Environmental heterogeneity at two spatial scales affects litter diversity-decomposition relationships.

The effects of biodiversity on ecological processes have been experimentally evaluated mainly at the local scale under homogeneous conditions. To scale up experimentally based biodiversity-functioning relationships, there is an urgent need to understand how such relationships are affected by the environmental heterogeneity that characterizes larger spatial scales. Here, we tested the effects of an 800-m elevation gradient (a large-scale environmental factor) and forest habitat (a fine-scale factor) on litter diversity-decomposition relationships. To better understand local and landscape scale mechanisms, we partitioned net biodiversity effects into complementarity, selection, and insurance effects as applicable at each scale. We assembled different litter mixtures in aquatic microcosms that simulated natural tree holes, replicating mixtures across blocks nested within forest habitats (edge, interior) and elevations (low, mid, high). We found that net biodiversity and complementarity effects increased over the elevation gradient, with their strength modified by forest habitat and the identity of litter in mixtures. Complementarity effects at local and landscape scales were greatest for combinations of nutrient-rich and nutrient-poor litters, consistent with nutrient transfer mechanisms. By contrast, selection effects were consistently weak and negative at both scales. Selection effects at the landscape level were due mainly to nonrandom overyielding rather than spatial insurance effects. Our findings demonstrate that the mechanisms by which litter diversity affects decomposition are sensitive to environmental heterogeneity at multiple scales. This has implications for the scaling of biodiversity-ecosystem function relationships and suggests that future shifts in environmental conditions due to climate change or land use may impact the functioning of aquatic ecosystems.

People perceive parasocial relationships to be effective at fulfilling emotional needs.

People regularly form one-sided, "parasocial" relationships (PSRs) with targets incapable of returning the sentiment. Past work has shown that people engage with PSRs to support complex psychological needs (e.g., feeling less lonely after watching a favorite movie). However, we do not know how people rate these relationships relative to traditional two-sided relationships in terms of their effectiveness in supporting psychological needs. The current research (Ntotal = 3085) examined how PSRs help people fulfil emotion regulation needs. In Studies 1 and 2, participants felt that both their YouTube creator and non-YouTube creator PSRs were more effective at fulfilling their emotional needs than in-person acquaintances, albeit less effective than close others. In Study 3, people with high self-esteem thought PSRs would be responsive to their needs when their sociometer was activated, just as they do with two-sided relationships.

How different attributes are weighted in professionals' decision-making in Pediatric Dentistry-a protocol for guiding discrete choice experiment focused on shortening the evidence-based practice implementation for dental care.

BACKGROUND: Important evidence has been constantly produced and needs to be converted into practice. Professional consumption of such evidence may be a barrier to its implementation. Then, effective implementation of evidence-based interventions in clinical practice leans on the understanding of how professionals value attributes when choosing between options for dental care, permitting to guide this implementation process by maximizing strengthens and minimizing barriers related to that. METHODS: This is part of a broader project investigating the potential of incorporating scientific evidence into clinical practice and public policy recommendations and guidelines, identifying strengths and barriers in such an implementation process. The present research protocol comprises a Discrete Choice Experiment (DCE) from the Brazilian oral health professionals' perspective, aiming to assess how different factors are associated with professional decision-making in dental care, including the role of scientific evidence. Different choice sets will be developed, either focusing on understanding the role of scientific evidence in the professional decision-making process or on understanding specific attributes associated with different interventions recently tested in randomized clinical trials and available as newly produced scientific evidence to be used in clinical practice. DISCUSSION: Translating research into practice usually requires time and effort. Shortening this process may be useful for faster incorporation into clinical practice and beneficial to the population. Understanding the context and professionals' decision-making preferences is crucial to designing more effective implementation and/or educational initiatives. Ultimately, we expect to design an efficient implementation strategy that overcomes threats and potential opportunities identified during the DCEs, creating a customized structure for dental professionals. TRIAL REGISTRATION: https://osf.io/bhncv .

Filial cannibalism of Nabis pseudoferus is not evolutionarily optimal foraging strategy.

Using a recursion model with real parameters of Nabis pseudoferus, we show that its filial cannibalism is an optimal foraging strategy for life reproductive success, but it is not an evolutionarily optimal foraging strategy, since it cannot maximize the descendant's number at the end of the reproductive season. Cannibalism is evolutionarily rational, when the number of newborn offspring produced from the cannibalized offspring can compensate the following two effects: (a) The cannibalistic lineage wastes time, since the individuals hatched from eggs produced by cannibalism start to reproduce later. (b) Cannibalism eliminates not only one offspring, but also all potential descendants from the cannibalized offspring during the rest of reproductive season. In our laboratory trials, from conspecific prey Nabis pseudoferus did not produce newborn nymphs enough to compensate the above two effects.

