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Abstract Natural killer (NK) cells recognize and may kill malignant cells via their cell surface receptors. Killer cell immunoglobulin-like receptor (KIR) genotypes of donors have been reported to adjust the risk of relapse after allogeneic stem cell transplantation (HSCT), particularly in patients with acute myeloid leukemia. To test whether non-KIR NK cell receptors have a similar effect, we screened 1,638 genetic polymorphisms in 21 non-KIR NK cell receptor genes for their associations with relapse and graft-versus-host disease (GVHD) after HSCT in 1,491 HSCT donors (from Finland, the UK, Spain, and Poland), divided into a discovery and replication cohort. Eleven polymorphisms regulating or located in CD226, CD244, FCGR3A, KLRD1, NCR3, and PVRIG were associated with the risks for relapse and GVHD. These associations could not be confirmed in the replication cohort. Blood donor NK cells carrying alleles showing genetic protection for relapse had a higher in vitro NK cell killing activity than non-carriers whereas those with alleles genetically protective for GVHD had lower cytotoxicity, potentially indicating functional effects. Taken together, these results show no robust effects of genetic variation in the tested non-KIR NK cell receptors on the outcome of HSCT.

Abstract Methadone is a synthetic long-acting opioid that is increasingly used in the replacement therapy of opioid-addicted patients, including pregnant women. However, methadone therapy in this population poses challenges, as it induces cognitive and behavioral impairments in infants exposed to this opioid during prenatal development. In animal models, prenatal methadone exposure results in detrimental consequences to the central nervous system, such as: (i) increased neuronal apoptosis; (ii) disruption of oligodendrocyte maturation and increased apoptosis and (iii) increased microglia and astrocyte activation. However, it remains unclear whether these deleterious effects result from a direct effect of methadone on brain cells. Therefore, our goal was to uncover the impact of methadone on single brain cell types in vitro. Primary cultures of rat neurons, oligodendrocytes, microglia, and astrocytes were treated for three days with 10 µM methadone to emulate a chronic administration. Apoptotic neurons were identified by cleaved caspase-3 detection, and synaptic density was assessed by the juxtaposition of presynaptic and postsynaptic markers. Apoptosis of oligodendrocyte precursors was determined by cleaved caspase-3 detection. Oligodendrocyte myelination was assessed by immunofluorescence, while microglia and astrocyte proinflammatory activation were assessed by both immunofluorescence and RT-qPCR. Methadone treatment increased neuronal apoptosis and reduced synaptic density. Furthermore, it led to increased oligodendrocyte apoptosis and a reduction in the myelinating capacity of these cells, and promoted the proinflammatory activation of microglia and astrocytes. We showed that methadone, the most widely used drug in opioid replacement therapy for pregnant women with opioid addiction, directly impairs brain cells in vitro, highlighting the need for developing alternative therapies to address opioid addiction in this population.

Abstract Rapidly waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires continued global access to affordable vaccines. Globally, inactivated SARS-CoV-2 vaccines have been widely used during the SARS-CoV-2 pandemic. In this proof-of-concept study we adapted an original-D614G SARS-CoV-2 virus to Vero cell culture as a strategy to enhance inactivated vaccine manufacturing productivity. A passage 60 (P60) virus showed enhanced fitness and 50-fold increased virus yield in a bioreactor compared to the original-D614G virus. It further remained susceptible to neutralization by plasma from SARS-CoV-2 vaccinated and convalescent individuals, suggesting exposure of relevant epitopes. Monovalent inactivated P60 and bivalent inactivated P60/omicron BA.1 vaccines induced neutralizing responses against original-D614G and BA.1 viruses in mice and hamsters, demonstrating that the P60 virus is a suitable vaccine antigen. Antibodies further cross-neutralized delta and BA.5 viruses. Importantly, the inactivated P60 vaccine protected hamsters against disease upon challenge with original-D614G or BA.1 virus, with minimal lung pathology and lower virus loads in the upper and lower airways. Antigenicity of the P60 virus was thus retained compared to the original virus despite the acquisition of cell culture adaptive mutations. Consequently, cell culture adaptation may be a useful approach to increase yields in inactivated vaccine antigen production.

