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Buildings account for about one-third of worldwide energy use alongside CO2 emission, and their energy demand is envisaged to increase in the upcoming decades, thus increasing the worries about climate change. Building energy management system (BEMS) is a strategic method that can assuage these impacts, balance the energy demand-supply mismatch, enhance building energy efficiency and whatnot. Information surrounding this subject should be readily available considering its significance. However, this is not the case as there is a dearth of such information in the form of a systematic review of scholarly contributions on BEMS in South Africa. Thus, this paper aims to fill the knowledge gap through an in-depth overview and analysis of recent research outputs from five prominent academic databases. Herein, the study unveils and discusses the BEMS in South Africa while drawing insights from five subsets namely: building typology; building services system; methodological approach and testbed; applied BEMS strategy; and focused energy management system task. The study synthesis revealed HVAC systems as the major building services system, while demand-side management is mostly considered as the ideal applied strategy, all which mainly manipulated in residential buildings. Based on the research findings, the paper proposes the utilization of novel data-driven methods for researchers and policymakers when developing models for energy datasets to achieve optimal results for monitoring building end-use energy patterns to improve energy saving and achieve the country’s ambitious goal of carbon neutrality.

Summary: Clostridioides difficile produces toxins that damage the colonic epithelium, causing colitis. Variation in disease severity is poorly understood and has been attributed to host factors and virulence differences between C. difficile strains. We test 23 epidemic ST1 C. difficile clinical isolates for their virulence in mice. All isolates encode a complete Tcd pathogenicity locus and achieve similar colonization densities. However, disease severity varies from lethal to avirulent infections. Genomic analysis of avirulent isolates reveals a 69-bp deletion in the cdtR gene, which encodes a response regulator for binary toxin expression. Deleting the 69-bp sequence in virulent R20291 strain renders it avirulent in mice with reduced toxin gene transcription. Our study demonstrates that a natural deletion within cdtR attenuates virulence in the epidemic ST1 C. difficile isolates without reducing colonization and persistence. Distinguishing strains on the basis of cdtR may enhance the specificity of diagnostic tests for C. difficile colitis.

Injuries to the meniscus are common and can impair physical activities. Bioprinted meniscal tissue offers an attractive alternative to donor tissue for meniscal repair but achieving the strength of native tissue is a challenge. Here we report the development of a tissue engineering bioreactor designed to apply repetitive force which may lead to an increase in the compressive modulus and durability of bioprinted meniscal tissues. The modular bioreactor system is composed of a sterilizable tissue culture vessel together with a dock that applies and measures mechanical force. The culture vessel allows for simultaneous compression cycling of two anatomically sized menisci. Using a hybrid linear actuator with a stepper motor, the dock can apply up to 300 N of force at speeds up to 20 mm/s, corresponding to the upper limits of anatomical force and motion in the knee. An interchangeable 22 N load cell was mated between the culture vessel and the dock to log changes in force. Both the culture vessel and dock are maintained in a standard cell culture incubator to provide heat and CO2, while the dock is powered and controlled externally using a step motor drive and customized software.

The meniscus is a key stabilizing tissue of the knee that facilitates proper tracking and movement of the knee joint and absorbs stresses related to physical activity. This review article describes the biology, structure, and functions of the human knee meniscus, common tears and repair approaches, and current research and development approaches using modern methods to fabricate a scaffold or tissue engineered meniscal replacement. Meniscal tears are quite common, often resulting from sports or physical training, though injury can result without specific contact during normal physical activity such as bending or squatting. Meniscal injuries often require surgical intervention to repair, restore basic functionality and relieve pain, and severe damage may warrant reconstruction using allograft transplants or commercial implant devices. Ongoing research is attempting to develop alternative scaffold and tissue engineered devices using modern fabrication techniques including three-dimensional (3D) printing which can fabricate a patient-specific meniscus replacement. An ideal meniscal substitute should have mechanical properties that are close to that of natural human meniscus, and also be easily adapted for surgical procedures and fixation. A better understanding of the organization and structure of the meniscus as well as its potential points of failure will lead to improved design approaches to generate a suitable and functional replacement.

Climate change mitigation can improve rural livelihoods through payment for environmental services (PES) approaches. However, participation in PES projects is voluntary, uncertain and some people's participation is more important than others. In this article, we use quantitative and qualitative methods to examine factors that determine local peoples’ participation in state (Rwoho and Kasagala) and private (‘Undisclosed’ and Hoima) forestry carbon projects in Uganda. We find that such determinants vary within and between projects. For example, older people with more land parcels were more likely to participate in private projects compared to their counterparts in state projects. In plantation forests, participation was motivated by access to forest products (timber and charcoal), while the desire to conserve water sources was important for participants adjacent to natural forests. While expected carbon payments were important in one state project, they were less significant in the others. Non-participation was linked to high entry costs, distrust for forest managers in state projects and non-ownership of natural forests. In all case studies, non-participation was mainly associated to limited project information. To gain broad participation, Reducing Emissions from Deforestation and forest Degradation (REDD+) and other PES mechanisms must critically identify and consider community specific needs, expectations and concerns in their design and implementation. This requires willingness to diagnose community concerns and allow adjustments.

