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Abstract A genomic database of all Earth’s eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.

Background: Parkinson’s, a degenerative disease characterized by motor and non-motor symptoms, gradually leads to disability and affects ordinary gestures, including patients’ home oral hygiene. Given that poor oral conditions, with decayed teeth, halitosis, and periodontal inflammation, can represent a critical issue in patients with low compliance in oral hygiene, the aim of this review was to investigate overall oral health in patients with Parkinson’s disease (PD). Methods: A search on PubMed, Cochrane Library and Scopus databases was conducted to identify relevant publications: studies concerning patients with PD, their oral health conditions, and oral hygiene, also in terms of inflammation and plaque control, were included. Risk of bias analysis and qualitative analysis were performed. Results: Of 226 records found through the electronic search, a total of 16 studies were finally included in the systematic review. Outcomes without consistent differences between PD patients and healthy patients (control group) mainly regarded: the frequency of brushing (at least twice a day), the brushing methods (generally variable) and the frequency of dental visits (mostly regular for both groups). In patients with PD, use of interdental devices was lower, and presence of plaque was higher: due to self-reported difficulties, 15–29% of them need help for oral care, against the 1% in the healthy group. Furthermore, the longer duration and higher severity of PD seem to adversely affect overall oral health conditions. Discussion: Since poor oral conditions of patients with PD are associated with their disability in conducting proper home procedures, it is necessary for dental practitioners to focus on specific and personalized instructions, to be easily delivered to caregivers.

Abstract Methods This study assessed data from two cohorts of patients with alpha‐synucleinopathies (University of Brescia and University of Rome Tor‐Vergata cohorts). Consecutive participants with video‐polysomnography‐confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I‐FP‐CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I‐FP‐CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls. Results The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age‐matched controls. Individuals with iRBD were categorized as RBD‐DAT− (n = 32) and RBD‐DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD‐DAT− showed an early involvement of the left insula, which increased in RBD‐DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18–10.27]. Interpretation In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non‐pharmacological interventions.

Abstract Background Access to safe, financial affordable health care is a key factor in reducing health disparities. The malaria is a major public health issue, with significant economic implications in Guinea where the free malaria care services were introduced in 2010. This paper analyzes the costs associated with the care pathway for malaria patients in the Republic of Guinea. Methods An analysis of the costs associated with malaria disease was conducted using data from a cross-sectional survey on the determinants of malaria care pathway between December 2022 and March 2023. The data were collected in health facilities and at community health workers. According to the patient’s perspective, Time-Driven Activity-Based Costing (TDABC) and micro-costing approaches were used to assess the costs associated with care-seeking, cases management, and income loss. Results A total of 3300 patients were recruited in 60 health facilities. The majority were in urban areas (64.8%). One third of the patients were children under five years old. Over half of the patients or caregivers were without formal education, and most households were headed by husbands (78.5%). The median monthly income of the head of households was $116.0. Furthermore, after diagnosis, 25.5% of cases were uncomplicated malaria, 19.2% were complicated, and 52.2% were malaria associated with other diseases. Globally 41% of cases were on their first care pathway. The costs of care-seeking varied according to type of malaria, from $3.5 and $13.5 respectively for uncomplicated and complicated cases. The median direct costs of case management at health facilities were $7.3 (IQR: $4.1,13.3) for uncomplicated and $30.5 (IQR: 15.7, 51.4) for complicated cases. The total costs associated with the global care pathway differed across types of malaria and age groups, with median costs estimated at $17.4 (IQR: 6.7, 34.8) for uncomplicated cases and $43.5 (IQR: $ 19.7, 74.0) for complicated malaria. A delay in appropriate care-seeking accounted for 19% of the costs incurred by malaria patients in Guinea (p

Abstract Background Bisphenol S (BPS) is the main substitute for bisphenol A (BPA), a well-known plasticiser and endocrine disruptor. BPS disrupts ovarian function in several species. Moreover, a few studies have reported that the effects of BPS might be modulated by the metabolic status, and none have characterised the granulosa cell (GC) proteome after chronic BPS exposure. Objectives This study aimed to decipher the mechanisms of action of chronic BPS exposure on the proteome of ewe GCs while considering the interaction between a deliberate contrasted metabolism and reproductive function. Methods Forty ewes were split into two groups with contrasted diets: restricted (R, n = 20) and well-fed (WF, n = 20). The R and WF ewes were subdivided according to the dose of BPS administered through the diet (0–50 µg/kg/day), forming four groups: R0, R50, WF0 and WF50. After 3-month BPS daily exposure, GCs were recovered during the pre-ovulatory stage and proteins were analysed by nano-liquid chromatography coupled with tandem mass spectrometry. Results Chronic exposure to BPS affected the GC proteome differently according to the ewe metabolic status. Fifty-nine out of 958 quantified proteins were differentially abundant between groups and are mainly involved in carbohydrate and lipid pathways. Unsupervised hierarchical clustering of differentially abundant proteins (DAPs) identified four clusters of 34, 6, 5 and 14 proteins according to the BPS exposure and diet interaction. Pairwise comparisons between groups also revealed a strong effect of BPS exposure and diet interaction. Functional analysis of DAPs highlighted that BPS upregulated β-glucuronidase (GUSB; p = 0.002), a protein especially able to deconjugate bisphenol glucuronides (BP-g). Moreover, among unexposed ewes, GUSB was detected only in well-fed ewes. Discussion Conjugation of glucuronides inhibits the oestrogenic activity of bisphenols. Upregulation of GUSB in ewes dosed with BPS would prolong the oestrogenic effects of BPS by deconjugating BPS-g into free BPS. In addition, literature has reported an up-regulation of GUSB in people suffering from obesity. Therefore, people suffering from obesity could be subjected to prolonged and aggravated exposure to BPS. These data highlighted the deleterious effects of BPS and its interaction with metabolic status.