Abstract Sjögren syndrome (SS) is an autoimmune disease characterized by chronic inflammatory infiltrates in the salivary and lacrimal glands. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T-cells, predominantly found in mucosal tissues with crucial role in epithelial homeostasis. Thus, MAIT cells may be implicated in mucosal alterations of SS patients. Activation markers, inflammatory and cytotoxic cytokines were examined in 23 SS patients and compared to 23 healthy controls (HC). Tissular MAIT cells in salivary gland (SG) biopsies were also analyzed. Circulating MAIT cells were decreased in SS patients with a higher expression of CD69 and a higher CD4/CD8 ratio of MAIT cells. MAIT cells showed a higher production of IFNγ, TNFα and GzB in SS compare to HC. Tissular MAIT cells were present within inflamed SG of SS patients, while they were absent in SG of HC. Overall, circulating MAIT cells are decreased in the peripheral blood of SS albeit producing higher amounts of IFNγ, TNFα, and GzB. Tissular MAIT cells are detected in salivary glands from SS with a proinflammatory tissular cytokine environment. MAIT cells with abnormal phenotype, functions and tissular homeostasis may contribute to epithelial damage in SS.

Abstract Psoriasis is a chronic skin disease that negatively impacts on patient’s life. A holistic approach integrating well-being assessment could improve disease management. Since a consensus definition of well-being in psoriasis is not available, we aim to achieve a multidisciplinary consensus on well-being definition and its components. A literature review and consultation with psoriasis patients facilitated the design of a two-round Delphi questionnaire targeting healthcare professionals and psoriasis patients. A total of 261 panellists (65.1% patients with psoriasis, 34.9% healthcare professionals) agreed on the dimensions and components that should integrate the concept of well-being: emotional dimension (78.9%) [stress (83.9%), mood disturbance (85.1%), body image (83.9%), stigma/shame (75.1%), self-esteem (77.4%) and coping/resilience (81.2%)], physical dimension (82.0%) [sleep quality (81.6%), pain/discomfort (80.8%), itching (83.5%), extracutaneous manifestations (82.8%), lesions in visible areas (84.3%), lesions in functional areas (85.8%), and sex life (78.2%)], social dimension (79.5%) [social relationships (80.8%), leisure/recreational activities (80.3%), support from family/friends (76.6%) and work/academic life (76.5%)], and satisfaction with disease management (78.5%) [treatment (78.2%), information received (75.6%) and medical care provided by the dermatologist (80.1%)]. This well-being definition reflects patients’ needs and concerns. Therefore, addressing them in psoriasis will optimise management, contributing to better outcomes and restoring normalcy to the patient’s life.

Abstract The aim of this study is to analyse the relationship between sport modalities practiced, physical fitness, body composition, and healthy habits in an active young population, using a statistical model for prediction. A total of 2255 (1528 boys and 727 girls) children and adolescents aged 6–17 years old who were involved in extracurricular sports from rural areas of Spain participated. Physical fitness was assessed through validated field test and, body composition was determinated using bioelectrical impedance analysis. Adherence to the Mediterranean diet was assessed by KIDMED questionnaire. The general sport variable was significant in VO2max when comparing the invasion and combat modalities to the reference level (court/net). The sex and age variables revealed significant differences in all physical fitness and body composition parameters. Health parameters, such as hours of additional practice, adherence to the Mediterranean diet, and previous experience, showed significant differences. The study concludes that the sport modality variables of training, sex, age, and maturational period have an impact on body composition and fitness parameters in this population. Therefore, by focusing on factors associated with lower values in health indicators, we can prevent health problems during adulthood, such as cardiorespiratory deficits.