Background & Aims: Gut dysbiosis is closely involved in the pathogenesis of inflammatory bowel disease (IBD). However, it remains unclear whether IBD-associated gut dysbiosis contributes to disease pathogenesis or is merely secondary to intestinal inflammation. We established a humanized gnotobiotic (hGB) mouse system to assess the functional role of gut dysbiosis associated with 2 types of IBD: Crohn's disease (CD) and ulcerative colitis (UC). Methods: Germ-free mice were colonized by the gut microbiota isolated from patients with CD and UC, and healthy controls. Microbiome analysis, bacterial functional gene analysis, luminal metabolome analysis, and host gene expression analysis were performed in hGB mice. Moreover, the colitogenic capacity of IBD-associated microbiota was evaluated by colonizing germ-free colitis-prone interleukin 10âdeficient mice with dysbiotic patients' microbiota. Results: Although the microbial composition seen in donor patients' microbiota was not completely reproduced in hGB mice, some dysbiotic features of the CD and UC microbiota (eg, decreased diversity, alteration of bacterial metabolic functions) were recapitulated in hGB mice, suggesting that microbial community alterations, characteristic for IBD, can be reproduced in hGB mice. In addition, colonization by the IBD-associated microbiota induced a proinflammatory gene expression profile in the gut that resembles the immunologic signatures found in CD patients. Furthermore, CD microbiota triggered more severe colitis than healthy control microbiota when colonized in germ-free interleukin 10âdeficient mice. Conclusions: Dysbiosis potentially contributes to the pathogenesis of IBD by augmenting host proinflammatory immune responses. Transcript profiling: GSE73882. Keywords: Dysbiosis, Microbiota, Crohn's Disease, Ulcerative Colitis

Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood.Objective. The aim was to investigate this question.Material and methods. A rat model of segmental hepatic ischemia was employed. Rats were pre-treated with the estrogen receptor antagonist ICI182,780 and/or the estrogen receptor agonist 17β-estradiol. Bile flow, blood concentrations of bilirubin and liver enzymes were measured, and liver histology was assessed.Results. Bile flow recovery immediately after the initiation of reperfusion was faster in females than in males. ICI182,780 reduced the rate of bile flow recovery in females but this reduction was not reversed by co-administration of 17 β-estradiol. In males, 17 β-estradiol alone did not enhance bile flow recovery. The changes in bile flow recovery observed under a given condition were correlated with small changes in blood liver enzymes and liver histology.Conclusions. Sex has a significant influence on the early recovery of liver function in the acute phase of IR injury. However, in female rats estrogen receptors play only a limited role in mediating enhanced recovery of liver function.

Increased climate impacts threaten coastal functions globally, highlighting the need for multifunctional coastal climate adaptation. Sand nourishment can adapt sandy coasts to sea level rise, mitigate erosion, increase flood safety, enhance ecological habitats and expand recreational space. Therefore, sand nourishment is increasingly regarded as a promising nature-based strategy for coastal climate adaptation. However, despite this growing recognition, the assessment of how sand nourishment design impacts multifunctional adaptation remains limited. In this perspective article, we argue for three key lessons for researchers to optimise assessing multifunctional coastal climate adaptation by sand nourishment. We conducted stakeholder workshops to scope and inform our perspective, performed semi-structured literature reviews to concretise and validate this for international applications, built a qualitative model to visualise our interdisciplinary overview of how nourishments impact coastal multifunctionality, reflected on this in expert workshops, and identified implications for researchers. In this manner, we assessed the effects of nourishment design on coastal morphology, ecology, socio-economics and ecosystem services in realising the key policy goals of flood safety, nature and recreation. We found that sand nourishment design can result in conflicts between policy goals, generate ambiguous outcomes and lead to system-wide feedback effects. As such, we identified three key lessons: (1) conflicts between policy goals require informing political decision-making on prioritisation between coastal functions, (2) concreteness is needed on otherwise ambiguous functions, and (3) ongoing, multidisciplinary system-wide monitoring is essential. We thus call for a holistic approach to sand nourishment design and encourage researchers from diverse expertise and localities to expand on and adapt our findings to optimise informing sand nourishment design for delivering multifunctional coastal climate adaptation worldwide.

Summary: Background: In industrialized countries, the incidence of inflammatory bowel disease (IBD) appears stabilized. This study examined the incidence and phenotype of IBD in Northern France over a 30-year period. Methods: Including all IBD patients recorded in the EPIMAD population-based registry from 1988 to 2017 in Northern France, we described the incidence and clinical presentation of IBD according to age, sex and time. Findings: A total of 22,879 incident IBD cases were documented (59% (n = 13,445) of Crohn’s disease (CD), 38% (n = 8803) of ulcerative colitis (UC), 3% (n = 631) of IBD unclassified (IBDU)). Over the study period, incidence of IBD, CD and UC was 12.7, 7.2 and 5.1 per 105 person-years, respectively. The incidence of CD increased from 5.1/105 in 1988–1990 to 7.9/105 in 2015–2017 (annual percent change (APC): +1.9%, p

