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Abstract Background Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC populations. Variations in MSCs’ secretory and proliferation profiles, and their proteomic and transcriptional characteristics significantly influence their therapeutic potency, highlighting the need for enhanced characterization methods to better predict their efficacy. This study aimed to evaluate the biological characteristics of MSCs from different tissue origins, selecting the most promising line for further validation in a K18-hACE2 mouse model of SARS-CoV-2 infection. Methods We studied nine MSC lines sourced from either bone marrow (hBMMSC), dental pulp (hDPMSC), or umbilical cord tissue (hUCMSC). The cells were assessed for their proliferative capacity, immunophenotype, trilineage differentiation, proteomic profile, and in vitro immunomodulatory potential by co-culture with activated lymphocytes. The most promising MSC line was selected for further experimental validation using the K18-hACE2 mouse model of SARS-CoV-2 infection. Results The analyzed cells met the minimum criteria for defining MSCs, including the expression of surface molecules and differentiation capacity, showing genetic stability and proliferative potential. Proteomic analysis revealed distinct protein profiles that correlate with the tissue origin of MSCs. The immunomodulatory response exhibited variability, lacking a discernible pattern associated with their origin. In co-culture assays with lymphocytes activated with anti-CD3/CD28 beads, all MSC lines demonstrated the ability to inhibit TNF-α, to induce TGF-β and Indoleamine 2,3-dioxygenase (IDO), with varying degrees of inhibition observed for IFN-γ and IL-6, or induction of IL-10 expression. A module of proteins was found to statistically correlate with the potency of IL-6 modulation, leading to the selection of one of the hUCMSCs as the most promising line. Administration of hUCMSC to SARS-CoV-2-infected K18 mice expressing hACE2 was effective in improving lung histology and modulating of a panel of cytokines. Conclusions Our study assessed MSCs derived from various tissues, uncovering significant variability in their characteristics and immunomodulatory capacities. Particularly, hUCMSCs demonstrated potential in mitigating lung pathology in a SARS-CoV-2 infection model, suggesting their promising therapeutic efficacy.

Abstract Background Bullying has been identified as a risk factor for many issues among adolescents. Although it was already considered a public health issue in Brazil before the COVID-19 pandemic, little is known about how the pandemic and associated public health measures have affected bullying behavior. Objective To explore changes in bullying victimization and perpetration among Brazilian high school students from 2019 to 2022. Methods This study utilizes data from the Longitudinal Study of Adolescent Lifestyle (ELEVA), employing a repeated cross-sectional with a nested cohort design. Adolescents (n = 1.987, 50.2% female, mean age 16.4 years) answered a questionnaire and bullying-related information were extracted from two different questions for victims and perpetrators. Multilevel logistic regression models were used. Results Bullying victimization decreased from 46% (95% CI: 40-52%) in 2019 to 30% (95% CI: 24-36%) in 2022 (OR: 0.46, 95% CI: 0.30–0.69, p

Abstract Myocardial infarction-associated transcript (MIAT), an intergenic long noncoding RNA (lncRNA), is conserved between rodents and humans and is directly linked to maladaptive cardiac remodeling in both patients and mouse models with various forms of heart failure (HF). We previously reported attenuation of cardiac stress, apoptosis, and fibrosis in a murine model of myocardial infarction (MI) with global MIAT ablation. Our transcriptomic profiling and mechanistic studies further revealed MIAT-induced activation of maladaptive genes, such as Hoxa4, Fmo2, Lrrn4, Marveld3, and Fat4. However, the source of MIAT and its contribution to MI and HF remain unknown. In this study, we generate a novel cardiomyocyte (CM)-specific MIAT conditional knockout mouse model, which exhibits improved cardiac function after MI. We further report that CM-specific MIAT ablation is sufficient to reduce cardiac damage, apoptosis, and fibrosis following chronic MI. Mechanistically, CM-specific MIAT deletion in mice leads to decreased expression of proapoptotic and pathological profibrotic genes, such as p53, Bak1, Col3a1, Col6a1, Postn, and Snail1 after chronic MI. These results enable us to begin to dissect cell-specific contributions to MIAT signaling and bolster the idea that MIAT plays a direct pathological role in CMs after MI.

Abstract Background Limb Girdle Muscular Dystrophy is defined as a group of progressive autosomal recessive (85%, 28 genes) and autosomal dominant (15%, 5 genes) muscular dystrophies described in at least two unrelated families, affecting individuals that achieve independent walking, with predominant proximal muscles weakness at presentation, elevated serum creatine kinase activity, dystrophic changes on muscle biopsy, and degeneration on muscle imaging over the course of the disease. Main body The aims of this review are: (1) to show the recent Limb Girdle Muscular Dystrophy (LGMD) genetic classification illustrated with clinical and physiopathological characteristics, and cellular localization of the main gene products; (2) to present muscle radiophenotypes with an algorithm for differential diagnosis; (3) to show the role of muscle biopsy for phenotypic characterization, and pathogenicity confirmation in the era of surgical-molecular pathology. Conclusion Pathologists may be aware of clinical, neurophysiological, laboratorial, imaging, molecular, and muscle biopsy modalities to provide a precise phenotypic-genotypic diagnosis for adequate rehabilitation care, and genetic counselling.

Abstract Background The two-component system (TCS) serves as a common intracellular signal transduction pathway implicated in various processes of plant development and response to abiotic stress. With regard to the important cereal crop barley, only partial information about the occurrence of TCS signaling elements in the genome and putative functions is available. Results In this study, we identified a total of 67 non-redundant TCS genes from all subgroups of the phosphorelay in the latest barley reference genome. Functional annotation and phylogenetic characterization was combined with a comprehensive gene expression analysis of the signaling components. Expression profiles hint at potential functions in vegetative and reproductive organs and tissue types as well as diverse stress responses. Apparently, a distinct subset of TCS genes revealed a stringent grain-specificity not being expressed elsewhere in the plant. By using laser capture microdissection (LCM)-based transcript analysis of barley grain tissues, we refined expression profiles of selected TCS genes and attributed them to individual cell types within the grain. Distinct TCS elements are exclusively expressed in the different maternal and filial cell types, particularly in the endosperm transfer cell (ETC) region. These genes are deemed to be selected in the domestication process of modern cultivars. Moreover, barley plants transformed with a synthetic sensor (TCSn::GFP) showed a high and specific activity in the ETC region of grains monitoring transcriptional output of the signaling system. Conclusions The results provide comprehensive insights into the TCS gene family in the temperate cereal crop barley and indicate implications in various agronomic traits. The dataset is valuable for future research in different aspects of plant development and will be indispensable not only for barley, but also for other crops of the Poaceae.