Abstract Three-dimensional (3D) geometrical models are potent tools for quantifying complex tissue features and exploring structure–function relationships. However, these models are generally incomplete due to experimental limitations in acquiring multiple (> 4) fluorescent channels in thick tissue sections simultaneously. Indeed, predictive geometrical and functional models of the liver have been restricted to few tissue and cellular components, excluding important cellular populations such as hepatic stellate cells (HSCs) and Kupffer cells (KCs). Here, we combined deep-tissue immunostaining, multiphoton microscopy, deep-learning techniques, and 3D image processing to computationally expand the number of simultaneously reconstructed tissue structures. We then generated a spatial single-cell atlas of hepatic architecture (Hep3D), including all main tissue and cellular components at different stages of post-natal development in mice. We used Hep3D to quantitatively study 1) hepatic morphodynamics from early post-natal development to adulthood, and 2) the effect on the liver's overall structure when changing the hepatic environment after removing KCs. In addition to a complete description of bile canaliculi and sinusoidal network remodeling, our analysis uncovered unexpected spatiotemporal patterns of non-parenchymal cells and hepatocytes differing in size, number of nuclei, and DNA content. Surprisingly, we found that the specific depletion of KCs results in morphological changes in hepatocytes and HSCs. These findings reveal novel characteristics of liver heterogeneity and have important implications for both the structural organization of liver tissue and its function. Our next-gen 3D single-cell atlas is a powerful tool to understand liver tissue architecture, opening up avenues for in-depth investigations into tissue structure across both normal and pathological conditions.

Abstract Huntington’s disease (HD) is caused by an aberrant expansion of CAG repeats in the HTT gene that mainly affects basal ganglia. Although striatal dysfunction has been widely studied in HD mouse models, other brain areas can also be relevant to the pathology. In this sense, we have special interest on the retina as this is the most exposed part of the central nervous system that enable health monitoring of patients using noninvasive techniques. To establish the retina as an appropriate tissue for HD studies, we need to correlate the retinal alterations with those in the inner brain, i.e., striatum. We confirmed the malfunction of the transgenic R6/1 retinas, which underwent a rearrangement of their transcriptome as extensive as in the striatum. Although tissue-enriched genes were downregulated in both areas, a neuroinflammation signature was only clearly induced in the R6/1 retina in which the observed glial activation was reminiscent of the situation in HD patient’s brains. The retinal neuroinflammation was confirmed in the slow progressive knock-in zQ175 strain. Overall, these results demonstrated the suitability of the mouse retina as a research model for HD and its associated glial activation.

Abstract Over the last decade we have witnessed an increasing number of studies revealing the functional role of non-coding RNAs in a multitude of biological processes, including cellular homeostasis, proliferation and differentiation. Impaired expression of non-coding RNAs can cause distinct pathological conditions, including herein those affecting the gastrointestinal and cardiorespiratory systems, respectively. miR-15/miR-16/miR-195 family members have been broadly implicated in multiple biological processes, including regulation of cell proliferation, apoptosis and metabolism within distinct tissues, such as heart, liver and lungs. While the functional contribution of miR-195a has been reported in multiple biological contexts, the role of miR-195b remains unexplored. In this study we dissected the functional role of miR-195b by generating CRISPR-Cas9 gene edited miR-195b deficient mice. Our results demonstrate that miR-195b is dispensable for embryonic development. miR-195b−/− mice are fertile and displayed no gross anatomical and/or morphological defects. Mechanistically, cell cycle regulation, metabolism and oxidative stress markers are distinctly impaired in the heart, liver and lungs of aged mice, a condition that is not overtly observed at midlife. The lack of overt functional disarray during embryonic development and early adulthood might be due to temporal and tissue-specific compensatory mechanisms driven by selective upregulation miR-15/miR-16/miR-195 family members. Overall, our data demonstrated that miR-195b is dispensable for embryonic development and adulthood but is required for cellular homeostasis in the elderly.