This paper explores the gap in the literature on social responsibility guidance for start-ups and start-up investors. It begins by evaluating research conducted in two different fields (namely, socially responsible investment (SRI) and responsible research and innovation (RRI)) and how they can guide social responsibility in STEM (Science, Technology, Engineering, Mathematics) start-ups. To do this, we evaluate an industry-standard SRI catalogue of metrics - the Global Impact Investing Network's (GIIN) Impact Reporting and Investment Standards (IRIS+) - and indicators from 12 EC-funded RRI projects. Based on this analysis, we propose a framework of 24 indicators to assess the social responsibility of start-ups and investors. The purpose of our framework is twofold: firstly, to provide clear guidance for start-ups aiming to implement socially responsible behaviours, and secondly, to provide start-up investors with criteria to identify if start-ups are socially responsible. While the indicators are phrased in a prescriptive way for start-ups, they can also be used by investors to identify if start-ups are implementing the indicators in practice.

Belief in a continuum of symptoms from mental health to mental illness (MI) has an impact on the social acceptance of people with MI. However, little is known about whether people's conception of MI itself and in particular how broad that conception is, has an impact on the social acceptance of individuals with MI or affects continuum beliefs. To address this research gap, it is necessary to capture and monitor public understanding of MI. Using 17 different statements that describe behaviors on a spectrum from mentally healthy to ambiguous to indicative of MI, we examine how the German public conceptualizes MI. Specifically, we develop a measure to capture the breadth of an individual's conception of MI. We find that a broader concept of MI is associated with greater social acceptability. In addition, we show that continuum beliefs and the breadth of the concept of MI interact – continuum beliefs are especially important for stigma reduction when individuals have a narrow concept of MI. For future research, this finding implies that with regard to social acceptance of people with MI, individuals with a narrow concept benefit from continuum interventions in particular.

Summary: Although adenosine deaminase 2 (ADA2) is considered an extracellular ADA, evidence questions the physiological relevance of this activity. Our study reveals that ADA2 localizes within the lysosomes, where it is targeted through modifications of its glycan structures. We show that ADA2 interacts with DNA molecules, altering their sequences by converting deoxyadenosine (dA) to deoxyinosine (dI). We characterize its DNA substrate preferences and provide data suggesting that DNA, rather than free adenosine, is its natural substrate. Finally, we demonstrate that dA-to-dI editing of DNA molecules and ADA2 regulate lysosomal immune sensing of nucleic acids (NAs) by modulating Toll-like receptor 9 (TLR9) activation. Our results describe a mechanism involved in the complex interplay between NA metabolism and immune response, possibly impacting ADA2 deficiency (DADA2) and other diseases involving this pathway, including autoimmune diseases, cancer, or infectious diseases.

Diatoms and bacteria play a vital role in investigating the ecological effects of heavy metals in the environment. Despite separate studies on metal interactions with diatoms and bacteria, there is a significant gap in research regarding heavy metal interactions within a diatom-bacterium system, which closely mirrors natural conditions. In this study, we aim to address this gap by examining the interaction of uranium(VI) (U(VI)) with Achnanthidium saprophilum freshwater diatoms and their natural bacterial community, primarily consisting of four successfully isolated bacterial strains (Acidovorax facilis, Agrobacterium fabrum, Brevundimonas mediterranea, and Pseudomonas peli) from the diatom culture. Uranium (U) bio-association experiments were performed both on the xenic A. saprophilum culture and on the four bacterial isolates. Scanning electron microscopy and transmission electron microscopy coupled with spectrum imaging analysis based on energy-dispersive X-ray spectroscopy revealed a clear co-localization of U and phosphorus both on the surface and inside A. saprophilum diatoms and the associated bacterial cells. Time-resolved laser-induced fluorescence spectroscopy with parallel factor analysis identified similar U(VI) binding motifs both on A. saprophilum diatoms and the four bacterial isolates. This is the first work providing valuable microscopic and spectroscopic data on U localization and speciation within a diatom-bacterium system, demonstrating the contribution of the co-occurring bacteria to the overall interaction with U, a factor non-negligible for future modeling and assessment of radiological effects on living microorganisms.

Global demand for vegetable oil is projected to expand to 28 Mt by 2028. Oilseed rape (OSR) is the predominant oilseed crop in Europe. Its nutritional value is determined by seed oil content and fatty acids (FAs) composition. Insect pollination increases seed oil content, however, its benefit on FAs composition remains unknown. In this study, we address this gap by investigating the variation of OSR seed oil content and FAs composition along a gradient of bee abundance in farmed OSR fields. We used a pollinator exclusion experiment to disentangle the contribution of pollination processes, i.e. wind, self and insect pollination. We show that bees improved OSR nutritional value by increasing amount of poly-unsaturated FAs and decreasing the amount saturated and trans-saturated FAs. In addition, oil content was higher in seeds with than without access to pollinators. Our study provides for the first time, to the best of our knowledge, evidence that insect pollination enhances the quality value of OSR oil by affecting FAs composition. Such effect implies potential negative consequences with any further decline of pollinator abundance. More investigations are also needed to better understand the mechanisms by which insect pollination affects FAs composition, and the way to enhance such mechanisms.

