CS) rate in the past decades, WHO has recommended the CS rate should not be higher than 10-15%. Whether it is achievable remains unknown. Methods: We collected the data of delivery from 2008 to 2017 in two typical regional hospitals in China: Longhua Hospital (national policies rigorously implemented) and Dongguan Hospital (national policies not rigorously implemented). We compared between the two hospitals the 10 years trend in annual rate of CS, standardized by age, education level, parity, and CS history, against the time of issuing relevant national, local, and hospital policies. Results: In 10 years, 42,441 women in Longhua and 36,935 women in Dongguan have given birth. China's first national policy on CS reduction was issued in 2010 and the formal relaxation of one-child policy was issued in 2015-2016. In Longhua, the standardized annual CS rate was around 35% in 2008-2009, which declined sharply since 2010 down to 13.1% in 2016 (p < 0.001) and then leveled off. In contrast, in Dongguan, the rate stayed around 25% at the beginning, increased to 36% in 2011, decreased sharply to 27% in 2012, and leveled off until 2015 (p < 0.001), and then bounced back to 35% in 2017. The proportion of women with the history of CS increased significantly in the two hospitals (both roughly from 6% before 2010 to 20% after 2015). Analyses stratified by modified Robson classification showed that CS rates reduced in all risk classes of delivery women in Longhua but only in the Robson class 2 group in Dongguan. Major complications did not differ by hospital. Conclusion: With vigorously implementing national policies at micro levels, the WHO-recommended CS rate could be achieved without increase in major complications.

An optimal control-based vehicle speed guidance strategy to improve traffic safety and efficiency against freeway jam waves.

Freeway jam waves create many problems, including capacity reduction, travel delays, and safety risks. The development of cooperative vehicle infrastructure system (CVIS) has prompted numerous new strategies, which can resolve jam waves by implementing microscopic car-following control actions to individual vehicles. However, most of those strategies aimed at eliminating freeway jam waves without considering the safety risks induced by the car-following control. This paper proposes an optimal control-based vehicle speed guidance strategy to improve both traffic efficiency and safety against jam waves. The optimal controller is developed based on a discrete first-order traffic flow model formulated in Lagrangian coordinates. The optimization of vehicles' driving speed is formulated as a linear programming problem, where the constraints concerning threshold safety measures are imposed. The proposed vehicle speed guidance strategy is tested using a modified Intelligent Driving Model (IDM+), which represents real traffic dynamics in CVIS environment. The proposed speed guidance strategy is compared with a state-of-the-art jam-absorption driving strategy, which also aimed to eliminate freeway jam waves. Simulation results show that the proposed strategy outperforms that strategy in terms of both total time spent saving and surrogate safety measures' reduction. The time exposed time-to-collision (TET) is reduced by 31%, and the time integrated time-to-collision (TIT) is reduced by 9.5% on average. Furthermore, the computation time of the linear optimization is only a few seconds, which is fast enough for the online application of the proposed strategy.

Directly targeting c-Myc contributes to the anti-multiple myeloma effect of anlotinib.

Despite the significant advances in the treatment of multiple myeloma (MM), this disease is still considered incurable because of relapse and chemotherapy resistance, underscoring the need to seek novel therapies with different mechanisms. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging antitumor activity in several preclinical and clinical trials, but its effect on MM has not been studied yet. In this study, we found that anlotinib exhibits encouraging cytotoxicity in MM cells, overcomes the protective effect of the bone marrow microenvironment and suppresses tumor growth in the MM mouse xenograft model. We further examined the underlying molecular mechanism and found that anlotinib provokes cell cycle arrest, induces apoptosis and inhibits multiple signaling pathways. Importantly, we identify c-Myc as a novel direct target of anlotinib. The enhanced ubiquitin proteasomal degradation of c-Myc contributes to the cell apoptosis induced by anlotinib. In addition, anlotinib also displays strong cytotoxicity against bortezomib-resistant MM cells. Our study demonstrates the extraordinary anti-MM effect of anlotinib both in vitro and in vivo, which provides solid evidence and a promising rationale for future clinical application of anlotinib in the treatment of human MM.

Analysis of factors influencing delivery e-bikes' red-light running behavior: A correlated mixed binary logit approach.

The red-light running (RLR) behavior of delivery e-bike (DEB) riders in cities has become the primary cause of traffic accidents associated with this group at signalized intersections. This study aimed to explore the influencing factors of red light running behavior and identify the differences between the DEB riders and the ordinary e-bike (OEB) riders to aid the development of countermeasures. In this study, the mixed (random parameter) binary logistic model was employed to capture the effects of unobserved heterogeneity. With this approach, factors including individual characteristics, behavioral variables, characteristics of signalized intersections, and the traffic environment were examined. Additionally, to account for the combined influence on the RLR occurrence, mixed logit framework was developed to reveal the correlations among the random parameters. The data of e-bike riders' crossing behaviors at four signalized intersections in Xi'an, China were collected, and 3335 samples were recorded. The results indicated showed that DEB riders are more likely to run red lights than OEB riders. Factors that affect RLR behaviors of the two groups are different. Factors associated with the unobserved heterogeneity include red-light stage, observation time, age and waiting position of the rider. The joint influence among random parameters further illustrates the complexity of the contributing factors of riders' crossing behavior. Results from the models provide insights into the development of intervention systems to improve the traffic safety of e-bike riders at intersections.

