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Epithelial–mesenchymal transition (EMT) is an essential step for tumor progression, although the mechanisms driving EMT are still not fully understood. In an effort to investigate these mechanisms, we observed that heregulin (HRG)-mediated activation of HER2, or HER2 overexpression, resulted in EMT, which is accompanied with increased expression of a known EMT regulator Slug, but not TWIST or Snail. We then investigated how HER2 induced Slug expression and found, for the first time, that there are four consensus HSF sequence-binding elements (HSEs), the binding sites for heat shock factor-1 (HSF-1), located in the Slug promoter. HSF-1 bound to and transactivated the Slug promoter independent of heat shock, leading to Slug expression in breast cancer cells. Mutation of the putative HSEs ablated Slug transcriptional activation induced by HRG or HSF-1 overexpression. Knockdown of HSF-1 expression by siRNA reduced Slug expression and HRG-induced EMT. The positive association between HSF-1 and Slug was confirmed by immunohistochemical staining of a cohort of 100 invasive breast carcinoma specimens. While investigating how HER2 activated HSF-1 independent of heat shock, we observed that HER2 activation resulted in concurrent phosphorylation of Akt and HSF-1. We then observed, also for the first time, that Akt directly interacted with HSF-1 and phosphorylated HSF-1 at S326. Inhibition of Akt using siRNA, dominant-negative Akt mutant, or small molecule inhibitors prevented HRG-induced HSF-1 activation and Slug expression. Conversely, constitutively active Akt induced HSF-1 phosphorylation and Slug expression. HSF-1 knockdown reduced the ability of Akt to induce Slug expression, indicating an essential role that HSF-1 plays in Akt-induced Slug upregulation. Altogether, our study uncovered the existence of a novel Akt-HSF-1 signaling axis that leads to Slug upregulation and EMT, and potentially contributes to progression of HER2-positive breast cancer.

Background The collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance. Methods This retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time. Results In the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard. Conclusions Surveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.

Background Early childhood is a critical period for growth and development, yet the association with physical activity during this important period is unknown. The aim of this review is to critically summarize the evidence on the prospective associations between physical activity and health and development in children aged < 5 years. Methods A systematic search in three electronic databases (Pubmed, PsycINFO, and Sportdiscus) was conducted to identify prospective studies examining the associations between physical activity (all types; specified by quantity) and health indicators (body composition, cardiometabolic health, bone health and risks/harm) or development (motor, cognitive and social-emotional development) in young children (mean age < 5 years at baseline). Two independent researchers assessed the methodological quality using the ‘Quality Assessment Tool for Quantitative Studies’ (EPHPP). This tool covers eight quality criteria: selection bias, study design, confounders, blinding, data collection methods, withdrawals and drop-outs, intervention integrity and data-analysis. Results Thirty-nine studies, predominantly conducted in preschoolers (ages 3–5 years), were included of which nine were rated as high methodological quality. There was moderate evidence for a positive association between physical activity and motor ( n  = 11 studies) and cognitive development ( n  = 10 studies) based on consistent findings from studies having low-to-moderate methodological quality. There was insufficient evidence for an association between physical activity and body composition ( n  = 15 studies), cardiometabolic health indicators ( n  = 7 studies), social-emotional development ( n  = 2 studies) and bone health ( n  = 2 studies) based on inconsistent findings from studies having weak-to-high methodological quality. Conclusions There is a need for more high-quality research in order to determine the dose-response relationship between physical activity and health and development in early childhood. Special attention should be paid to studies in children below the age of 3 years.

Background Improving access to early diagnosis and treatment (EDT) has increasingly proven to be a major contributor to decreasing malaria incidence in low-transmission settings. The Malaria Elimination Task Force (METF) has deployed malaria posts set up in Eastern Myanmar, providing free uninterrupted community-based access to EDT in more than 1200 villages. Ensuring high quality services are provided by these malaria posts is essential to reaching elimination targets. The present study aimed to determine the functionality of the malaria posts in the METF programme. Methods This report analysed routinely collected data (weekly reports, individual consultation, diagnostic test quality control) and data collected specifically during monitoring and evaluation visits using descriptive statistics and univariate logistic regression. The presence of major dysfunctions (stock-outs and reported closing; likely to impair the ability of the population to access EDT) or minor dysfunctions (no formal METF training, lack of regular salary, forms and manual not on-site, and low frequency of supervisor visits) and the ability to anticipate dysfunctions through analysis of weekly reports were assessed. Results A total of 65% of malaria posts had no major dysfunction identified during monitoring and evaluation visits, while 86% of malaria posts were fully stocked with tests and medicines used for treatment. Diagnosis was correctly conducted with few false positives and rare mis-speciation of results. Malaria post worker knowledge of malaria treatments showed few gaps, mostly in the treatment of more complex presentations. Malaria posts were well utilized in the population, with 94% of consultations occurring within the first 3 days of fever. In the regression analysis, reported stock-outs and delayed weekly reports were associated with observed major and minor dysfunctions in monitoring and evaluation visits, emphasizing the need to reinforce support to malaria post supervisors, who were responsible for the local logistics of supply and data transmission and day-to-day supervision. Conclusion The malaria posts operating under the METF programme perform to a high standard, with the majority offering uninterrupted access to diagnosis and treatment, and high service uptake in the villages serviced by the programme. However, programme operations can be strengthened by increasing malaria post supervisor visits and re-training malaria post workers.