Summary: Background: In the CALCIPHYX trial, we investigated hexasodium fytate, an inhibitor of vascular calcification, for the treatment of calcific uraemic arteriolopathy (calciphylaxis), a rare condition characterised by painful, non-healing skin lesions. Methods: In this international, phase 3, randomised, double-blind, placebo-controlled trial, adults with an ulcerated calciphylaxis lesion and pain visual analogue scale (VAS) score ≥50/100 were randomised 1:1 to hexasodium fytate 7 mg/kg or placebo intravenously during maintenance haemodialysis. Primary efficacy outcomes were an 8-item modification of the Bates-Jensen Wound Assessment Tool (BWAT-CUA) and Pain VAS in the intention-to-treat population. ClinicalTrials.gov number: NCT04195906. Findings: Overall, 34/37 patients randomised to hexasodium fytate and 26/34 patients randomised to placebo completed the 12-week randomised treatment period. At Week 12, both groups (hexasodium fytate versus placebo) showed similar improvements in BWAT-CUA (mean [standard deviation (SD)], −5.3 [5.2] versus −6.0 [6.2]; least squares mean difference, 0.3 [96% confidence interval (CI): −2.5, 3.0]; p = 0.88) and Pain VAS (mean [SD], −19.5 [26.9] versus −32.2 [38.5]; least squares mean difference, 11.5 [96% CI: −4.8, 27.8]; p = 0.15). One patient randomised to placebo briefly received hexasodium fytate in error. Serious adverse events through Week 12 included: calciphylaxis-related events leading to hospitalisation (2/38 [5%] versus 11/33 [33%]) and death (1/38 [3%] versus 5/33 [15%]). During the subsequent 12 weeks of open-label hexasodium fytate and 4 weeks of follow-up, there were no additional calciphylaxis-related events leading to hospitalisation. Over the course of the entire trial, deaths were 2/38 [5%] for the hexasodium fytate group and 7/33 [21%] for the placebo group. Interpretation: In patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group. Funding: Funded by Sanifit, a CSL Vifor company.

In viticulture, the risk of spring frost is mainly due to earlier budbreak, increasing the vulnerability of buds and green organs to freezing temperatures. Active Spring Frost Protection Methods (ASFPMs) aim to mitigate this risk by increasing the temperature in the bud area. ASFPMs are often seen as highly labour-intensive and resource consuming practices. ASFPM technologies are diverse and influenced by different external drivers, affecting differently their application strategies and the required equipment for efficiency. This study proposes a framework for analysing and comparing ASFPMs’ potential environmental impacts using Life Cycle Assessment (LCA) methodology. We illustrate this proposal with an example: Winter cover, wind machine, sprinkler and anti-frost candles comparison in Loire Valley conditions. We modeled the attributional LCAs with Impact world + characterisation method using Abribalyse 3.1 and Ecoinvent 3.8 databases. Application and climatic scenarios were elaborated to set conditions of ASFPMs use. The overall combination of attributional LCAs and external scenarios designs a context-specific LCA. Required time of application for each ASFPM to protect 1 ha during frost hours was determined using linear regression of ASFPM application time in function of total seasonal frost hours based on a recent decade (2013–2023). Sensitivity analysis consisted in varying frost hours theoretically with a step of 1 unit, using the lowest and highest frost hour numbers from 2013 to 2023 as boundaries. Overall, the ranking between ASFPM environmental scores changes based on the theoretical frost duration. The implementation of context-specific elements allowed for the development of system boundaries in attributional LCA, enabling the analysis and comparison of different types of technologies. The framework of this study showed its relevance in the context of ASFPM technologies through a concrete example in Loire Valley viticulture. Future research may consider other contextual elements and ASFPM technologies. This framework could be used in different fields of study to analyse and compare contrasted technologies in terms of environmental impacts.

Artificial Intelligence (AI) is on the verge of impacting every domain of our lives. It is increasingly being used as an advisor to assist in making decisions. The present study aimed at investigating the influence of moral arguments provided by AI-advisors (i.e., decision aid tool) on human moral decision-making and the associated neural correlates. Participants were presented with sacrificial moral dilemmas and had to make moral decisions either by themselves (i.e., baseline run) or with AI-advisors that provided utilitarian or deontological arguments (i.e., AI-advised run), while their brain activity was measured using an fNIRS device. Overall, AI-advisors significantly influenced participants. Longer response times and a decrease in right dorsolateral prefrontal cortex activity were observed in response to deontological arguments than to utilitarian arguments. Being provided with deontological arguments by machines appears to have led to a decreased appraisal of the affective response to the dilemmas. This resulted in a reduced level of utilitarianism, supposedly in an attempt to avoid behaving in a less cold-blooded way than machines and preserve their (self-)image. Taken together, these results suggest that motivational power can led to a voluntary up- and down-regulation of affective processes along moral decision-making.

