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Abstract Background Fire blight, caused by Erwinia amylovora, is the most destructive bacterial disease affecting plants in the Rosaceae family, leading to significant economic losses. In Algeria, this disease has been reported since 2010. This study aimed to investigate the origin of fire blight in Algeria, in order to increase knowledge of the epidemiology of this serious disease and contribute to its management. A comprehensive characterization of 18 E. amylovora isolates recovered from northern Algeria between 2016 and 2021 to evaluate their phenotypical and genotypical diversity was conducted. Results Phenotypic differences, particularly in growth kinetics, virulence, and fatty acid profiles, allowed differentiation of strains into five groups, possibly indicating distinct introduction events. Genetic characterization revealed that only one strain lacked the ubiquitous plasmid pEA29, which is correlated with reduced virulence, while none harbored the pEI70 plasmid. Phylogenetic analysis using concatenated sequences of the recA, groEL, rpoS, ams, and hrpN genes grouped Algerian strains with those from a broadly prevalent clade. CRISPR genotyping identified a novel CR1 pattern and three genotypes, two of them previously unreported. Conclusions This study represents the first phenotypic, genetic, and phylogenetic investigation of E. amylovora strains in the region, and provides valuable information on the possible pathways of the introduction of this fire blight pathogen in northern Africa. The findings suggest one or more introduction events from a common ancestor, likely originating in northern Italy, followed by dispersal in various regions of Algeria.

Abstract The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. Here we compare PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrate different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we perform CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We find that 20.6% of brain cells have at least one Mb-scale CNV, with some supported by bulk sequencing or single-cells from other brain regions. Our study highlights the importance of selecting whole genome amplification method and reference genome for CNV calling, while supporting the existence of somatic CNVs in healthy and diseased human brain.

Proponemos en este artículo una aproximación al cómic como pedagogía pública crítica en la representación racial y narrativas antirracistas. El análisis explora cómo se conforman diversos procesos de racialización y otredad en autoras españolas a partir de la pedagogía crítica pública, la teoría crítica racial y los estudios del cómic sobre raza. Se ofrecen tres aproximaciones con tres tipos de cómics diferentes: La construcción de la otredad en cómics con fines humanitarios, el humor como pedagogía crítica y la autobiografía como exploración de procesos racializantes. Lo que busca este artículo es contribuir a un debate mucho más establecido fuera de nuestras fronteras sobre inclusión, diversidad y representación en el cómic, que resulta igualmente necesario en el ámbito nacional. In this paper, I study racial representation and antiracist narratives on comics as critical public pedagogy. I analyze how Spanish artists depict a set of racializing and “othering” processes through the lense of critical public pedagogy, Critical Race Theory and comics studies on race. I provide three approaches on three different sets of comics: the construction of the “other” in comics funded by humanitarian organizations, humor as critical public pedagoy and autobiography as an exploration of racializing processes. The aim of this article is to contribute to discussions about inclusion, diversity and representation in comics that are already well-established and expanding outside Spain but hardly developed in the national context.

Abstract Background Antiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania. Results We followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count

Abstract Gaucher Disease (GD) is an autosomal recessive, lysosomal storage disease caused by pathogenic variants in the glucocerebrosidase gene, leading to the loss of β-glucocerebrosidase (GCase) enzymatic activity. Enzyme replacement therapy (ERT) with recombinant GCase is the standard of care in GD patients. Our study investigates the combined use of in silico molecular evolution, synthetic biology and gene therapy approaches to develop a new synthetic recombinant enzyme. We engineered four GCases containing missense mutations in the signal peptide (SP) from four selected mammalian species, and compared them with human GCase without missense mutations in the SP. We investigated transcriptional regulation with CMV and hEF1a promoters alongside a GFP control construct in 293-FT human cells. One hEF1a-driven mutant GCase shows a 5.2-fold higher level of transcription than control GCase. In addition, this mutant exhibits up to a sixfold higher activity compared with the mock-control, and the predicted tertiary structure of this mutant GCase aligns with human GCase. We also evaluated conserved and coevolved residues mapped to functionally important positions. Further studies are needed to assess its functionality in a GD animal model. Altogether, our findings provide in vitro evidence of the potential of this engineered enzyme for improved therapeutic effects for GD. Article highlights. Conservation and coevolution analysis of amino acid frequencies in GBA1 homologs of pathogenic variants associated with Gaucher disease, Parkinson’ disease risk or Dementia with Lewy bodies risk. Graphic Abstract

Abstract Microgravity (µG) experienced during space flights promotes adaptation in several astronauts’ organs and tissues, with skeletal muscles being the most affected. In response to reduced gravitational loading, muscles (especially, lower limb and antigravity muscles) undergo progressive mass loss and alteration in metabolism, myofiber size, and composition. Skeletal muscle precursor cells (MPCs), also known as satellite cells, are responsible for the growth and maintenance of muscle mass in adult life as well as for muscle regeneration following damage and may have a major role in µG-induced muscle wasting. Despite the great relevance for astronaut health, very few data are available about the effects of real µG on human muscles. Based on the MyoGravity project, this study aimed to analyze: (i) the cellular and transcriptional alterations induced by real µG in human MPCs (huMPCs) and (ii) the response of human skeletal muscle to normal gravitational loading after prolonged exposure to µG. We evaluated the transcriptomic changes induced by µG on board the International Space Station (ISS) in differentiating huMPCs isolated from Vastus lateralis muscle biopsies of a pre-flight astronaut and an age- and sex-matched volunteer, in comparison with the same cells cultured on the ground in standard gravity (1×g) conditions. We found that huMPCs differentiated under real µG conditions showed: (i) upregulation of genes related to cell adhesion, plasma membrane components, and ion transport; (ii) strong downregulation of genes related to the muscle contraction machinery and sarcomere organization; and (iii) downregulation of muscle-specific microRNAs (myomiRs). Moreover, we had the unique opportunity to analyze huMPCs and skeletal muscle tissue of the same astronaut before and 30 h after a long-duration space flight on board the ISS. Prolonged exposure to real µG strongly affected the biology and functionality of the astronaut’s satellite cells, which showed a dramatic reduction of responsiveness to activating stimuli and proliferation rate, morphological changes, and almost inability to fuse into myotubes. RNA-Seq analysis of post- vs. pre-flight muscle tissue showed that genes involved in muscle structure and remodeling are promptly activated after landing following a long-duration space mission. Conversely, genes involved in the myelination process or synapse and neuromuscular junction organization appeared downregulated. Although we have investigated only one astronaut, these results point to a prompt readaptation of the skeletal muscle mechanical components to the normal gravitational loading, but the inability to rapidly recover the physiological muscle myelination/innervation pattern after landing from a long-duration space flight. Together with the persistent functional deficit observed in the astronaut’s satellite cells after prolonged exposure to real µG, these results lead us to hypothesize that a condition of inefficient regeneration is likely to occur in the muscles of post-flight astronauts following damage.