Decoding phenotypic screening: A comparative analysis of image representations.

Biomedical imaging techniques such as high content screening (HCS) are valuable for drug discovery, but high costs limit their use to pharmaceutical companies. To address this issue, The JUMP-CP consortium released a massive open image dataset of chemical and genetic perturbations, providing a valuable resource for deep learning research. In this work, we aim to utilize the JUMP-CP dataset to develop a universal representation model for HCS data, mainly data generated using U2OS cells and CellPainting protocol, using supervised and self-supervised learning approaches. We propose an evaluation protocol that assesses their performance on mode of action and property prediction tasks using a popular phenotypic screening dataset. Results show that the self-supervised approach that uses data from multiple consortium partners provides representation that is more robust to batch effects whilst simultaneously achieving performance on par with standard approaches. Together with other conclusions, it provides recommendations on the training strategy of a representation model for HCS images.

An Insertion Within SIRPß1 Shows a Dual Effect Over Alzheimer's Disease Cognitive Decline Altering the Microglial Response.

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.

Potentially toxic elements fluxes in 210Pb-dated sediment cores from a large coastal lagoon (southern Gulf of Mexico) under environmental stress.

Terminos Lagoon (TL), in the southern Gulf of Mexico, has been under intensive anthropogenic pressure (e.g., oil-industry development) since the 1970s. Historical changes in flux ratios of potentially toxic elements (PTEs; As, Cd, Cr, Cu, Ni, Pb, V, Zn) were, for the first time, assessed inside TL by using 210Pb-dated sediment cores. Sediments showed minor enrichments for Cd, Ni, Pb, and V. However, according to international benchmarks, the As, Cr, Cu, and Ni concentrations could pose a risk for benthic biota. Sedimentary processes involved in the accumulation of PTEs were identified through a chemometric approach. Increments in PTEs flux ratios concur with the recent (⁓50 years) and extensive land-use changes, particularly the transport and deposit of materials delivered by rivers. These findings are expected to be used in managing this crucial natural resource, the larger Mexican coastal lagoon ecosystem, to mitigate the effects of global change.

Pathogenic Variants Associated with Epigenetic Control and the NOTCH Pathway Are Frequent in Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) constitutes a B-cell neoplasm derived from germinal center lymphocytes. Despite high cure rates (80-90%) obtained with the current multiagent protocols, a significant proportion of cHL patients experience recurrences, characterized by a lower sensitivity to second-line treatments. The genomic background of chemorefractory cHL is still poorly understood, limiting personalized treatment strategies based on molecular features. In this study, using a targeted next-generation sequencing (NGS) panel specifically designed for cHL research, we compared chemosensitive and chemorefractory diagnostic tissue samples of cHL patients. Furthermore, we longitudinally examined paired diagnosis-relapsesamples of chemorefractory cHL in order to define patterns of dynamic evolution and clonal selection. Pathogenic variants in NOTCH1 and NOTCH2 genes frequently arise in cHL. Mutations in genes associated with epigenetic regulation (CREBBP and EP300) are particularly frequent in relapsed/refractory cHL. The appearance of novel clones characterized by mutations previously not identified at diagnosis is a common feature in cHL cases showing chemoresistance to frontline treatments. Our results expand current molecular and pathogenic knowledge of cHL and support the performance of molecular studies in cHL prior to the initiation of first-line therapies.

Regional assessment of the historical trends of mercury in sediment cores from Wider Caribbean coastal environments.

Spatial and temporal variations of mercury (Hg) concentrations, enrichment, and potential ecological risks were studied in a suite of lead-210 (210Pb) dated sediment cores from 13 Wider Caribbean Region coastal environments. Broad variability of Hg concentrations (19-18761 ng g-1) was observed, encompassing even background levels (38-100 ng g-1). Most Hg concentration profiles exhibited a characteristic upward trend, reaching their peak values in the past two decades. Most of the sediment sections, showing from moderately to very severe Hg enrichment, were found in cores from Havana Bay and Sagua River Estuary (Cuba), Port-au-Prince Bay (Haiti), and Cartagena Bay (Colombia). These were also the most seriously contaminated sites, which can be considered regional Hg 'hotspots'. Both Havana Bay and Port-au-Prince Bay reportedly receive waste from large cities with populations exceeding 2 million inhabitants, and watersheds affected by high erosion rates. The records from the Sagua River Estuary and Cartagena Bay reflected historical Hg contamination associated with chloralkali plants, and these sites are of very high ecological risk. These results constitute a major contribution to the scarce regional data on contaminants in the Wider Caribbean Region and provide reference information to support the evaluation of the effectiveness of the Minamata Convention.