Abstract Separated endodontics instruments and high-density obturating materials produce metal artifacts on cone-beam computed tomography (CBCT) scans. This study evaluated a novel methodology to detect separated instruments using artifact suppression and color map algorithms with CBCT post-processing software and compared with periapical radiographs (PRs). Endodontic instruments were incorporated into 168 root canals filled with four sealers. Additionally, 40 root canals were only filled, serving as control. CBCT scans were acquired in PreXion-3D-Elite, and digital PRs were taken in distoradial, mesioradial, orthoradial, and proximal directions. The treated teeth were analyzed using an artifact suppression algorithm combined with a color map algorithm. The separated instruments appear in the color map with larger expansion in red to allow identification. This map provides valuable information by showing dynamic visualization toward the point of expansion of the high-density object, hence suggesting a separated instrument. The chi-square test was used to compare the separated instruments among the imaging methods. Bonferroni correction was used for multiple comparisons. Statistical significance was considered P

Abstract Mixed Se–Te glasses are unique materials for infrared optical applications due to their exceptional IR transparency, molding and fiber-drawing capability, environmental stability, and tailored physical properties. In this work, the effect of the gradual substitution of Sb with P in bulk PxGa5Ge20Sb10−xSe45Te20 glasses is studied with structural methods, optical spectroscopy, and differential scanning calorimetry (DSC). Non-isothermal and isothermal DSC studies reveal crystallization of several phases, some of them following the non-conventional anti-Arrhenius behavior of crystallization kinetics. The thermal stability of the glass is shown to increase with P concentration, and the glasses with x = 7, 9, 10 do not fully crystallize during the regular DSC heating scans. Their time–temperature-transformation curves reveal a known “nose”-like shape, suggesting crystallization at close proximity to the melting points of corresponding crystalline phases. It is found that the substitution of Sb with P in glass composition leads to a slight decrease in the optical gap and shift of the main Raman signal at ~ 150 cm−1 to higher wavenumbers.

Abstract Background Deep Brain Stimulation (DBS) of the anterior cingulum has been recently proposed to treat refractory chronic pain but its safety and its efficacy have not been evaluated in controlled conditions. Our objective was to evaluate the respective feasibility and safety of sensory thalamus (Thal-DBS) combined with anterior cingulate (ACC-DBS) DBS in patients suffering from chronic neuropathic pain. Methods We conducted a bicentric study (clinicaltrials.gov NCT03399942) in patients suffering from medically-refractory chronic unilateral neuropathic pain surgically implanted with both unilateral Thal-DBS and bilateral ACC-DBS, to evaluate successively: Thal-DBS only; combined Thal-DBS and ACC-DBS; ACC-DBS “on” and “off” stimulation periods in randomized cross-over double-blinded conditions; and a 1-year open phase. Safety and efficacy were evaluated by repeated neurological examination, psychiatric assessment, comprehensive assessment of cognitive and affective functioning. Changes on pain intensity (Visual Analogic Scale) and quality of life (EQ-5D scale) were used to evaluate DBS efficacy. Results All the patients (2 women, 6 men, mean age 52,1) completed the study. Adverse events were: epileptic seizure (2), transient motor or attention (2), persistent gait disturbances (1), sleep disturbances (1). No patient displayed significant cognitive or affective change. Compared to baseline, the quality of life (EQ-5D utility score) was significantly improved during the ACC-DBS “On” stimulation period (p = 0,039) and at the end of the study (p = 0,034). Conclusion This pilot study confirmed the safety of anterior cingulate DBS alone or in combination with thalamic stimulation and suggested that it might improve quality of life of patients with chronic refractory neuropathic pain. Trial registration The study has been registered on 20,180,117 (clinicaltrials.gov NCT03399942).

Abstract Background and aims Liver cancer is the third leading cause of cancer related death due to treatment resistance and late onset of symptoms (Rumgay in J Hepatol 77: 1598–1606, 2022). The role of external beam radiotherapy (EBRT) in treatment of unresectable liver cancer needs to be defined. The use of particle therapy such as carbon ion radiation therapy (CIRT) with high linear energy transfer (LET) could increase efficacy of EBRT while limiting the toxic effects of radiation on non-cancerous liver tissue. Promising effects of CIRT have been described in several studies during the past decades, mostly in Japan. To date, no standardized treatment protocol has been established and European data on CIRT for liver cancer is lacking. This retrospective analysis aims to investigate efficacy and safety of hypofractionated CIRT compared to photon-based stereotactic body radiation (SBRT) in primary liver cancer. Method Thirty-six (n = 36) and twenty (n = 20) patients with primary malignant liver tumors were treated with hypofractionated CIRT (4 fractions) and photon-based SBRT, respectively, between 2011 and 2022 and were retrospectively evaluated for survival, local control, and toxicity. Results Two-year local control rate after CIRT was 92.3%. Compared to photon- based SBRT, CIRT scores with a significantly longer median distant progression free survival (3.1 versus 0.9 years). In a matched pair comparison of the two treatment regimens, the CIRT cohort demonstrated both longer 2-year overall survival (100% versus 59.6%) and longer 2-year distant PFS (75.7% versus 22.9%). No significant impairment of liver function was observed in either cohort. Conclusion In this retrospective analysis, patients who received CIRT presented excellent local tumor control and had better oncologic outcomes than patients who received photon-based SBRT. SBRT with carbon ions is a promising local ablative treatment option that needs further investigation in large prospective trials.

Abstract The specific role of chromatin modifying factors in the timely execution of transcriptional changes in gene expression to regulate organ size remains largely unknown. Here, we report that in Drosophila melanogaster depletion of the histone demethylase dLsd1 results in the reduction of wing size. dLsd1 depletion affects cell proliferation and causes an increase in DNA damage and cell death. Mechanistically, we have identified Transposable Elements (TEs) as critical dLsd1 targets for organ size determination. We found that upon dLsd1 loss many TE families are upregulated, and new TE insertions appear. By blocking this new TE activity, we could rescue the wing size phenotype. Collectively, our results reveal that the histone demethylase dLsd1 and maintenance of TE homeostasis are required to ensure proper wing size.

Background and aims – The Serra do Ambrósio is a mountain with a unique vegetation called carrasco. The carrasco is characterised by sandy soils of high granulometry and is home to rare species. During the current research on the Arecaceae flora of the Diamantina Plateau, a new Syagrus species was discovered, which is described here. Material and methods – The morphology and anatomy are described based on field collections. The pinnae anatomy was analysed using LM (free-hand cross sections). The new species belongs to the Syagrus glaucescens complex, and an identification key and a distribution map were created. Key results – Syagrus harenae resembles S. glaucescens, but some characteristics easily differentiate it, such as the small size, lax pinnae, symmetric pinnae tips, ramenta scales, a scattered thin indumentum on the peduncle, inflorescences and fruits orangish-yellow, and pistil with indumentum. The new species also possesses flowers arranged in tetrads and pentads and is the first species of Syagrus showing two sepals, petals with imbricate tips, staminodes with anthers, and frequently lacks staminodial rings. The pinnae anatomy of the new species also resembles S. glaucescens, which indicates their relatedness. However, reliable differences in pinnae anatomy set the new species apart, such as the fibrous ring reaching the abaxial hypodermis and the large first adaxial fibre bundle near the margin. The new species is assessed as critically endangered. Conclusion – Syagrus harenae is the first endemic species of the genus described for the Serra do Ambrósio and possesses striking characteristics, such as the re-greening of the pistillate flowers and flowers arranged in tetrads and pentads. The type population corroborates the Diamantina Plateau and its disjunctions as one of the centres of diversity for Syagrus. The discovery of this new species reinforces the uniqueness of the local flora and its classification as a priority area for conservation.