Abstract Recent developments in deep learning have shown success in accurately predicting the location of biological markers in Optical Coherence Tomography (OCT) volumes of patients with Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). We propose a method that automatically locates biological markers to the Early Treatment Diabetic Retinopathy Study (ETDRS) rings, only requiring B-scan-level presence annotations. We trained a neural network using 22,723 OCT B-Scans of 460 eyes (433 patients) with AMD and DR, annotated with slice-level labels for Intraretinal Fluid (IRF) and Subretinal Fluid (SRF). The neural network outputs were mapped into the corresponding ETDRS rings. We incorporated the class annotations and domain knowledge into a loss function to constrain the output with biologically plausible solutions. The method was tested on a set of OCT volumes with 322 eyes (189 patients) with Diabetic Macular Edema, with slice-level SRF and IRF presence annotations for the ETDRS rings. Our method accurately predicted the presence of IRF and SRF in each ETDRS ring, outperforming previous baselines even in the most challenging scenarios. Our model was also successfully applied to en-face marker segmentation and showed consistency within C-scans, despite not incorporating volume information in the training process. We achieved a correlation coefficient of 0.946 for the prediction of the IRF area.

Abstract Influenza A virus (IAV) defective interfering particles (DIPs) are considered as new promising antiviral agents. Conventional DIPs (cDIPs) contain a deletion in the genome and can only replicate upon co-infection with infectious standard virus (STV), during which they suppress STV replication. We previously discovered a new type of IAV DIP “OP7” that entails genomic point mutations and displays higher antiviral efficacy than cDIPs. To avoid safety concerns for the medical use of OP7 preparations, we developed a production system that does not depend on infectious IAV. We reconstituted a mixture of DIPs consisting of cDIPs and OP7 chimera DIPs, in which both harbor a deletion in their genome. To complement the defect, the deleted viral protein is expressed by the suspension cell line used for production in shake flasks. Here, DIP preparations harvested are not contaminated with infectious virions, and the fraction of OP7 chimera DIPs depended on the multiplicity of infection. Intranasal administration of OP7 chimera DIP material was well tolerated in mice. A rescue from an otherwise lethal IAV infection and no signs of disease upon OP7 chimera DIP co-infection demonstrated the remarkable antiviral efficacy. The clinical development of this new class of broad-spectrum antiviral may contribute to pandemic preparedness.

Abstract The study of mild cognitive impairment (MCI) is critical to understand the underlying processes of cognitive decline in Parkinson’s disease (PD). Functional connectivity (FC) disruptions in PD-MCI patients have been observed in several networks. However, the functional and cognitive changes associated with the disruptions observed in these networks are still unclear. Using a data-driven methodology based on independent component analysis, we examined differences in FC RSNs among PD-MCI, PD cognitively normal patients (PD-CN) and healthy controls (HC) and studied their associations with cognitive and motor variables. A significant difference was found between PD-MCI vs PD-CN and HC in a FC-trait comprising sensorimotor (SMN), dorsal attention (DAN), ventral attention (VAN) and frontoparietal (FPN) networks. This FC-trait was associated with working memory, memory and the UPDRS motor scale. SMN involvement in verbal memory recall may be related with the FC-trait correlation with memory deficits. Meanwhile, working memory impairment may be reflected in the DAN, VAN and FPN interconnectivity disruptions with the SMN. Furthermore, interactions between the SMN and the DAN, VAN and FPN network reflect the intertwined decline of motor and cognitive abilities in PD-MCI. Our findings suggest that the memory impairments observed in PD-MCI are associated with reduced FC within the SMN and between SMN and attention networks.

