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Long-term monitoring of species assemblages provides a unique opportunity to test hypotheses regarding environmentally induced directional trajectories of freshwater species assemblages. We used 57 years of lockchamber fish rotenone and boat electrofishing survey data (1957–2014) collected by the Ohio River Valley Water Sanitation Commission (ORSANCO) to test for directional trajectories in taxonomy, trophic classifications, and life history strategies of freshwater fish assemblages in the Ohio River Basin. We found significant changes in taxonomic and trophic composition of freshwater fishes in the Ohio River Basin. Annual species richness varied from 31 to 90 species and generally increased with year. Temporal trajectories were present for taxonomic and trophic assemblages. Assemblage structure based on taxonomy was correlated with land use change (decrease in agriculture and increase in forest). Taxonomic assemblage structure was also correlated with altered hydrology variables of increased minimum discharge, decreased fall rate, and increased rise rate. Trophic composition of fish catch correlated with land use change (decrease in agriculture and increase in forest) and altered hydrology. Altered hydrology of increased minimum discharge, increased fall discharge, decreased base flows, and increased number of high pulse events was correlated with increased counts of herbivore-detritivores and decreased counts of piscivores and planktivores. We did not find directional changes in life history composition. We hypothesized a shift occurred from benthic to phytoplankton production throughout the basin that may have decreased secondary production of benthic invertebrates. This may also be responsible for lower trophic position of invertivore and piscivore fishes observed in other studies. [ABSTRACT FROM AUTHOR]

Tcf4 is a transcription factor which regulates neurogenesis and neuronal migration in the brain. In humans, loss of function of Tcf4 leads to the rare neurodevelopmental disorder Pitt-Hopkins syndrome, which is characterized by intellectual disability, developmental delay and autistic behavior. We analyzed the consequences of functional loss of Tcf4 on dendritic spines in mature principal neurons. To this end, we crossed mice in which the DNA-binding domain of the Tcf4 gene is flanked by LoxP sites to mice expressing tamoxifen-inducible cre recombinase in a sparse subset of fluorescently labelled neurons (SlickV line). This resulted in a mouse model with an inducible functional knockout of Tcf4 in a subset of cortical and hippocampal neurons, in which we analyzed dendritic spines, which are the morphological correlate of excitatory postsynapses. Heterozygous as well as homozygous loss of Tcf4 led to a reduction in the number of dendritic spines in the cortex as well as in the hippocampus. This was accompanied by morphological changes of dendritic spines. These results suggest that Tcf4 is involved in synaptic plasticity in mature neurons, and functional loss of Tcf4 may contribute to the neurological symptoms in Pitt-Hopkins syndrome. [ABSTRACT FROM AUTHOR]

Lower respiratory tract bacterial infections are characterized by neutrophilic inflammation in the airways. The carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 8 is expressed in and released by human granulocytes. Our study demonstrates that human granulocytes release CEACAM8 in response to bacterial DNA in a TLR9-dependent manner. Individuals with a high percentage of bronchial lavage fluid (BALF) granulocytes were more likely to have detectable levels of released CEACAM8 in the BALF than those with a normal granulocyte count. Soluble, recombinant CEACAM8-Fc binds to CEACAM1 expressed on human airway epithelium. Application of CEACAM8-Fc to CEACAM1-positive human pulmonary epithelial cells resulted in reduced TLR2-dependent inflammatory responses. These inhibitory effects were accompanied by tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) of CEACAM1 and by recruitment of the phosphatase SHP-1, which could negatively regulate Toll-like receptor 2-dependent activation of the phosphatidylinositol 3-OH kinase-Akt kinase pathway. Our results suggest a new mechanism by which granulocytes reduce pro-inflammatory immune responses in human airways via secretion of CEACAM8 in neutrophil-driven bacterial infections. [ABSTRACT FROM AUTHOR]

Bone mass is maintained by osteoclasts that resorb bone and osteoblasts that promote matrix deposition and mineralization. Bone homeostasis is altered in chronic inflammation as well as in post-menopausal loss of estrogen, which favors osteoclast activity that leads to osteoporosis. The MAPK p38α is a key regulator of bone loss and p38 inhibitors preserve bone mass by inhibiting osteoclastogenesis. p38 function is regulated by two upstream MAPK kinases, namely MKK3 and MKK6. The goal of this study was to assess the effect of MKK3- or MKK6-deficiency on osteoclastogenesis in vitro and on bone loss in ovariectomy-induced osteoporosis in mice. We demonstrated that MKK3 but not MKK6, regulates osteoclast differentiation from bone marrow cells in vitro. Expression of NFATc1, a master transcription factor in osteoclastogenesis, is decreased in cells lacking MKK3 but not MKK6. Expression of osteoclast-specific genes Cathepsin K, osteoclast-associated receptor and MMP9, was inhibited in MKK3−/− cells. The effect of MKK-deficiency on ovariectomy-induced bone loss was then evaluated in female WT, MKK3−/− and MKK6−/− mice by micro-CT analysis. Bone loss was partially inhibited in MKK3−/− as well as MKK6−/− mice, despite normal osteoclastogenesis in MKK6−/− cells. This correlated with the lower osteoclast numbers in the MKK-deficient ovariectomized mice. These studies suggest that MKK3 and MKK6 differentially regulate bone loss due to estrogen withdrawal. MKK3 directly mediates osteoclastogenesis while MKK6 likely contributes to pro-inflammatory cytokine production that promotes osteoclast formation. [ABSTRACT FROM AUTHOR]

Tropical dry forests (TDFs) are highly endangered tropical ecosystems being replaced by a complex mosaic of patches of different successional stages, agricultural fields and pasturelands. In this context, it is urgent to understand how taxa playing critical ecosystem roles respond to habitat modification. Because Phyllostomid bats provide important ecosystem services (e.g. facilitate gene flow among plant populations and promote forest regeneration), in this study we aimed to identify potential patterns on their response to TDF transformation in sites representing four different successional stages (initial, early, intermediate and late) in three Neotropical regions: México, Venezuela and Brazil. We evaluated bat occurrence at the species, ensemble (abundance) and assemblage level (species richness and composition, guild composition). We also evaluated how bat occurrence was modulated by the marked seasonality of TDFs. In general, we found high seasonal and regional specificities in phyllostomid occurrence, driven by specificities at species and guild levels. For example, highest frugivore abundance occurred in the early stage of the moistest TDF, while highest nectarivore abundance occurred in the same stage of the driest TDF. The high regional specificity of phyllostomid responses could arise from: (1) the distinctive environmental conditions of each region, (2) the specific behavior and ecological requirements of the regional bat species, (3) the composition, structure and phenological patterns of plant assemblages in the different stages, and (4) the regional landscape composition and configuration. We conclude that, in tropical seasonal environments, it is imperative to perform long-term studies considering seasonal variations in environmental conditions and plant phenology, as well as the role of landscape attributes. This approach will allow us to identify potential patterns in bat responses to habitat modification, which constitute an invaluable tool for not only bat biodiversity conservation but also for the conservation of the key ecological processes they provide. [ABSTRACT FROM AUTHOR]

Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β−/−), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity. [ABSTRACT FROM AUTHOR]

A major barrier for a broad applicability of brain-computer interfaces (BCIs) based on electroencephalography (EEG) is the large number of EEG sensor electrodes typically used. The necessity for this results from the fact that the relevant information for the BCI is often spread over the scalp in complex patterns that differ depending on subjects and application scenarios. Recently, a number of methods have been proposed to determine an individual optimal sensor selection. These methods have, however, rarely been compared against each other or against any type of baseline. In this paper, we review several selection approaches and propose one additional selection criterion based on the evaluation of the performance of a BCI system using a reduced set of sensors. We evaluate the methods in the context of a passive BCI system that is designed to detect a P300 event-related potential and compare the performance of the methods against randomly generated sensor constellations. For a realistic estimation of the reduced system's performance we transfer sensor constellations found on one experimental session to a different session for evaluation. We identified notable (and unanticipated) differences among the methods and could demonstrate that the best method in our setup is able to reduce the required number of sensors considerably. Though our application focuses on EEG data, all presented algorithms and evaluation schemes can be transferred to any binary classification task on sensor arrays. [ABSTRACT FROM AUTHOR]