Summary: Background: Early-onset Group B Streptococcus (EOGBS) infection leads to substantial morbidity and mortality in newborn infants. Intrapartum antibiotic prophylaxis (IAP) prevents EOGBS infection, but IAP strategies vary. The approach to the provision of IAP can be risk-based, universal or a combination of the two strategies. Previous systematic reviews reported that universal strategies might be most optimal in lowering EOGBS infection, but there is no consensus. Therefore, we aimed to provide up-to-date evidence on effectiveness of different strategies by comparing perinatal outcomes. Methods: A systematic search for EOGBS prevention strategies was performed in MEDLINE, Embase and Web of Science on May 2024. Studies were included if they reported on different strategies and outcomes of interest, including EOGBS infection, IAP administration and antimicrobial resistance regardless of publication date. Summary data was extracted from published reports. Study quality was assessed using the ROBINS-I tool. Random-effects meta-analyses were used to determine risk ratios (RR) and 95%-confidence intervals. PROSPERO registration CRD42023411806. Findings: A total of 6293 records were identified, of which 72 observational studies were included for synthesis with more than 10 million live births. Meta-analysis demonstrated that implementation of any strategy (n = 34 studies, RR 0.46 (0.36–0.60)), risk-based strategies (n = 11 studies, RR 0.65 (0.48–0.87)), or universal strategies (n = 16 studies, RR 0.37 (0.25–0.55)) was associated with a reduced risk of EOGBS infection compared to no strategy. In direct comparison, universal strategies were associated with a reduced risk of EOGBS compared to a risk-based strategy (n = 17 studies, RR 0.41 (0.30–0.55)), while the proportion of women receiving IAP did not differ between risk-based (16%) and universal (21%) strategies (n = 9 studies, RR 1.29 (0.95–1.75)). There was no antimicrobial resistance of EOGBS isolates to penicillin or ampicillin (n = 11 studies). Interpretation: Any IAP strategy could reduce the risk of EOGBS infection without evidence of increasing antimicrobial resistance. Universal strategies give the largest reduction in the EOGBS burden, while not exposing a significantly higher proportion of pregnancies to IAP compared to risk-based strategies. Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, a cosponsored programme executed by the World Health Organization.

Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62–84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2–7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.

The ELN gene encodes tropoelastin which is used to generate elastic fibers that insure proper tissue elasticity. Decreased amounts of elastic fibers and/or accumulation of bioactive products of their cleavage, named elastokines, are thought to contribute to aging. Cellular senescence, characterized by a stable proliferation arrest and by the senescence-associated secretory phenotype (SASP), increases with aging, fostering the onset and progression of age-related diseases and overall aging, and has so far never been linked with elastin. Here, we identified that decrease in ELN either by siRNA in normal human fibroblasts or by knockout in mouse embryonic fibroblasts results in premature senescence. Surprisingly this effect is independent of elastic fiber degradation or elastokines production, but it relies on the rapid increase in HMOX1 after ELN downregulation. Moreover, the induction of HMOX1 depends on p53 and NRF2 transcription factors, and leads to an increase in iron, further mediating ELN downregulation-induced senescence. Screening of iron-dependent DNA and histones demethylases revealed a role for histone PHF8 demethylase in mediating ELN downregulation-induced senescence. Collectively, these results unveil a role for ELN in protecting cells from cellular senescence through a non-canonical mechanism involving a ROS/HMOX1/iron accumulation/PHF8 histone demethylase pathway reprogramming gene expression towards a senescence program.

This study assessed the microbial agents that cause CRBSIs and their antibiotic resistance patterns among patients with CVC undergoing maintenance haemodialysis. Patients undergoing maintenance haemodialysis (MHD) via CVC, at a tertiary hospital, between September 2021 to April 2022 were assessed in a cross-sectional study. Microbial cultures with respective antibiotic sensitivity patterns were determined for samples taken from blood, catheter insertion sites, catheters’ lumen, and tips. Antibiotic sensitivity patterns were determined using the disc diffusion methods.The culture positivity rate was 32.7% with a CRBSI prevalence rate of 34.2%. 47.1% of the bacteria cultured were Gram positive and 52.9% of the organisms cultured were Gram negative. Among the Gram positives, Coagulase negative Staphylococci (20.6%) was the most cultured organism, and these organisms were highly sensitive to vancomycin. Acinetobacter baumannii (17.6%) was the most common Gram negative organism isolated. All Gram negative organisms were susceptible to amikacin except for one resistant isolate of Acinetobacter baumannii.There is a high rate of antimicrobial resistance among patients on haemodialysis using CVCs. From the antibiogram, vancomycin and amikacin should be used as empiric antibiotics in treating CRBSIs among patients on MHD.

Polyphenolic compounds are a class of phytonutrients that play important roles in plants and contribute to human health when incorporated into our diet through fruit consumption. A large proportion occur as glycoconjugates but the enzymes responsible for their glycosylation are poorly characterized. Here, we report the biochemical and structural characterization of two glycosyltransferases from sweet cherry named PaUGT1 and PaUGT2. Both are promiscuous glucosyltransferases active on diverse anthocyanidins and flavonols, as well as phenolic acids in the case of PaUGT1. They also exhibit weaker galactosyltransferase activity. The expression of the gene encoding PaUGT1, the most active of the two proteins, follows anthocyanin accumulation during fruit ripening, suggesting that this enzyme is the primary glycosyltransferase involved in flavonoid glycosylation in sweet cherry. It can potentially be used to synthesize diverse glycoconjugates of flavonoids for integration into bioactive formulations, and for generating new fruit cultivars with enhanced health-promoting properties using breeding methods.