Abstract Sirtuin 1 (SIRT1) is a key physiological regulator of metabolism and a target of therapeutic interventions for cardiometabolic and ageing-related disorders. Determining the factors and possible mechanisms of acute and adaptive SIRT1 response to exercise is essential for optimising exercise interventions aligned to the prevention and onset of disease. Exercise-induced SIRT1 upregulation has been reported in animals, but, to date, data in humans have been inconsistent. This exploratory systematic review and meta-analysis aims to assess various exercise interventions measuring SIRT1 in healthy participants. A total of 34 studies were included in the meta-analysis (13 single bout exercise, 21 training interventions). Studies were grouped according to tissue sample type (blood, muscle), biomarkers (gene expression, protein content, enzyme level, enzyme activity), and exercise protocols. A single bout of high-intensity or fasted exercise per se increases skeletal muscle SIRT1 gene expression as measured by qPCR or RT-PCR, while repeated resistance training alone increases blood SIRT1 levels measured by ELISA. A limited number of studies also show a propensity for an increase in muscle SIRT1 activity as measured by fluorometric or sirtuin activity assay. In conclusion, exercise acutely upregulates muscle SIRT1 gene expression and chronically increases SIRT1 blood enzyme levels.

Abstract The demanding nature of elite football requires players to be closely monitored to ensure optimal performance and minimize injury risk. This study aimed to evaluate the relationship between physical demands, skin temperature, and well-being status in 30 elite football players over a 12-week competitive period. Thermography assessments, weekly Well-being questionnaires, and daily training and match load recordings were used to gather data. Results indicated that along the microcycles there was a decrease in high-intensity accelerations and decelerations distance completed, while maintaining other high-intensity actions. Furthermore, it was found that high-intensity movements contribute to the generation of thermal asymmetries in the thighs; the adductor thermal asymmetry showed a positive relationship with stress and muscle soreness, the knee thermal asymmetry had a positive relationship with fatigue and a negative relationship with rest and quality of rest, and finally the hamstrings muscles exhibited significant differences between the thermal asymmetry groups, with the high asymmetry completing less high intensity actions than the low asymmetry group. In conclusion, this study highlights the interconnections between physical demands, skin temperature, and well-being in elite football players and provides valuable insights for coaches and trainers in their efforts to optimize performance and health.

Abstract Previous research indicates that some important cocoa cultivated areas in West Africa will become unsuitable for growing cocoa in the next decades. However, it is not clear if this change will be mirrored by the shade tree species that could be used in cocoa-based agroforestry systems (C-AFS). We characterized current and future patterns of habitat suitability for 38 tree species (including cocoa), using a consensus method for species distribution modelling considering for the first time climatic and soil variables. The models projected an increase of up to 6% of the potential suitable area for cocoa by 2060 compared to its current suitable area in West Africa. Furthermore, the suitable area was highly reduced (14.5%) once considering only available land-use not contributing to deforestation. Regarding shade trees, 50% of the 37 shade tree species modelled will experience a decrease in geographic rate extent by 2040 in West Africa, and 60% by 2060. Hotspots of shade tree species richness overlap the current core cocoa production areas in Ghana and Côte d’Ivoire, suggesting a potential mismatch for the outer areas in West Africa. Our results highlight the importance of transforming cocoa-based agroforestry systems by changing shade tree species composition to adapt this production systems for future climate conditions.

Abstract An investigation of the deactivation of pathogens using electromagnetic waves in the microwave region of the spectrum is achieved using custom-built waveguide structures. The waveguides feature sub-wavelength gratings to allow the integration of an air cooling system without disturbing the internal propagating fields. The waveguides are tapered to accommodate an experimental sample internally with sufficient surrounding airflow. The proposed methodology allows for precise control over power densities due to the well-defined fundamental mode excited in each waveguide, in addition to temperature control of the sample due to microwave exposure over time. Human coronavirus (HCoV-229E) is investigated over the 0–40 GHz range, where a peak 3-log viral reduction is observed in the 15.0–19.5 GHz sub-band. We conclude HCoV-229E has an intrinsic resonance in this range, where nonthermal structure damage is optimal through the structure-resonant energy transfer effect.