Hsp90/C terminal Hsc70-interacting protein regulates the stability of Ikaros in acute myeloid leukemia cells.

The stability of Ikaros family zinc finger protein 1 (Ikaros), a critical hematopoietic transcription factor, can be regulated by cereblon (CRBN) ubiquitin ligase stimulated by immunomodulatory drugs in multiple myeloma. However, other stabilization mechanisms of Ikaros have yet to be elucidated. In this study, we show that the pharmacologic inhibition or knockdown of Hsp90 downregulates Ikaros in acute myeloid leukemia (AML) cells. Proteasome inhibitor MG132 but not autophagy inhibitor chloroquine could suppress the Hsp90 inhibitor STA-9090-induced reduction of Ikaros, which is accompanied with the increased ubiquitination of Ikaros. Moreover, Ikaros interacts with E3 ubiquitin-ligase C terminal Hsc70 binding protein (CHIP), which mediates the STA-9090-induced ubiquitination of Ikaros. In addition, the knockdown of Ikaros effectively inhibits the proliferation of leukemia cells, but this phenomenon could be rescued by Ikaros overexpression. Collectively, our findings indicate that the interplay between HSP90 and CHIP regulates the stability of Ikaros in AML cells, which provides a novel strategy for AML treatment through targeting the HSP90/Ikaros/CHIP axis.

Predicting the success of vaginal birth after caesarean delivery: a retrospective cohort study in China.

OBJECTIVES: To develop a nomogram to predict the likelihood of vaginal birth after caesarean section (VBAC) among women after a previous caesarean section (CS). DESIGN: A retrospective cohort study. SETTING: Two secondary hospitals in Guangdong Province, China. PARTICIPANTS: Inclusion criteria were as follows: pregnant women with singleton fetus, age ≥18 years, had a history of previous CS and scheduled for trial of labour after caesarean delivery (TOLAC). Patients with any of the following were excluded from the study: preterm labour (gestational age <37 weeks), two or more CSs, contradictions for vaginal birth, history of other uterine incision such as myomectomy, and incomplete medical records. PRIMARY OUTCOME MEASURE: The primary outcome was VBAC, which was retrospectively abstracted from computerised medical records by clinical staff. RESULTS: Of the women who planned for TOLAC, 84.0% (1686/2006) had VBAC. Gestational age, history of vaginal delivery, estimated birth weight, body mass index, spontaneous onset of labour, cervix Bishop score and rupture of membranes were independently associated with VBAC. An area under the receiver operating characteristic curve (AUC) in the prediction model was 0.77 (95% CI 0.73 to 0.81) in the training cohort. The validation set showed good discrimination with an AUC of 0.70 (95% CI 0.60 to 0.79). CONCLUSIONS: TOLAC may be a potential strategy for decreasing the CS rate in China. The validated nomogram to predict success of VBAC could be a potential tool for VBAC counselling.

Codon usage bias in the N gene of rabies virus.

Since its emergence, rabies virus (RABV) has been a major worldwide concern especially in developing countries. The nucleoprotein (N) of RABV is highly conserved and key for genetic typing, thus a better understanding of the N gene evolutionary trajectory can assist the development of control measures. We found that the N gene of RABV has a low codon usage bias with a mean effective number of codons (ENC) value of 56.33 influenced by both mutation pressure and natural selection. However, neutrality analysis indicated that natural selection dominates over mutation pressure. Additionally, we found that dinucleotide bias partly contributed to RABV codon usage bias. On the other hand, based on the clades of phylogenetic tree, we found that the evolutionary rate of the Africa 2 clade was the highest with a mean value of 3.75×10-3 substitutions per site per year. Above all, our results regarding N gene of RABV codon usage will serve future RABV evolution research.

A study of driver's route choice behavior based on evolutionary game theory.

This paper proposes a route choice analytic method that embeds cumulative prospect theory in evolutionary game theory to analyze how the drivers adjust their route choice behaviors under the influence of the traffic information. A simulated network with two alternative routes and one variable message sign is built to illustrate the analytic method. We assume that the drivers in the transportation system are bounded rational, and the traffic information they receive is incomplete. An evolutionary game model is constructed to describe the evolutionary process of the drivers' route choice decision-making behaviors. Here we conclude that the traffic information plays an important role in the route choice behavior. The driver's route decision-making process develops towards different evolutionary stable states in accordance with different transportation situations. The analysis results also demonstrate that employing cumulative prospect theory and evolutionary game theory to study the driver's route choice behavior is effective. This analytic method provides an academic support and suggestion for the traffic guidance system, and may optimize the travel efficiency to a certain extent.