Abstract Background Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in school-aged children. Macrolides are the first-line treatment for this infection. However, it is unclear whether macrolides are effective in treating M. pneumoniae CAP, mainly due to limitations in microbiological diagnosis of previous studies. The extensive global use of macrolides has led to increasing antimicrobial resistance. The overall objective of this trial is to produce efficacy data for macrolide treatment in children with M. pneumoniae CAP. Methods The MYTHIC Study is a randomized, double-blind, placebo-controlled, multicenter, non-inferiority trial in 13 Swiss pediatric centers. Previously healthy ambulatory and hospitalized children aged 3–17 years with clinically diagnosed CAP will be screened with a sensitive and commercially available M. pneumoniae-specific IgM lateral flow assay from capillary blood. Mycoplasma pneumoniae infection in screened patients will be verified retrospectively by respiratory PCR (reference test) and IgM antibody-secreting cell enzyme-linked immunospot (ELISpot) assay (confirmatory test for distinguishing between carriage and infection). Patients will be randomized 1:1 to receive a 5-day treatment of macrolides (azithromycin) or placebo. The co-primary endpoints are (1) time to normalization of all vital signs, including body temperature, respiratory rate, heart rate, and saturation of peripheral oxygen (efficacy), and (2) CAP-related change in patient care status (i.e., admission, re-admission, or intensive care unit transfer) within 28 days (safety). Secondary outcomes include adverse events (AEs), as well as antimicrobial and anti-inflammatory effects. For both co-primary endpoints, we aim to show non-inferiority of placebo compared to macrolide treatment. We expect no macrolide effect (hazard ratio of 1, absolute risk difference of 0) and set the corresponding non-inferiority margins to 0.7 and −7.5%. The “at least one” success criterion is used to handle multiplicity with the two co-primary endpoints. With a power of 80% to reject at least one null hypothesis at a one-sided significance level of 1.25%, 376 patients will be required. Discussion This trial will produce efficacy data for macrolide treatment in children with M. pneumoniae CAP that might help to reduce the prescription of antibiotics and therefore contribute to the global efforts toward reducing antimicrobial resistance. Trial registration ClinicalTrials.gov, NCT06325293. Registered on 24 April 2024

The diverse physiography of the Portuguese land and marine territory, spanning from continental Europe to the Atlantic archipelagos, has made it an important repository of biodiversity throughout the Pleistocene glacial cycles, leading to a remarkable diversity of species and ecosystems. This rich biodiversity is under threat from anthropogenic drivers, such as climate change, invasive species, land use changes, overexploitation, or pathogen (re)emergence. The inventory, characterisation, and study of biodiversity at inter- and intra-specific levels using genomics is crucial to promote its preservation and recovery by informing biodiversity conservation policies, management measures, and research. The participation of researchers from Portuguese institutions in the European Reference Genome Atlas (ERGA) initiative and its pilot effort to generate reference genomes for European biodiversity has reinforced the establishment of Biogenome Portugal. This nascent institutional network will connect the national community of researchers in genomics. Here, we describe the Portuguese contribution to ERGA’s pilot effort, which will generate high-quality reference genomes of six species from Portugal that are endemic, iconic, and/or endangered and include plants, insects, and vertebrates (fish, birds, and mammals) from mainland Portugal or the Azores islands. In addition, we outline the objectives of Biogenome Portugal, which aims to (i) promote scientific collaboration, (ii) contribute to advanced training, (iii) stimulate the participation of institutions and researchers based in Portugal in international biodiversity genomics initiatives, and (iv) contribute to the transfer of knowledge to stakeholders and engaging the public to preserve biodiversity. This initiative will strengthen biodiversity genomics research in Portugal and fuel the genomic inventory of Portuguese eukaryotic species. Such efforts will be critical to the conservation of the country’s rich biodiversity and will contribute to ERGA’s goal of generating reference genomes for European species.

Abstract Iron overload and cellular senescence have been implicated in liver fibrosis, but their possible mechanistic connection has not been explored. To address this, we have delved into the role of iron and senescence in an experimental model of chronic liver injury, analyzing whether an iron chelator would prevent liver fibrosis by decreasing hepatocyte senescence. The model of carbon tetrachloride (CCl4) in mice was used as an experimental model of liver fibrosis. Results demonstrated that during the progression of liver fibrosis, accumulation of iron occurs, concomitant with the appearance of fibrotic areas and cells undergoing senescence. Isolated parenchymal hepatocytes from CCl4-treated mice present a gene transcriptomic signature compatible with iron accumulation and senescence, which correlates with induction of Reactive Oxygen Species (ROS)-related genes, activation of the Transforming Growth Factor-beta (TGF-β) pathway and inhibition of oxidative metabolism. Analysis of the iron-related gene signature in a published single-cell RNA-seq dataset from CCl4-treated livers showed iron accumulation correlating with senescence in other non-parenchymal liver cells. Treatment with deferiprone, an iron chelator, attenuated iron accumulation, fibrosis and senescence, concomitant with relevant changes in the senescent-associated secretome (SASP), which switched toward a more anti-inflammatory profile of cytokines. In vitro experiments in human hepatocyte HH4 cells demonstrated that iron accumulates in response to a senescence-inducing reagent, doxorubicin, being deferiprone able to prevent senescence and SASP, attenuating growth arrest and cell death. However, deferiprone did not significantly affect senescence induced by two different agents (doxorubicin and deoxycholic acid) or activation markers in human hepatic stellate LX-2 cells. Transcriptomic data from patients with different etiologies demonstrated the relevance of iron accumulation in the progression of liver chronic damage and fibrosis, correlating with a SASP-related gene signature and pivotal hallmarks of fibrotic changes. Altogether, our study establishes iron accumulation as a clinically exploitable driver to attenuate pathological senescence in hepatocytes.

Abstract Aligned with global goals for healthy and sustainable cities, urban compactness significantly promotes residents’ transport-related physical activity and health. In Japan, amid demographic changes, municipalities have begun formulating Location Normalization Plans focused on making cities more compact. This study examines the associations between health and transport-related physical activity considerations in urban plans, including Location Normalization Plans, the demographic characteristics of municipalities, and the development of infrastructure that supports leisure-time physical activity. Analyzing responses from 725 of 1,374 Japanese municipalities, our research reveals that 38% of urban plans integrated health and physical activity in goals/visions, and 28% recognized these as challenges. The development of physical activity infrastructure such as sports facilities (48%), metropolitan parks (21%), and bicycle paths (14%) was more prevalent in larger municipalities. However, the incorporation of health and physical activity in planning goals/visions or challenges was not exclusive to larger municipalities; smaller ones also demonstrated this capability. Logistic regression analyses revealed that municipalities that included health considerations in their plans’ goals/visions and challenges were more likely to develop or renovate physical activity infrastructure. Prioritizing health and physical activity in planning has the potential to support leisure-time and transport-related physical activity, helping to create healthy and sustainable cities.

Chemical desiccation is widely used in agriculture to anticipate harvest and mitigate the effects of adverse environmental conditions. It is applied to both grains and seeds. Although this practice is widely used, there are still significant gaps in understanding the effects of different herbicide application times on seed quality and plant physiological responses. The objective of this study was to evaluate the effects of different herbicide application times on cowpea, focusing on seed quality, physiological responses, and biochemical composition, including chlorophylls, carotenoids, sugars, and proline, under nocturnal desiccation. In the first experiment, eight herbicides and two mixtures were applied at night: diquat, flumioxazin, diquat + flumioxazin, glufosinate ammonium, saflufenacil, carfentrazone, diquat + carfentrazone, atrazine, and glyphosate. All of the tested herbicides caused a reduction in normal seedling formation, with the diquat + carfentrazone combination resulting in 100% abnormal seedlings. A significant decrease in chlorophyll levels (chlorophyll a: 63.5%, chlorophyll b: 50.2%) was observed using diquat, which indicates damage to photosynthetic processes, while the carotenoid content increased. Total soluble sugars and proline were also negatively impacted, reflecting physiological stress and metabolic changes in seedlings. In the second experiment, three application times were tested with diquat, diquat + flumioxazin, and diquat + carfentrazone. Nocturnal application showed the most significant reduction in chlorophyll levels and increased carotenoid levels. Application at noon and late afternoon also significantly changed the soluble sugar and proline levels. These results indicate that the herbicide application time directly influences the seeds’ physiological quality.