Background: Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI). Objective: Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB. Methods: Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens. Results: Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-c ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs. Conclusion: Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB. [ABSTRACT FROM AUTHOR]

Background: Naturally occurring CD4+CD25+Foxp3+ regulatory T (Treg) cells develop in the thymus and represent a mature T cell subpopulation critically involved in maintaining peripheral tolerance. The differentiation of Treg cells in the thymus requires T cell receptor (TCR)/CD28 stimulation along with cytokine-promoted Foxp3 induction. TCR-mediated nuclear factor kappa B (NF-kB) activation seems to be involved in differentiation of Treg cells because deletion of components of the NF-κB signaling pathway, as well as of NF-κB transcription factors, leads to markedly decreased Treg cell numbers in thymus and periphery. Methodology/Principal Findings: To investigate if Treg cell-intrinsic NF-κB activation is required for thymic development and peripheral homeostasis of Treg cells we used transgenic (Tg) mice with thymocyte-specific expression of a stable IkBa mutant to inhibit NF-κB activation solely within the T cell lineage. Here we show that Treg cell-intrinsic NF-κB activation is important for the generation of cytokine-responsive Foxp32 thymic Treg precursors and their further differentiation into mature Treg cells. Treg cell development could neither be completely rescued by the addition of exogenous Interleukin 2 (IL-2) nor by the presence of wild-type derived cells in adoptive transfer experiments. However, peripheral NF-κB activation appears to be required for IL-2 production by conventional T cells, thereby participating in Treg cell homeostasis. Moreover, pharmacological NF-κB inhibition via the IκB kinase b (IKKb) inhibitor AS602868 led to markedly diminished thymic and peripheral Treg cell frequencies. Conclusion/Significance: Our results indicate that Treg cell-intrinsic NF-κB activation is essential for thymic Treg cell differentiation, and further suggest pharmacological NF-κB inhibition as a potential therapeutic approach for manipulating this process. [ABSTRACT FROM AUTHOR]

Background: The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy. Methodology/Principal Findings: We expressed the globular HA receptor binding domain, referred to here as HA63-286- RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA63-286-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model. Conclusions/Significance: Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy. [ABSTRACT FROM AUTHOR]

Background: Although it has been estimated that pandemic Influenza A H1N1/2009 has infected millions of people from April to October 2009, a more precise figure requires a worldwide large-scale diagnosis of the presence of Influenza A/ H1N1/2009 antibodies within the population. Assays typically used to estimate antibody titers (hemagglutination inhibition and microneutralization) would require the use of the virus, which would seriously limit broad implementation. Methodology/Principal Findings: An ELISA method to evaluate the presence and relative concentration of specific Influenza A/H1N1/2009 antibodies in human serum samples is presented. The method is based on the use of a histidine-tagged recombinant fragment of the globular region of the hemagglutinin (HA) of the Influenza A H1N1/2009 virus expressed in E. coli. Conclusions/Significance: The ELISA method consistently discerns between Inf A H1N1 infected and non-infected subjects, particularly after the third week of infection/exposure. Since it does not require the use of viral particles, it can be easily and quickly implemented in any basic laboratory. In addition, in a scenario of insufficient vaccine availability, the use of this ELISA could be useful to determine if a person has some level of specific antibodies against the virus and presumably at least partial protection. [ABSTRACT FROM AUTHOR]

Background: The high mortality rate associated with epithelial ovarian carcinoma (EOC) reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy. Methodology/Principal Findings: Here we report combined molecular genetic and morphologic analyses of normal human ovarian tissues and early stage cancers, from both BRCA mutation carriers and the general population, indicating that EOCs frequently arise from dysplastic precursor lesions within epithelial inclusion cysts. In pathologically normal ovaries, molecular evidence of oncogenic stress was observed specifically within epithelial inclusion cysts. To further explore potential very early events in ovarian tumorigenesis, ovarian tissues from women not known to be at high risk for ovarian cancer were subjected to laser catapult microdissection and gene expression profiling. These studies revealed a quasineoplastic expression signature in benign ovarian cystic inclusion epithelium compared to surface epithelium, specifically with respect to genes affecting signal transduction, cell cycle control, and mitotic spindle formation. Consistent with this gene expression profile, a significantly higher cell proliferation index (increased cell proliferation and decreased apoptosis) was observed in histopathologically normal ovarian cystic compared to surface epithelium. Furthermore, aneuploidy was frequently identified in normal ovarian cystic epithelium but not in surface epithelium. Conclusions/Significance: Together, these data indicate that EOC frequently arises in ovarian cystic inclusions, is preceded by an identifiable dysplastic precursor lesion, and that increased cell proliferation, decreased apoptosis, and aneuploidy are likely to represent very early aberrations in ovarian tumorigenesis. [ABSTRACT FROM AUTHOR]

The adjuvanticity of bacterial adenylate cyclase toxins has been ascribed to their capacity, largely mediated by cAMP, to modulate APC activation, resulting in the expression of Th2-driving cytokines. On the other hand, cAMP has been demonstrated to induce a Th2 bias when present during T cell priming, suggesting that bacterial cAMP elevating toxins may directly affect the Th1/Th2 balance. Here we have investigated the effects on human CD4+ T cell differentiation of two adenylate cyclase toxins, Bacillus anthracis edema toxin (ET) and Bordetella pertussis CyaA, which differ in structure, mode of cell entry, and subcellular localization. We show that low concentrations of ET and CyaA, but not of their genetically detoxified adenylate cyclase defective counterparts, potently promote Th2 cell differentiation by inducing expression of the master Th2 transcription factors, c-maf and GATA-3. We also present evidence that the Th2-polarizing concentrations of ET and CyaA selectively inhibit TCR-dependent activation of Akt1, which is required for Th1 cell differentiation, while enhancing the activation of two TCR-signaling mediators, Vav1 and p38, implicated in Th2 cell differentiation. This is at variance from the immunosuppressive toxin concentrations, which interfere with the earliest step in TCR signaling, activation of the tyrosine kinase Lck, resulting in impaired CD3ζ phosphorylation and inhibition of TCR coupling to ZAP-70 and Erk activation. These results demonstrate that, notwithstanding their differences in their intracellular localization, which result in focalized cAMP production, both toxins directly affect the Th1/Th2 balance by interfering with the same steps in TCR signaling, and suggest that their adjuvanticity is likely to result from their combined effects on APC and CD4+ T cells. Furthermore, our results strongly support the key role of cAMP in the adjuvanticity of these toxins. [ABSTRACT FROM AUTHOR]

During the second third of last century, the Orinoco Crocodile (Crocodylus intermedius) underwent a hunting process driven by the demand from the North American, European, and Japanese leather industry, resulting in a sharp decline of its populations. Currently, only two known remaining populations of this Critically Endangered species persist in the Colombian Orinoquía: in the Guayabero-Duda-Lozada and the Cravo Norte-Ele-Lipa River Systems. The latter has been the only population subject of study, including recent surveys and local conservation initiatives such as egg and hatchling ranching. Despite suggestions for population recovery based on the observed increase in clutches in the area, information regarding its genetic status has been pending assessment. This research aims to provide a genetic characterization of this remaining population and to evaluate the diversity recovered during a period of the egg ranching initiative. For this purpose, we utilized variable molecular markers, specifically 17 microsatellite loci, nuclear DNA. Despite revealing intermediate levels of genetic diversity, we identified an effective population size of 11.5-17, well below the minimum values proposed for short-term subsistence. While no evidence of inbreeding was found, it is acknowledged as a potential risk based on the population's history. Additionally, we detected a historical bottleneck possibly influenced by arid periods affecting the region since the Pleistocene. While the evaluated population presents a unique opportunity for C. intermedius conservation, it also exposes a high risk of entering the