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The immunosuppressive tumour microenvironment (TME) plays a critical role in cancer progression and relapse by significantly influencing cancer pathogenesis through autocrine and paracrine signalling. Trefoil factor 3 (TFF3), a secreted protein, has been implicated in modulating the TME to promote cancer advancement. Herein, we investigated the potential association between TFF3 and key immunosuppressive TME components to distinguish a co-targetable oncotherapeutic strategy. The TFF3-PVRL2 association were identified and investigated by integrating multiple bioinformatic-tools. The virtual compound screening for PVRL2 inhibitors was done with EasyVS. The TFF3-PVRL2 protein-level correlation was validated by immunoblotting, and the effectiveness of co-inhibiting TFF3 and PVRL2 was assessed using siRNA and AMPC (a TFF3 inhibitor). Analysis of the TISIDB database revealed a positive correlation between TFF3 and PVRL2 mRNA levels across multiple cancer types. This correlation was confirmed at the protein level through immunoblot analysis. Further evaluation using TCGA pan-cancer datasets demonstrated that TFF3 and PVRL2 interact to establish an immunosuppressive TME, promoting cancer progression in BRCA, LUAD, PAAD, PRAD, and STAD. Enrichment analyses of positively correlated genes, PPI network hub proteins, and ceRNA networks involving TFF3 and PVRL2, conducted using LinkedOmics, STRING, and Cytoscape, provided insights into their potential co-functions in cancer. A cell-based assay was performed to evaluate the combined therapeutic efficacy of targeting both, TFF3 and PVRL2 and virtual screening identified potential drugs for inhibiting PVRL2. PVRL2 has emerged as a promising immunoinhibitory target with significant associations with TFF3 and represents a key co-targetable molecule for effective oncotherapeutic strategies. [Display omitted] • Elevated TFF3 expression is positively correlated with changes in immunosuppressive TME, thereby progressing tumour. • TFF3 and PVRL2 both contribute to an immunosuppressive TME and disease progression. • In vitro analyses confirmed a positive association between TFF3 and PVRL2 in multiple cancers. • Co-targeting TFF3 and PVRL2 has emerged as an effective and promising strategy for cancer treatment [ABSTRACT FROM AUTHOR]

Optimal complementary feeding practice is a child feeding practice that fulfills the minimum dietary diversity, the minimum meal frequency, continuing breastfeeding with complementary feeding, and initiation of complementary feeding from 6 to 8 months. A community-based comparative cross-sectional study was conducted on a total of 732 randomly selected mothers having children 6 to 23 months of age from March 10 to April 21 /2021.Data were collected using a pre-tested interviewer-administered questionnaire. Data entry was performed by using Epi data version 3.1 and was exported to Stata version 14.1. Descriptive statistics were done. Multivariable Logistic regression was used to predict the role of independent variables on optimal complementary feeding. Findings with a p -value <0.05 at a 95% confidence interval (CI) were considered statistically significant in the final model. The overall proportion of mothers with optimal complementary feeding practice was 18.1% (95% C I 15.3% – 21.0). Only 90 (25.1%, 95% CI = 20.6–29.7) of mothers were found to have optimal complementary feeding practice in NGO supported kebeles but only 37 (10.8%, 95% CI = 7.5–14.1) practiced optimal complementary feeding is not NGO-supported kebeles. Mothers from Kebeles with no NGO support were 46% (AOR = 0.54, 95% CI 0.31, 0.96) less likely to practice optimal complementary feeding. On the other hand, mothers of children aged20–23 months were four times (AOR = 4.47, 95% CI 2.02–9.91) more likely to practice optimal complementary feeding than mothers having children 6–8 months of age. Different interventions have been implemented by governmental and non-governmental organizations to improve this condition in Dessie Zuria District. But, there is limited data on the extent to which intervention by governmental and non-governmental organizations reduces this improving condition. The aim of this study was to assess the Optimal Complementary Feeding Practice and Associated Factors among Mothers Having Children Aged 6–23 Months, Ethiopia 2021. Optimal complementary feeding practices among mothers in NGO-supported kebeles were higher than not supported kebeles. Therefore, strengthening and scaling up the program to not-supported kebeles is recommended to improve the optimal complementary feeding practiced. [ABSTRACT FROM AUTHOR]

A study examining the relationship between per capital real gross domestic product with per capita energy consumption in 19 African countries is presented. For the purpose of this study, data for the period from 1971 to 2001 is considered, and the method suggested by M.H. Pesaran, Y. Shin, and R. Smith is used.