The impact of reduced muscular fitness on cardiometabolic risk factors in children aged 9-11 years.

AIM: To analyse the relationships between muscular fitness (MF), fat mass (FM), fat-free mass (FFM) and its combined ratio with cardiometabolic risk (CMR) and whether the relationship between MF and CMR is mediated by body composition in schoolchildren. METHODS: A cross-sectional study was conducted on schoolchildren from Cuenca, Spain, between September and November 2017. FM and FFM were estimated using bioimpedance analysis. The CMR index was calculated from triglycerides-HDL-c ratio, arterial pressure and fasting insulin. The MF index was assessed using handgrip and standing long jump tests. Analysis of covariance models assessed CMR index differences across the MF index and the FM/FFM ratio categories. Mediation analysis examined whether the MF index and the CMR index association were mediated by FM, FFM or FM/FFM ratio. RESULTS: The analyses involved 485 schoolchildren aged 9-11 years (55.4% girls). Children with a higher MF index had a lower CMR index (p < 0.05). This association did not persist after controlling for FM/FFM. FM, FFM and FM/FFM ratio mediated the relationship between the MF index and the CMR index. CONCLUSION: Better levels of MF are associated with better cardiometabolic profile, but a healthy body composition is determinant to improve future health.

Prevalence and Distribution of MUTYH Pathogenic Variants, Is There a Relation with an Increased Risk of Breast Cancer?

BACKGROUND: MUTYH has been implicated in hereditary colonic polyposis and colorectal carcinoma. However, there are conflicting data refgarding its relationship to hereditary breast cancer. Therefore, we aimed to assess if MUTYH mutations contribute to breast cancer susceptibility. METHODS: We retrospectively reviewed 3598 patients evaluated from June 2018 to June 2023 at the Hereditary Cancer Unit of La Paz University Hospital, focusing on those with detected MUTYH variants. RESULTS: Variants of MUTYH were detected in 56 patients (1.6%, 95%CI: 1.2-2.0). Of the 766 patients with breast cancer, 14 patients were carriers of MUTYH mutations (1.8%, 95%CI: 0.5-3.0). The prevalence of MUTYH mutation was significantly higher in the subpopulation with colonic polyposis (11.3% vs. 1.1%, p < 0.00001, OR = 11.2, 95%CI: 6.2-22.3). However, there was no significant difference in the prevalence within the subpopulation with breast cancer (1.8% vs. 1.5%, p = 0.49, OR = 1.2, 95%CI: 0.7-2.3). CONCLUSION: In our population, we could not establish a relationship between MUTYH and breast cancer. These findings highlight the necessity for a careful interpretation when assessing the role of MUTYH mutations in breast cancer risk.

Genomic and phenotypic analysis of invasive Streptococcus suis isolated in Spain reveals genetic diversification and associated virulence traits.

Streptococcus suis is a zoonotic pathogen that causes a major health problem in the pig production industry worldwide. Spain is one of the largest pig producers in the world. This work aimed to investigate the genetic and phenotypic features of invasive S. suis isolates recovered in Spain. A panel of 156 clinical isolates recovered from 13 Autonomous Communities, representing the major pig producers, were analysed. MLST and serotyping analysis revealed that most isolates (61.6%) were assigned to ST1 (26.3%), ST123 (18.6%), ST29 (9.6%), and ST3 (7.1%). Interestingly, 34 new STs were identified, indicating the emergence of novel genetic lineages. Serotypes 9 (27.6%) and 1 (21.8%) prevailed, followed by serotypes 7 (12.8%) and 2 (12.2%). Analysis of 13 virulence-associated genes showed significant associations between ST, serotype, virulence patterns, and clinical features, evidencing particular virulence traits associated with genetic clusters. The pangenome was generated, and the core genome was distributed in 7 Bayesian groups where each group included a variable set of over- and under-represented genes of different categories. The study provides comprehensive data and knowledge to improve the design of new vaccines, antimicrobial treatments, and bacterial typing approaches.