extinction vortex. The primary action to be taken is to support the egg and hatchling ranching program, which successfully recovered most of the genetic diversity present in the population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Castillo-Rodríguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Machine learning-based approaches are particularly suitable for identifying essential genes as they allow the generation of predictive models trained on features from multi-source data. Gene essentiality is neither binary nor static but determined by the context. The databases for essential gene annotation do not permit the personalisation of the context, and their update can be slower than the publication of new experimental data. We propose HELP (Human Gene Essentiality Labelling & Prediction), a computational framework for labelling and predicting essential genes. Its double scope allows for identifying genes based on dependency or not on experimental data. The effectiveness of the labelling method was demonstrated by comparing it with other approaches in overlapping the reference sets of essential gene annotations, where HELP demonstrated the best compromise between false and true positive rates. The gene attributes, including multi-omics and network embedding features, lead to high-performance prediction of essential genes while confirming the existence of essentiality nuances., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Granata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Intercepting moving targets is a fundamental skill in human behavior, influencing various domains such as sports, gaming, and other activities. In these contexts, precise visual processing and motor control are crucial for adapting and navigating effectively. Nevertheless, there are still some gaps in our understanding of how these elements interact while intercepting a moving target. This study explored the dynamic interplay among eye movements, pupil size, and interceptive hand movements, with visual and motion uncertainty factors. We developed a simple visuomotor task in which participants used a joystick to interact with a computer-controlled dot that moved along two-dimensional trajectories. This virtual system provided the flexibility to manipulate the target's speed and directional uncertainty during chase trials. We then conducted a geometric analysis based on optimal angles for each behavior, enabling us to distinguish between simple tracking and predictive trajectories that anticipate future positions of the moving target. Our results revealed the adoption of a strong interception strategy as participants approached the target. Notably, the onset and amount of optimal interception strategy depended on task parameters, such as the target's speed and frequency of directional changes. Furthermore, eye-tracking data showed that participants continually adjusted their gaze speed and position, continuously adapting to the target's movements. Finally, in successful trials, pupillary responses predicted the amount of optimal interception strategy while exhibiting an inverse relationship in trials without collisions. These findings reveal key interactions among visuomotor parameters that are crucial for solving complex interception tasks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Márquez, Treviño. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In prion diseases (PrDs), aggregates of misfolded prion protein (PrPSc) accumulate not only in the brain but also in extraneural organs. This raises the question whether prion-specific pathologies arise also extraneurally. Here we sequenced mRNA transcripts in skeletal muscle, spleen and blood of prion-inoculated mice at eight timepoints during disease progression. We detected gene-expression changes in all three organs, with skeletal muscle showing the most consistent alterations. The glutamate-ammonia ligase (GLUL) gene exhibited uniform upregulation in skeletal muscles of mice infected with three distinct scrapie prion strains (RML, ME7, and 22L) and in victims of human sporadic Creutzfeldt-Jakob disease. GLUL dysregulation was accompanied by changes in glutamate/glutamine metabolism, leading to reduced glutamate levels in skeletal muscle. None of these changes were observed in skeletal muscle of humans with amyotrophic lateral sclerosis, Alzheimer's disease, or dementia with Lewy bodies, suggesting that they are specific to prion diseases. These findings reveal an unexpected metabolic dimension of prion infections and point to a potential role for GLUL dysregulation in the glutamate/glutamine metabolism in prion-affected skeletal muscle., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Caredio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Large-scale studies of gene expression are commonly influenced by biological and technical sources of expression variation, including batch effects, sample characteristics, and environmental impacts. Learning the causal relationships between observable variables may be challenging in the presence of unobserved confounders. Furthermore, many high-dimensional regression techniques may perform worse. In fact, controlling for unobserved confounding variables is essential, and many deconfounding methods have been suggested for application in a variety of situations. The main contribution of this article is the development of a two-stage deconfounding procedure based on Bow-free Acyclic Paths (BAP) search developed into the framework of Structural Equation Models (SEM), called SEMbap(). In the first stage, an exhaustive search of missing edges with significant covariance is performed via Shipley d-separation tests; then, in the second stage, a Constrained Gaussian Graphical Model (CGGM) is fitted or a low dimensional representation of bow-free edges structure is obtained via Graph Laplacian Principal Component Analysis (gLPCA). We compare four popular deconfounding methods to BAP search approach with applications on simulated and observed expression data. In the former, different structures of the hidden covariance matrix have been replicated. Compared to existing methods, BAP search algorithm is able to correctly identify hidden confounding whilst controlling false positive rate and achieving good fitting and perturbation metrics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Grassi, Tarantino. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Natural Language Processing (NLP) is a subset of artificial intelligence that enables machines to understand and respond to human language through Large Language Models (LLMs)‥ These models have diverse applications in fields such as medical research, scientific writing, and publishing, but concerns such as hallucination, ethical issues, bias, and cybersecurity need to be addressed. To understand the scientific community's understanding and perspective on the role of Artificial Intelligence (AI) in research and authorship, a survey was designed for corresponding authors in top medical journals. An online survey was conducted from July 13th, 2023, to September 1st, 2023, using the SurveyMonkey web instrument, and the population of interest were corresponding authors who published in 2022 in the 15 highest-impact medical journals, as ranked by the Journal Citation Report. The survey link has been sent to all the identified corresponding authors by mail. A total of 266 authors answered, and 236 entered the final analysis. Most of the researchers (40.6%) reported having moderate familiarity with artificial intelligence, while a minority (4.4%) had no associated knowledge. Furthermore, the vast majority (79.0%) believe that artificial intelligence will play a major role in the future of research. Of note, no correlation between academic metrics and artificial intelligence knowledge or confidence was found. The results indicate that although researchers have varying degrees of familiarity with artificial intelligence, its use in scientific research is still in its early phases. Despite lacking formal AI training, many scholars publishing in high-impact journals have started integrating such technologies into their projects, including rephrasing, translation, and proofreading tasks. Efforts should focus on providing training for their effective use, establishing guidelines by journal editors, and creating software applications that bundle multiple integrated tools into a single platform., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Salvagno et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over half of the world's arable land is acidic, which constrains cereal production. In South America, different rice-growing regions (Cerrado in Brazil and Llanos in Colombia and Venezuela) are particularly affected due to high aluminum toxicity levels. For this reason, efforts have been made to breed for tolerance to aluminum toxicity using synthetic populations. The breeding program of CIAT-CIRAD is a good example of the use of recurrent selection to increase productivity for the Llanos in Colombia. In this study, we evaluated the performance of genomic prediction models to optimize the breeding scheme by hastening the development of an improved synthetic population and elite lines. We characterized 334 families at the S0:4 generation in two conditions. One condition was the control, managed with liming, while the other had high aluminum toxicity. Four traits were considered: days to flowering (FL), plant height (PH), grain yield (YLD), and zinc concentration in the polished grain (ZN). The population presented a high tolerance to aluminum toxicity, with more than 72% of the