Abstract We have prepared lycopene aggregates with low scattering in an acetone–water suspension. The aggregates exhibit highly distorted absorption, extending from the UV up to 568 nm, as a result of strong excitonic interactions. We have investigated the structural organization of these aggregates by resonance Raman and TEM, revealing that the lycopene aggregates are not homogeneous, containing at least four different aggregate species. Transient absorption measurements upon excitation at 355, 515, and 570 nm, to sub-select these different species, reveal significant differences in dynamics between each of the aggregate types. The strong excitonic interactions produce extremely distorted transient electronic signatures, which do not allow an unequivocal identification of the excited states at times shorter than 60 ps. However, these experiments demonstrate that all the lycopene aggregated species form long-living triplets via singlet fission.

Abstract The common bottlenose dolphin is a cosmopolitan species that can be found worldwide in all oceans except polar and sub-polar waters. This wide distribution is associated with a certain level of morphological variation, which seems consistent with the presence of a globally distributed pelagic/offshore ecotype and several coastal/inshore ecotypes distributed along the continental shelf. In the Mediterranean Sea, the common bottlenose dolphin is a regularly occurring species and the second most sighted cetacean after the striped dolphin. According to some studies, the Mediterranean bottlenose dolphin is more closely related to the Atlantic coastal ecotype, while others suggest a closer link with the pelagic ecotype. This apparent contradiction could stem from the coexistence of two ecotypes also within the Mediterranean Sea, as suggested by genetic analyses. We analysed data collected from 2004 to 2019 by 43 different research groups, distributed in different areas of the basin, and shared on the web-based GIS platform Intercet. We analysed the distribution and movements of 4919 bottlenose dolphins, individually identified through their natural dorsal fin markings, in relation to bathymetry and in particular to the 200-meter isobath that marks the edge of the continental shelf. In addition, we reconstructed the associations between individuals within connectivity networks, to identify possible segregations between ecotypes. Our results show that most bottlenose dolphin geographical units find their habitat over the continental shelf, while the analysed data do not support the coexistence of different ecotypes (pelagic vs. coastal) living in parapatry, as described in the adjacent waters of the eastern Atlantic Ocean.

Abstract Purpose To test the effects of a physical activity intervention program on symptoms of mental disorders among adolescents. Methods This study is a 12-week cluster randomized controlled trial. The sample consisted of 306 adolescents (45,8% male, age: 13,6 [0,72] years; 54.2% female, age: 13.5 [0.69] years), randomized into an intervention group (N = 165) and a control group (N = 141). The physical activity program involved sessions including muscle strengthening and cardiorespiratory exercises and lifestyle guidance. The mental health indicators analyzed were: anxiety, depression, sleep, and psychological well-being. Intervention effects were analyzed by generalized estimating equations. Results After 12 weeks, no significant improvements were observed in the intervention group for sleep; anxiety; depression, and psychological well-being. In the subgroup analysis, significant group×time interactions were observed for adolescents who were classified with moderate symptoms of depression (mean difference: -0.97, p = 0.002) and anxiety (mean difference: -3.03, p = 0.01) with favorable effects for intervention group. Conclusion After the 12-week intervention period, it can be concluded that 12 weeks of school-based physical activity intervention significantly reduced symptoms of anxiety and depression in adolescents with moderate/severe symptoms. Furthermore, the intervention contributed to the maintenance of psychological well-being, since the control group showed a significant reduction in this mental health indicator.

Abstract Background Maternal depression is pregnancy and childbirth-related depression during pregnancy (prenatal depression (PND)) or after delivery (postpartum depression (PPD)). It is a recognized global public health concern with extensive repercussions adversely affecting women’s well-being and the developmental progress of infants. Mindfulness-based interventions (MBIs) have been shown to be effective in maternal depression. Technology-supported MBI could be an effective preventive strategy for maternal depression, especially in low- and middle-income countries (LMICs) where lack of important resources limits the accessibility to standard care. However, the limited available studies assessing the effect of technology-supported MBIs for maternal depression might be insufficient to reach a definitive conclusion. This systematic review aimed to evaluate the pooled estimated effect of technology-supported MBIs for maternal depression, identify available studies, and reveal applicable health technologies with MBIs. Method This study was conducted according to the PRISMA-P 2020 and the review protocol was registered in PROSPERO; CRD42024537853. The risk of bias was evaluated using the PEDro scale. The meta-analysis was done with R. Result Data from 18 articles, none from low-income countries (LICs), were included in the systematic review, representing 2,481 participants, 15 studies were included in the meta-analysis. The pooled effect size indicated that technology-supported MBIs had a positive effect on maternal depression (SMD − 0.55, 95% CI [− 0.70; −0.40], p

Abstract Objective Staphylococcus capitis is part of the human microbiome and an opportunistic pathogen known to cause catheter-associated bacteraemia, prosthetic joint infections, skin and wound infections, among others. Detection of S. capitis in normally sterile body sites saw an increase over the last decade in England, where a multidrug-resistant clone, NRCS-A, was widely identified in blood samples from infants in neonatal intensive care units. To address a lack of complete genomes and antibiograms of S. capitis in public databases, we performed long- and short-read whole-genome sequencing, hybrid genome assembly, and antimicrobial susceptibility testing of 22 diverse isolates. Data description We present complete genome assemblies of two S. capitis type strains (subspecies capitis: DSM 20326; subspecies urealyticus: DSM 6717) and 20 clinical isolates (NRCS-A: 10) from England. Each genome is accompanied by minimum inhibitory concentrations of 13 antimicrobials including vancomycin, teicoplanin, daptomycin, linezolid, and clindamycin. These 22 genomes were 2.4–2.7 Mbp in length and had a GC content of 33%. Plasmids were identified in 20 isolates. Resistance to teicoplanin, daptomycin, gentamicin, fusidic acid, rifampicin, ciprofloxacin, clindamycin, and erythromycin was seen in 1–10 isolates. Our data are a resource for future studies on genomics, evolution, and antimicrobial resistance of S. capitis.

Abstract: The aim of our study was to analyze the potential survival benefit associated with hematopoietic stem cell transplantation (HSCT) according to clinicobiological scores, which incorporate mutation-enhanced international prognostic score system (MIPSS) to facilitate decision-making in this context. One transplant (n = 241) and 1 nontransplant cohort (n = 239) were used to test the hypothesis that patients with primary myelofibrosis with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference. Weighted Cox proportional hazard models and logistic regression analyses were performed. Overall, 105 patients who did not receive transplant could be matched to the 239 patients who did receive transplants. HSCT was associated with a higher 6-year overall survival rate in intermediate-2 (60.1% vs 41.5%) and high-risk DIPSS patients (44.4% vs 6.55%), high-risk MIPSS70 (46.5% vs 23.9%), high-risk (73.2% vs 39.7%) or very high-risk MIPSS70+V2 (51.8% vs 24%). Patients with intermediate MIPSS70 scores have an advantage of survival with HSCT only when their myelofibrosis transplant scoring system (MTSS) were low or intermediate. Patients who received transplant had an increased mortality risk the first year, but a significant benefit with HSCT after the 1-year landmark was observed in higher risk patients. This study confirms that, similar to DIPSS, MIPSS70 and MIPSS70+V2 risk score in addition to MTSS can be used to determine which patients with primary myelofibrosis have survival benefit from HSCT over non-HSCT strategies.