Abstract The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson’s disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The presence of ecto-GPR37 peptides in the cerebrospinal fluid (CSF) of PD, MSA, CBD and PSP patients was assessed through an in-house nanoluciferase-based immunoassay. This study identified increased receptor processing in early-stage LBD within the PFC and striatum, key brain areas in neurodegeneration. In MSA only the 52 kDa form of GPR37 appeared in the striatum. This form was also significantly elevated in the striatum of AD necropsies. On the contrary, GPR37 processing remained unchanged in the brains of CBD and PSP patients. Furthermore, while CSF ecto-GPR37 increased in PD patients, its levels remained unchanged in MSA, CBD, and PSP subjects. Importantly, patients with PD with rapid progression of the disease did not have elevated ecto-GPR37 in the CSF, while those with slow progression showed a significant increase, suggesting a possible prognostic use of ecto-GPR37 in PD. This research underscores the distinctive processing and density patterns of GPR37 in neurodegenerative diseases, providing crucial insights into its potential role as an indicator of PD progression rates.

Abstract SARS-CoV-2 caused the pandemic situation experienced since the beginning of 2020, and many countries faced the rapid spread and severe form of the disease. Mechanisms of interaction between the virus and the host were observed during acute phase, but few data are available when related to immunity dynamics in convalescents. We conducted a longitudinal study, with 51 healthy donors and 62 COVID-19 convalescent patients, which these had a 2-month follow-up after symptoms recovery. Venous blood sample was obtained from all participants to measure blood count, subpopulations of monocytes, lymphocytes, natural killer cells and dendritic cells. Serum was used to measure cytokines, chemokines, growth factors, anti-N IgG and anti-S IgG/IgM antibodies. Statistic was performed by Kruskal–Wallis test, and linear regression with days post symptoms and antibody titers. All analysis had confidence interval of 95%. Less than 35% of convalescents were anti-S IgM+, while more than 80% were IgG+ in D30. Anti-N IgG decreased along time, with loss of seroreactivity of 13%. Eosinophil count played a distinct role on both antibodies during all study, and the convalescence was orchestrated by higher neutrophil-to-lymphocyte ratio and IL-15, but initial stages were marked by increase in myeloid DCs, B1 lymphocytes, inflammatory and patrolling monocytes, G-CSF and IL-2. Later convalescence seemed to change to cytotoxicity mediated by T lymphocytes, plasmacytoid DCs, VEGF, IL-9 and CXCL10. Anti-S IgG antibodies showed the longest perseverance and may be a better option for diagnosis. The inflammatory pattern is yet present on initial stage of convalescence, but quickly shifts to a reparative dynamic. Meanwhile eosinophils seem to play a role on anti-N levels in convalescence, although may not be the major causative agent. We must highlight the importance of immunological markers on acute clinical outcomes, but their comprehension to potentialize adaptive system must be explored to improve immunizations and further preventive policies.

Abstract This novel study applies targeted functional proteomics to examine tissues and cells obtained from a cohort of individuals with severe obesity who underwent bariatric surgery (BS), using a Reverse-Phase Protein Array (RPPA). In obese individuals, visceral adipose tissue (VAT), but not subcutaneous adipose tissue (SAT), shows activation of DNA damage response (DDR) markers including ATM, ATR, histone H2AX, KAP1, Chk1, and Chk2, alongside senescence markers p16 and p21. Additionally, stress-responsive metabolic markers, such as survivin, mTOR, and PFKFB3, are specifically elevated in VAT, suggesting both cellular stress and metabolic dysregulation. Conversely, peripheral blood mononuclear cells (PBMCs), while exhibiting elevated mTOR and JNK levels, did not present significant changes in DDR or senescence markers. Following BS, unexpected increases in phosphorylated ATM, ATR, and KAP1 levels, but not in Chk1 and Chk2 nor in senescence markers, were observed. This was accompanied by heightened levels of survivin and mTOR, along with improvement in markers of mitochondrial quality and health. This suggests that, following BS, pro-survival pathways involved in cellular adaptation to various stressors and metabolic alterations are activated in circulating PBMCs. Moreover, our findings demonstrate that the DDR has a dual nature. In the case of VAT from individuals with obesity, chronic DDR proves to be harmful, as it is associated with senescence and chronic inflammation. Conversely, after BS, the activation of DDR proteins in PBMCs is associated with a beneficial survival response. This response is characterized by metabolic redesign and improved mitochondrial biogenesis and functionality. This study reveals physiological changes associated with obesity and BS that may aid theragnostic approaches.

The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of EGFR mutations or ALK gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations. The aim of the current work is to review the available evidence on the use of targeted treatments in the non-metastatic setting, together with a summary of the ongoing trials designed for actionable gene alterations other than EGFR and ALK. To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB–IIIA (TNM 7th edition). The use of osimertinib after chemo-radiation in stage III unresectable EGFR-mutated NSCLC showed the relevant PFS improvement. In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)–IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease.

Purpose: To compare Hill-RBF 3.0 with Barrett Universal II (BU II), SRK/T, Hoffer Q, Haigis, and Holladay 1 in predicting the accuracy of post-cataract surgery refractive outcomes in Indian eyes. Methods: In this prospective, comparative, observational study, consecutive patients with uncomplicated age-related cataracts undergoing uneventful phacoemulsification with posterior chamber intraocular lens (IOL) implantation were included. The mean absolute errors (MAEs) and median absolute errors were used to determine the accuracy of predicted postoperative target refractions. Results: A total of 219 eyes of 173 patients were enrolled. Based on the axial lengths (AL), the patients were classified into: AL 24.5 mm (long). BU II exhibited the lowest MAE for normal ALs (0.2683 ± 0.2790 D) as well as for the entire population (0.2764 ± 0.2764 D). For the short ALs, Hill RBF 3.0 exhibited the lowest MAE (0.3268 ± 0.3268 D), while for the long ALs, SRK/T showed the lowest MAE (0.2823 ± 0.2642 D). BU II exhibited the highest percentage of eyes of 57.5%, 95.4%, and 98.6% within ±0.25, ±0.75, and ±1.0 D of postoperative target refractions respectively, whereas Hill RBF 3.0 had the highest percentages of eyes (88.1%) within ±0.5 D of postoperative target refraction. Conclusion: Hill-RBF 3.0 exhibited the least MAE for patients with short ALs, while BU II showed the least MAE for normal ALs as well as for the entire population and SRK/T for long ALs. This study is likely to aid surgeons in selecting the most appropriate IOL power formula, which thereby improves the refractive outcomes with utmost accuracy.

Anchovy is one of potential commodities widely found and caught by fishermen in FMA-572 West Sumatra. Examining its exploitation rate is a part of taking control and monitor toward the fishing activities to avoid overfishing possibility. This recent study aims to calculate exploitation rate and oceanographic characteristics of anchovy fishing grounds. The data was collected from Bungus Oceanic Fishing Port, West Sumatra in 2018-2022. Meanwhile, sea surface temperature and chlorophyll data were obtained from https://marine.copernicus.eu/ and https://oceancolor.gsfc.nasa.gov 2018-2022, respectively. The results showed that the exploitation rate of anchovies in 2020 and 2022 has exceeded maximum sustainable yield categorized as overexploitation with a percentage of 130.44% and 112.84%. Anchovy catches are significantly influenced by oceanographic factors with F value 0.00000115 (α 0.05). An increase in CPUE value is align with chlorophyll increase and in contrary to sea surface temperature. The findings are expected to give an overview related to anchovy fishing activities implementation and become an input for fisheries governance that lead to sustainable fisheries management. Keywords: FMA-572 MSY Overfishing Sustainable fisheries Stolephorus sp

Abstract In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients.