families showing a higher yield under aluminum conditions. The performance of the families under the aluminum toxicity condition was predicted using four different models: a single-environment model and three multi-environment models. The multi-environment models differed in the way they integrated genotype-by-environment interactions. The best predictive abilities were achieved using multi-environment models: 0.67 for FL, 0.60 for PH, 0.53 for YLD, and 0.65 for ZN. The gain of multi-environment over single-environment models ranged from 71% for YLD to 430% for FL. The selection of the best-performing families based on multi-trait indices, including the four traits mentioned above, facilitated the identification of suitable families for recombination. This information will be used to develop a new cycle of recurrent selection through genomic selection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bartholomé et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The temporal variability of fish habitat utilization is poorly understood in tropical deltaic systems due to high water turbidity, which limits visual censuses, and to the lack of long-term data incorporating climate variability events. We aimed to assess the influence of body size and El Niño Southern Oscillation (ENSO) variability on the cross-habitat utilization rate of 14 fish species of commercial relevance in the Ciénaga Grande de Santa Marta (CGSM). We estimated the utilization of mangroves and coastal lagoons based on relative catch frequencies from encircling gillnets used within a long-term catch monitoring program, and then tested for significant changes in each species' habitat utilization as a function of body size and climate variability. Six species showed a high dependence on mangroves and four on coastal lagoons for most body size classes (including juveniles) and ENSO conditions. One species (Elops smithi) showed a high utilization of mangroves in some ENSO phases and body size classes, while three species showed a high utilization of both mangroves and coastal lagoons. Mangrove utilization by six species (Megalops atlanticus, E. smithi, Centropomus undecimalis, Mugil incilis, Mugil liza, and Ariopsis canteri) increased in larger body sizes at low depths, which usually occurs under dry ENSO conditions, when predatory risk is higher in coastal lagoons. Another species (Caquetaia kraussi) increased its mangrove utilization from the body size at which its feeding habits change. Mangroves and coastal lagoons are important nurseries and habitats for adults of the main commercial fish species in the CGSM. Seascape habitats and fringe/riverine mangroves must be conserved in tropical deltas to promote not only nurseries but also fish lifecycles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sánchez-Núñez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: We investigated the performance of enzyme linked immunospot (ELISpot) assay for the diagnosis of invasive aspergillosis (IA) in high-risk patients with hematologic malignancies., Methods: We prospectively enrolled two cohorts of patients undergoing intensive myelosuppressive or immunosuppressive treatments at high risk for IA. ELISpot was performed to detect Aspergillus-specific T cells producing Interleukin-10., Results: In the discovery cohort, a derived cut-off of 40 spot forming cells (SFCs)/106 PBMCs has shown to correctly classify IA cases with a sensitivity and specificity of 89.5% and 88.6%, respectively. This cut-off is lowered to 25 SFC when considering the subset of possible IA patients, with sensitivity and specificity of 76% and 93%, respectively. The application of the 40 SFCs cut-off to the validation cohort resulted in a positivity rate of 83.3% in proven/probable cases and a negativity rate of 92.5% in possible/non-IA cases. Adopting the 25 SCFs cut-off, the assay resulted positive in 83.3% of proven/probable cases while it resulted negative in 66.7% of possible/non-IA cases., Conclusions: ELISpot shows promises in the diagnosis of IA and the possibility to use two distinct cut-offs with similar diagnostic performances according to patients' different pre-test probability of infection can widen its use in patients at risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: M. Luppi, L. Potenza and P. Barozzi have applied for an Italian patent regarding clinical applications of the ELISpot assay for the diagnosis of Aspergillus infection [PCT: WO2008/075395A3, IT2007/000867]. M. Luppi, L. Potenza, D. Vallerini, P. Barozzi and F. Forghieri have applied for an Italian and US patent regarding clinical applications of the ELISpot assay for the diagnosis of Mucorales infection [PCT: WO2012073160 A1, IT MI20102224, US 2013/0260395]. This does not alter the authors’ adherence to all Journal policies. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors of this manuscript have no conflicts of interest related to the study to disclose., (Copyright: © 2024 Bettelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The transformation of the food and industrial agricultural production system into adaptative and sustainable systems capable of being productive within social, environmental, and economic limits is a crucial factor in reducing the risk to food security and to economic growth. However, the analysis structure of the effect of these variables in sustainable environments remains unknown, whereby the technology and processes are considered as variables of the equivalent critical level as those already described. The purpose of this study is to design a model that enables the characterisation of the agri-food sector based on the determination of sustainable variables from a sustainable and integral systemic approach. Tools, such as the viable system model, are employed to analyse the dynamics and generate the balanced scorecard, to which the items of learning and continuous improvement are added. Lastly, the impact of the principles of sustainability versus the variation of sustainability in the agri-food system is revealed, which is useful in determining the appropriate levels to guarantee a balance in the foundations of circularity. From a systemic approach, this model can be adopted by agronomists and scientists to design alternative strategies for the management of food sustainability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Leon-Romero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diversity, equity, and inclusion (DEI) mission statements continue to be adopted by academic institutions in general, and by dental schools around the globe in particular. But DEI content seems to be under-developed in dental education. The objectives of this study were two-fold: to extract information from all the PBL cases at University of British Columbia's Faculty of Dentistry curriculum in terms of the diversity, equitable representation, and inclusion of patient and provider characteristics, context, and treatment outcomes; and; to compare these findings with the composition of the British Columbia census population, dental practice contextual factors, and the evidence on treatment outcomes within patient care. Information from all the 58 PBL cases was extracted between January and March 2023, focusing on patient and provider characteristics (e.g., age, gender, ethnicity), context (e.g., type of insurance), and treatment outcomes (e.g., successful/unsuccessful). This information was compared with the available literature. From all the 58 PBL cases, 0.4% included non-straight patients, while at least 4% of BC residents self-identify as non-straight; there were no cases involving First Nations patients although they make up 6% of the British Columbia population. Less than 10% of the cases involved older adults who make up almost 20% of the population. Only Treatments involving patients without a disability were 5.74 times more likely to be successful compared to those involving patients with a disability (p<0.05). The characteristics of the patients, practice context, and treatment outcomes portrayed in the existing PBL cases seem to differ from what is known about the composition of the British Columbia population, treatment outcome success, and practice context; a curriculum disconnect seems to exist. The PBL cases should be revised to better represent the population within which most students will practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Brondani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Invasive aspergillosis causes significant morbidity and mortality in immunocompromised patients. Natural killer (NK) cells are pivotal for antifungal defense. Thus far, CD56 is the only known pathogen recognition receptor on NK cells triggering potent antifungal activity against Aspergillus fumigatus. However, the underlying cellular mechanisms and the fungal ligand of CD56 have remained unknown. Using purified cell wall components, biochemical treatments, and ger mutants with altered cell wall composition, we herein found that CD56 interacts with the A. fumigatus cell wall carbohydrate galactosaminogalactan (GAG). This interaction induced NK-cell activation, degranulation, and secretion of immune-enhancing chemokines and cytotoxic effectors. Supernatants from GAG-stimulated NK cells elicited antifungal activity and enhanced antifungal effector responses of polymorphonuclear cells. In conclusion, we identified A. fumigatus GAG as a ligand of CD56 on human primary NK cells, stimulating potent antifungal effector responses and activating other immune cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Heilig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adeno-associated