Abstract Background Following non-pharmaceutical interventions (NPI) lifting in 2021, an important surge in childhood lower respiratory tract infections (LRTI) was reported in several countries, raising major concerns about the middle-term consequences of such interventions. Whether this recent upsurge overwhelms the initial benefit of NPI remains unknown. Methods We conducted an interrupted time-series analysis based on exhaustive national surveillance systems. All hospitalisations from January 2015 to March 2023 and all ambulatory visits for LRTI from a network of 110 paediatricians from June 2017 to March 2023 were included. The main outcome was the monthly incidence of children hospitalised for LRTI per 100,000 over time, assessed by a seasonally adjusted quasi-Poisson regression model. Results We included 845,047 hospitalisations. The incidence of hospitalisation for LRTI significantly decreased during the NPI period (− 61.7%, 95% CI − 98.4 to − 24.9) and rebounded following NPI lifting, exceeding the pre-NPI baseline trend (+ 12.8%, 95% CI 6.7 to 19.0). We observed similar trends for hospitalisation due to bronchiolitis, pneumonia and pneumonia with pleural effusion, along with ambulatory LRTI. Overall, despite the recent rebound, 31,777 (95% CI, 25,375 to 38,179) hospitalisations for paediatric LRTI were averted since NPI implementation up to 2023. Conclusions Three years after their implementation, despite an increase in LRTI incidence, the middle-term impact of NPI remains highly beneficial in preventing overall paediatric LRTI. The implementation of some societally acceptable NPI, particularly during epidemics, may be considered in the future to further reduce the burden of paediatric LRTI.

Abstract Halorhodospira (Hlr.) halophila strain BN9622 is an extremely halophilic and alkaliphilic phototrophic purple sulfur bacterium isolated from a hypersaline lake in the Libyan Desert whose total salinity exceeded 35% at pH 10.7. Here we present a cryo-EM structure of the native LH1–LH2 co-complex from strain BN9622 at 2.22 Å resolution. Surprisingly, the LH1–LH2 co-complex consists of a double-ring cylindrical structure with the larger LH1 ring encircling a smaller LH2 ring. The Hlr. halophila LH1 contains 18 αβ-subunits and additional bacteriochlorophyll a (BChl a) molecules that absorb maximally at 797 nm. The LH2 ring is composed of 9 αβ-subunits, and the BChl a molecules in the co-complex form extensive intra- and inter-complex networks to allow near 100% efficiency of energy transfer to its surrounding LH1. The additional LH1-B797 BChls a are located in such a manner that they facilitate exciton transfer from monomeric BChls in LH2 to the dimeric BChls in LH1. The structural features of the strain BN9622 LH1–LH2 co-complex may have evolved to allow a minimal LH2 complex to maximize excitation transfer to the core complex and effectively harvest light in the physiologically demanding ecological niche of this purple bacterium.

Abstract Background Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 are responsible for 20–25% of apparently sporadic PBMAH cases and 80% of familial presentations. ARMC5 screening is now routinely performed for PBMAH patients and families. Based on literature review and own observation, this study aims to give an overview of both published and unpublished ARMC5 genetic alterations and to compile the available evidence to discriminate pathogenic from benign variants. Results 146 different germline variants (110 previously published and 36 novel) are identified, including 46% missense substitutions, 45% truncating variants, 3% affecting splice sites, 4% in-frame variants and 2% large deletions. In addition to the germline events, somatic 16p loss-of-heterozygosity and 104 different somatic events are described. The pathogenicity of ARMC5 variants is established on the basis of their frequency in the general population, in silico predictions, familial segregation and tumor DNA sequencing. Conclusions This is the first extensive review of ARMC5 pathogenic variants. It shows that they are spread on the whole coding sequence. This is a valuable resource for genetic investigations of PBMAH and will help the interpretation of new missense substitutions that are continuously identified.

Abstract Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different fields and has found substantial variability among results despite analysts having the same data and research question. Many of these studies have been in the social sciences, but one small “many analyst” study found similar variability in ecology. We expanded the scope of this prior work by implementing a large-scale empirical exploration of the variation in effect sizes and model predictions generated by the analytical decisions of different researchers in ecology and evolutionary biology. We used two unpublished datasets, one from evolutionary ecology (blue tit, Cyanistes caeruleus, to compare sibling number and nestling growth) and one from conservation ecology (Eucalyptus, to compare grass cover and tree seedling recruitment). The project leaders recruited 174 analyst teams, comprising 246 analysts, to investigate the answers to prespecified research questions. Analyses conducted by these teams yielded 141 usable effects (compatible with our meta-analyses and with all necessary information provided) for the blue tit dataset, and 85 usable effects for the Eucalyptus dataset. We found substantial heterogeneity among results for both datasets, although the patterns of variation differed between them. For the blue tit analyses, the average effect was convincingly negative, with less growth for nestlings living with more siblings, but there was near continuous variation in effect size from large negative effects to effects near zero, and even effects crossing the traditional threshold of statistical significance in the opposite direction. In contrast, the average relationship between grass cover and Eucalyptus seedling number was only slightly negative and not convincingly different from zero, and most effects ranged from weakly negative to weakly positive, with about a third of effects crossing the traditional threshold of significance in one direction or the other. However, there were also several striking outliers in the Eucalyptus dataset, with effects far from zero. For both datasets, we found substantial variation in the variable selection and random effects structures among analyses, as well as in the ratings of the analytical methods by peer reviewers, but we found no strong relationship between any of these and deviation from the meta-analytic mean. In other words, analyses with results that were far from the mean were no more or less likely to have dissimilar variable sets, use random effects in their models, or receive poor peer reviews than those analyses that found results that were close to the mean. The existence of substantial variability among analysis outcomes raises important questions about how ecologists and evolutionary biologists should interpret published results, and how they should conduct analyses in the future.

Abstract Background Gastrointestinal myiasis is a rare form of infestation by fly larvae which typically occurs due to ingestion of contaminated food or water, especially in regions with poor hygiene. This report presents a rare and persistent case of intestinal myiasis caused by Oestrus ovis in a Nigerian university student, highlighting the challenges posed by persistent symptoms despite prolonged standard anti-helminthic treatments. Case presentation A 24-year-old male Nigerian university student presented with the passage of live maggots in his stool for 1 year likely due to exposure to contaminated food from unsanitary campus vendors. He had received multiple anti-helminthic treatments without improvement. Clinical evaluations, including imaging and laboratory tests, were mostly normal, with live maggots confirmed as Oestrus ovis larvae in stool samples. Initial treatment with standard anti-helminthics failed, leading to prolonged treatment with ivermectin, nitazoxanide, and colonic washes, combined with levofloxacin for Helicobacter pylori eradication, resulting in the resolution of symptoms with no recurrence after 6 months. Conclusion This case emphasizes the need for clinicians to consider rare parasitic infections such as Oestrus ovis myiasis, especially in endemic regions with poor hygiene, and highlights the importance of extended or alternative treatment protocols for resistant cases. It also emphasizes the need for increased awareness of food safety and hygiene in high-risk environments and further research into resistance mechanisms in myiasis treatment.