Abstract The red-legged partridge Alectoris rufa plays a crucial role in the ecosystem of southwestern Europe, and understanding its genetics is vital for conservation and management. Here we sequence, assemble, and annotate a highly contiguous and nearly complete version of its genome. This assembly encompasses 96.9% of the avian genes flagged as essential in the BUSCO aves_odb10 dataset. Moreover, we pinpointed RNA and protein-coding genes, 95% of which had functional annotations. Notably, we observed significant chromosome rearrangements in comparison to quail (Coturnix japonica) and chicken (Gallus gallus). In addition, a comparative phylogenetic analysis of these genomes suggests that A. rufa and C. japonica diverged roughly 20 million years ago and that their common ancestor diverged from G. gallus 35 million years ago. Our assembly represents a significant advancement towards a complete reference genome for A. rufa, facilitating comparative avian genomics, and providing a valuable resource for future research and conservation efforts for the red-legged partridge.

Abstract Untargeted metabolomic analysis is a powerful tool used for the discovery of novel biomarkers. Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease that affects 6–7 million people with approximately 30% developing cardiac manifestations. The most significant clinical challenge lies in its long latency period after acute infection, and the lack of surrogate markers to predict disease progression or cure. In this cross-sectional study, we analyzed sera from 120 individuals divided into four groups: 31 indeterminate CD, 41 chronic chagasic cardiomyopathy (CCC), 18 Latin Americans with other cardiomyopathies and 30 healthy volunteers. Using a high-throughput panel of 986 metabolites, we identified three distinct profiles among individuals with cardiomyopathy, indeterminate CD and healthy volunteers. After a more stringent analysis, we identified some potential biomarkers. Among peptides, phenylacetylglutamine and fibrinopeptide B (1–13) exhibited an increasing trend from controls to ICD and CCC. Conversely, reduced levels of bilirubin and biliverdin alongside elevated urobilin correlated with disease progression. Finally, elevated levels of cystathionine, phenol glucuronide and vanillactate among amino acids distinguished CCC individuals from ICD and controls. Our novel exploratory study using metabolomics identified potential biomarker candidates, either alone or in combination that if confirmed, can be translated into clinical practice.

Abstract Background Animal bacterial symbionts are established early in life, either through vertical transmission and/or by horizontal transmission from both the physical and the social environment, such as direct contact with con- or heterospecifics. The social environment particularly can influence the acquisition of both mutualistic and pathogenic bacteria, with consequences for the stability of symbiotic communities. However, segregating the effects of the shared physical environment from those of the social interactions is challenging, limiting our current knowledge on the role of the social environment in structuring bacterial communities in wild animals. Here, we take advantage of the avian brood-parasite system of Eurasian magpies (Pica pica) and great spotted cuckoos (Clamator glandarius) to explore how the interspecific social environment (magpie nestlings developing with or without heterospecifics) affects bacterial communities on uropygial gland skin. Results We demonstrated interspecific differences in bacterial community compositions in members of the two species when growing up in monospecific nests. However, the bacterial community of magpies in heterospecific nests was richer, more diverse, and more similar to their cuckoo nest-mates than when growing up in monospecific nests. These patterns were alike for the subset of microbes that could be considered core, but when looking at the subset of potentially pathogenic bacterial genera, cuckoo presence reduced the relative abundance of potentially pathogenic bacterial genera on magpies. Conclusions Our findings highlight the role of social interactions in shaping the assembly of the avian skin bacterial communities during the nestling period, as exemplified in a brood parasite—host system.

Abstract Background Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated. Methods Cytokine concentrations were measured using the xMAP technology. Their ability to discriminate between responding (Rs) and non-responding (NRs) patients was assessed by Receiver Operating Characteristics analysis. PFS and OS were estimated with the Kaplan–Meier method. The Cox proportional hazard model was used in the univariate and multivariate analyses to estimate crude and adjusted hazard ratios with 95% confidence intervals. Results CCL4 and LIF were undetectable in the majority of samples. The median osteopontin concentration at T0 and T2 was significantly higher in NRs than in Rs. The median T0 and T2 values of IL-8 were also higher in NRs than in Rs, although the statistical significance was not reached. No differences were detected for BDNF. In 39 Rs with matched T0, T2, and TP samples, osteopontin and IL-8 significantly decreased from T0 to T2 and rose again at TP, while BDNF levels remained unchanged. In NRs, none of the cytokines showed a significant decrease at T2. Only osteopontin demonstrated a good ability to discriminate between Rs and NRs. A high IL-8 T0 level was associated with significantly shorter PFS and OS and higher risk of progression and mortality, and remained an independent negative prognostic factor for OS in multivariate analysis. An elevated osteopontin T0 concentration was also significantly associated with worse OS and increased risk of death. Patients with high IL-8 and high osteopontin showed the lowest PFS and OS, and in multivariate analysis this cytokine combination remained independently associated with a three- to six-fold increased risk of mortality. Conclusion Circulating IL-8 and osteopontin appear useful biomarkers to refine prognosis evaluation of patients undergoing targeted therapy, and deserve attention as potential targets to improve its clinical efficacy.

Abstract Background Coaching on Lifestyle (CooL) is a two-year healthcare intervention for people with overweight or obesity, stimulating weight reduction by promoting sustained healthier behavior. The objective of this study is to investigate the effects of CooL on participants’ anthropometrics, personal factors and behavioral factors over the two-year timeframe of CooL. Methods A descriptive case series study, using a broad set of routinely collected data on anthropometrics, personal factors and behavioral factors of adults living across the Netherlands. The data were collected between November 2018 and December 2021 among participants of CooL (N = 746) at three moments during the intervention: at baseline (T0), at 8 months (T1) after completion of phase 1 and at 24 months (T2) after ending CooL. Changes over time were analyzed using paired t-tests comparing baseline to T1 and baseline to T2. In addition, potential differences on outcomes in subgroups based on education level, weight status and group size were examined using paired t-tests and ANOVA-tests. Results The results showed positive changes on all outcomes at 24 months compared to baseline. The largest effects were on perceived health, attentiveness towards meal size and meal composition (large effect size). Mean weight loss was 4.13 kg (SD 7.54), and mean waist circumference decreased with 4.37 centimeters (SD 8.59), indicating a medium to large effect size. Changes were consistent across subgroups varying in educational level, BMI at baseline and group size. Conclusion The study demonstrated sustained weight-related effects of CooL over 24 months supporting its two-year duration. The results indicate that CooL, though not for every individual, is in general appropriate and effective for different group sizes and for a wide variety of participants regardless of level of education, or BMI at baseline. Trial registration Dutch Trial Register NTRNL6061 (13-01-2017). Registered at Overview of Medical Research in the Netherlands (OMON), via https://www.onderzoekmetmensen.nl/ .

Following a few considerations on the role of catalogues as primary sources for the history of book trade in the early modern period, the article focuses on the series of indices librorum published by Aldus Manutius and his heirs over a century (1497-1597). The article will then present a selection of issues and topics that will be developed in the course of some wider research, devoted to exploring the use of catalogues as advertising ploys by the Aldine press.

Abstract The anticipated increase in urban population of 2.5 billion people by 2050 poses significant environmental challenges. While the various environmental impacts of urbanisation have been studied individually, integrated approaches are rare. This study introduces a spatially explicit model to assess urbanization’s effects on ecosystem services (green infrastructure availability, cooling, stormwater retention) and the environmental impact of building construction (material demand, greenhouse gas emissions, land use). Applied to the Netherlands from 2018 to 2050, our results show that integrating green infrastructure development with building construction could increase green areas by up to 5% and stabilize or increase ecosystem service provisioning. Dense building construction with green infrastructure development is generally more beneficial across the Netherlands, reducing resource use and enhancing ecosystem services. Conversely, sparse construction with green infrastructure is more advantageous for newly built areas. These findings offer insights into the environmental consequences of urbanization, guiding sustainable urban planning practices.