Abstract Background Despite medication being the most common healthcare intervention and medication-related incidents being common in hospitals, many rural and remote hospitals in Australia lack onsite pharmacy services due to resource constraints. A Virtual Clinical Pharmacy Service (VCPS) staffed by two senior, rural generalist hospital pharmacists assigned to four hospitals each was implemented in rural and remote facilities to determine whether the VCPS increased adherence to National Safety and Quality Health Service Standards (NSQHS). Methods A stepped-wedge randomised controlled trial was employed to sequentially implement a telehealth pharmacy service at one-month intervals in eight hospitals. The primary outcomes were patient-level medication reconciliation completion rates on admission and discharge. Secondary measures evaluated compliance with other NSQHS standards (including Best Possible Medication History, Medication Reconciliation and venous thromboembolism risk assessment), patient outcomes (including representation within 48 h, readmission within 28 days and length of stay), and detection of potential medication-related harms (including pharmacist identified medication related problems, reported medication errors and falls). Patients were invited to complete a patient-reported experience questionnaire. Data were collected from electronic medical records and analysed using mixed logistic regression models to estimate the effectiveness of the VCPS. Antimicrobial usage, falls, and medication errors were analysed at the facility level, while other data were analysed at the patient level. Results Compared to control (n = 535), patients in the intervention period (n = 527) were more likely to have an admission medication reconciliation completed (Odds Ratio (OR) 11.16, 95% confidence interval (CI) 5.59–22.30, p

Abstract DNA damage occurs in all living cells. γ-H2AX imaging by fluorescent microscopy is widely used across disciplines in the analysis of double-strand break (DSB) DNA damage. Here we demonstrate a method for the quantitative analysis of such DBSs. Ionising radiation, well known to induce DSBs, is used in this demonstration, and additional DBSs are induced if high-Z nanoparticles are present during irradiation. As a deliberate test of the methodology, cells are exposed to a spatially fractionated ionising radiation field, characterised by regions of high and low absorbed radiation dose that are only ever qualitatively verified biologically via γ-H2AX imaging. Here we validate our bio-dosimetric quantification method using γ-H2AX assays in the assessment of DSB enhancement. Our method reliably quantifies DSB enhancement in cells when exposed to either a spatially contiguous or fractionated irradiation fields. Using the γ-H2AX assay, we deduce the biological dose response, and for the first time, demonstrate equivalence to the independently measured physical absorbed dose. Using our novel method, we are also able quantify the nanoparticle DSB enhancement at the cellular level, which is not possible using physical dose measurement techniques. Our method therefore provides a new paradigm in γ-H2AX image quantification of DSBs, as well as an independently validated bio-dosimetry technique.

Abstract Mpox is a zoonotic viral disease that presents significant public health challenges. Despite the pivotal role of healthcare workers, research on their knowledge and attitudes towards mpox is limited. This study aimed to assess healthcare workers’ knowledge, awareness and attitude regarding mpox as well as associated factors at Rivers State University Teaching Hospital in Nigeria. A descriptive cross-sectional study design was employed, utilizing a 34-item semi-structured questionnaire. Knowledge levels were categorized as good (> 70% score), fair (50–69%), or poor ( 70% score), moderate (50–69%), or negative ( 40 years (p = 0.008), years of experience (6–10 years; (p

Abstract Increasing biological nitrogen (N) fixation (BNF) in maize production could reduce the environmental impacts of N fertilizer use, but reactive N in the rhizosphere of maize limits the BNF process. Using non-transgenic methods, we developed gene-edited strains of Klebsiella variicola (Kv137-2253) and Kosakonia sacchari (Ks6-5687) bacteria optimized for root-associated BNF and ammonium excretion in N-rich conditions. The aim of this research was to elucidate the mechanism of action of these strains. We present evidence from in vitro, in planta and field experiments that confirms that our genetic remodeling strategy derepresses BNF activity in N-rich systems and increases ammonium excretion by orders of magnitude above the respective wildtype strains. BNF is demonstrated in controlled environments by the transfer of labeled 15N2 gas from the rhizosphere to the chlorophyll of inoculated maize plants. This was corroborated in several 15N isotope tracer field experiments where inoculation with the formulated, commercial-grade product derived from the gene-edited strains (PIVOT BIO PROVEN® 40) provided on average 21 kg N ha-1 to the plant by the VT-R1 growth stages. Data from small-plot and on-farm trials suggest that this technology can improve crop N status pre-flowering and has potential to mitigate the risk of yield loss associated with a reduction in synthetic N fertilizer inputs.

Abstract Myasthenia gravis (MG) is a rare autoantibody-mediated disease affecting the neuromuscular junction. We performed a genome-wide association study of 5708 MG cases and 432,028 controls of European ancestry and a replication study in 3989 cases and 226,643 controls provided by 23andMe Inc. We identified 12 independent genome-wide significant hits (P

Abstract Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in

Abstract Background Non-cystic fibrosis (non-CF) bronchiectasis (BE) is defined as a clinical syndrome of recurrent, persistent wet cough and abnormal bronchial dilatation on chest High Resolution Computed Tomography (HRCT) scans. The aims of this study were to characterize the pattern of the trajectories of lung function parameters and to consider the relationship between the lung function and radiological severity according to the modified Reiff score. Methods The study retrospectively considered 86 children (46.5% male, median age of 4 years) with non-CF BE, admitted at the Paediatric Pneumology Unit of Buzzi Children’s Hospital from January 2015 to December 2022. The diagnosis of BE was made according to the presence of a suggestive clinical history and symptoms and key features of BE evidenced on chest HRCT scans. The modified Reiff score was adapted to quantify the severity of BE. Spirometry (COSMED MicroQuark spirometer) was performed at median age of 5.78 years (baseline or T0) and after 1 and 2 years from the baseline (T1 and T2, respectively). The general trends of lung function parameters were estimated by ANOVA models for repeated measurements. For each lung function parameter, a longitudinal regression model was fitted. The analysis was performed with the software R release 4.2.3. The statistical significance was deemed when the p-value resulted lower than 0.05. Results The general trends of lung function parameters showed a statistically significant variation of forced vital capacity (FVC%) and forced expiratory volume in 1s (FEV1%) from T0 to T1 (p = 0.0062, 0.0009) and no significant change for FVC%, FEV1% and forced expiratory flow 25–75% of VC (FEF25/75%) from T1 to T2 (p = 0.145, 0.210, 0.600, respectively). Notably, we found no correlation between the age at diagnosis and the lung function parameters at T0 (r = 0.149, 0.103 and 0.042 for FVC%, FEV1% and FEF25/75%, respectively). Instead, a poor negative correlation resulted between the Reiff score and FVC%, FEV1% e FEF25/75% at baseline (Spearman coefficients: rho=-0.156, -0.204, -0.103, respectively). Conclusions A stable pulmonary function is detectable within 2 years follow up from baseline spirometry. The modified Reiff score should be considered as a good tool not only to quantify the radiological lung involvement but also the degree of pulmonary function impairment.