Alternaria species have often been reported as plant pathogens and are commonly isolated from diseased plant hosts. During an investigation of this genus in Algeria, seven Embellisia-like isolates were collected from Apiaceae. Phylogenetic analysis using sequences at four loci, the internal transcribed spacer of the rDNA region (ITS), glyceraldehyde-3-phosphate dehydrogenase (gpd), translation elongation factor 1-alpha (tef1), and RNA polymerase second largest subunit (rpb2), revealed that these isolates grouped into three sections, namely Embellisia, Embellisioides, and Eureka. Four isolates had significant differences with their closest species and were determined to be new species, namely Alternaria longiformis and A. radicicola spp. nov. The three other isolates of section Eureka were identified as A. eureka and A. hungarica, the latter species being described as a new record in Algeria. Detailed descriptions of new species are provided based on colony color, aspect, diameter, conidial size, septa, sporulation patterns and compared with other relevant Alternaria species within same sections. All these species were weakly pathogenic on carrot, coriander, and fennel under greenhouse experiments. Apiaceae may constitute a reservoir of Alternaria species that could represent potential pathogens for other plant families.

Abstract: Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. In this multicentric retrospective observational study, we enrolled 167 adult patients with ITP, followed at 13 centers in Italy, United Kingdom, and the United States. Patients underwent NGS evaluation after a median of 3.6 years from ITP onset, and 83% had received at least 1 therapy line, for a median of 2 lines (range, 0-9); 51 of 167 patients (30%) had at least 1 mutation. After exclusion of germ line variants and polymorphisms, 31 of 167 (18.5%) were defined as having clonal hemopoiesis. Most commonly mutated genes were TET2, DNMT3A, SRSF2, and ASXL1 (median variant allele frequency, 29%); 19 of 31 patients (68%) had high-risk variants, and 8 had multiple mutations. Mutated patients were more frequently older males and showed a shorter time from first to second-line therapy, particularly with thrombopoietin receptor agonist (TPO-RA). Additionally, clonal hematopoiesis was associated with increased thrombotic risk (26% vs 8% in NGS-negative cases; P = .01), independently from TPO-RA exposure, though with an age effect. These data demonstrated the prevalence of clonal hematopoiesis in 18% of adult patients with ITP, which is associated with older age, relapsed/refractory disease, and high risk of thrombotic complications.

Emotion recognition plays a critical role in understanding how individuals perceive and interact with the world by accurately inferring emotions from various sources, such as physical signals and physiological responses. Anomalous emotion recognition, in particular, focuses on identifying emotions that deviate significantly from expected patterns in specific contexts or individuals, including abrupt emotional shifts, inconsistencies across different emotional signals, or persistent, atypical emotional patterns. The importance of recognizing anomalous emotions has grown, particularly in intelligent systems designed for mental health monitoring and crime prevention, where early detection can enhance context-sensitive interventions. This study presents a systematic review that investigates the link between emotional variations and anomalous behaviors across diverse settings. By examining the relationship between emotional shifts and deviant behaviors, the study sheds light on the challenges of detecting emotional anomalies and assesses the efficacy of various recognition methods. A thorough analysis of 102 relevant studies highlights the potential and limitations of current approaches, emphasizing the need for more diverse datasets, improved algorithm robustness, and broader applications to enhance performance in real-world scenarios.

Background: The aim of this study was to assess whether parasternal block with multihole catheters inserted before surgical incision enables to alleviate postoperative analgesia and opioid reduction in cardiac surgery patients with sternotomy. Methods: Twenty-six adult patients scheduled for cardiac surgery with sternotomy aged between 18 and 84 olds were included in this prospective, monocentric, open, single-group trial. Two parasternal multihole catheters were inserted on each side of the sternum before the surgical skin incision for cardiac surgery and 10 mL of ropivacaine 7.5 mg mL–1 was initially administered in each catheter. Local anesthetic administration followed by continued infusion at 3 mL hr–1 of ropivacaine 2 mg mL–1 per catheter for 48 h postoperatively upon patient arrival in the intensive care unit. The efficacy of the parasternal block was assessed according to a composite endpoint including pain score at rest, pain score during movements (dynamic pain), and morphine consumption over 48 hours. Results: The treatment failed in 11 patients and was considered effective in 15 patients. Sixteen patients out of 26 had a sternal pain score ≤≤3/10 on more than 75% of observations, and the treatment was considered successful. In 23/26 patients (88%), the mean pain score at cough was ≤≤3.5/10 and the treatment was considered successful. Morphine consumption over 48 h was significantly lower in the intervention group compared to the control group 7 mg [6; 21] versus 142 mg [116; 176] (P < 0.001). Conclusions: Parasternal block with multihole catheters inserted before the surgical incision is an effective technique for postoperative analgesia and opioid reduction.

El objetivo principal de este artículo es analizar los cambios ocurridos en las bandas civiles en Portugal, con una especial atención al municipio de Águeda (distrito de Aveiro), en el último cuarto de siglo XX, un periodo especialmente desconocido en el ámbito de las agrupaciones musicales. El enfoque metodológico incluye la consulta bibliográfica, la recopilación de artículos de prensa, la investigación de colecciones y archivos y la realización de entrevistas. El análisis de los datos recogidos pone de manifiesto la revalorización de la banda de música civil como agrupación, especialmente si se toma como referencia el periodo precedente, y aun teniendo en cuenta la persistencia de ciertas dificultades como pueden ser las económicas. Dicha revalorización se debió a una combinación de factores entre los que destaca el aumento de la disponibilidad de los recursos humanos. En virtud de la práctica ausencia de un estudio sobre el tema, este proyecto de investigación arroja luz sobre estas agrupaciones, especialmente en el municipio de Águeda en el tiempo que se examina.

Abstract Background Intensive rehabilitation through challenging and individualized tasks are recommended to enhance upper limb recovery after stroke. Robot-assisted therapy (RAT) and serious games could be used to enhance functional recovery by providing simultaneous motor and cognitive rehabilitation. Objective The aim of this study is to clinically validate the dynamic difficulty adjustment (DDA) mechanism of ROBiGAME, a robot serious game designed for simultaneous rehabilitation of motor impairments and hemispatial neglect. Methods A proof of concept, with 24 participants in subacute and chronic stroke, was conducted using a 5-day protocol (two days were dedicated to assessment and three days to consecutive training sessions). Participants performed three consecutive ROBiGAME sessions during which overall task difficulty was determined through simultaneous DDA of motor and attentional parameters. Relationships between clinical and robotic assessment scores with respective task-difficulty parameters were analyzed using a multivariate regression model and a principal component analysis. Results Game difficulty rapidly (within approximately thirty minutes) auto-adapted to match individual impairment levels. The relationship between task-difficulty parameters with motor (Fugl Meyer Assessment: r = 0.84 p

Abstract Background Apple breeding schemes can be improved by using genomic prediction models to forecast the performance of breeding material. The predictive ability of these models depends on factors like trait genetic architecture, training set size, relatedness of the selected material to the training set, and the validation method used. Alternative genotyping methods such as RADseq and complementary data from near-infrared spectroscopy could help improve the cost-effectiveness of genomic prediction. However, the impact of these factors and alternative approaches on predictive ability beyond experimental populations still need to be investigated. In this study, we evaluated 137 prediction scenarios varying the described factors and alternative approaches, offering recommendations for implementing genomic selection in apple breeding. Results Our results show that extending the training set with germplasm related to the predicted breeding material can improve average predictive ability across eleven studied traits by up to 0.08. The study emphasizes the usefulness of leave-one-family-out cross-validation, reflecting the application of genomic prediction to a new family, although it reduced average predictive ability across traits by up to 0.24 compared to 10-fold cross-validation. Similar average predictive abilities across traits indicate that imputed RADseq data could be a suitable genotyping alternative to SNP array datasets. The best-performing scenario using near-infrared spectroscopy data for phenomic prediction showed a 0.35 decrease in average predictive ability across traits compared to conventional genomic prediction, suggesting that the tested phenomic prediction approach is impractical. Conclusions Extending the training set using germplasm related with the target breeding material is crucial to improve the predictive ability of genomic prediction in apple. RADseq is a viable alternative to SNP array genotyping, while phenomic prediction is impractical. These findings offer valuable guidance for applying genomic selection in apple breeding, ultimately leading to the development of breeding material with improved quality.