This systematic review describes the effect of exercise training on physical performance in frail older people. Randomized controlled trials were identified from searches in PubMed, EMBASE and CENTRAL from January 1995 through August 2007. Two reviewers independently screened the trials for eligibility, rated their quality, and extracted data. Randomized controlled trials that examined the effects on performance-based measures of physical function among frail older adults were included. The systematic search identified 20 studies, examining 23 different exercise programmes. The methodological quality score (0-9) of the trials ranged from 2 to 7 points. Sixteen of the studies were scored as high quality. There was a large variety in the studies concerning sample size, degree of frailty, types of interventions and types of assessments. The majority of the programmes were facility-based, group-exercise programmes that were performed three times a week for 45-60 minutes. The intervention programmes comprised resistance training (n = 9), Tai Chi training (n = 2), or multi-component training (n = 12). Six of the total selected 20 studies did not find a beneficial exercise effect on functional performance. This systematic review suggests that older adults with different levels of abilities can improve their functional performance by regular exercise training. To determine the most appropriate design of the exercise programme (type, intensity, frequency and duration of exercise) for functional improvement or prevention of loss of function, more high-quality trials are needed in which different training protocols are compared.

Microalgal biomass and its cellular components are used as substrates for the production of fuels. A valuable group among the components of microalgal biomass is lipids, which act as a precursor for the production of biodiesel in the transesterification process. Some methods, including the creation of stressful conditions, are applied to increase the accumulation of lipids. This study aimed to determine the effect of limited nutrient access on the growth and development of the microalga Chlorella vulgaris and the amount of lipids stored in its cells. Aquaculture wastewater (AWW) was used in the study as a source of nutrients at doses of 20%, 40%, 60%, 80% and 100%. The amount of microalgal biomass, optical density, lipid content after extraction of the biomass in Soxhlet apparatus and chlorophyll a content were determined. It was observed that the microalgae efficiently used the nutrients contained in the AWW. The largest amount of biomass was obtained in AWW80 (727 ± 19.64 mg·L−1). The OD680 (0.492 ± 0.00) determined under the same conditions was almost five times higher in AWW than in the synthetic medium. Under nutrient-stress conditions, the content of lipids in biomass ranged from 5.75% (AWW80) to 11.81% (AWW20). The highest content of chlorophyll a in microalgal cells was obtained in AWW20 (206 ± 11.33 mg∙m−3).

The Lunar Environment heliospheric X-ray Imager (LEXI) is a wide field-of-view soft Xray telescope developed to study solar wind-magnetosphere coupling. LEXI is part of the Blue Ghost 1 mission comprised of 10 payloads to be deployed on the lunar surface. LEXI monitors the dayside magnetopause position and shape as a function of time by observing soft X-rays (0.1–2 keV) emitted from solar wind charge-exchange between exospheric neutrals and high charge-state solar wind plasma in the dayside magnetosheath. Measurements of the shape and position of the magnetopause are used to test temporal models of mesoand macro-scale magnetic reconnection. To image the boundary, LEXI employs lobster-eye optics to focus X-rays to a microchannel plate detector with a 9.1◦ × 9.1◦ field of view.

Anaerobic digestion is a well-known technology for renewable energy generation. Its efficiency depends on the substrate composition and its biodegradability. Microalgae are considered a promising feedstock due to their rapid growth, high protein and lipid content, and potential for wastewater treatment. However, the mono-digestion is often limited by a low carbon-to-nitrogen (C/N) ratio and a recalcitrant cell wall structure. This study evaluated the potential of co-digesting microalgal biomass with bakery waste under batch conditions. Two types of bakery residues (stale wheat bread and stale wheat rolls), were tested. Each was added to the microalgal biomass at proportions of 25%, 50%, and 75% based on volatile solids (VS). The experiment was carried out in a semi-technical anaerobic digester under mesophilic conditions. During the anaerobic digestion, the biogas volume, gas composition, and the energy potential of the substrates were analysed. The highest biogas yield (494.34 L·kg−1 VS) was obtained from the mixture of microalgae and 75% bread. Although mono-digestion of microalgal biomass resulted in the highest methane concentration, the differences compared to co-digested samples were not significant. The lowest hydrogen sulphide concentration (234.20 ppm) was measured in the 25% rolls variant, while the control sample (100% microalgae) showed the highest H2S levels. From an energy perspective, the most beneficial result was obtained with the addition of 75% bread.