Abstract Background Healthcare systems data (HCSD) could improve the efficiency of clinical trials, but their accuracy and validity are uncertain. Our objective was to assess the accuracy of HCSD as the sole method of outcome detection in the REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) compared with adjudicated questionnaire follow-up and compare estimates of treatment effect. Methods RESTART was a prospective, open, assessor-blind, parallel-group randomised controlled trial (RCT) of antiplatelet therapy after intracerebral haemorrhage (ICH) in the UK. We included 496 (92%) of 537 RESTART participants, who were resident in England or Scotland at randomisation. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. RESTART used annual questionnaires to detect its primary outcome (recurrent ICH) and secondary outcome (a composite of haemorrhagic or ischemic major adverse cardiovascular events [MACE]) over a median of 2.0 years; an independent adjudication committee verified outcomes using medical records and brain imaging. We obtained ICD10-coded HCSD on hospital admissions and deaths in England and Scotland to identify primary and secondary outcomes. We compared HCSD with a reference standard of adjudicated outcomes. We estimated the effects of antiplatelet therapy using HCSD alone in a Cox proportional hazards model adjusted for minimisation variables. Results In the original RESTART trial, 31 people experienced a primary outcome event. HCSD had sensitivity of 84% (95% CI 66 to 95%) and positive predictive value of 68% (51 to 82%) for recurrent ICH. HCSD estimated an effect of antiplatelet therapy (adjusted hazard ratio [aHR] 0.51, 95% CI 0.27 to 0.98; p = 0.044) that was almost identical to adjudicated outcomes (aHR 0.51, 95% CI 0.25 to 1.03; p = 0.060). HCSD had sensitivity of 84% (76 to 91%) and positive predictive value of 78% (69 to 85%) for MACE, on which HCSD estimated an effect of antiplatelet therapy (aHR 0.81, 95% CI 0.56 to 1.16; p = 0.247) that was similar to adjudicated outcomes (aHR 0.65, 95% CI 0.44 to 0.95; p = 0.025). Conclusions In a RCT of antiplatelet therapy for people with ICH, HCSD was reasonably accurate and provided similar estimates of treatment effect compared with adjudicated outcomes. Trial registration ISRCTN71907627 . Registered on 25 April 2013.

Abstract My Kidneys & Me (MK&M), a digital health intervention delivering specialist health and lifestyle education for people with CKD, was developed and its effects tested (SMILE-K trial, ISRCTN18314195, 18/12/2020). 420 adult patients with CKD stages 3–4 were recruited and randomised 2:1 to intervention (MK&M) (n = 280) or control (n = 140) groups. Outcomes, including Patient Activation Measure (PAM-13), were collected at baseline and 20 weeks. Complete case (CC) and per-protocol (PP) analyses were conducted. 210 (75%) participants used MK&M more than once. PAM-13 increased at 20 weeks compared to control (CC: +3.1 (95%CI: −0.2 to 6.4), P = 0.065; PP: +3.6 (95%CI: 0.2 to 7.0), P = 0.041). In those with low activation at baseline, significant between-group differences were observed (CC: +6.6 (95%CI: 1.3 to 11.9), P = 0.016; PP: +9.2 (95%CI: 4.0 to 14.6), P

Abstract Background Certain groups are commonly under-served by health research due to exclusionary models of research design/delivery. Working in partnership with under-served groups is key to improving inclusion. This project aimed to explore the use of a knowledge mobilisation approach to start building partnerships with under-served groups based on trust and mutual understanding. Methods This co-produced public involvement project employed a knowledge mobilisation approach. The project team involved public contributors from four community organisations and staff from two Universities. A series of ‘community conversations’ were co-produced. These involved open discussions with local people in community settings. The conversations provide an informal space to engage in a multi-directional dialogue about health research and incorporated approaches such as prompt questions, live illustrations, and themed boards. The findings were reviewed collectively. Dissemination/feedback activities and lessons learned for future engagement with community organisations and under-served groups were also co-produced. Results Over 100 people attended the community conversations. Attendees varied widely in their sociodemographic characteristics (e.g., socioeconomic status and ethnicity) and brought diverse lived experiences (e.g., experiences of homelessness and disability). A strong appetite for change and desire to mobilise public knowledge were evident. Attendees reported wide-ranging barriers to inclusion in health research and suggested ways to address them. Three inter-related take-home messages were identified: ensure relevance, appreciation, and trust; prioritise language and accessibility needs; and maximise flexibility in all research-related activities. Feedback about the community conversations and dissemination activities was largely positive, with all parties planning to continue the partnership building. The lessons learned provide practical suggestions for promoting inclusion in research and highlight the importance of addressing research teams’ training/support needs. Conclusions Knowledge mobilisation was a valuable approach for facilitating multi-directional dialogues and relationship building between local communities and university teams. This approach enabled co-creation of new knowledge related to inclusion and partnership working in health research. The project has provided a firm foundation to build upon. However, creating sustainable, inclusive public partnerships is likely to require systemic changes, such as weighting of fundings schemes to projects that prioritise inclusion of under-served groups throughout the research cycle.

Objective The objective of this study was to assess 52‐week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/−MTX) treatment at baseline. Methods We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease‐modifying antirheumatic drug [bDMARD]‐naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi‐IR]), and the BE VITAL open‐label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo‐randomized patients received bimekizumab. Missing data were imputed using non‐responder imputation, multiple imputation, or worst‐category imputation. Results Through Week 52, similar proportions of bimekizumab‐treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and −MTX (BE OPTIMAL: 54.4% +MTX, 54.7% −MTX; BE COMPLETE: 56.3% +MTX, 48.0% −MTX). Similar proportions of bimekizumab‐treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and −MTX groups. Similar trends were seen in placebo/bimekizumab‐treated patients. Through Week 52, the proportion of bimekizumab‐treated patients with ≥1 treatment‐emergent adverse event were similar between the +MTX and −MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab. Conclusion Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD‐naïve and TNFi‐IR patients with PsA and was well tolerated, irrespective of concomitant MTX.

In the aftermath of World War II, Western nations witnessed unprecedented growth in university enrollments, particularly in business schools, driven by the expansion of the publicly funded higher education system. This growth has prompted higher education providers to re-evaluate the critical role of student satisfaction in shaping learning, engagement, and overall institutional success. While the impact of student satisfaction on engagement and academic outcomes is well documented, its influence on broader university enrollments remains underexplored. Using longitudinal data from the Australian Government-funded Quality Indicators for Learning and Teaching (QILT) surveys and universities’ annual reports (2012-2017), we find that universities with higher student satisfaction show significantly higher enrollment rates. Moreover, the positive impact of student satisfaction on enrollment is more pronounced in metropolitan universities. Beyond contributing to social justice theory, this study provides actionable insights for government and higher education management to improve equitable access to higher education and reduce social disparities through strategically allocating resources, capabilities, and support services.

Proteomics has been little used for the identification of novel prognostic and/or therapeutic markers in isocitrate dehydrogenase (IDH)‐wildtype glioblastoma (GB). In this study, we analyzed 50 tumor and 30 serum samples from short‐ and long‐term survivors of IDH‐wildtype GB (STS and LTS, respectively) by data‐independent acquisition mass spectrometry (DIA‐MS)‐based proteomics, with the aim of identifying such markers. DIA‐MS identified 5422 and 826 normalized proteins in tumor and serum samples, respectively, with only three tumor proteins and 26 serum proteins displaying significant differential expression between the STS and LTS groups. These dysregulated proteins were principally associated with the detoxification of reactive oxygen species (ROS). In particular, GB patients in the STS group had high serum levels of malate dehydrogenase 1 (MDH1) and ribonuclease inhibitor 1 (RNH1) and low tumor levels of fatty acid‐binding protein 7 (FABP7), which may have enabled them to maintain low ROS levels, counteracting the effects of the first‐line treatment with radiotherapy plus concomitant and adjuvant temozolomide. A blood score built on the levels of MDH1 and RNH1 expression was found to be an independent prognostic factor for survival based on the serum proteome data for a cohort of 96 IDH‐wildtype GB patients. This study highlights the utility of circulating MDH1 and RNH1 biomarkers for determining the prognosis of patients with IDH‐wildtype GB. Furthermore, the pathways driven by these biomarkers, and the tumor FABP7 pathway, may constitute promising therapeutic targets for blocking ROS detoxification to overcome resistance to chemoradiotherapy in potential GB STS.