Abstract Background Autoimmune hepatitis is a chronic liver disease marked by immune-mediated inflammation, necrosis, and the potential to progress to cirrhosis if not treated. This case report presents a rare and atypical presentation of autoimmune hepatitis in a Nigerian adolescent girl, highlighting diagnostic challenges in resource-limited settings. The case is unique owing to the absence of jaundice, a common symptom of liver dysfunction, and features such as delayed menarche and bilateral leg swelling. Case presentation The patient was a 16-year-old Black female patient of Igbo ethnicity from Nigeria, who presented with a 6-month history of bilateral leg swelling and delayed menarche. She had no history of jaundice and abdominal pain, and she had no significant past medical history. She was initially misdiagnosed, delaying appropriate management. Following a comprehensive diagnostic workup, including liver function tests, imaging, and autoantibody testing, which were positive for antinuclear and antismooth muscle antibodies, she was correctly diagnosed with type 1 autoimmune hepatitis. Treatment was initiated with corticosteroids (prednisolone) and azathioprine, which resulted in clinical improvement. However, her serum albumin levels remained low as a result of the preexisting cirrhosis. Conclusions This case highlights the diagnostic challenges of autoimmune hepatitis in adolescents, particularly in regions where infectious liver diseases are more commonly suspected. It emphasizes the need for increased awareness and better diagnostic resources to improve early detection and management of autoimmune hepatitis in sub-Saharan Africa. Early intervention with immunosuppressive therapy is essential, even in the absence of classic liver-related symptoms, to prevent progression to advanced liver disease.

Abstract Background Improvements in diagnostics and clinical care have allowed more women of childbearing age, suffering from neurological diseases, to safely have pregnancy, reducing peripartum complications. However, these patients remain at risk and are a constant challenge for anesthesiologists in the delivery room. Methods To assess the type of anesthesiologic management performed for delivery in obstetric patients with preexisting neurological disease and who reported significant neurological symptoms during pregnancy, a retrospective observational study was carried out between 1 October 2008 and 30 September 2021. Results Data from 49,202 pregnant women were assessed over 13 years; 239 pregnant women with a diagnosis of preexisting neurological disease and who reported significant neurological symptoms during pregnancy were identified (prevalence 0.49%). The main neurological disorders that affected pregnant women included vascular abnormalities and intracranial bleeding (N = 42, 17.6%), central nervous system tumors (N = 35, 14.6%), epilepsy and episodic and paroxysmal disorders of the central nervous system (N = 34, 14.2%), diseases of the neuromuscular junction and muscles (N = 26, 10.9%), demyelinating central nervous system diseases (N = 24, 10%). A total of 234 (97.9%) pregnant women with neurological disorders and significant neurological symptoms underwent cesarean section: 192 (80.3% of the total cesarean sections) were elective, 39 (16.3%) were urgent type 2 and 3; 3 (1.2%) were emergency cesarean sections. General anesthesia was administered to 73 patients (30.5%), while 166 patients (69.5%) were managed with neuraxial techniques. 2 patients who had had neuraxial block reported worsening neurological symptoms that required a change in medical therapy. Postoperative multiparameter monitoring was performed for less than 24 h in the recovery room for 226 patients (94.6%). 3 patients (1.2%) were observed with multiparameter monitoring in the post-anesthesia care unit (PACU) for more than 24 hours; 10 patients (4.2%) were moved to the postoperative intensive care unit (ICU). The median hospitalization duration was 4 days (with an interquartile difference of 3–6 days). Conclusions In our experience, when neuraxial anesthesia was feasible, it proved to be a safe option for pregnant patients with symptomatic neurological disease, resulting in uncommon maternal complications.

Abstract The Last Ice Area—located to the north of Greenland and the northern Canadian Arctic Archipelago—is expected to persist as the central Arctic Ocean becomes seasonally ice-free within a few decades. Projections of the Last Ice Area, however, have come from relatively low resolution Global Climate Models that do not resolve sea ice export through the waterways of the Canadian Arctic Archipelago and Nares Strait. Here we revisit Last Ice Area projections using high-resolution numerical simulations from the Community Earth System Model, which resolves these narrow waterways. Under a high-end forcing scenario, the sea ice of the Last Ice Area thins and becomes more mobile, resulting in a large export southward. Under this potentially worst-case scenario, sea ice of the Last Ice Area could disappear a little more than one decade after the central Arctic Ocean has reached seasonally ice-free conditions. This loss would have profound impacts on ice-obligate species.

This article presents the results of morphological studies, as well as comparisons and phylogenetic analyzes of sequences of four arbuscular mycorrhizal fungi (AMF, phylum Glomeromycota): Dominikia indica, Dominikia indica strain 211, Isolate 517, and Isolate 524. Dominikia indica strain 211 was previously characterized only by sequences of the 45S nuc rDNA region (= 18S, partial, ITS-1-5.8S-ITS2, 28S, partial) and the rpb1 gene (without any morphological data) that were deposited in GenBank under the incorrect name “Dominikia indica strain 211”. Its 45S sequences differed from the original D. indica sequences and, consequently, resulted in erroneous phylogenetic classification of this species. Isolate 517 and Isolate 524 slightly differed in morphology from Macrodominikia compressa (formerly D. compressa) and Microkamienskia perpusilla (formerly Kamienskia perpusilla), respectively. Microkamienskia perpusilla was originally found in a maritime dune site of Italy in 2009 and not yet reported from any other habitat in the world. Our sequence comparisons and analyses showed that D. indica represents a new genus, here created under the name Delicatispora gen. nov. with De. indica comb. nov., and Dominikia indica strain 211 is a new species, described as Dominikia paraminuta sp. nov. These analyses also indicated that Isolate 517 is conspecific to M. compressa and confirmed the correctness of the transfer of D. compressa by other AMF researchers to Macrodominikia gen. nov. with M. compressa comb. nov. Morphological studies of our M. compressa specimens grown in culture showed that the original description of this species is incomplete and, therefore, the description was emended. Phylogenetic analyses of Isolate 524 proved its conspecificity to Mk. perpusilla and thus revealed its second site of occurrence, i.e., the coastal dunes of the Hel Peninsula in northern Poland.

s, also known as drones, are increasingly used in several applications and a variety of cyber attacks can be performed on them using several tools. Some examples of these attacks include breaking the connection between the drone and the controller with deauthentication attacks, discovering a password or cryptographic key used in a communication protocol, gaining control of the drone through command/code injection, and attacks. This paper covers drone attacks by analyzing different components of the drone, including the remote controller and communication protocols. The main purpose is to provide an overview of the possible ways in which cyber attacks can be executed. This analysis concludes that drones, designed for diverse purposes, are vulnerable to a range of cyber attacks. The paper also reviews existing penetration testing methodologies for UAVs, which provide a logical framework for their realization. This review covers the different cyber attack methods and tools used against a UAV, intending to improve defense mechanisms.