Plant cell wall researchers were asked their view on what the major unanswered questions are in their field. This article summarises the feedback that was received from them in five questions. In this issue you can find equivalent syntheses for researchers working on bacterial, unicellular parasite and fungal systems.

Summary: Resistance to chemotherapies such as temozolomide is a major hurdle to effectively treat therapy-resistant glioblastoma. This challenge arises from the activation of phosphatidylinositol 3-kinase (PI3K), which makes it an appealing therapeutic target. However, non-selectively blocking PI3K kinases PI3Kα/β/δ/γ has yielded undesired clinical outcomes. It is, therefore, imperative to investigate individual kinases in glioblastoma’s chemosensitivity. Here, we report that PI3K kinases were unequally expressed in glioblastoma, with levels of PI3Kβ being the highest. Patients deficient of O6-methylguanine-DNA-methyltransferase (MGMT) and expressing elevated levels of PI3Kβ, defined as MGMT-deficient/PI3Kβ-high, were less responsive to temozolomide and experienced poor prognosis. Consistently, MGMT-deficient/PI3Kβ-high glioblastoma cells were resistant to temozolomide. Perturbation of PI3Kβ, but not other kinases, sensitized MGMT-deficient/PI3Kβ-high glioblastoma cells or tumors to temozolomide. Moreover, PI3Kβ-selective inhibitors and temozolomide synergistically mitigated the growth of glioblastoma stem cells. Our results have demonstrated an essential role of PI3Kβ in chemoresistance, making PI3Kβ-selective blockade an effective chemosensitizer for glioblastoma.

Background: Our study explores the role of bats as reservoirs of coronaviruses. Methods: We conducted virological screening of bats hibernating in military bunkers at the Natura 2000 site “Nietoperek” in Western Poland collecting oral and anal swab samples from 138 bats across six species to apply a combination of pan-coronavirus and SARS-CoV-2 specific PCR assays. Results: Only one anal swab tested positive for coronavirus. No SARS-CoV-2 was detected in any of the samples. The low prevalence of coronavirus in the studied colony contrasts with higher rates found in other regions and may be influenced by hibernation. Conclusions: Hibernating bats may show a low prevalence of coronavirus, potentially due to the hibernation process itself. This finding indicates that hibernating bats may not be the most optimal subjects for screening zoonotic pathogens. However, biomonitoring of bats for emerging and reemerging diseases is recommended for comprehensive epidemiological insights.

Objectives: We evaluated the diagnostic accuracy of cerebrospinal fluid (CSF) inflammatory markers for diagnosing bacterial meningitis in neonates with sepsis and/or meningitis. Methods: Cases were identified from a prospective multicenter study including patients aged 0-3 months with Group B Streptococcal (GBS) or Escherichia coli culture positive sepsis/meningitis. CSF CXCL10, MDC, IL-6, IL-8, IL-10, TNF- α, MIF, IL-1RA, CXCL13, IL-1β, CRP and procalcitonin concentrations were measured with Luminex technology. Results: In 61/373 patients (17%) residual CSF from the lumbar puncture was available, of whom 16 (26%) had definitive meningitis, 15 (25%) probable meningitis and 30 (49%) had sepsis. All biomarkers were detectable in CSF and showed significantly higher concentrations in definitive meningitis versus sepsis patients and six biomarkers in probable meningitis versus sepsis patients. Discrimination between definitive meningitis and sepsis was excellent for IL-1RA (area under the receiver operating characteristic curve [AUC] 0.93), TNF-α (AUC 0.92), CXCL10 (AUC 0.90), IL-1β (AUC 0.92), IL-6 (AUC 0.94), IL-10 (AUC 0.93) and a combination of IL-1RA, TNF-α, CXCL-10 and CSF leukocyte count (AUC 0.95). CSF leukocyte count remained the predictor with the highest diagnostic accuracy (AUC 0.96). Conclusion: CSF inflammatory markers can be used to differentiate between neonatal sepsis and meningitis.

In Benin, adaptation to climate change in the livestock sector has led cattle farmers to develop different livestock practices. Most research has focused on evaluating the effects of these practices on livestock productivity. However, information on the effect of these practices on carbon (C) sequestration in farmland soils is lacking. Soil C sequestration has been identified as a potential strategy to offset greenhouse gas emissions. Thus, the present study aimed at filling this gap. The calculation was one hand based on inventory data obtained from literature sources (excrement production of each cattle category, moisture content of each crop, ratio of crop residue to main product, and C content of the main product and excrement) and on the other hand on activity data (cattle herd size, manure applied, land use area, crop yield, and crop residues management) obtained from surveys carried out among 360 cattle farmers belonging to 3 cattle farming types. The results revealed that whatever the cattle farming type, annual C input from manure was higher (p˂0.05) than C input from crop residues. Annual C sequestration in farmland soil of farms integrating livestock with cereal-legume and forage crops was significantly higher (Type 2: 158.07 ± 1.79 kg C ha−1 year−1) followed by farms integrating livestock with cereal-legume crops (Type 1: 99.51 ± 0.95 kg C ha−1 year−1), which in turn had a higher value than farms practicing pastoral mobility (Type 3: 78.46 ± 0.70 kg C ha−1 year−1). These results highlight the potential for climate change mitigation through these farming practices. This is justified because the quantity of C sequestered in farmland soil of all cattle farming types was significant. Thus, for future research, it is necessary to include soil C sequestration in the calculations of farms' carbon footprint.