Abstract Lack of significant and durable clinical benefit from anti-cancer immunotherapies is partly due to the failure of cytotoxic immune cells to infiltrate the tumor microenvironment. Immune infiltration is predominantly dependent on the chemokine network, which is regulated in part by chemokine and atypical chemokine receptors. We investigated the impact of hypoxia in the regulation of Atypical Chemokine Receptor 2 (ACKR2), which subsequently regulates major pro-inflammatory chemokines reported to drive cytotoxic immune cells into the tumor microenvironment. Our in silico analysis showed that both murine and human ACKR2 promoters contain hypoxia response element (HRE) motifs. Murine and human colorectal, melanoma, and breast cancer cells overexpressed ACKR2 under hypoxic conditions in a HIF-1α dependent manner; as such overexpression was abrogated in melanoma cells expressing non-functional deleted HIF-1α. We also showed that decreased expression of ACKR2 in HIF-1α-deleted cells under hypoxia was associated with increased CCL5 levels. Chromatin immunoprecipitation data confirmed that ACKR2 is directly regulated by HIF-1α at its promoter in B16-F10 melanoma cells. This study provides new key elements on how hypoxia can impair immune infiltration in the tumor microenvironment.

Abstract The land sector is anticipated to play an important role in achieving U.S. GHG emissions targets by reducing emissions and increasing sequestration from the atmosphere. This study assesses how much different levels of investment could stimulate land-based mitigation activities in the U.S. By applying a dynamic economic model of the land use sectors, with representation of 26 forestry and agricultural mitigation strategies across 11 U.S. regions, the study shows that annual investments of $2.4 billion could deliver abatement of around 80 MtCO2e annually. Under an optimal allocation of investments, the forestry sector and the Corn Belt are projected to receive the largest share of funds. Restricting land-based activities eligible for funds significantly reduces overall potential mitigation. For instance, if $24 billion investments are allocated only to agricultural activities, mitigation declines by 48% to 54 MtCO2e/yr over the next ten years. Finally, the level of abatement from each policy depends on the timing of implementation as the lowest cost mitigation actions are generally taken by the policy implemented first.

Abstract Background Immune dysregulation is a hallmark of autoimmune diseases of the central nervous system (CNS), characterized by an excessive immune response, and primary CNS tumors (pCNS-tumors) showing a highly immunosuppressive parenchymal microenvironment. Methods Aiming to provide novel insights into the pathogenesis of CNS autoimmunity and cerebral tumor immunity, we analyzed the peripheral blood (PB) and cerebrospinal fluid (CSF) of 81 autoimmune limbic encephalitis (ALE), 148 relapsing–remitting multiple sclerosis (RRMS), 33 IDH-wildtype glioma, 9 primary diffuse large B cell lymphoma of the CNS (CNS-DLBCL), and 110 controls by flow cytometry (FC). Additionally, an in-depth immunophenotyping of the PB from an independent cohort of 20 RRMS and 18 IDH-wildtype glioblastoma patients compared to 19 controls was performed by FC combined with unsupervised computational approaches. Results We identified alterations in peripheral and intrathecal adaptive immunity, mainly affecting the T cell (Tc) but also the B cell (Bc) compartment in ALE, RRMS, and pCNS-tumors compared to controls. ALE, RRMS, and pCNS-tumors featured higher expression of the T cell activation marker HLA-DR, which was even more pronounced in pCNS-tumors than in ALE or RRMS. Glioblastoma patients showed signs of T cell exhaustion that were not visible in RRMS patients. In-depth characterization of the PB revealed differences mainly in the T effector and memory compartment between RRMS and glioblastoma patients and similar alterations in the Bc compartment, including atypical Bc, CD19+CD20− double negative Bc, and plasma cells. PB and CSF mFC together with CSF routine parameters could reliably differentiate ALE and RRMS from pCNS-tumors facilitating early diagnosis and treatment. Conclusions ALE, RRMS, and pCNS-tumors show distinct but partially overlapping changes mainly in HLA-DR+ Tc, memory Tc, exhausted Tc, and Bc subsets providing insights into disease pathogenesis. Moreover, mFC shows diagnostic potential facilitating early diagnosis and treatment. Graphical Abstract

Granulosa cell tumor (GCT) is the most common nonepithelial ovarian malignancy. Still, it is considered rare, with a paucity of high-level evidence guiding management, particularly in the metastatic setting. Advancements in molecular pathology allowed the identification of several targetable mutations that play an important role in GCT pathogenesis. Although current management approaches rely on guidelines extrapolated from the more common epithelial subtype, the unique histopathologic and molecular characteristics of GCTs entail a more focused approach. Systemic therapy remains the cornerstone treatment for advanced disease, and although chemotherapy has been the standard for decades, targeted treatments have gained considerable attention lately. Due to the rarity of this disease, validation of new therapies in large trials is the rate-limiting step for developing evidence-based recommendations. This review sheds light on pathogenesis, clinical and molecular characteristics, and prognostic factors, and discusses current treatment options including the role of novel therapies and immune checkpoint inhibitors in advanced GCT.

This study aimed to assess the attitude, and Practice of female sex workers towards Pre-exposure Prophylaxis for HIV prevention in the Kicukiro district, Rwanda. The study used a descriptive cross-sectional design, using a probability sampling method, and the Yamane formula was used to calculate the sample size of 300 female sex workers including a 10% non-response rate. Primary data was collected using a structured questionnaire, at 10 health centers. Analysis was conducted using IBM SPSS software, with chi-square tests and logistic regression for inferential analysis. The ethical clearance was acquired from the Mount Kenya University ethics committee and the Young Women Christian Association Rwanda. The study findings showed that (60%) of female sex workers have a positive attitude towards PrEP, and 60.4% of respondents were using PrEP. Demographic factors like age group, marital status, and Ubudehe category were significantly associated with practices. Female sex workers aged between 25 and 29 had 4 times more chance to have good practices. This study provides insights into improving PrEP education and interventions targeting female sex workers and other key populations. These findings highlighted the concerns about stigma and privacy, and the need for public health interventions that target it in the community.