Abstract West Africa, the largest cocoa‐producing region globally, has experienced significant deforestation in recent decades, leading countries to implement large‐scale agroforestry policies; however, most studies on farmers' adoption of agroforestry fail to consider the social (Who?), historical (When?), geographical (Where?), and ecological (What?) factors that influence their motivations to value trees. Drawing from a sample of 150 farmers responsible for the management of 12,096 trees, we quantified the motivations of farmers for 10 material and immaterial uses of trees and used a Bayesian modelling framework to explore the relative importance of the 4 W framework in explaining general motivations, specific to each use, as well as the varying levels of specialization in tree management strategies among farmers. The distribution of use values by category shows that the highest values are associated with (i) agronomic uses (such as shade for cocoa trees and soil fertilization), (ii) food for human consumption, (iii) social purposes, and (iv) medicinal uses. All four aspects of the 4 W framework significantly contribute to understanding farmers' deep motivations, while the influence of each 4 W determinant varies based on the specific material and immaterial uses being considered. The level of specialization or diversification in cocoa farmers' motivations is significantly influenced by their knowledge of tree species and cocoa tree density, with knowledgeable farmers exhibiting greater diversification, while higher cocoa tree density and the presence of remnant trees lead to more specialized strategies that hinder agroforestry adoption. From a political perspective, it is urgent that stakeholders involved in the promotion of agroforestry consider all dimensions of the farmer‐field system. The diversity of farmers' life histories (Who), of cultivated landscapes (Where), of field systems (What), and of time trajectories (When) present both constraints and opportunities with which farmers must contend to transition to much‐desired agroforestry systems. Read the free Plain Language Summary for this article on the Journal blog.

Abstract How does the fig tree Ficus benguetensis protect its investment in the production of figs and pollinating fig wasps against parasitism from non-pollinating fig wasps? This study documents a previously overlooked defense mechanism: fig abscission—the natural shedding of the fig fruit as a defense mechanism. Our bagging experiments showed that both the absence of pollination and high parasitism levels lead to the abortion of F. benguetensis figs, with positive correlations between parasitism levels, increased abscission rates, and decreased pollinator production. Moreover, we found that high parasitism corresponds to shortened fig development periods until abscission, while medium parasitism levels result in fewer pollinators. Our findings suggest that abscission may function as a resource conservation strategy, as most of the tree’s investment in the figs occurs post-pollination. This study uncovers for the first time the use of fig abscission as a unique defense against non-pollinating fig wasp parasites, broadening our understanding of plant defense mechanisms within mutualistic interactions.

Abstract Dispersal is an important life history trait that plays a key role in the demography and evolution of species. We employed a combined approach of DNA sequencing and transmission electron microscopy to examine the changes in the microbiome during the ontogeny and dispersal of the coral-excavating sponge Thoosa mismalolli. The results show that sponge can acquired their associated bacteria via both vertical (VT) and horizontal transmission (HT). Adult sponges, brooding larvae, and early free-swimming sponge larvae harbor a similar high-diversity microbial assemblage, dominated by Proteobacteria and Chloroflexi, which change throughout the larval dispersal phase. Larvae collected offshore showed a reorganization of their microbiome with a significant reduction of the dominance of inherited bacteria (Proteobacteria and Chloroflexi), and an enrichment of environmentally derived bacteria taxa (Bacteroidetes, Tenericutes, and Firmicutes). TEM confirmed a substantial change in cell structure and microbial composition, attributed to symbionts’ massive phagocytosis. This research provides information on microbiome dynamics through the sponge ontogeny and sheds on their possible role in the dispersal capacity of their larvae.

Abstract The Sydney funnel-web spider Atrax robustus O. Pickard-Cambridge, 1877 is an iconic Australian species and considered among the most dangerously venomous spiders for humans. Originally described in 1877 from a single specimen collected in “New Holland”, this spider has a complex taxonomic history. The most recent morphological revision of funnel-web spiders (Atracidae) lists this species as both widespread and common in the Sydney Basin bioregion and beyond, roughly 250 km from the Newcastle area south to the Illawarra, and extending inland across the Blue Mountains. Morphological variability and venom diversity in this species appear to be unusually high, raising questions about species concepts and diversity in these spiders. In this study, we use a combination of molecular phylogenetics, divergence time analyses and morphology to establish the Sydney funnel-web spider as a complex of three species. The “real” Sydney funnel-web spider Atrax robustus is relatively widespread in the Sydney metropolitan region. A second species, Atrax montanus (Rainbow, 1914), which is revalidated here, overlaps but mainly occurs further south and west, and a third larger species, Atrax christenseni sp. nov., is found in a small area surrounding Newcastle to the north. The revised taxonomy for funnel-web spiders may have practical implications for antivenom production and biochemical studies on spider venoms. Although no human fatalities have occurred since the development of antivenom in the 1980s, antivenom for Sydney funnel-web spiders might be optimized by considering biological differentiation at the species level.

Abstract The High Atlas Mountains of Morocco are recognized as a global hotspot for rapid environmental change, but there is limited information about how communities and households are responding. Rural livelihoods that are dependent on agriculture are highly vulnerable to intensifying climate extremes, especially when these stressors intersect with long-term socioeconomic trends, including out-migration to urban centers. In 2022–2023, we carried out a a household survey and focus group discussions to understand the evolution of livelihood strategies in four Amazigh villages in Imegdal Commune in the western High Atlas. Results suggest that water shortages are causing cropping systems to simplify, as households stop planting some crop species and reduce the area planted of others. Households are also reducing livestock numbers in response to drought and reductions in labor availability created by migration. Other natural resource-based activities, including beekeeping and collecting wild herbs, are being abandoned. This study suggests that decreasing precipitation is rapidly undermining the viability of agricultural activities in the High Atlas. In the absence of viable adaptation strategies, this could lead to a profound restructuring of rural livelihoods across the region.

Abstract Background Presentations and outcomes of acute myocardial infarction (MI) differ between women and men, with the worst outcomes being reported in younger women. Mental stress induced ischemia and sympathetic activation have been suggested to play a prominent role in the pathogenesis of MI in younger women, however, the impact of sex hormones on these parameters remains unknown. Methods The effect of sex hormones and age on myocardial infarct size and myocardial sympathetic activity (MSA) was assessed in male and female, as well as young (4–6 months) and aged (20–22 months) FVB/N mice (n = 106, 60 gonadectomized and 46 sham-operated animals) who underwent in vivo [11C]meta-hydroxyephedrine ([11C]mHED) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging 24 h after a 30 min myocardial ischemic injury. Results MSA and catecholamine levels following myocardial injury were highest in young males (p = 0.008 and p = 0.043 vs. young females, respectively) and were reduced by orchiectomy. Accordingly, testosterone serum levels correlated positively with MSA (r = 0.66, p