Newcastle disease (ND) has a great impact on poultry health and welfare with its most virulent (velogenic) strain. In addition, issues exacerbated by the increase in global temperatures necessitates a greater understanding of the host immune response when facing a combination of biotic and abiotic stress factors in poultry production. Previous investigations have revealed that the host immune response is tissue-specific. The goal of this study was to identify genes and/or signaling pathways associated with immune response to NDV (Newcastle disease virus) in the trachea, an essential organ where NDV replicate after the infection, by profiling the tissue specific transcriptome response in two genetically distinct inbred chicken lines when exposed to both abiotic and biotic stressors. Fayoumis appear to be able to respond more effectively (lower viral titer, higher antibody levels, immune gene up-regulation) and earlier than Leghorns. Our results suggest NDV infection in Fayoumis appears to elicit proinflammatory processes, and pathways such as the inhibition of cell viability, cell proliferation of lymphocytes, and transactivation of RNA, more rapidly than in Leghorns. These differences in immune response converge at later timepoints which may indicate that Leghorns eventually regulate its immune response to infection. The profiling of the gene expression response in the trachea adds to our understanding of the chicken host response to NDV infection and heat stress on a whole genome level and provides potential candidate genes and signaling pathways for further investigation into the characterization of the time-specific and pathway specific responses in Fayoumis and Leghorns.

Abstract Computer-assisted diagnosis (CAD) algorithms have shown its usefulness for the identification of pulmonary nodules in chest x-rays, but its capability to diagnose lung cancer (LC) is unknown. A CAD algorithm for the identification of pulmonary nodules was created and used on a retrospective cohort of patients with x-rays performed in 2008 and not examined by a radiologist when obtained. X-rays were sorted according to the probability of pulmonary nodule, read by a radiologist and the evolution for the following three years was assessed. The CAD algorithm sorted 20,303 x-rays and defined four subgroups with 250 images each (percentiles ≥ 98, 66, 33 and 0). Fifty-eight pulmonary nodules were identified in the ≥ 98 percentile (23,2%), while only 64 were found in lower percentiles (8,5%) (p

Abstract Given the barriers to early detection of gestational diabetes mellitus (GDM), this study aimed to develop an artificial intelligence (AI)-based prediction model for GDM in pregnant Mexican women. Data were retrieved from 1709 pregnant women who participated in the multicenter prospective cohort study ‘Cuido mi embarazo’. A machine-learning-driven method was used to select the best predictive variables for GDM risk: age, family history of type 2 diabetes, previous diagnosis of hypertension, pregestational body mass index, gestational week, parity, birth weight of last child, and random capillary glucose. An artificial neural network approach was then used to build the model, which achieved a high level of accuracy (70.3%) and sensitivity (83.3%) for identifying women at high risk of developing GDM. This AI-based model will be applied throughout Mexico to improve the timing and quality of GDM interventions. Given the ease of obtaining the model variables, this model is expected to be clinically strategic, allowing prioritization of preventative treatment and promising a paradigm shift in prevention and primary healthcare during pregnancy. This AI model uses variables that are easily collected to identify pregnant women at risk of developing GDM with a high level of accuracy and precision.

Abstract Previous studies using immunoassays for steroid measurements have focused on the association between steroid hormone levels and bone mineral density (BMD) in postmenopausal women, obtaining contradictory results. This study aimed to assess this association using a highly sensitive bioanalytical method. A total of 68 postmenopausal women, aged 65–89 years, were enrolled in a cross-sectional study. Measurements of the BMD of the hip and lumbar spine were performed using dual energy X-ray absorptiometry, and serum hormone levels were quantified by gas chromatography and tandem mass spectrometry. Associations between estradiol (E2), testosterone, dehydroepiandrosterone (DHEA), androstenedione and T score levels of the hip and lumbar spine were evaluated, after adjustment for confounding variables. The analysis revealed a statistically significant association between testosterone and the T score of the hip (p = 0.035), but not that of the lumbar spine. No statistically significant associations were found between E2, DHEA, androstenedione and the T scores of the hip and the lumbar spine. Using a highly sensitive hormone assay method, our study identified a significant association between testosterone and BMD of the hip in women over 65 years of age, suggesting that lower testosterone increases the risk of osteoporosis.