The aim of this systematic review was to evaluate the in vitro accuracy of dental implant impressions taken using digitally coded healing abutments (CHAs) compared with impressions taken with conventional techniques (CI) and/or within the CHA group at varying degrees of angulations for multiple implant units. Two independent reviewers conducted a systematic electronic search in the MedLine, PubMed, Google Scholar, Cochrane Library, Web of Science, and Scopus databases. Some of the employed key terms, combined with the help of Boolean operators, were: “digitally coded healing abutments”, “encode healing abutment”, “dental implants”, “impression accuracy”, “digital impression”, and “conventional impression”. Publication dates ranged from January 2010 to November 2022. A total of 7 articles fulfilled the inclusion criteria: 6 studies compared the accuracy of CHA with conventional pick-up impression techniques, and one study only used CHAs at different angulations and heights to compare accuracy within the group. The results were divided into Group A (elastomeric impression of CHA) and Group B (CHA + Intraoral scanner). According to the results of this systematic review, elastomeric impression of CHA performed poorly when compared to CI for multiple implants, although an intraoral scan of CHA appears to be more accurate. Within the CHA group, the angulation and visible height of CHA play a significant role in impression accuracy. However, more studies are needed before CHA can be recommended for all non-parallel multiple implant-supported restorations.

Floating photovoltaics (FPV) is emerging as a promising renewable energy technology which enables the production of electricity on surface waters. While this technology could potentially make an important contribution to the energy transition, the current uncertainty about the water quality effects of FPV deployment poses a major barrier to FPV project development and implementation. In this study, we investigated the water quality effects of three distinctive FPV system designs, implemented as part of a 1-year pilot project at the Oostvoornse lake, the Netherlands. A water quality monitoring campaign was set up to monitor on a continuous basis a set of key water quality parameters, including light intensity, water temperature and dissolved oxygen concentration. The measurements were conducted below each of the three FPV systems and contrasted with reference measurements at open water adjacent to the systems. Our monitoring results show that of the water quality parameters considered, the impact of the FPV systems on light intensity was found to be most pronounced, with a light reduction between 73% and 100% relative to the reference measurements. We found limited evidence to corroborate that the FPV systems induced changes to the water temperature and dissolved oxygen concentration. However, it must be noted that this study took place under highly specific conditions due the limited size of the FPV pilot systems and the brackish water of the Oostvoornse lake. This means that the water quality effects reported here may not be representative for a larger scale application of the FPV designs, and may not be one-on-one transferable to other, non-brackish project locations elsewhere.

Summary: Background: Digital health interventions can be effective for blood pressure (BP) control, but a comparison of the effectiveness and application of these types of interventions has not yet been systematically evaluated in low- and middle-income countries (LMICs). This study aimed to compare the effectiveness of digital health interventions according to the World Health Organisation (WHO) classifications of patients in terms of BP control, lifestyle behaviour changes, and adherence to medication in patients with hypertension in LMICs. Methods: In this systematic review and meta-analysis, we searched the PubMed, Scopus, Web of Science, Embase, CINAHL, and Cochrane Library databases for randomised controlled trials (RCTs) published in English, comprised of adults (≥18 years old) with hypertension and the intervention consisted of digital health interventions according to WHO's classifications for patients in LMICs between January 1, 2009, and July 17, 2023. We excluded RCTs that considered patients with hypertension comorbidities such as diabetes and hypertension-mediated target organ damage (HMTOD). The references were downloaded into Mendeley Desktop and imported into the Rayyan web tool for deduplication and screening. The risk of bias was assessed using Cochrane Risk of Bias 2. Data extraction was done according to Cochrane's guidelines. The main outcome measures were mean systolic blood pressure (SBP) and BP control which were assessed using the random-effect DerSimonian-Laird and Mantel-Haenszel models. We presented the BP outcomes, lifestyle behaviour changes and medication adherence in forest plots as well as summarized them in tables. This study is registered with PROSPERO, CRD42023424227. Findings: We identified 9322 articles, of which 22 RCTs from 12 countries (n = 12,892 respondents) were included in the systematic review. The quality of the 22 studies was graded as high risk (n = 7), had some concerns (n = 3) and low risk of bias (n = 12). A total of 19 RCTs (n = 12,418 respondents) were included in the meta-analysis. Overall, digital health intervention had significant reductions in SBP [mean difference (MD) = −4.43 mmHg (95% CI −6.19 to −2.67), I2 = 92%] and BP control [odds ratio (OR) = 2.20 (95% CI 1.64–2.94), I2 = 78%], respectively, compared with usual care. A subgroup analysis revealed that short message service (SMS) interventions had the greatest statistically significant reduction of SBP [MD = −5.75 mm Hg (95% Cl −7.77 to −3.73), I2 = 86%] compared to mobile phone calls [MD = 3.08 mm Hg (−6.16 to 12.32), I2 = 87%] or smartphone apps interventions [MD = −4.06 mm Hg (−6.56 to −1.55), I2 = 79%], but the difference between groups was not statistically significant (p = 0.14). The meta-analysis showed that the interventions had a significant effect in supporting changes in lifestyle behaviours related to a low salt diet [standardised mean difference (SMD) = 1.25; (95% CI 0.64–1.87), I2 = 89%], physical activity [SMD = 1.30; (95% CI 0.23–2.37), I2 = 94%] and smoking reduction [risk difference (RR) = 0.03; (95% CI 0.01–0.05), I2 = 0%] compared to the control group. In addition, improvement in medication adherence was statistically significant and higher in the intervention group than in the control group [SMD = 1.59; (95% CI 0.51–2.67), I2 = 97%]. Interpretation: Our findings suggest that digital health interventions may be effective for BP control, changes in lifestyle behaviours, and improvements in medication adherence in LMICs. However, we observed high heterogeneity between included studies, and only two studies from Africa were included. The combination of digital health interventions with clinical management is crucial to achieving optimal clinical effectiveness in BP control, changes in lifestyle behaviours and improvements in medication adherence. Funding: None.