virus (AAV) serotypes from primates are being developed and clinically used as vectors for human gene therapy. However, the evolutionary mechanism of AAV variants is far from being understood, except that genetic recombination plays an important role. Furthermore, little is known about the interaction between AAV and its natural hosts, human and nonhuman primates. In this study, natural AAV capsid genes were subjected to systemic evolutionary analysis with a focus on selection drives during the diversification of AAV lineages. A number of positively selected sites were identified from these AAV lineages with functional relevance implied by their localization on the AAV structures. The selection drives of the two AAV2 capsid sites were further investigated in a series of biological experiments. These observations did not support the evolution of the site 410 of the AAV2 capsid driven by selection pressure from the human CD4+ T-cell response. However, positive selection on site 548 of the AAV2 capsid was directly related to host humoral immunity because of the profound effects of mutations at this site on the immune evasion of AAV variants from human neutralizing antibodies at both the individual and population levels. Overall, this work provides a novel interpretation of the genetic diversity and evolution of AAV lineages in their natural hosts, which may contribute to their further engineering and application in human gene therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Accurate DNA quantification is key for downstream application including library preparations for whole genome sequencing (WGS) and the quantification of standards for quantitative PCR. Two commonly used technologies for nucleic acid quantification are based on spectrometry, such as NanoDrop, and fluorometry, such as Qubit. The DS-11+ Series spectrophotometer/fluorometer (DeNovix) is a UV spectrophotometry-based instrument and is a relatively new spectrophotometric method but has not yet been compared to established platforms. Here, we compared three DNA quantification platforms, including two UV spectrophotometry-based techniques (DeNovix and NanoDrop) and one fluorometry-based approach (Qubit). We used genomic prokaryotic DNA extracted from Streptococcus pneumoniae using a Roche DNA extraction kit. We also evaluated purity assessment and effect of a single freeze-thaw cycle. Spectrophotometry-based methods reported 3 to 4-fold higher mean DNA concentrations compared to Qubit, both before and after freezing. The ratio of DNA concentrations assessed by spectrophotometry on the one hand, and Qubit on the other hand, was function of the A260/280. In case DNA was pure (A260/280 between 1.7 and 2.0), the ratio DeNovix or Nanodrop vs. Qubit was close or equal to 2, while this ratio showed an incline for DNA with increasing A260/280 values > 2.0. The A260/280 and A260/230 purity ratios exhibited negligible variation across spectrophotometric methods and freezing conditions. The comparison of DNA concentrations from before and after freezing revealed no statistically significant disparities for each technique. DeNovix exhibited the highest Spearman correlation coefficient (0.999), followed by NanoDrop (0.81), and Qubit (0.77). In summary, there is no difference between DeNovix and NanoDrop in estimated gDNA concentrations of S. pneumoniae, and the spectrophotometry methods estimated close or equal to 2 times higher concentrations compared to Qubit for pure DNA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Versmessen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In plants, small RNAs (sRNAs), mainly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have been described as key regulators of plant development, growth, and abiotic and biotic responses. Despite reports indicating the involvement of certain sRNAs in regulating the interaction between Botrytis cinerea (a major necrotrophic fungal phytopathogen) and host plants, there remains a lack of analysis regarding the potential regulatory roles of plant sRNAs during early stages of the interaction despite early immune responses observed then during infection. We present the first transcriptome-wide analysis of small RNA expression on the early interaction between the necrotrophic fungus Botrytis cinerea and the model plant Arabidopsis thaliana. We found that evolutionary conserved A. thaliana miRNAs were the sRNAs that accumulated the most in the presence of B. cinerea. The upregulation of miR167, miR159 and miR319 was of particular interest because these, together with their target transcripts, are involved in the fine regulation of the plant hormone signaling pathways. We also describe that miR173, which triggers the production of secondary siRNAs from TAS1 and TAS2 loci, as well as secondary siRNAs derived from these loci, is upregulated in response to B. cinerea. Thus, at an early stage of the interaction there are transcriptional changes of sRNA-guided silencing pathway genes and of a subset of sRNAs that targeted genes from the PPR gene superfamily, and these may be important mechanisms regulating the interaction between A. thaliana and B. cinerea. This work provides the basis for a better understanding of the regulation mediated by sRNAs during early B. cinerea-plant interaction and may help in the development of more effective strategies for its control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2024 Padilla-Padilla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Aedes aegypti cadherin-like protein (Aae-Cad) and the membrane-bound alkaline phosphatase (Aae-mALP) are membrane proteins identified as putative receptors for the larvicidal Cry toxins produced by Bacillus thuringiensis subsp. israelensis bacteria. Cry toxins are the most used toxins in the control of different agricultural pest and mosquitos. Despite the relevance of Aae-Cad and Aae-mALP as possible toxin-receptors in mosquitoes, previous efforts to establish a clear functional connection among them and Cry toxins activity have been relatively limited. In this study, we used CRISPR-Cas9 to generate knockout (KO) mutations of Aae-Cad and Aae-mALP. The Aae-mALP KO was successfully generated, in contrast to the Aae-Cad KO which was obtained only in females. The female-linked genotype was due to the proximity of aae-cad gene to the sex-determining loci (M:m). Both A. aegypti KO mutant populations were viable and their insect-development was not affected, although a tendency on lower egg hatching rate was observed. Bioassays were performed to assess the effects of these KO mutations on the susceptibility of A. aegypti to Cry toxins, showing that the Aae-Cad female KO or Aae-mALP KO mutations did not significantly alter the susceptibility of A. aegypti larvae to the mosquitocidal Cry toxins, including Cry11Aa, Cry11Ba, Cry4Ba, and Cry4Aa. These findings suggest that besides the potential participation of Aae-Cad and Aae-mALP as Cry toxin receptors in A. aegypti, additional midgut membrane proteins are involved in the mode of action of these insecticidal toxins., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pacheco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The prevalence of neurodegenerative disorders, particularly dementia, is on the rise across many countries worldwide. This negative trend calls for improving our understanding of cognitive aging. While motor-cognitive dual-task approaches have already been proven valuable for clinical diagnosis, comparatively less research is available on the application of Cognitive-Cognitive Dual-Tasking (CCDT), across several cognitive domains. Moreover, there is limited understanding about how healthy aging affects performance in such dual-tasks in the general population. CCDT entails engaging individuals in multiple cognitive tasks simultaneously and holds promise for remote e-Health interventions. In this cross-sectional study, our objective was to evaluate the suitability of a newly developed, self-administered, online tool for examining age-related differences in memory performance under dual-tasking. 337 healthy adults aged 50-90 underwent a visual memory test (Memo) under both single and dual-task conditions (attend to auditory letters). Additional measures included questionnaires on subjective memory complaints (MAC-Q), on cognitive reserve (CR), and a cognitive screening (auto-GEMS). As expected, the accuracy of visual memory performance exhibited a negative correlation with age and MAC-Q, and a positive correlation with CR and auto-GEMS scores. Dual-tasking significantly impaired performance, and its detrimental effect decreased with increasing age. Furthermore, the protective effect of cognitive reserve diminished with advancing age. These findings suggest that the commonly observed age-related increase in dual-task costs is not universally applicable across all tasks and cognitive domains. With further refinement, a longitudinal implementation of this approach may assist in identifying individuals with a distinct cognitive trajectory and potentially at a higher risk of developing cognitive decline., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Contemori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Longer times between diagnosis and treatments of cancer patients have been estimated as effects of the COVID-19 pandemic. However, relatively few studies attempted to estimate actual delay to treatment at the patient level., Objective: To assess changes in delays to first treatment and surgery among newly diagnosed patients with localized breast cancer (BC) during the COVID-19 pandemic., Methods: We used data from the PAPESCO-19 multicenter cohort study, which included patients from 4 French comprehensive cancer centers. We measured the delay to first treatment as the number of days between diagnosis and the first treatment regardless of whether this was neoadjuvant chemotherapy or surgery. COVID-19 pandemic exposure was estimated with a composite index that considered both the severity of the pandemic and the level of lockdown restrictions. We ran generalized linear models with a log link function and a gamma distribution to model the association between delay and the pandemic., Results: Of the 187 patients included in the analysis, the median delay to first treatment was 42 (IQR:32-54) days for patients diagnosed before and after the start of the 1st lockdown (N = 99 and 88, respectively). After adjusting for age and centers of inclusion, a higher composite pandemic index (> = 50 V.S. <50) had only a small, non-significant effect on times to treatment. Longer delays were associated with factors other than the COVID-19 pandemic., Conclusion: We found evidence of no direct impact of the pandemic on the actual delay to treatment among patients with localized BC., Competing Interests: The authors declare no conflict of interest with this research., (Copyright: © 2024 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Serious illness conversations aim to align the care process with the goals and preferences of adult patients suffering from any advanced disease. They represent a challenge for healthcare professionals and require specific skills. Conversation guides consistent with task-centered instructional strategies may be particularly helpful to improve the quality of communication. This study aims to develop, validate, and preliminarily evaluate an educational booklet to support Italian social and healthcare professionals in serious illness conversations. A three-step approach, including development, validation, and evaluation, was followed. A co-creation process with meaningful stakeholders led to the development of the booklet, validated by 15 experts on clarity, completeness, coherence, and relevance. It underwent testing on readability (Gulpease index, 0 = lowest-100 = maximum) and design (Baker Able Leaflet Design criteria, 0 = worst to 32 = best). Twenty-two professionals with different scope of practice and care settings evaluated acceptability (acceptable if score ≥30), usefulness, feasibility to use (1 = not at all to 10 = extremely), and perceived acquired knowledge (1 = not at all to 5 = extremely). After four rounds of adjustments, the booklet scored 97% for relevance, 60 for readability, and 25/32 for design. In all, 18 (81.8%), 19 (86.4%) and 17 (77.3%) professionals deemed the booklet acceptable, moderate to highly useful, and feasible to use, respectively; 18/22 perceived gain in knowledge and all would recommend it to colleagues. The booklet has good readability, excellent design, high content validity, and a high degree of perceived usefulness and acquired knowledge. The booklet is tailored to users' priorities, mirrors their most frequent daily practice challenges, and offers 1-minute, 2-minute and 5-minute solutions for each scenario. The co-creation process ensured the development of an educational resource that could be useful regardless of the scope of practice and the care setting to support professionals in serious illness conversations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gonella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A randomized clinical trial to evaluate the effect of a Mediterranean-style diet on vascular health indices such as endothelial function indices, serum lipid and ceramide plasma and some adipokine serum levels. We recruited all consecutive patients at high risk of cardiovascular diseases admitted to the Internal Medicine and Stroke Care ward at the University Hospital of Palermo between September 2017 and December 2020., Materials and Methods: The enrolled subjects, after the evaluation of the degree of adherence to a dietary regimen of the Mediterranean-style diet, were randomised to a Mediterranean Diet (group A) assessing the adherence to a Mediterranean-style diet at each follow up visit (every three months) for the entire duration of the study (twelve months) and to a Low-fat diet (group B) with a dietary "counselling" starting every three months for the entire duration of the study (twelve months).The aims of the study were to evaluate: the effects of adherence to Mediterranean Diet on some surrogate markers of vascular damage, such as endothelial function measured by means of the reactive hyperaemia index (RHI) and augmentation index (AIX), at the 6-(T1) and 12-month (T2) follow-ups; the effects of adherence to Mediterranean Diet on the lipidaemic profile and on serum levels of ceramides at T1 and T2 follow-ups; the effects of adherence to Mediterranean Diet on serum levels of visfatin, adiponectin and resistin at the 6- and 12-month follow-ups., Results: A total of 101 patients were randomised to a Mediterranean Diet style and 52 control subjects were randomised to a low-fat diet with a dietary "counselling". At the six-month follow-up (T1), subjects in the Mediterranean Diet group showed significantly lower mean serum total cholesterol levels, and significantly higher increase in reactive hyperaemia index (RHI) values compared to the low-fat diet group. Patients in the Mediterranean Diet group also showed lower serum levels of resistin and visfatin at the six-month follow-up compared to the control group, as well as higher values ​​of adiponectin, lower values of C24:0, higher values of C22:0 and higher values of the C24:0/C16:0 ratio. At the twelve-month follow-up (T2), subjects in the Mediterranean Diet group showed lower serum total cholesterol levels and lower serum LDL cholesterol levels than those in the control group. At the twelve-month follow-up, we also observed a further significant increase in the mean RHI in the Mediterranean Diet group, lower serum levels of resistin and visfatin, lower values of C24:0 and of C:18:0,and higher values of the C24:0/C16:0 ratio., Discussion: The findings of our current study offer a further possible explanation with regard to the beneficial effects of a higher degree of adherence to a Mediterranean-style diet on multiple cardiovascular risk factors and the underlying mechanisms of atherosclerosis. Moreover, these findings provide an additional plausible interpretation of the results from observational and cohort studies linking high adherence to a Mediterranean-style diet with lower total mortality and a decrease in cardiovascular events and cardiovascular mortality., Trial Registration: ClinicalTrials.gov Identifier: NCT04873167. https://classic.clinicaltrials.gov/ct2/show/NCT04873167., Competing Interests: I have no competing interests, (Copyright: © 2024 Daidone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Whether 30-day modified Rankin Scale (mRS) scores can predict 90-day scores is unclear. This study derived and validated a model to predict ordinal 90-day mRS score in an intracerebral hemorrhage (ICH) population using 30-day mRS values and routinely available baseline variables. Adults enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) trial between May 2011 and September 2015 with acute ICH, who were alive at 30 days and had mRS scores reported at both 30 and 90 days were included in this post-hoc analysis. A proportional odds regression model for predicting ordinal 90-day mRS scores was developed and internally validated using bootstrapping. Variables in the model included: mRS score at 30 days, age (years), hematoma volume (cm3), hematoma location (deep [basal ganglia, thalamus], lobar, or infratentorial), presence of intraventricular hemorrhage (IVH), baseline Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale (NIHSS) score at randomization. We assessed model fit, calibration, discrimination, and agreement (ordinal, dichotomized functional independence), and EuroQol-5D ([EQ-5D] utility weighted) between predicted and observed 90-day mRS. A total of 898/1000 participants were included. Following bootstrap internal validation, our model (calibration slope = 0.967) had an optimism-corrected c-index of 0.884 (95% CI = 0.873-0.896) and R2 = 0.712 for 90-day mRS score. The weighted ĸ for agreement between observed and predicted ordinal 90-day mRS score was 0.811 (95% CI = 0.787-0.834). Agreement between observed and predicted functional independence (mRS score of 0-2) at 90 days was 74.3% (95% CI = 69.9-78.7%). The mean ± SD absolute difference between predicted and observed EQ-5D-weighted mRS score was negligible (0.005 ± 0.145). This tool allows practitioners and researchers to utilize clinically available information along with the mRS score 30 days after ICH to reliably predict the mRS score at 90 days., Competing Interests: WLB and GF have no conflicts of interest to report. MS reports receiving research grants from Bristol Myers Squibb, Bayer, and Javelin Medical; and consulting fees from Janssen, HLS Therapeutics, AstraZeneca, and Bayer. AC has received fees for serving on an adjudication committee from Boehringer Ingelheim and AbbVie; grant support and fees for serving on committees from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer; consulting fees from Janssen, Portola Pharmaceuticals, and Ono Pharmaceuticals; and fees for serving on a steering committee and consulting fees from Bayer. MJC is a previous employee of AstraZeneca. MO and BC are employees of AstraZeneca. TEM has nothing to disclose. CIC has received research funding