Abstract Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma that is incurable with existing therapies, and therefore presents a significant unmet clinical need. The ability of this disease to overcome therapy, including those that target the B cell receptor pathway which has a pathogenic role in MCL, highlights the need to develop new treatment strategies. Herein, we demonstrate that a distinguishing feature of lymph node resident MCL cells is the expression of phosphatidylinositol 3-kinase γ (PI3Kγ), a PI3K isoform that is not highly expressed in other B cells or B-cell malignancies. By exploring the role of PI3K in MCL using different PI3K isoform inhibitors, we provide evidence that duvelisib, a dual PI3Kδ/γ inhibitor, has a greater effect than PI3Kδ- and PI3Kγ-selective inhibitors in blocking the proliferation of primary MCL cells and MCL cell lines, and in inhibiting tumour growth in a mouse xenograft model. In addition, we demonstrated that PI3Kδ/γ signalling is critical for migration of primary MCL cells and cell lines. Our data indicates that aberrant expression of PI3Kγ is a critical feature of MCL pathogenesis. Thus, we suggest that the dual PI3Kδ/γ duvelisib would be effective for the treatment of mantle cell lymphoma.

Abstract In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.

Abstract Tools for the evaluation of COVID-19 severity would help clinicians with triage decisions, especially the decision whether to admit to ICU. The aim of this study was to evaluate SeptiCyte RAPID, a host immune response assay (Immunexpress, Seattle USA) as a triaging tool for COVID-19 patients requiring hospitalization and potentially ICU care. SeptiCyte RAPID employs a host gene expression signature consisting of the ratio of expression levels of two immune related mRNAs, PLA2G7 and PLAC8, measured from whole blood samples. Blood samples from 146 adult SARS-CoV-2 (+) patients were collected within 48 h of hospital admission in PAXgene blood RNA tubes at Hospital del Mar, Barcelona, Spain, between July 28th and December 1st, 2020. Data on demographics, vital signs, clinical chemistry parameters, radiology, interventions, and SeptiCyte RAPID were collected and analyzed with bioinformatics methods. The performance of SeptiCyte RAPID for COVID-19 severity assessment and ICU admission was evaluated, relative to the comparator of retrospective clinical assessment by the Hospital del Mar clinical care team. In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity: critical vs. mild (AUC = 0.93, p

Abstract The gut microbiome plays an essential role in the immune system of invertebrates and vertebrates. Pre and pro-biotics could enhance the shrimp immune system by increasing the phenoloxidase (PO), prophenoloxidase (ProPO), and superoxide dismutase activities. During viral infection, the host immune system alteration could influence the gut microbiome composition and probably lead to other pathogenic infections. Since the JAK/STAT pathway is involved in white spot syndrome virus (WSSV) infection, we investigated the intestine immune genes of STAT-silenced shrimp. During WSSV infection, expression levels of PmVago1, PmDoral, and PmSpätzle in PmSTAT-silenced shrimp were higher than normal. In addition, the transcription levels of antimicrobial peptides, including crustinPm1, crustinPm7, and PmPEN3, were higher in WSSV-challenged PmSTAT-silenced shrimp than the WSSV-infected normal shrimp. Meanwhile, PmSTAT silencing suppressed PmProPO1, PmProPO2, and PmPPAE1 expressions during WSSV infection. The microbiota from four shrimp tested groups (control group, WSSV-infected, PmSTAT-silenced, and PmSTAT-silenced infected by WSSV) was significantly different, with decreasing richness and diversity due to WSSV infection. The relative abundance of Bacteroidetes, Actinobacteria, and Planctomycetes was reduced in WSSV-challenged shrimp. However, at the species level, P. damselae, a pathogen to human and marine animals, significantly increased in WSSV-challenged shrimp. In constrast, Shewanella algae, a shrimp probiotic, was decreased in WSSV groups. In addition, the microbiota structure between control and PmSTAT-silenced shrimp was significantly different, suggesting the importance of STAT to maintain the homeostasis interaction with the microbiota.