Cerebrovascular accidents, also known as strokes, are the leading cause of permanent disability in society, presenting significant socioeconomic and healthcare costs. They can be caused by ischemic factors or hemorrhages, with ischemic strokes being the most common among the population. Therapies for patients suffering from this condition are limited and primarily focus on acute-phase treatment. In recent years, there has been an increase in cellular therapies, employing Stem Cells to mitigate or eliminate the consequences arising from this disease. Mesenchymal Stem Cells (MSCs) hold substantial therapeutic potential in Nervous System pathologies due to their low antigenicity and capacity to differentiate into various human tissues, such as adipogenic, chondrogenic, and osteogenic tissues. This study conducts a literature review using the “clinical trials” and “Pubmed” database, summarizing all ongoing clinical trials for ischemic strokes that utilize MSCs as treatment.

This paper reviews the nutritional quality and safety of edible farmed insects from the point of view of the Czech-Slovenian bilateral project: Quality, Safety and Authenticity of Insect Protein-based Food and Feed (INPROFF). Insects as a sustainable source of dietary protein for animal feed and even humans, when integrated into the European agrifood system, could offer a solution to Europe’s feed protein deficit and help alleviate environmental pressure from increasing protein demand, such as declining availability of land, water, marine and energy resources, the overuse of pesticides and reduced biodiversity. However, despite a growing interest in the European Union (EU) in farming edible insects, many economic, scientific, technological, and social barriers remain. In response, Slovenia, represented by the Jožef Stefan Institute, the Biotechnical Faculty of the University of Ljubljana, and Jata Emona d.o.o. (the leading supplier of feedstuffs for the Slovenian market), a country with no history of insect rearing but an interest in alternative protein, joined with the Czech University of Life Sciences Prague, representing the Czech Republic—a country with a history of insect rearing and research into edible insects—to establish INPROFF a three-year bilateral project that aims to close the knowledge gap regarding the quality and safety of insect-based products and boost the farmed insect food and feed value chain. Specifically, it comprises three thematic pillars: (P1) nutritional enhancement, (P2) safety and quality and (P3) authenticity, traceability, and consumer acceptance. The paper also discusses the gaps in the metrological challenges of analysing insects, which will be critical for ensuring safety, quality, and sustainability. The paper finds that although much work has been done, many exciting avenues remain for new research.

Abstract Many cancer patients do not benefit from PD-L1/PD-1 blockade immunotherapies. PD-1 and LAG-3 co-upregulation in T-cells is one of the major mechanisms of resistance by establishing a highly dysfunctional state in T-cells. To identify shared features associated to PD-1/LAG-3 dysfunctionality in human cancers and T-cells, multiomic expression profiles were obtained for all TCGA cancers immune infiltrates. A PD-1/LAG-3 dysfunctional signature was found which regulated immune, metabolic, genetic, and epigenetic pathways, but especially a reinforced negative regulation of the TCR signalosome. These results were validated in T-cell lines with constitutively active PD-1, LAG-3 pathways and their combination. A differential analysis of the proteome of PD-1/LAG-3 T-cells showed a specific enrichment in ubiquitin ligases participating in E3 ubiquitination pathways. PD-1/LAG-3 co-blockade inhibited CBL-B expression, while the use of a bispecific drug in clinical development also repressed C-CBL expression, which reverted T-cell dysfunctionality in lung cancer patients resistant to PD-L1/PD-1 blockade. The combination of CBL-B-specific small molecule inhibitors with anti-PD-1/anti-LAG-3 immunotherapies demonstrated notable therapeutic efficacy in models of lung cancer refractory to immunotherapies, overcoming PD-1/LAG-3 mediated resistance.

Abstract Background The Mediterranean diet (MD), known to prevent obesity, overweight and the related non communicable diseases (NCD), is based on typical dishes, foods and on a common cultural milieu. Although MD is the basis of dietary guidelines, the prevalence of obesity, overweight and NCD, is increasing both in Western regions, and even more in Middle Eastern regions (MER). This study aimed to analyze (i) the impact of different levels of adherence to the MD, in Italy and MER, on body mass index (BMI) (ii) the bromatological composition of a simulated 7-days food plan (7-DFP) based on Italian or MER typical meals, following MD criteria and the Italian or MER food base dietary guideline; (iii) the optimization of nutrients impacting on NCD. Methods The 7-DFPs were implemented using a dietary software. The association between adherence to MD and BMI was evaluated by pooled estimated ORs (with 95% confidence intervals and p-values). Pooled measures were obtained by the methods appropriate for meta-analysis. The different food-based guidelines have been compared. Results The pooled ORs of obese status comparing medium vs. high adherence to MD were: 1.19 (95% C.I.: 0.99; 1.42, p-value = 0.062) and 1.12 (95% C.I.: 0.90; 1.38, p-value = 0.311) for MER and Italy respectively. For the comparison of low vs. high adherence, the pooled ORs were 1.05 (95% C.I.: 0.88; 1.24, p-value = 0.598) for MER, and 1.20 (95% C.I.: 1.02; 1.41, p-value = 0.031) for Italy when outliers are removed. High adherence to the MD resulted as potential protective factor against obesity. In MER 7-DFP: total fats is higher (34.5 E%) vs. Italian 7-DFP (29.4 E%); EPA (20 mg) and DHA (40 mg) are lower than recommended (200 mg each); sugars (12.6 E%) are higher than recommended (

Abstract Background Gut dysbiosis has been associated with colorectal cancer (CRC), the third most prevalent cancer in the world. This study compares microbiota taxonomic and abundance results obtained by 16S rRNA gene sequencing (16S) and whole shotgun metagenomic sequencing to investigate their reliability for bacteria profiling. The experimental design included 156 human stool samples from healthy controls, advanced (high-risk) colorectal lesion patients (HRL), and CRC cases, with each sample sequenced using both 16S and shotgun methods. We thoroughly compared both sequencing technologies at the species, genus, and family annotation levels, the abundance differences in these taxa, sparsity, alpha and beta diversities, ability to train prediction models, and the similarity of the microbial signature derived from these models. Results As expected, the results showed that 16S detects only part of the gut microbiota community revealed by shotgun, although some genera were only profiled by 16S. The 16S abundance data was sparser and exhibited lower alpha diversity. In lower taxonomic ranks, shotgun and 16S highly differed, partially due to a disagreement in reference databases. When considering only shared taxa, the abundance was positively correlated between the two strategies. We also found a moderate correlation between the shotgun and 16S alpha-diversity measures, as well as their PCoAs. Regarding the machine learning models, only some of the shotgun models showed some degree of predictive power in an independent test set, but we could not demonstrate a clear superiority of one technology over the other. Microbial signatures from both sequencing techniques revealed taxa previously associated with CRC development, e.g., Parvimonas micra. Conclusions Shotgun and 16S sequencing provide two different lenses to examine microbial communities. While we have demonstrated that they can unravel common patterns (including microbial signatures), shotgun often gives a more detailed snapshot than 16S, both in depth and breadth. Instead, 16S will tend to show only part of the picture, giving greater weight to dominant bacteria in a sample. Therefore, we recommend choosing one or another sequencing technique before launching a study. Specifically, shotgun sequencing is preferred for stool microbiome samples and in-depth analyses, while 16S is more suitable for tissue samples and studies with targeted aims.