Abstract Background Quantification of pulmonary edema in patients with acute respiratory distress syndrome (ARDS) by chest computed tomography (CT) scan has not been validated in routine diagnostics due to its complexity and time-consuming nature. Therefore, the single-indicator transpulmonary thermodilution (TPTD) technique to measure extravascular lung water (EVLW) has been used in the clinical setting. Advances in artificial intelligence (AI) have now enabled CT images of inhomogeneous lungs to be segmented automatically by an intensive care physician with no prior radiology training within a relatively short time. Nevertheless, there is a paucity of data validating the quantification of pulmonary edema using automated lung segmentation on CT compared with TPTD. Methods A retrospective study (January 2016 to December 2021) analyzed patients with ARDS, admitted to the intensive care unit of the Department of Anesthesiology and Critical Care Medicine, University Hospital Mannheim, who underwent a chest CT scan and hemodynamic monitoring using TPTD at the same time. Pulmonary edema was estimated using manually and automated lung segmentation on CT and then compared to the pulmonary edema calculated from EVLW determined using TPTD. Results 145 comparative measurements of pulmonary edema with TPTD and CT were included in the study. Estimating pulmonary edema using either automated lung segmentation on CT or TPTD showed a low bias overall (− 104 ml) but wide levels of agreement (upper: 936 ml, lower: − 1144 ml). In 13% of the analyzed CT scans, the agreement between the segmentation of the AI algorithm and a dedicated investigator was poor. Manual segmentation and automated segmentation adjusted for contrast agent did not improve the agreement levels. Conclusions Automated lung segmentation on CT can be considered an unbiased but imprecise measurement of pulmonary edema in mechanically ventilated patients with ARDS.

Abstract Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomic resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomic resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, anti-predator strategies, and resilience and adaptive responses. They also serve as essential models for studying broad genomic traits, such as evolutionary genome expansions and contractions, as they exhibit the widest range of genome sizes among all animal taxa and possess multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The emergence of long-read sequencing technologies, combined with advanced molecular and computational techniques that improve scaffolding and reduce computational workloads, is now making it possible to address some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC, https://mvs.unimelb.edu.au/amphibian-genomics-consortium ) in early 2023. This burgeoning community already has more than 282 members from 41 countries. The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and call on the research and conservation communities to unite as part of the AGC to enable amphibian genomics research to “leap” to the next level.

Abstract Cognitive impairment (CI) is common in α-synucleinopathies, i.e., Parkinson’s disease, Lewy bodies dementia, and multiple system atrophy. We summarize data from systematic reviews/meta-analyses on neuroimaging, neurophysiology, biofluid and genetic diagnostic/prognostic biomarkers of CI in α-synucleinopathies. Diagnostic biomarkers include atrophy/functional neuroimaging brain changes, abnormal cortical amyloid and tau deposition, and cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers, cortical rhythm slowing, reduced cortical cholinergic and glutamatergic and increased cortical GABAergic activity, delayed P300 latency, increased plasma homocysteine and cystatin C and decreased vitamin B12 and folate, increased CSF/serum albumin quotient, and serum neurofilament light chain. Prognostic biomarkers include brain regional atrophy, cortical rhythm slowing, CSF amyloid biomarkers, Val66Met polymorphism, and apolipoprotein-E ε2 and ε4 alleles. Some AD/amyloid/tau biomarkers may diagnose/predict CI in α-synucleinopathies, but single, validated diagnostic/prognostic biomarkers lack. Future studies should include large consortia, biobanks, multi-omics approach, artificial intelligence, and machine learning to better reflect the complexity of CI in α-synucleinopathies.

Abstract Eimeria tenella is among the protozoan parasites that cause the infectious disease coccidiosis in chickens, incurring huge economic losses to the global poultry industry. Surface antigens (EtSAGs) involved in host-parasite interaction are potential targets for control strategies. However, the occurrence of genetic diversity for EtSAGs in field populations is unknown, as is the risk of such diversity to the efficacy of EtSAG-based control approaches. Here, the extent of EtSAG genetic diversity and its implications on protein structure and function is assessed. Eighty-seven full-length EtSAG genomic sequences were identified from E. tenella genome assemblies of isolates sampled from continents including North America (United States), Europe (United Kingdom), Asia (Malaysia and Japan) and Africa (Nigeria). Limited diversity was observed in the EtSAG sequences. However, distinctive patterns of polymorphism were identified between EtSAG subfamilies, suggesting functional differences among these antigen families. Polymorphisms were sparsely distributed across isolates, with a small number of variants exclusive to specific geographical regions. These findings enhance our understanding of EtSAGs, particularly in elucidating functional differences among the antigens that could inform the development of more effective and long-lasting anticoccidial control strategies.

Abstract Whether DNA methylation changes follow human physical trauma is uncertain. We aimed to investigate if severe trauma was associated with DNA methylation changes. In a prospective, observational, clinical study, we included severely injured adults and adults undergoing elective surgery (controls). Blood was obtained from trauma patients (n = 60) immediately- and 30-45 days post-trauma, and from surgical patients (n = 57) pre-, post-, and 30-45 days post-surgery. Epigenome-wide DNA methylation profiling was performed and analyzed for significant differentially methylated CpGs and -regions (DMRs) within and between groups. Within the trauma group we identified 10,126 significant differentially methylated CpGs and 1169 DMRs. No significant differential methylation was found in the surgical group. In the trauma group, differentially methylated sites were enriched in genes and pathways involved in blood coagulation and inflammatory response. Severe trauma was associated with profound alterations in the DNA methylome of circulating leucocytes, and differential methylation was located in trauma-relevant genes.

Norovirus is a leading cause of acute gastroenteritis and imposes a substantial disease burden. In California, USA, norovirus surveillance is limited. We evaluated correlations between wastewater norovirus concentrations and available public health surveillance data. Wastewater surveillance for norovirus genotype GII in California provided timely, localized, and actionable data for public health authorities.

Bacterial cellulose is a versatile material with applications in many industries. However, the widespread uptake of bacterial cellulose faces challenges including high production costs and lack of scalability. One approach to address these obstacles is the use of alternative substrates and media, compared to the Hestrin–Schramm (HS) media. By evaluating and selecting appropriate media and substrates, the production of bacterial cellulose can be more efficient: enabling sustainable systems and supply chains where less energy and materials are lost, and the output production is increased. The purpose of this paper is to analyze the current landscape of bacterial cellulose alternative media and substrates (ingredients). Through a systematic review of 198 papers, this review identifies 299 alternative substrates from 12 industries and 101 bacterial cellulose-producing strains, which were systematically compared. This review also finds that there are methodological gaps in this field such as data variability, papers mislabelling the HS media or not using a comparison media, and a lack of strain names. This alternative substrate analysis for bacterial cellulose production demonstrates that overall, for some applications alternative substrates can be taken into consideration that are not only cheaper, but also produce higher yields than HS media.