and/or consulting honoraria from Janssen Pharmaceuticals, Bayer AG, and AstraZeneca., (Copyright: © 2024 Baker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Aim of the present study was to assess personality and psychopathological characteristics in patients with functional movement disorders (FMDs) compared to patients with other neurological disorders (OND)., Methods: In this cross-sectional study, patients affected by clinically established FMDs and OND who attended the Neurologic Unit of the University-Hospital "Policlinico-San Marco" of Catania from the 1st of December 2021 to the 1st of June 2023 were enrolled. Personality characteristics were assessed with the Rorschach test coded according to Exner's comprehensive system and the Structured Clinical Interview for DSM-5 (SCID-II)., Results: Thirty-one patients with FMDs (27 women; age 40.2±15.5 years; education 11.7±3.2 years; disease duration 2.3±2.5 years) and 24 patients affected by OND (18 women; age 35.8±16.3 years; education 11.9±2.9 years; disease duration 3.4±2.8 years) were enrolled. At the Rorschach, FMDs presented a significantly higher frequency of Popular (P) and sum of all Human content codes (SumH>5) responses and avoidant coping than OND., Conclusion: FMDs presented "conformity behaviors", excessive interest in others than usual a maladaptive avoidant style of coping and a difficulty in verbalizing emotional distress. These psychopathological characteristics may favor the occurrence of FMDs., Competing Interests: No authors have competing interests, (Copyright: © 2024 Luca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Inflamm-aging refers to the chronic low-grade inflammation that occurs with aging and cellular senescence, and it is linked to various diseases. Understanding the markers involved in inflammation and aging, as well as their interaction with environmental factors and bodily control mechanisms, can provide crucial tools for assessing the resilience (i.e. the ability to adapt and improve) of the human body, particularly in the presence of chronic degenerative conditions or vulnerable life stages, that place the individual and the community to which he belongs in a state of potential fragility. HEBE focuses on physical exercise, along with nutritional and lifestyle recommendations, to reduce systemic inflammation and promote healthy aging. HEBE encompasses multiple research lines (LR). In the ongoing LR1 ("proof of concept"), healthy lifestyle recommendations were provided to University of Milan employees, and changes in quality of life and well-being were assessed using a specialized questionnaire. The first 100 eligible subjects, who expressed their willingness to participate, underwent a personalized physical exercise protocol based on clinical and objective assessments. Biomedical samples were collected at baseline (T0) and follow-up (T1) to establish a shared biobank and identify non-invasive biomarkers that monitor the impact of physical exercise on individual characteristics such as cardiovascular and metabolic health. Subsequently (LR2-LR10), the proof of concept findings will be expanded to include various conditions of vulnerability such as obesity, cancer, endocrine disorders, cardiovascular diseases, infertility, functional syndromes, respiratory disorders, neurodegenerative diseases, and autoimmune conditions. The research lines will leverage the expertise of the 94 participating investigators to form a collaborative network that maximizes the potential for investigation and knowledge exchange. This approach fosters a culture of health promotion and disease prevention. ClinicalTrials.gov Identifier: NCT05815732., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bianchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human-induced pluripotent stem cells (hiPSCs), reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signaling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism that cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fasciani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neuronal death could be responsible for the cognitive impairments found in astronauts exposed to spaceflight, highlighting the need to identify potential countermeasures to ensure neuronal health in microgravity conditions. Therefore, differentiated HT22 cells were exposed to simulated microgravity by random positioning machine (RPM) for 48 h, treating them with a single administration of Trolox, recombinant irisin (r-Irisin) or both. Particularly, we investigated cell viability by MTS assay, Trypan Blue staining and western blotting analysis for Akt and B-cell lymphoma 2 (Bcl-2), the intracellular increase of reactive oxygen species (ROS) by fluorescent probe and NADPH oxidase 4 (NOX4) expression, as well as the expression of brain-derived neurotrophic factor (BDNF), a major neurotrophin responsible for neurogenesis and synaptic plasticity. Although both Trolox and r-Irisin manifested a protective effect on neuronal health, the combined treatment produced the best results, with significant improvement in all parameters examined. In conclusion, further studies are needed to evaluate the potential of such combination treatment in counteracting weightlessness-induced neuronal death, as well as to identify other potential strategies to safeguard the health of astronauts exposed to spaceflight., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bonanni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Navigation in the Mediterranean in the Neolithic is studied here through the boats that were used, the degree of technical specialisation in their construction and, above all, their chronology. After a brief explanation of the exceptional site of La Marmotta, the characteristics and chronology of the five canoes found at the settlement and one of the nautical objects linked to Canoe 1 are discussed. This will allow a reflection on the capability of Neolithic societies for navigation owing to their high technological level. This technology was an essential part in the success of their expansion, bearing in mind that in a few millennia they occupied the whole Mediterranean from Cyprus to the Atlantic seaboard of the Iberian Peninsula., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gibaja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In vivo noninvasive imaging of neurometabolites is crucial to improve our understanding of the underlying pathophysiological mechanism in neurodegenerative diseases. Abnormal changes in synaptic organization leading to synaptic degradation and neuronal loss is considered as one of the primary factors driving Alzheimer's disease pathology. Magnetic resonance based molecular imaging techniques such as chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) can provide neurometabolite specific information which may relate to underlying pathological and compensatory mechanisms. In this study, CEST and short echo time single voxel MRS was performed to evaluate the sensitivity of cerebral metabolites to beta-amyloid (Aβ) induced synaptic deficit in the hippocampus of a mouse model of Alzheimer's disease. The CEST based spectra (Z-spectra) were acquired on a 9.4 Tesla small animal MR imaging system with two radiofrequency (RF) saturation amplitudes (1.47 μT and 5.9 μT) to obtain creatine-weighted and glutamate-weighted CEST contrasts, respectively. Multi-pool Lorentzian fitting and quantitative T1 longitudinal relaxation maps were used to obtain metabolic specific apparent exchange-dependent relaxation (AREX) maps. Short echo time (TE = 12 ms) single voxel MRS was acquired to quantify multiple neurometabolites from the right hippocampus region. AREX contrasts and MRS based metabolite concentration levels were examined in the ARTE10 animal model for Alzheimer's disease and their wild type (WT) littermate counterparts (age = 10 months). Using MRS voxel as a region of interest, group-wise analysis showed significant reduction in Glu-AREX and Cr-AREX in ARTE10, compared to WT animals. The MRS based results in the ARTE10 mice showed significant decrease in glutamate (Glu) and glutamate-total creatine (Glu/tCr) ratio, compared to WT animals. The MRS results also showed significant increase in total creatine (tCr), phosphocreatine (PCr) and glutathione (GSH) concentration levels in ARTE10, compared to WT animals. In the same ROI, Glu-AREX and Cr-AREX demonstrated positive associations with Glu/tCr ratio. These results indicate the involvement of neurotransmitter metabolites and energy metabolism in Aβ-mediated synaptic degradation in the hippocampus region. The study also highlights the feasibility of CEST and MRS to identify and track multiple competing and compensatory mechanisms involved in heterogeneous pathophysiology of Alzheimer's disease in vivo., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shahid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Discovering mathematical equations that govern physical and biological systems from observed data is a fundamental challenge in scientific research. We present a new physics-informed framework for parameter estimation and missing physics identification (gray-box) in the field of Systems Biology. The proposed framework-named AI-Aristotle-combines the eXtreme Theory of Functional Connections (X-TFC) domain-decomposition and Physics-Informed Neural Networks (PINNs) with symbolic regression (SR) techniques for parameter discovery and gray-box identification. We test the accuracy, speed, flexibility, and robustness of AI-Aristotle based on two benchmark problems in Systems Biology: a pharmacokinetics drug absorption model