Abstract Photoionization can initiate structural reorganization of molecular matter and drive formation of new chemical bonds. Here, we used time-resolved extreme ultraviolet (EUV) pump – EUV probe Coulomb explosion imaging of carbon dioxide dimer ion $${\left({{{\rm{C}}}}{{{{\rm{O}}}}}_{2}\right)}_{2}^{+}$$ C O 2 2 + dynamics, that combined with ab initio molecular dynamics simulations, revealed unexpected asymmetric structural rearrangement. We show that ionization by the pump pulse induces rearrangement from the slipped-parallel (C2h) geometry of the neutral $${{{\rm{C}}}}{{{{\rm{O}}}}}_{2}$$ C O 2 dimer towards a T-shaped (C2v) structure on the ~100 fs timescale, although the most stable slipped-parallel (C2h) structure of the ionic dimer. Moreover, we find that excited states of the ionized $${{{\rm{C}}}}{{{{\rm{O}}}}}_{2}$$ C O 2 dimer can exhibit formation of a $${{{{\rm{CO}}}}}_{3}$$ CO 3 moiety in the $${{{{\rm{C}}}}}_{2}{{{{\rm{O}}}}}_{4}^{+}\,$$ C 2 O 4 + complex that can persist even after a suitably time-delayed second photoionization in a metastable $${{{{\rm{C}}}}}_{2}{{{{\rm{O}}}}}_{4}^{2+}$$ C 2 O 4 2 + dication. Our results suggest that charge asymmetry plays an important role in the ionization-induced dynamics in such dimers that are present in $${{{\rm{C}}}}{{{{\rm{O}}}}}_{2}$$ C O 2 rich environments.

Abstract Background Variations in body weight (BW) remain a significant challenge within broiler flocks, despite uniform management practices. Chicken growth traits are influenced by gut microbiota, which are in turn shaped by early-life events like different hatching environments and timing of first feeding. Chicks hatched in hatcheries (HH) experience prolonged feed deprivation, which could adversely impact early microbiota colonization. Conversely, hatching on-farm (HOF) allows early feeding, potentially fostering a more favorable gut environment for beneficial microbial establishment. This study investigates whether BW differences among broilers are linked to the disparities in gut microbiota characteristics and whether hatching systems (HS) impact the initial microbial colonization of broilers differing in BW, which in turn affects their growth patterns. Male Ross-308 chicks, either hatched in a hatchery or on-farm, were categorized into low (LBW) and high (HBW) BW groups on day 7, making a two-factorial design (HS × BW). Production parameters were recorded periodically. On days 7, 14, and 38, cecal volatile fatty acid (VFA) and microbiota composition and function (using 16 S rRNA gene sequencing and PICRUSt2) were examined. Results HOF chicks had higher day 1 BW, but HH chicks caught up within first week, with no further HS-related performance differences. The HBW chicks remained heavier attributed to higher feed intake rather than improved feed efficiency. HBW group had higher acetate concentration on day 14, while LBW group exhibited higher isocaproate on day 7 and isobutyrate on days 14 and 38. Microbiota analyses revealed diversity and composition were primarily influenced by BW than by HS, with HS having minimal impact on BW-related microbiota. The HBW group on various growth stages was enriched in VFA-producing bacteria like unclassified Lachnospiraceae, Alistipes and Faecalibacterium, while the LBW group had higher abundances of Lactobacillus, Akkermansia and Escherichia-Shigella. HBW microbiota presented higher predicted functional potential compared to the LBW group, with early colonizers exhibiting greater metabolic activity than late colonizers. Conclusions Despite differences in hatching conditions, the effects of HS on broiler performance were transient, and barely impacting BW-related microbiota. BW variations among broilers are likely linked to differences in feed intake, VFA profiles, and distinct microbiota compositions and functions.

Abstract This work presents the development and design of aptasensor employing porous silicon (PSi) Fabry‒Pérot thin films that are suitable for use as optical transducers for the detection of lactoferrin (LF), which is a protein biomarker secreted at elevated levels during gastrointestinal (GI) inflammatory disorders such as inflammatory bowel disease and chronic pancreatitis. To overcome the primary limitation associated with PSi biosensors—namely, their relatively poor sensitivity due to issues related to complex mass transfer phenomena and reaction kinetics—we employed two strategic approaches: First, we sought to optimize the porous nanostructure with respect to factors including layer thickness, pore diameter, and capture probe density. Second, we leveraged convection properties by integrating the resulting biosensor into a 3D-printed microfluidic system that also had one of two different micromixer architectures (i.e., staggered herringbone micromixers or microimpellers) embedded. We demonstrated that tailoring the PSi aptasensor significantly improved its performance, achieving a limit of detection (LOD) of 50 nM—which is >1 order of magnitude lower than that achieved using previously-developed biosensors of this type. Moreover, integration into microfluidic systems that incorporated passive and active micromixers further enhanced the aptasensor’s sensitivity, achieving an additional reduction in the LOD by yet another order of magnitude. These advancements demonstrate the potential of combining PSi-based optical transducers with microfluidic technology to create sensitive label-free biosensing platforms for the detection of GI inflammatory biomarkers.

O movimento olímpico da modernidade e o processo de industrialização emergem praticamente no mesmo momento, quando o esporte é vislumbrado como um instrumento benéfico para manter o corpo produtivo e controlado. Nessa direção, as máquinas e as aspirações de ruptura com as representações culturais identificadas com o antigo fazem-se necessárias à conformação de outro imaginário social. O hipismo é uma das práticas esportivas que pode exemplificar a construção de descontinuidades e continuidades de representações na dinâmica entre o antigo e o moderno. O objetivo da pesquisa é investigar que representações culturais da modalidade do salto do hipismo foram estabelecidas por meio de fotografias veiculadas em reportagens sobre a participação brasileira nos Jogos Olímpicos entre os anos de 1948 e 1996. O recorte temporal da pesquisa situa-se entre o ano de 1948, quando, pela primeira vez, atletas brasileiros da modalidade Salto do Hipismo representaram o país em Jogos Olímpicos, e estende-se até o ano de 1996, o qual baliza a conquista da primeira medalha olímpica brasileira na referida modalidade hípica. De tal modo, atrelamos dois artefatos de modernidade e sua relação com o movimento olímpico, ao aplicarmos, como metodologia, a análise de imagens veiculadas pelas reportagens sobre as delegações brasileiras no cenário olímpico. Além disto, foram submetidos, à análise documental, jornais, revistas e demais periódicos que continham a temática disponível na Hemeroteca Digital (BNDigital) da Fundação Biblioteca Nacional. Ademais, foram acessadas imagens disponíveis em centros de memória do esporte, sites da Confederação Brasileira de Hipismo (CBH), de federações estaduais e da Federação Equestre Internacional (FEI). Diante da problemática da imagem como operador da memória esportiva e artefato de modernidade, a interpretação dos indícios está amparada no campo da Nova História Cultural, a fim de compreender como sucedeu o registro e quais as suas funções na composição de um artefato ou lugar de memória. Do mesmo modo, buscamos interpenetrar os registros que se conservam e aqueles que não permanecem, ao empenharmo-nos em cruzar aqueles que estão disponíveis nos centros de memória e nos sites oficiais com os demais encontrados na imprensa do período.