Aim Injudicious usage of antibiotics has led to the emergence of antibiotic resistance which is a major health-care problem in developing countries such as India. Our aim was to show how antibiotic therapy based on serial procalcitonin (PCT) assay can help in antibiotic de-escalation in septic patients. Materials and Methods A pre–post interventional study was conducted among 300 septic patients admitted to an intensive care unit (ICU). All septic patients admitted 2 months before and 2 months after the introduction of monitoring of PCT were included and they were divided into Group P (with PCT monitoring) and Group C (without PCT monitoring). The proportion of patients for whom antimicrobials were de-escalated, the average time taken to de-escalate antimicrobials, and the average duration of ICU stay were compared. Proportions and averages with standard deviations were calculated to describe the data. A test of proportions was done to compare the proportion de-escalated and a Student’s t-test was done to compare the average duration of antibiotic therapy. Results The proportion of patients in whom de-escalation of antimicrobials was done was 125 (83.33%) in Group P as compared to 92 (61.33%) in Group C. The time taken to de-escalate was 3.04 ± 0.83 days (95% confidence interval [CI] 2.89–3.18) in Group P compared to 4.7 ± 1.4 days (CI 4.41–4.98) in Group C. The duration of ICU stay was also less in Group P - 3.08 ± 0.91 days (CI 3.08–3.38) as compared to Group C - 5.16 ± 2.17 days (4.80–5.51). Conclusion Serial PCT assay-based antimicrobial therapy helped to wean patients with sepsis off antimicrobials earlier thus reducing the duration of ICU stay.

Abstract Perceptual expertise is typically domain-specific and rarely generalises beyond an expert’s domain of experience. Forensic feature-comparison examiners outperform the norm in domain-specific visual comparison, but emerging research suggests that they show advantages on other similar tasks outside their domain of expertise. For example, fingerprint examiners not only outperform novices in fingerprint comparison, but also in face comparison. Yet, the extent to which their skills generalise is poorly understood. In this study, we investigated the generalisability of perceptual expertise amongst forensic examiners by comparing their performance to novices and other examiners within and outside their area of expertise. We recruited 85 experts from three forensic disciplines (face, fingerprint, and firearms) and asked them to complete four different visual comparison tasks: faces, fingerprints, firearms, and novel-objects. Examiners displayed domain-specific expertise: they outperformed novices and other examiners within their domain of visual comparison expertise. Yet, some of their skill also generalised: examiners also outperformed novices outside their area of expertise. However, while individual differences in examiners’ performance within their domain of experience were associated with their performance in a novel comparison task, they were not related to their performance on tasks outside their expert domain. These results provide key insight into the domain-specific and domain-general contributions of forensic examiners’ perceptual expertise. Forensic expertise lends some generalisable skill to other visual comparison tasks, but best performance is still seen within examiners’ domain of expertise.

Abstract Background Aging is a complex process that involves all tissues in an organism and shows sex dimorphism. While transcriptional changes in aging have been well characterized, the majority of studies have focused on a single sex and sex differences in gene expression in aging are poorly understood. In this study, we explore sex dimorphism in gene expression in aging mice across three tissues. Methods We collected gastrocnemius muscle, liver and white adipose tissue from young (6 months, n = 14) and old (24 months, n = 14) female and male C57BL/6NIA mice and performed RNA-seq. To investigate sex dimorphism in aging, we considered two levels of comparisons: (a) differentially expressed genes between females and males in the old age group and (b) comparisons between females and males across the aging process. We utilized differential expression analysis and gene feature selection to investigate candidate genes. Gene set enrichment analysis was performed to identify candidate molecular pathways. Furthermore, we performed a co-expression network analysis and chose the gene module(s) associated with aging independent of sex or tissue-type. Results We identified both tissue-specific and tissue-independent genes associated with sex dimorphism in aged mice. Unique differentially expressed genes between old males and females across tissues were mainly enriched for pathways related to specific tissue function. We found similar results when exploring sex differences in the aging process, with the exception that in the liver genes enriched for lipid metabolism and digestive system were identified in both females and males. Combining enriched pathways across analyses, we identified amino acid metabolism, digestive system, and lipid metabolism as the core mechanisms of sex dimorphism in aging. Although the vast majority of age-related genes were sex and tissue specific, we identified 127 hub genes contributing to aging independent of sex and tissue that were enriched for the immune system and signal transduction. Conclusions There are clear sex differences in gene expression in aging across liver, muscle and white adipose. Core pathways, including amino acid metabolism, digestive system and lipid metabolism, contribute to sex differences in aging.

Abstract The aim of this study was to quantify the number of non-airborne bacteria that can passively penetrate the layers of four mask types (surgical mask, community face mask type 1 (CFM1), biocidal CFM1 and CFM2) and to determine the influence of wearing conditions for the surgical type. A mask wearer simulator consisting of a 3D anatomical replica of the upper airway connected to a breathing pump was used. Wearing time, filtration quality of the mask, fit (loose vs. tight) and breathing parameters (tidal volume, respiratory rate) were tested. A Staphylococcus epidermidis inoculum was applied to the inner layer. After the wearing simulation, the layers were separated and the bacteria counted. After four hours, no or only a few bacteria were present in the middle and outer layers. Most remained in the inner layer. Surgical mask and CFM1 retained more bacteria and provided a breeding ground for germs. The biocidal CFM1 rapidly reduced the number in the inner layer. The breathing parameters had no influence, in contrast to fit and wearing time. These results confirm that the standard test for bacterial filtration efficiency, which includes the active penetration of airborne bacteria into aerosol droplets, is the most objective measure of the ability of bacteria to penetrate through the mask layers, as the passive penetration ability of non-airborne bacteria is insignificant.

Abstract Background Evaluation approaches such as ripple effects mapping (REM) and realist evaluation have emerged as popular methodologies to evidence impact, and the processes of change within public health as part of whole systems approaches. Despite the various examples of their implementation across different evaluation settings, there has been little or no evidence of how they might be effective when combined. Methods With REM’s potential to pragmatically illustrate impact, and realist evaluation’s strength to identify how and why impacts emerge, this paper develops a rationale and process for their amalgamation. Following this, we outline a realist-informed ripple effects mapping (RREM) protocol drawing upon a physical activity based case study in Essex that may be suitable for application within evaluation settings in a range of public health, whole system and physical activity settings. Discussion Combining these two approaches has the potential to more effectively illuminate the impacts that we see within public health and whole system approaches and initiatives. What is more, given the complexity often imbued within these approaches and initiatives, they hold capability for also capturing the causal mechanisms that explain these impacts. Conclusions It is our conclusion that when combined, this novel approach may help to inspire future research as well as more effective evaluation of public health and whole system approaches. This is crucial if we are to foster a culture for learning, refinement and reflection.