and an ultradian endocrine model for glucose-insulin interactions. We compare the two machine learning methods (X-TFC and PINNs), and moreover, we employ two different symbolic regression techniques to cross-verify our results. To test the performance of AI-Aristotle, we use sparse synthetic data perturbed by uniformly distributed noise. More broadly, our work provides insights into the accuracy, cost, scalability, and robustness of integrating neural networks with symbolic regressors, offering a comprehensive guide for researchers tackling gray-box identification challenges in complex dynamical systems in biomedicine and beyond., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahmadi Daryakenari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Life tables are one of the most common tools to describe the biology of insect species and their response to environmental conditions. Although the benefits of life tables are beyond question, we raise some doubts about the completeness of the information reported in life tables. To substantiate these doubts, we consider a case study (Corcyra cephalonica) for which the raw dataset is available. The data suggest that the Gaussian approximation of the development times which is implied by the average and standard error usually reported in life tables does not describe reliably the actual distribution of the data which can be misleading and hide interesting biological aspects. Furthermore, it can be risky when life table data are used to build models to predict the demographic changes of the population. The present study highlights this aspect by comparing the impulse response generated by the raw data and by its Gaussian approximation based on the mean and the standard error. The conclusions of this paper highlight: i) the importance of adding more information to life tables and, ii) the role of raw data to ensure the completeness of this kind of studies. Given the importance of raw data, we also point out the need for further developments of a standard in the community for sharing and analysing data of life tables experiments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rossini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Schizophrenia, a complex neuropsychiatric disorder, is believed to be influenced by various factors including environmental exposures. A potential environmental factor is the infection by the obligate intracellular parasitic protozoan, Toxoplasma gondii which affects neurotransmitter levels, which could potentially exacerbate, trigger symptoms of schizophrenia or make them worst., Objective: To investigate the association between Toxoplasma gondii seropositivity and psychopathological presentation in persons with schizophrenia in Ecuador., Methods: This study was conducted at the Neuroscience Institute of Guayaquil, Ecuador. Among 368 inpatients, 104 were selected based on specific inclusion and exclusion criteria. Descriptive statistics captured patient characteristics and mental health outcomes. Logistic regression models estimated the effect of toxoplasmosis on various mental health outcomes, controlling for demographic and health-related variables., Results: 86.5% of participants were seropositive for toxoplasmosis. Toxoplasma-seropositive schizophrenic patients had a lower risk of depression but a significantly higher risk of disorientation. The most prevalent mental health outcomes were Language Impairments (70.2%) and Bizarre Behavior (76.0%)., Conclusion: Our findings suggest that Toxoplasma gondii seropositivity may have specific effects on mental functions in schizophrenic patients, particularly reducing the risk of depression but increasing the risk of disorientation. Further studies are required to clarify these associations and the potential underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rosado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Long COVID syndrome can have a major impact on life organization. Its persistent symptoms may cause a potentially disabling condition that affects the quality of life of those suffering from it. The resulting loss of functional independence hinders the ability to return to normal life. Many research studies carried out on this novel syndrome have focused on describing its extensive symptomatology. Studies on later repercussions, however, such as disability or loss of significant roles, remain scarce. This study examines the loss of socioemotional and occupational roles experienced by individuals suffering from Long COVID, as a result of the disease. A secondary objective is to analyze the sociodemographic and clinical factors associated with this loss of roles., Patients and Methods: A cross-sectional study was conducted with the participation of 100 patients diagnosed with Long COVID, over the age of 18, and attended by Primary Health Care in the Autonomous Community of Aragon. The main study variable was the loss of significant socioemotional and occupational roles by the participants. Sociodemographic and clinical data were also collected through a structured interview. Subsequently, a descriptive, correlational, and regression-based statistical analysis was performed using the SPSS Statistics program., Results: Based on the 100 study participants, the median number of roles lost was 3 (IQR 2) and the median number of valuable roles lost was 2 (IQR 2). More cognitive impairment and not having an active work role were predictors of a greater loss of valuables roles., Conclusion: Long COVID symptoms hinder the development of socioemotional and occupational roles. Healthcare professionals should consider this when intervening to ensure that their patients may recover their life as it was before the disease., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 León-Herrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Both the basic human values approach and the economic preference approach have been developed and applied to represent fundamental drivers of human behavior in various domains by measuring people's underlying preferences and motivations. Both of them have been used, however, in isolation from each other, the former primarily in social psychology studies and the latter mainly in economic studies. But how similar are they? Finding that they differ may suggest that combining them to explain human behavior might be beneficial. To the best of our knowledge, only a few studies have attempted to explore and empirically examine the theoretical and empirical link between variables in both approaches. The current study tries to fill this gap by examining relations between basic human values and major economic preferences. We examine the associations between the values of self-transcendence, self-enhancement, openness to change and conservation, and the economic preferences of risk aversion (or seeking), altruism, trust, and positive and negative reciprocity. We propose mechanisms as to how they may be associated with one another. For example, we expect an association between conservation and risk aversion as both are motivated by attributing importance to stability and the status quo, or between self-transcendence and altruism, as both are motivated by concern for others. For the empirical analysis we employed convenience samples collected in Poland and Germany. Results in both samples support our expectations: several values and economic preferences are linked in theoretically predictable ways, but only to a weak or moderate extent. We conclude that they are not mutually exclusive but may rather be complementary, and therefore likely both relevant for investigations into explaining behavior., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Scharfbillig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diabetes and poor glycemic control are significant predictors of severity and death in the COVID-19 disease. The perception of this risk in individuals with type 2 diabetes (T2D) could modify coping styles, leading to behaviors associated with better self-care and metabolic control. Theoretically, active coping is associated with better glycemic control in patients with T2D. Nonetheless, information during extreme risk like the COVID-19 pandemic is still limited. Our objective was to evaluate the association between coping styles and risk perception in the COVID-19 pandemic and the change in metabolic parameters. This is a prospective study that included individuals with T2D treated in a tertiary care center during the COVID-19 outbreak who returned to follow-up one year later. We assessed coping styles and risk perception with the Extreme Risk Coping Scale and the risk perception questionnaire. Clinical characteristics and metabolic parameters were registered in both visits. Groups were compared using Kruskal Wallis tests, and changes in metabolic parameters were assessed with Wilcoxon rank sum tests. Our sample included 177 participants at baseline, and 118 concluded the study. Passive coping was more frequent in women. Low-risk perception was associated with higher age, lower psychiatric comorbidities, and lower frequency of psychiatric treatment compared with other risk perception groups. Patients with active coping plus high-risk perception did not have a change in metabolic parameters at follow-up, whereas patients with other coping styles and lower risk perception had an increase in total cholesterol, LDL-cholesterol, and triglycerides. There were no differences by coping group or by risk perception in glycemic control., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alcántara-Garcés et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)