Resumen: Introducción: La enfermedad renal diabética (ERD) es la causa más común de enfermedad renal crónica (ERC) terminal, condicionando a estos pacientes a un peor pronóstico renal y mayor mortalidad cardiovascular y/o requerimiento de terapia renal sustitutiva. El uso de novedosas tecnologías de la información y la comunicación (TIC) enfocadas al ámbito de la salud puede facilitar una mejor calidad de vida y control de la enfermedad en estos pacientes. Nuestro objetivo es evaluar el efecto de monitorización de pacientes con ERD utilizando la aplicación NORA (NORA-app). Materiales y métodos: Estudio prospectivo de viabilidad/validación de la aplicación NORA-app en pacientes con ERD en estadio G3bA3 o superior, seguidos en consultas externas de un hospital de atención terciaria. NORA-app es una aplicación para teléfonos inteligentes diseñada para controlar los factores de riesgo, compartir información médica educativa, comunicarse vía chat con profesionales de la salud, aumentar el cumplimiento del tratamiento (Morisky-Green), así como evaluación de ansiedad y depresión utilizando la Escala Hospitalaria de Ansiedad y Depresión (HAD). Las variables clínico-analíticas se recogieron al inicio y a los tres meses, comparándose con los pacientes que desistieron del uso de NORA-app (grupo control). Resultados: Desde el 1 de enero de 2021 al 3 de marzo de 2022 se ofreció el uso de NORA-app a 118 pacientes, 82 aceptaron y 36 rechazaron (controles). Después de un periodo medio de seguimiento de 6,04 meses, 71 (86,6%) pacientes de NORA-app siguen siendo usuarios activos, dos han completado el seguimiento al año y nueve están inactivos (tres por fallecimiento y seis por no localizables). No hubo diferencias en las características basales, incluida la creatinina (2,1 [1,6-2,4] vs. 1,9 [1,5-2,5]) mg/dL y la alb/creat (962 [475-1.784] vs. 1.036 [560-2.183]) mg/g entre los pacientes NORA-app y grupo control, respectivamente. La tasa de cumplimiento terapéutico en el grupo NORA-app fue de 77%, mejorando a los 90 días a 91%. Los pacientes del grupo de NORA-app mostraron niveles significativamente más bajos de alb/creat que los controles (768 [411-1.971] mg/g vs. 2.039 [974-3.214]; p = 0,047) a los 90 días de seguimiento. Conclusiones: En pacientes con ERD que mantuvieron el uso de NORA-app a largo plazo, llevó a presentar altos niveles de cumplimiento del tratamiento, logrando un mejor control de la enfermedad. Nuestro estudio sugiere que el uso generalizado de las TIC puede ayudar en el seguimiento personalizado de estos pacientes para retrasar la progresión de la enfermedad renal. Abstract: Introduction: Diabetic kidney disease (DKD) is the most common cause of end-stage chronic kidney disease (CKD), conditioning these patients to a worse renal prognosis and higher cardiovascular mortality and/or requirement for renal replacement therapy. The use of novel information and communication technologies (ICTs) focused on the field of health, may facilitates a better quality of life and disease control in these patients. Our objective is to evaluate the effect of monitoring DKD patients using NORA-app. Material and methods: Prospective feasibility/validation study of NORA-app in patients with DKD stage G3bA3 or higher, followed in outpatient clinics of a tertiary care hospital. NORA-app is an application for smartphones designed to control risk factors, share educational medical information, communicate via chat with health professionals, increase treatment compliance (Morisky-Green), and collect patient reported outcomes such as anxiety and depression using HADs scale. Clinical-laboratory variables were collected at 3 months and compared to control patients who declined using NORA-app. Results: From 01/01/2021 to 03/03/2022 the use of NORA-app was offered to 118 patients, 82 accepted and 36 declined (controls). After a mean follow-up period of 6.04 months and at the time of data extraction 71 (86.6%) NORA-app patients remain active users, 2 have completed the follow-up at one year and 9 are inactive (3 due to death and 6 due to non-locatable). There were no differences in baseline characteristics including creatinine [2.1 (1.6–2.4) vs. 1.9 (1.5–2.5)] mg/dL and alb/creat [962 (475–1784) vs. 1036 (560–2183)] mg/g between Nora and control patients, respectively. The therapeutic compliance rate in the NORA-app group was 77%, improving at 90 days to 91%. Patients in the NORA-group showed significantly lower levels of alb/creat than controls (768 (411–1971) mg/g vs. 2039 (974–3214), p = 0.047) at 90-day follow-up. Conclusions: In patients with DKD the use of NORA-app was maintained in the long-term, leading to high levels of treatment compliance, and achieving a better disease control. Our study suggests that the generalized use of ICTs may help in the personalized monitoring of these patients to delay the progression of kidney disease.

Abstract: Introduction and aim: Pictograms can make taking medication safer. However, little is known about how pictograms on a medication package influence the subjective assessment of a medication. Methods: In this online study, 276 participants were presented with a fictitious package that contained 0 to 5 pictograms of possible side effects. Participants had to assess the probability of side effects occurring as well as the benefits and harms of the medication, both before and after consulting the package insert. Results: The number of pictograms (leveling out at 2 pictograms) influenced the assessment of the probability of side effects occurring. In addition, the assessment of this measure served as an anchor for assessing all subsequent measures (e.g., benefit). Although participants adjusted their measures after package insert consultation - these adjustments were insufficient (as expected from a normative probability account). Discussion and conclusion: Pictograms influence medication assessment, and humans can process only a limited number of pictograms.

The perception of well-being through tourism improves the quality of life of tourists, and for senior tourists, this relationship is even more promising. While the association between tourism and mental health is clear, the processes involved are not always clarified. Thus, this systematic literature review aims to explore and systematise the benefits of senior tourism for well-being, happiness, and satisfaction with life. Following the PRISMA method, the search was undertaken on platforms SCOPUS and Web of Science, using the research terms “senior tourism”, “elderly tourism”, “well-being”, and “life satisfaction”. Articles were included, if published after 2018, peer-reviewed, in English, concerning an overview of senior well-being and tourism. After applying the inclusion and exclusion criteria, the final sample comprised 16 articles. Senior tourists experience higher well-being, happiness, and satisfaction with life when their goals are of high valence, more likely to be achieved, coherent with the activities, and when they feel pleasure associated with achieving those goals. Still, senior tourists' happiness, life satisfaction and well-being are associated with four central elements: interpersonal relationships; time and resource management; achievement of goals and objectives; and management of the personal meaning attributed to the experience. Theoretical and empirical implications are further discussed.

Abstract Hyperspectral imaging (HSI) is a new emerging modality useful for the noncontact assessment of free flap perfusion. This measurement technique relies on the optical properties within the tissue. Since the optical properties of hemoglobin (Hb) and melanin overlap, the results of the perfusion assessment and other tissue-specific parameters are likely to be distorted by the melanin, especially at higher melanin concentrations. Many spectroscopic devices have been shown to struggle with a melanin related bias, which results in a clinical need to improve non-invasive perfusion assessment, especially for a more pigmented population. This study investigated the influence of skin tones on tissue indices measurements using HSI. In addition, other factors that might affect HSI, such as age, body mass index (BMI), sex or smoking habits, were also considered. Therefore, a prospective feasibility study was conducted, including 101 volunteers from whom tissue indices measurements were performed on 16 different body sites. Skin tone classification was performed using the Fitzpatrick skin type classification questionnaire, and the individual typology angle (ITA) acquired from the RGB images was calculated simultaneously with the measurements. Tissue indices provided by the used HSI-device were correlated to the possible influencing factors. The results show that a dark skin tone and, therefore, higher levels of pigmentation influence the HSI-derived tissue indices. In addition, possible physiological factors influencing the HSI-measurements were found. In conclusion, the HSI-based tissue indices can be used for perfusion assessment for people with lighter skin tone levels but show limitations in people with darker skin tones. Furthermore, it could be used for a more individual perfusion assessment if different physiological influencing factors are respected.

Reciprocal Peer Observation involves a pair of teachers with similar degrees of experience and status who mutually agree to observe each other’s practice. Both act as observer and observee. Individual reflection and mutual constructive feedback are provided, enabling the sharing of knowledge to identify goals for improving their teaching practice. In this study, 228 primary and secondary teachers followed a four-stage cycle of peer observation: pre-observation meeting; observation and brief report by observee; feedback meeting; and reflective writing by observee with a learning goal. Using different instruments (post-observation report, audio recording of the feedback meeting, final reflective synthesis; evaluation questionnaire and group interviews), the study has shown that most teachers identified the learning goal in the three stages of the cycle, which allowed them to refine it based on their own reflections and those of the observer; and to make better use of the feedback. Consequently, this process has led to higher quality learning goals. However, these same teachers also formulate – to a lesser extent – lower quality goals. The study provides criteria to further guide reciprocal peer observation towards the improvement of teacher learning.