The emergence of plant pathogens is often associated with waves of unique evolutionary and epidemiological events. Xanthomonas hortorum pv. gardneri is one of the major pathogens causing bacterial spot disease of tomatoes. After its first report in the 1950s, there were no formal reports on this pathogen until the 1990s, despite active global research on the pathogens that cause tomato and pepper bacterial spot disease. Given the recently documented global distribution of X. hortorum pv. gardneri, our objective was to examine genomic diversification associated with its emergence. We sequenced the genomes of X. hortorum pv. gardneri strains collected in eight countries to examine global population structure and pathways of emergence using phylodynamic analysis. We found that strains isolated post-1990 group by region of collection and show minimal impact of recombination on genetic variation. A period of rapid geographic expansion in X. hortorum pv. gardneri is associated with acquisition of a large plasmid conferring copper tolerance by horizontal transfer and coincides with the burgeoning hybrid tomato seed industry through the 1980s. The ancestry of X. hortorum pv. gardneri is consistent with introduction to hybrid tomato seed production and dissemination during the rapid increase in trade of hybrid seeds. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Climate disruption today represents a threat to the environment and sustainable development. Climate-Smart Agriculture (CSA) is an appropriate adaptation approach to climate change. It allows producers to improve their production and act on their food security, despite the conditions of climate change while limiting the causes arising from agriculture. The objective of this study is to evaluate the impact of CSA, through the use of harvest residues in cassava fields, on the income and food security of cassava producing households in Savalou. The three-stage sampling method made it possible to draw a random sample of 360 cassava producers including 180 users of pigeon pea, mucuna and peanut harvest residues. The average income from cassava production during the last 12 months (until July 2023) is 366,400 FCFA with 387,340 FCFA for beneficiaries compared to 322,060 FCFA for non-beneficiaries. The impact analysis was done with the matching method based on propensity scores. The results of this impact study showed that this adoption contributes to improving income from cassava production by 35,135 FCFA and household food security by 0.10 points, on average per household per year. It would therefore be useful to promote and improve this type of agriculture, in order to ensure sustainable development of the agricultural sector and improve food security.

Abstract Hawking’s black hole area theorem provides a geometric realization of the second law of thermodynamics and constrains gravitational processes. In this work we explore a one-parameter extension of this constraint formulated in terms of the monotonicity properties of Rényi entropies. We focus on black hole mergers in asymptotically AdS space and determine new restrictions which these Rényi second laws impose on the final state. We evaluate the entropic inequalities starting from the thermodynamic ensembles description of black hole geometries, and find that for many situations they set more stringent bounds than those imposed by the area increase theorem.

Abstract Background Chronic obstructive pulmonary disease (COPD) represents an important health challenge, despite being preventable and manageable thanks to up-to-date recommendations. In Italy, the pharmaceutical care of COPD patients is still ill-timed and inaccurate. This study aimed to describe the treatment of COPD patients in Italy and possible switches following an exacerbation. Methods This observational retrospective analysis of Italian administrative healthcare data from the Fondazione Ricerca e Salute (ReS) database identified patients aged ≥ 45 years with COPD in 2019 and 2020. At least 6 years of look-back period and absence of concomitant asthma were required. COPD patients were categorized by treatment (SI–single/MI–multiple inhalers, TT–triple therapy, DT–dual therapy, other respiratory treatments, untreated) at index date (first dispensation during accrual period). Occurrence of moderate/severe exacerbation during one-year preceding index date and treatments during one-year preceding the exacerbation (possible switch) were evaluated. Results From ~ 4.7 million beneficiaries of the Italian National Health Service in 2019 and 2020, respectively, 105,828 and 103,729 (43 and 41 × 1,000 inhabitants aged ≥ 45 years) were identified as having COPD. Of 2019/2020 patients: 3.4%/5.2% received SI-TT, 20.7%/17.5% MI-TT, 35.9%/38.1% DT, 33.0%/33.1% other treatments, and 7.0%/6.0% were untreated. Males were prevalent and median age was > 73 years for all groups. Of 2019/2020 cohorts, heart failure and coronary artery disease affected 24/20%, 18/17%, and 11%/16% patients with SI-TT, MI-TT, DT, and other treatments, respectively. A previous moderate/severe exacerbation (2019/2020 patients) occurred to 60.5%/56.6%, 39.9%/37.4%, 30.8%/29.2% and 31.9%/29.7% patients treated with SI-TT, MI-TT, DT, and other treatments, respectively. Of 2019/2020 patients experiencing moderate/severe exacerbation: 6.0%/7.0% receiving DT, 5.1%/7.0% receiving other treatments and 4.5%/10.0% untreated, switched to SI-TT; 23.7%/16.9% receiving DT, 21.4%/17.7% receiving other treatments and 15.4%/12.0% untreated, switched to MI-TT. Conclusions COPD patients receiving TT were older and had more comorbidities, especially cardiovascular diseases, than patients receiving DT or other treatments. The limited number of patients switching after exacerbation suggests that many COPD patients may be inappropriately treated. Ensuring early and adequate treatment, combination of in-hospital and outpatient management, and integration of specialist and primary care is pivotal for the appropriate clinical management of COPD patients.

Abstract As images of international mobility circulate quickly and widely through digital and social media, they form a fundamental part of the discursive formations around border policies and material migration practices. Through a multi-modal visual analysis of the Twitter images accompanying the post of the four major migration institutions in the EU and Canada, this article explores in a comparative perspective how their visual narratives interact with the broader migration narrative across the two contexts. The study findings show that EUAA, FRONTEX, CBSA, and IRCC participate in the border spectacle as leading actors, and their visual communication while allows them to reinforce some of their respective migration governance key messages and display their multiple organizational identities at the same time enables the concealment of some of the critical themes of the EU and Canada migration governance.

Abstract Contrary to expert readers, children learning to read have limited ability to preprocess letters in parafoveal vision. Parafoveal letters induce crowding cost: the features of neighboring letters interfere with target letter identification. We longitudinally studied the weight of parafoveal cost and benefit in two group of children (N = 42), during their first school year (Group 1) and at the end of second school year (Groupe 2). Using a novel digit-tracking method, a blurred text was presented and rendered unblurred by touching the screen, allowing the user to discover a window of visible text as the finger moved along it. We compared two conditions: (1) a large window, where crowding was enhanced by the presence of parafoveal information; (2) a small window, where crowding was suppressed by blurred parafoveal information. Finger kinematics were simultaneously recorded. We found that at the beginning of first-grade, digital fixations - brief slowing or stopping of the finger on a specific point - are significantly longer in the large compared to the small window condition, as parafoveal crowding increases text processing difficulty. This effect diminishes and disappears at the end of second-grade as reading performance improves. In the large window condition, longer digital saccades - rapid movements of the finger changing position - appear by the end of first grade suggesting that parafoveal exposure become more beneficial than harmful when children acquire basic reading skills. Our results show that in beginning readers, crowding has a cognitive cost that interfere with the speed of the learning reading process. Our findings are relevant to the field of education by showing that visual crowding in first grade should not be underestimated.