In this article, I critically review the conceptualisation and applications of time in geographical studies of migration with a particular focus on refugees. Work that engages with time and temporality – the subjectively and/or experientially referenced aspect of time – has grown quickly over the last three decades. However, much of this work treats time in the refugee experience either as a linear, teleological sequence from uprooting in one place to 'full integration' in another, or as a non-linear, subjective and embodied experience with no clear pattern. While both linear and non-linear approaches of time can explain migratory experiences, neither of them can be exclusive to one another. In this review, I discuss the importance of applying dynamic conceptual framing that combines both refugees' experiences and the time–space context through which these experiences are enacted and expressed. I consider grounding refugee migration in relation to three core concepts of time that have been in human geographical discourse since the 1970s: timespace, time-geography, and rhythms. [ABSTRACT FROM AUTHOR]

Introduction: Outsole parameters of the shoe can be adapted to offload regions of pain or region of high pressures. Previous studies already showed reduced plantar pressures in the forefoot due to a proximally placed apex position and higher longitudinal bending stiffness (LBS). The aim of this study was to determine the effect of changes in rocker radii and high LBS on the plantar pressure profile during gait.Method: 10 participants walked in seven shoe conditions of which one control shoe and six rocker shoes with small, medium and large rocker radii and low and high longitudinal bending stiffness. Pedar in-shoe plantar pressure measuring system was used to quantify plantar pressures while walking on a treadmill at self-selected walking speed. Peak plantar pressure, maximum mean pressure and force-time integral were analyzed with Generalized Estimated Equation (GEE) and Tukey post hoc correction (α = .05).Results: Significantly lower plantar pressures were found in the first toe, toes 2-5, distal and proximal forefoot in all rocker shoe conditions as compared to the control shoe. Plantar pressures in the first toe and toes 2-5 were significantly lower in the small radius compared to medium and large radii. For the distal forefoot both small and medium radii significantly reduced plantar pressure compared to large radii. Low LBS reduced plantar pressure at the first toe significantly compared to high LBS independent of the rocker radius. Plantar pressures in the distal forefoot and toes 2-5 were lower in high LBS compared to low LBS.Conclusion: Manipulation of the rocker radius and LBS can effectively reduce peak plantar pressures in the forefoot region during gait. In line with previous studies, we showed that depending on the exact target location for offloading, different combinations of rocker radius and LBS need to be adopted to maximize treatment effects. [ABSTRACT FROM AUTHOR]

Bistable mechanisms are prevalent across a broad spectrum of applications due to their ability to maintain two distinct stable states. Their energy consumption is predominantly confined to the process of state transitions, thereby enhancing their efficiency. However, the transition often requires two distinct digital inputs, implicating the requirement of multiple actuators. Here, we propose an elastic and contactless design strategy for inducing state transitions in bistable mechanisms, requiring only a single digital input. The strategy leverages internal information, interpreted as system state, as an extra input to make a weighted decision for transitioning to the subsequent state. We characterize the behavior using a spring-based rigid-body model, consisting of a column near bifurcation, combined with a non-linear spring connected to a bistable element that represents the information state. The results show that a nonlinear spring with a quadratic stiffness function, i.e., representing internal instability, is crucial for regulating state-switching behavior. We then demonstrate this design strategy by developing a monolithic and compliant design embodiment and experimentally evaluate its behavior. [Display omitted] • Design method for state switching in bistable mechanisms with a single digital input. • Quadratic stiffness was identified as key to state-switching behavior. • Developed and experimentally validated a compliant design for state-switching. [ABSTRACT FROM AUTHOR]