Abstract Background Sepsis-associated encephalopathy (SAE) may be worsened by early systemic insults. We aimed to investigate the association of early systemic insults with outcomes of critically ill patients with severe SAE. Methods We performed a retrospective analysis using data from the French OUTCOMEREA prospective multicenter database. We included patients hospitalized in intensive care unit (ICU) for at least 48 h with severe SAE (defined by a score on the Glasgow Coma Scale (GCS) ≤ 13 and severe sepsis or septic shock (SEPSIS 2.0 criteria)) requiring invasive ventilation and who had no primary brain injury. We analyzed early systemic insults (abnormal glycemia ( 200 mmHg), carbon dioxide abnormalities ( 13. Results We included 995 patients with severe SAE, of whom 883 (89%) exhibited at least one early systemic insult that persisted through day 3. Compared to non-survivors, survivors had significantly less early systemic insults (hypoglycemia, hypotension, hypothermia, and anemia) within the first 48 h of ICU admission. The absence of correction of the following systemic insults at day 3 was independently associated with mortality: blood pressure (adjusted hazard ratio (aHR) = 1.77, 95% confidence interval (CI) 1.34–2.34), oxygenation (aHR = 1.78, 95% CI 1.20–2.63), temperature (aHR = 1.46, 95% CI 1.12–1.91) and glycemia (aHR = 1.41, 95% CI 1.10–1.80). Persistent abnormal blood pressure, temperature and glycemia at day 3 were associated with decreased chances of awakening. Conclusions In patients with severe SAE, the persistence of systemic insults within the first three days of ICU admission is associated with increased mortality and decreased chances of awakening.

Abstract In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer’s disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan. Plasma Aβ42/40 ratio, neurofilament light chain and p-tau181 were also available for a sub-sample of participants. Multivariate linear regressions were performed and stratified by APOE4 genotype. The median age was 74.0 years, 85.2% were infected with HSV-1. Infected participants tended to have a lower cortical amyloid load than uninfected participants (β = -0.08, p = 0.06), especially those suspected of reactivating HSV-1 most frequently (i.e. with a high anti-HSV-1 IgG level; n = 58, β = -0.09 p = 0.04). After stratification, the association was only significant in APOE4 carriers (n = 43, β = -0.21 p = 0.01). No association was found with the plasma biomarkers. The trend toward lower cortical amyloid load in HSV-1-infected participants was unexpected given the pre-existing literature and may be explained either by a modified immune response in HSV-1 infected subjects which could favour the clearance of amyloid deposits or by a selection bias.

Abstract Meat consumption has significant implications for both individual health and the environment. Understanding individuals’ attachment to meat is crucial for designing effective interventions to reduce consumption. The MAQ is a tool developed to assess individuals’ attachment to meat. This study aims to translate and validate the MAQ into French for use in a general practice population in France. The study was conducted in three phases: translation, pretesting through cognitive interviews, and testing through a cross-sectional study of general practice patients. Descriptive, factorial, and internal consistency analyses were performed to validate the French version of the MAQ. The French version of the MAQ consists of 17 items in four dimensions: Hedonism, Affinity, Entitlement, and Dependence. Face validity was confirmed by cognitive interviews. The RMSEA and CFI were 0.06 and 0.92 respectively, showing acceptable goodness-of-fit. Internal consistency was demonstrated with Cronbach’s alpha and Loevinger’s H coefficients exceeding 0.7 and 0.3, respectively. The French version of the MAQ is a valid and reliable tool for assessing individuals’ attachment to meat in a general practice population. Its application shows promise for the design of targeted interventions to reduce meat consumption, benefiting both individual health and environmental sustainability.

Abstract Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documentation of how inflammatory processes are associated with neural activity in patients with depression. We therefore tested the hypothesis that the peripheral inflammation markers IL-6 and TNF-α correlate with neural resting state network functional connectivity in depression using functional magnetic resonance imaging (fMRI) and compared it with healthy controls. We used fMRI to investigate the functional connectivity (FC) of the resting state Default Mode Network (DMN) and Salience/Ventral Attention Network (SAL) and their association with the peripheral inflammation markers IL-6 and TNF-α in 25 patients with depression and compared it to 24 healthy subjects. Results of this imaging study revealed that both DMN and SAL resting state networks are differentially associated with distinct immunological pathways depending on whether a person has a depressive phenotype or is healthy. While the DMN FC correlated with the concentration of the cytokine IL-6 in healthy subjects, SAL FC’s connectivity correlated with the cytokine TNF-α's concentration. This study highlights the importance of peripheral inflammatory processes in depression and suggests a modulatory effect on neural resting state networks depending on the state of depression.

Abstract Topological magnetic solitons, such as skyrmions, exhibit intriguing particle-like properties that make them attractive for fundamental research and practical applications. While many magnetic systems can host skyrmions as statically stable configurations, chiral magnets stand out for their ability to accommodate a wide diversity of skyrmions with arbitrary topological charges and varied morphologies. Despite extensive investigation, a complete understanding of chiral magnetic skyrmions has remained elusive. We present a classification of all chiral skyrmions, demonstrating three classes based on their response to external magnetic field pulses: stationary, translating, and rotating. We highlight the role of magnetic texture symmetry in this classification. Skyrmions with varied dynamics offer avenues for exploring phenomena like skyrmion-skyrmion scattering that might be crucial for future applications.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options and a poor prognosis. The critical role of epigenetic alterations such as changes in DNA methylation, histones modifications, and chromatin remodeling, in pancreatic tumors progression is becoming increasingly recognized. Moreover, in PDAC these aberrant epigenetic mechanisms can also limit therapy efficacy. This study aimed to investigate the expression and prognostic significance of a key epigenetic complex encompassing DNA methyltransferase-1 (DNMT1), the histone methyltransferase G9a, and the scaffold protein UHRF1 in PDAC. We also evaluated the therapeutic potential of an innovative inhibitor targeting these epigenetic effectors. Methods Immunohistochemical analysis of DNMT1, G9a, and UHRF1 expression was conducted in human PDAC tissue samples. Staining was semi-quantitatively scored, and overexpression was defined as moderate to strong positivity. The prognostic impact was assessed by correlating protein expression with patient survival. The antitumoral effects of the dual DNMT1-G9a inhibitor CM272 were tested in PDAC cell lines, followed by transcriptomic analyses to identify underlying mechanisms. The in vivo antitumoral efficacy of CM272 was evaluated in PDAC xenograft and syngeneic mouse models, both alone and in combination with anti-PD1 immunotherapy. Results DNMT1, G9a, and UHRF1 were significantly overexpressed in PDAC cells and stroma compared to normal pancreatic tissues. Simultaneous overexpression of the three proteins was associated with significantly reduced survival in resected PDAC patients. CM272 exhibited potent antiproliferative activity in PDAC cell lines, inducing apoptosis and altering key metabolic and cell cycle-related genes. CM272 also enhanced chemotherapy sensitivity and significantly inhibited tumor growth in vivo without detectable toxicity. Combination of CM272 with anti-PD1 therapy further improved antitumor responses and immune cell infiltration, particularly CD4 + and CD8 + T cells. Conclusions The combined overexpression of DNMT1, G9a, and UHRF1 in PDAC is a strong predictor of poor prognosis. CM272, by targeting this epigenetic complex, shows promising therapeutic potential by inducing apoptosis, reprogramming metabolic pathways, and enhancing immune responses. The combination of CM272 with immunotherapy offers a novel, effective treatment strategy for PDAC.