Mountainous grassland soils are considered one of the most unique biological hotspots, rich in organic carbon (OC). At the same time, they are exposed to great threats, as climate warming is more pronounced in mountainous regions than in lowland areas. In this study, we assessed the effect of simulated warming (+1K, +2K, and + 3 K) on OC stocks and soil structure in grassland soils of the Northern Limestone Alps in Germany by translocating plant-soil mesocosms from high- (1260 m a.s.l., Rendzic Phaeozem) and mid- (860 m a. s. l., Haplic Cambisol) to low-elevation (600 m a.s.l). Plant-soil mesocosms were exposed to both extensive and intensive grassland management practices. Four years after translocation, we observed a rapid decrease of topsoil SOC stocks under intensive (−1.0 t C ha yr−1) and extensive management (-2.2 t C ha yr−1), under the highest temperature increase. Intensive management with about 1 t C ha−1 yr−1 higher manure C return than extensive management (1.6 vs. 0.8 t C ha−1 yr−1 intensive and extensive, respectively) may explain the difference in SOC losses between different management treatments. Under both management practices, the loss of SOC was mainly associated with a decrease of large macroaggregates, at both management practices. In addition, different aggregate specific OC loss rates resulted in an altered distribution of OC among the aggregate size classes. Our study provides evidence that simulated climate change induced a rapid and substantial decline of SOC in mountainous, OC-rich grassland soils, which may be attributed to decreased physical OC protection within large macroaggregates. Optimized grassland management in form of increased application of organic fertilizers could only partially offset the SOC loss by improved formation of small macroaggregates.

Introduction: Visceral fat gain and the progressive onset of metabolic disorders in middle-aged mice induce alteration of the cerebral vascular tree in association with mild cognitive impairment. This precipitates stroke risk and might prompt the middle-aged population to cognitive decline. In this context, an endogenous peptide named apelin-13 and its receptor APJ are suspected to link metabolic disorders at middle age to the consequences of ischemic stroke on brain tissue, as well as vasomotor and cognitive functions. Apelin-13 induces neuroprotection after experimental ischemic stroke, but this action has not been examined under metabolic disturbances. The aim of our study is to evaluate the role of apelin-13 as a new therapeutic target in ischemic stroke under high-fat diet-induced metabolic disturbances at middle-age. Methods: C57Bl/6 mice were fed for 6 months with normal diet (ND) or high-fat diet (HFD) before 30-minute middle cerebral artery occlusion (MCAO). Metabolic parameters, as well as circulating apelin-13 levels were evaluated every 3 months before MCAO. APJ brain expression and plasmatic apelin rate were assess at acute phase (24h post-stroke) and after behavioral (motor and cognitive) evaluation at chronic phase (10 days after MCAO). Results: Mice under HFD developed overweight, hyperglycemia and hypercholesterolemia. Plasmatic apelin slowly decreased with age and was different between overweight and lean mice, but not between HFD and ND. The onset of MCAO under HFD induced 49% higher mortality than under ND. At acute phase, mice under HFD had a 25% decreased plasmatic apelin rate whereas mice under ND had a 2.5% of reduction. APJ brain expression in HFD mice was 59% reduced compared to ND. After 10 days, worsened behavioral impairment was observed in HFD mice compared to ND mice. Plasmatic apelin levels were reduced whatever the diet. Discussion: These first results highlight the contribution of the apelinergic system to the influence of metabolic disturbances on stroke severity, that should be considered in therapeutic studies.