Abstract Pollination is a key ecosystem service crucial for supporting agricultural production, economic growth, social inclusion, and environmental protection. Understanding the economic value of pollination and its impact on human health and nutrition is essential for effective pollinator conservation and management. This study evaluates the economic and nutritional value of pollination services in Nepal and quantifies historic changes in pollinator reliance. Using public data on agricultural production and commodity prices, in combination with published nutritional composition values, we employ the dependency-ratio method to quantify economic and nutritional value across different regions of the country and through time. We conservatively estimate the annual economic value of pollination services in Nepal at US $477 million, representing 9% of total agricultural revenue. Pollinator-dependent crops, particularly fruits and vegetables are the source of essential nutrients; 40% of plant-based vitamin A and 14% of vitamin C are directly attributable to insect pollination. The cultivated area of these pollinator-dependent crops has increased by 91% in Nepal over 20 years – 3.7 times faster than equivalent increases in non-pollinator-dependent crops. The decline in wild pollinators during the same time period poses a threat, leading to potential pollination deficits and crop losses. Our study underscores the importance of conserving and managing pollinators to ensure sustainable agriculture, food security, and nutrition. Targeted efforts, including policy interventions and conservation strategies, are needed to safeguard pollinator populations and enhance pollination services.

Abstract Good data quality is vital for personalising plans in rehabilitation. Machine learning (ML) improves prognostics but integrating it with Multiple Imputation (MImp) for dealing missingness is an unexplored field. This work aims to provide post-stroke ambulation prognosis, integrating MImp with ML, and identify the prognostic influential factors. Stroke survivors in intensive rehabilitation were enrolled. Data on demographics, events, clinical, physiotherapy, and psycho-social assessment were collected. An independent ambulation at discharge, using the Functional Ambulation Category scale, was the outcome. After handling missingness using MImp, ML models were optimised, cross-validated, and tested. Interpretability techniques analysed predictor contributions. Pre-MImp, the dataset included 54.1% women, 79.2% ischaemic patients, median age 80.0 (interquartile range: 15.0). Post-MImp, 368 non-ambulatory patients on 10 imputed datasets were used for training, 80 for testing. The random forest (the validation best-performing algorithm) obtained 75.5% aggregated balanced accuracy on the test set. The main predictors included modified Barthel index, Fugl-Meyer assessment/motricity index, short physical performance battery, age, Charlson comorbidity index/cumulative illness rating scale, and trunk control test. This is among the first studies applying ML, together with MImp, to predict ambulation recovery in post-stroke rehabilitation. This pipeline reliably exploits the potential of incomplete datasets for healthcare prognosis, identifying relevant predictors.

Abstract In track cycling, performance in the team pursuit depends on the mechanical and physiological abilities of each member of the team, but also on the choice of racing strategy. Athletes must cover the 4000 m of the race, sharing the effort between them in successive relays. This raises the question of the optimum strategy. We propose a method for resolving this question by coupling a mechanical model of the race to physiological models (digital twins) of the athletes. The mechanical model enables one to predict a theoretical finishing time for a given strategy, while the physiological model enables one to determine whether or not a given strategy is feasible. By coupling the two models and using numerical optimization, an optimal strategy for a given team can then be predicted. Simplified team composition case studies are explored. For each case studied, an optimal strategy to maximize performance is obtained and composed of a set of three variables: relay lengths, power values for each relay, and the starting order of cyclists. The proposed method can be used for real athletes and extended to other disciplines.

Abstract Genetically encoded fluorescent biosensors became indispensable tools for biological research, enabling real-time observation of physiological processes in live cells. Recent protein engineering efforts have resulted in the generation of a large variety of fluorescent biosensors for a wide range of biologically relevant processes, from small ions to enzymatic activity and signaling pathways. However, biosensors for imaging sulfate ions, the fourth most abundant physiological anion, in mammalian cells are still lacking. Here, we report the development and characterization of a green fluorescent biosensor for sulfate named Thyone. Thyone, derived through structure-guided design from bright green fluorescent protein mNeonGreen, exhibited a large negative fluorescence response upon subsecond association with sulfate anion with an affinity of 11 mM in mammalian cells. By integrating mutagenesis analyses with molecular dynamics simulations, we elucidated the molecular mechanism of sulfate binding and revealed key amino acid residues responsible for sulfate sensitivity. High anion selectivity and sensitivity of Thyone allowed for imaging of sulfate anion transients mediated by sulfate transporter heterologously expressed in cultured mammalian cells. We believe that Thyone will find a broad application for assaying the sulfate transport in mammalian cells via anion transporters and exchangers.

Abstract Background Many countries have introduced school food standards to improve the dietary intakes of school-aged children. England has school food standards (SFS) legislation in place but little is known about how well secondary schools comply with this. We aimed to assess compliance with the SFS legislation in English secondary schools and explore the impact of the SFS on pupils’ nutritional intake. Methods We conducted a cross-sectional study with English secondary schools from 2019 to 2022. We compared SFS compliance and pupil nutritional intake in schools mandated or not mandated to comply with the SFS legislation, and explored the association between school compliance and pupil nutritional intake. We assessed the percentage of SFS (%SFS) complied with by reviewing school food menus and observing food served in school canteens. We assessed pupil nutritional intake using a 24-hour dietary recall measure (Intake24) and estimated intakes of free sugar (primary outcome) and other nutrients/foods. We used adjusted multilevel models to compare pupil intakes in the SFS-mandated and SFS-non-mandated schools, and to explore the association between school SFS compliance and pupil intakes. Results 36 schools (23 not mandated and 13 mandated to comply with the SFS) and 2,273 pupils participated. The median %SFS complied with was 63.9% (interquartile range 60.0–70.0%). This was similar for SFS-non-mandated (64.5%) and SFS-mandated schools (63.3%). Compliance was highest for standards applying to lunchtime (median = 81.3%) and lowest for those applying across the whole school day (median = 41.7%). It was also lower for standards restricting high fat, sugar and energy-dense items (median = 26.1%) than for standards aiming to increase dietary variety (median = 92.3%). Pupils from SFS-mandated schools had a lower mean lunchtime intake of free sugar (g) (adjusted mean difference: -2.78g; 95% CI: -4.66g to -0.90g). There were few significant associations between %SFS complied with and pupil nutritional intake. Conclusions English secondary schools do not fully comply with SFS legislation regardless of whether they are mandated to comply. Schools and caterers may require monitoring and support to fully comply. There is little evidence that SFS compliance is associated with better pupil nutritional intake. Food environments outside of school also need to be considered. Study registration ISRCTN68757496 (17-10-2019).