Abstract The aim of this study was to analyse the differences in the A–S profile of elite football players induced by playing position and the microcycle day. Players belonged to a second division club in the Spanish La Liga competition. They were classified into five playing positions: central defenders (CD), full backs (FB), midfielders (MF), wide midfielders (WMF) and forwards (FW). Microcycle days were categorised according to the days until matchday (MD, MD-1, MD-2, MD-3, MD-4 and MD-5). Data was collected along six microcycles, including one match per microcycle. The variables analysed were: maximal theoretical acceleration (A0), maximal theoretical speed (S0), maximal acceleration (ACCmax), maximal speed (Smax) and A–S slope (ASslope). Significant differences were found within positions and microcycle day for all variables (p

Abstract The magnonic band structure of two-dimensional chiral magnonic crystals is theoretically investigated. The proposed metamaterial involves a three-dimensional architecture, where a thin ferromagnetic layer is in contact with a two-dimensional periodic array of heavy-metal square islands. When these two materials are in contact, an anti-symmetric exchange coupling known as the Dzyaloshinskii–Moriya interaction (DMI) arises, which generates nonreciprocal spin waves and chiral magnetic order. The Landau–Lifshitz equation and the plane-wave method are employed to study the dynamic magnetic behavior. A systematic variation of geometric parameters, the DMI constant, and the filling fraction allows the examination of spin-wave propagation features, such as the spatial profiles of the dynamic magnetization, the isofrequency contours, and group velocities. In this study, it is found that omnidirectional flat magnonic bands are induced by a sufficiently strong Dzyaloshinskii–Moriya interaction underneath the heavy-metal islands, where the spin excitations are active. The theoretical results were substantiated by micromagnetic simulations. These findings are relevant for envisioning applications associated with spin-wave-based logic devices, where the nonreciprocity and channeling of the spin waves are of fundamental and practical scientific interest.

Abstract The present article is a continuation of our previous works on the anomalies in the decay rates and the capacitance measurements inside a modified Faraday cage. Here we present the anomalous variations in the measurements of inductance when a coil is placed inside an interleaving structure of metal and organic material. The fluctuation in the inductance values was found to be in the range − 0.007 to 0.018 mH. Additionally, it was observed that the temperature coefficient which was 0.0062 mH/°C initially jumped to two distinct levels, 0.0095 mH/°C and 0.0145 mH/°C, respectively. A multiple factor analysis of our results revealed a very strong correlation (R2 = 95.2%) between the inductance and the combination of the temperature and the relative humidity both measured inside the cage, next to the inductor.

This study focuses on virus isolation of avian reoviruses from a tenosynovitis outbreak between September 2015 and June 2018, the molecular characterization of selected isolates based on partial S1 gene sequences, and the full genome characterization of seven isolates. A total of 265 reoviruses were detected and isolated, 83.3% from tendons and joints, 12.3% from the heart and 3.7% from intestines. Eighty five out of the 150 (56.6%) selected viruses for sequencing and characterization were successfully detected, amplified and sequenced. The characterized reoviruses grouped in six distinct genotypic clusters (GC1 to GC6). The most represented clusters were GC1 (51.8%) and GC6 (24.7%), followed by GC2 (12.9%) and GC4 (7.2%), and less frequent GC5 (2.4%) and GC3 (1.2%). A shift on cluster representation throughout time occurred. A reduction of GC1 and an increase of GC6 classified strains was noticed. The highest homologies to S1133 reovirus strain were detected in GC1 (~77%) while GC2 to GC6 homologies ranged between 58.5 and 54.1%. Over time these homologies have been maintained. Seven selected isolates were full genome sequenced. Results indicated that the L3, S1 and M2 genes, coding for proteins located in the virus capsid accounted for most of the variability of these viruses. The information generated in the present study helps the understanding of the epidemiology of reoviruses in California. In addition, provides insights on how other genes that are not commonly studied add variability to the reovirus genome.