The management of Invasive Alien Species (IAS) is often hindered by ecological, social and economic factors, resulting in inadequate biodiversity protection and inefficient use of public money. A clear example of such inefficient management in aquatic ecosystems is the European catfish Silurus glanis L. in southern Europe. Native to central Eurasia, S. glanis is an emblematic and controversial freshwater fish, being the subject of extensive and profitable trophy angling in central Europe and of commercial fishing in eastern Europe. Concurrently, in western and southern Europe where it was introduced in the XIX century, S. glanis is considered a problematic invader. The lack of comprehensive information on S. glanis invasive populations has limited effective management, which is critical to successfully control the spread and minimize negative impacts on native ecosystems and species. LIFE PREDATOR, started in September 2022 with a budget of € 2.85 million and a consortium of six partners from three countries, aims at developing a multidisciplinary and transnational approach to control established populations of S. glanis, and prevent further spreading and future introductions in southern European lakes and reservoirs. The project will develop and test an early warning system based on eDNA and citizen science and identify the most effective and selective capture techniques to reduce the abundance of catfish, particularly in Natura 2000 lakes, actively involving anglers and professional fishermen on this. Massive raising awareness campaigns will be conducted targeting anglers but also the general public, and protocols and best practices will be transferred to management authorities. For the long-term sustainability of the project, a South European Management Group will be created. Additionally, in northern Italy, where the catfish invasion is more advanced, a local circular economy will be implemented, involving the increase in fishing pressure by encouraging catfish consumption as food.

Abstract Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; η2p = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; η2p = 0.06) and C-reactive protein (CRP) (p = 0.03; η2p = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.

Abstract Background Eating disorders in adolescence are associated with high psychological distress, impaired function and high comorbidity. Despite the severity, eating disorders remain highly underdiagnosed and untreated. Digital technology provides promising opportunities for treatment, however studies focusing on digital treatments for adolescents with eating disorders are lacking. The main aim of this study was to explore the perspectives of adolescents with lived experience of eating disorders on factors they deemed to be relevant in the development of a novel digital treatment. Methods A qualitative intervention development study using semi-structured individual interviews. Data collection, coding and analysis were conducted using the principles of reflexive thematic analysis. Participants were adolescents aged 16–19 years, with a self-reported diagnosis of anorexia nervosa, bulimia nervosa or binge eating disorder, currently in the final phase or completed psychological treatment for an eating disorder within the last five years. Results A total of 16 adolescents participated in the study, all females. Mean age was 17 ½ years (SD = 1.01). An in-depth understanding of the adolescents’ perspectives was developed into three themes: Facilitating self-awareness and readiness to change; Strengthening interpersonal relationships and decreasing social isolation; Ensuring feeling seen and motivating regular use. Conclusions This study provides a unique insight into the perspectives of adolescents with lived experience of eating disorders. The uptake and engagement can be optimized in a novel digital treatment for eating disorders by taking the adolescents perspectives into consideration.

Penelitian ini merupakan penelitian eksperimen yang menilai risiko audit dengan mempertimbangkan salah saji dan rotasi auditor. Berdasarkan Theory of planned behavior, auditor dalam menentukan suatu risiko audit dipengaruhi oleh sikap, kode etik, serta aturan. Tinggi rendahnya risiko audit berhubungan dengan kesediaan auditor dalam menanggung risiko bahwa laporan keuangan mengandung salah saji material ketika opini wajar tanpa pengecualian telah diberikan, sehingga semakin rendah (tinggi) risiko audit menjelaskan bahwa salah saji yang terdapat di dalam laporan keuangan adalah material (tidak material). Sedangkan rotasi auditor menjelaskan lamanya perikatan audit terhadap klien yang sama. Semakin lama auditor melakukan perikatan audit pada klien yang sama akan menyebabkan klien dapat membaca pola pemeriksaan yang dilakukan oleh auditor tersebut sehingga kecenderungan manipulasi yang dilakukan oleh klien dapat tidak terdeteksi oleh auditor. Hal ini menyebabkan laporan keuangan klien semakin berisiko tinggi sehingga risiko audit semakin rendah. Penelitian ini menggunakan responden mahasiswa S1 yang sedang skripsi. Hasil penelitian ini adalah kesediaan untuk menanggung risiko audit pada laporan keuangan yang mengandung salah saji material lebih rendah dibandingkan pada laporan keuangan yang tidak mengandung salah saji material, serta kesediaan auditor lebih rendah dalam menanggung risiko audit untuk klien dengan akumulasi perikatan 7 tahun atau lebih dibandingkan dengan yang kurang dari 7 tahun.

Rubber bullets are projectiles whose use is potentially lethal. Between 1976 and 2017, they have caused at least 23 deaths and dozens of injuries in Spain, many of them serious, with loss of sight being the main cause. In the period 2000 - 2020 alone, more than 40 people have been affected. However, the data available do not reflect, in quantitative terms, the reality of the problem which, far from the figures for other contexts, shows qualitative impacts, both individual and collective. This article reviews the trajectory of the last twenty years, emphasising those key aspects that have made a difference in the process towards the prohibition of this weapon in different territories of the state, as well as evaluating the psychosocial impacts that its use has caused.

Abstract Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens.

Abstract The development of robust tools for segmenting cellular and sub-cellular neuronal structures lags behind the massive production of high-resolution 3D images of neurons in brain tissue. The challenges are principally related to high neuronal density and low signal-to-noise characteristics in thick samples, as well as the heterogeneity of data acquired with different imaging methods. To address this issue, we design a framework which includes sample preparation for high resolution imaging and image analysis. Specifically, we set up a method for labeling thick samples and develop SENPAI, a scalable algorithm for segmenting neurons at cellular and sub-cellular scales in conventional and super-resolution STimulated Emission Depletion (STED) microscopy images of brain tissues. Further, we propose a validation paradigm for testing segmentation performance when a manual ground-truth may not exhaustively describe neuronal arborization. We show that SENPAI provides accurate multi-scale segmentation, from entire neurons down to spines, outperforming state-of-the-art tools. The framework will empower image processing of complex neuronal circuitries.

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) represents a rare and clinically and genetically heterogeneous disease that constitutes 10–15% of newly diagnosed pediatric ALL cases. Despite improved outcomes of these children, the survival rate after relapse is extremely poor. Moreover, the survivors must also endure the acute and long-term effects of intensive therapy. Although recent studies have identified a number of recurrent genomic aberrations in pediatric T-ALL, none of the changes is known to have prognostic significance. The aim of our study was to analyze the cytogenomic changes and their various combinations in bone marrow cells of children with T-ALL and to correlate our findings with the clinical features of the subjects and their treatment responses. Results We performed a retrospective and prospective comprehensive cytogenomic analysis of consecutive cohort of 66 children (46 boys and 20 girls) with T-ALL treated according to BFM-based protocols and centrally investigated cytogenetics and immunophenotypes. Using combinations of cytogenomic methods (conventional cytogenetics, FISH, mFISH/mBAND, arrayCGH/SNP and MLPA), we identified chromosomal aberrations in vast majority of patients (91%). The most frequent findings involved the deletion of CDKN2A/CDKN2B genes (71%), T-cell receptor (TCR) loci translocations (27%), and TLX3 gene rearrangements (23%). All chromosomal changes occurred in various combinations and were rarely found as a single abnormality. Children with aberrations of TCR loci had a significantly better event free (p = 0.0034) and overall survival (p = 0.0074), all these patients are living in the first complete remission. None of the abnormalities was an independent predictor of an increased risk of relapse. Conclusions We identified a subgroup of patients with TCR aberrations (both TRA/TRD and TRB), who had an excellent prognosis in our cohort with 5-year EFS and OS of 100%, regardless of the presence of other abnormality or the translocation partner. Our data suggest that escalation of treatment intensity, which may be considered in subsets of T-ALL is not needed for nonHR (non-high risk) patients with TCR aberrations.