Implication of intestinal microbiota in the etiopathogenesis of fibromyalgia: A systematic review.

Fibromyalgia (FM) is a highly prevalent chronic disease. About 4.7% of the world's population suffers from generalized pain and hypersensitivity, in addition to a wide range of physical and psychological symptoms. The etiopathogenesis of this disease is multifactorial, which makes its diagnosis and treatment challenging. Recently, the increase in the number of studies on microbiota has provided new data that can help to understand the onset and development of FM. An updated systematic review of the causes of FM has been carried out in this work. Particularly in the last decade, research has focused on the gut-brain axis, which has emerged as a crucial mechanism for microbiota-host crosstalk. In FM patients, quantitative imbalances of the intestinal microbiota (dysbiosis) and bacterial metabolites with differential relative abundance have been found, especially short-chain fatty acids and lipopolysaccharides. Furthermore, the microbiota has been found to indirectly influence host neurotransmitter mechanisms, mainly through the serotonin precursor, glutamate, and gamma-aminobutyric acid. Thus, all these mechanisms and their influence on the etiopathogenesis of FM are discussed in this review.

Genetic Variation and Evolutionary Analysis of Eggplant Mottled Dwarf Virus Isolates from Spain.

The genetic variation and population structure of gene N (nucleocapsid) and part of gene L (replicase) from 13 eggplant mottle dwarf virus (EMDV) isolates from Spain were evaluated and compared with sequences of EMDV isolates from other countries retrieved from GenBank. Phylogenetic inference of part of gene L showed three main clades, one containing an EMDV isolate from Australia and the other two containing isolates from Iran and Europe, as well as four subclades. EMDV isolates from Spain were genetically very similar and grouped in a subclade together with one isolate from Germany and one from the UK. No new recombination events were detected in addition to one recombination previously reported, suggesting that recombination is rare for EMDV. The comparison of synonymous and non-synonymous rates showed that negative selection played an important role, and only two codons were under positive selection. Genetic differentiation (Fst test), phylogenetic and nucleotide diversity analyses suggest a unique introduction of EMDV to Spain and low gene flow with other countries. In contrast, Greece and Italy showed diverse populations with high gene flow between both.

Enzyme-Linked DNA Displacement (ELIDIS) Assay for Ultrasensitive Electrochemical Detection of Antibodies.

Here we report the development of a method for the electrochemical ultrasensitive detection of antibodies that couples the programmability and versatility of DNA-based systems with the sensitivity provided by enzymatic amplification. The platform, termed Enzyme-Linked DNA Displacement (ELIDIS), is based on the use of antigen-DNA conjugates that, upon the bivalent binding of a specific target antibody, induce the release of an enzyme-DNA hybrid strand from a preformed duplex. Such enzyme-DNA hybrid strand can then be electrochemically detected with a disposable electrode with high sensitivity. We applied ELIDIS to demonstrate the sensitive (limit of detection in the picomolar range), specific and multiplexed detection of five different antibodies including three clinically relevant ones. ELIDIS is also rapid (it only requires two reaction steps), works well in complex media (serum) and is cost-effective. A direct comparison with a commercial ELISA kit for the detection of Cetuximab demonstrates the promising features of ELIDIS as a point-of-care platform for antibodies detection.

Interrelation between gut microbiota, SCFA, and fatty acid composition in pigs.

The gut microbiota is a key player in the host metabolism. Some bacteria are able to ferment non-digestible compounds and produce short-chain fatty acids that the host can later transform and accumulate in tissue. In this study, we aimed to better understand the relationships between the microorganisms and the short-chain fatty acid composition of the rectal content, including the possible linkage with the fatty acid composition in backfat and muscle of the pig. We studied a Duroc × Iberian crossbred population, and we found significant correlations between different bacterial and archaeal genera and the fatty acid profile. The abundance of n-butyric acid in the rectal content was positively associated with Prevotella spp. and negatively associated with Akkermansia spp., while conversely, the abundance of acetic acid was negatively and positively associated with the levels of Prevotella spp. and Akkermansia spp., respectively. The most abundant genus, Rikenellaceae RC9 gut group, had a positive correlation with palmitic acid in muscle and negative correlations with stearic acid in backfat and oleic acid in muscle. These results suggest the possible role of Prevotella spp. and Akkermansia spp. as biomarkers for acetic and n-butyric acids, and the relationship of Rikenellaceae RC9 gut group with the lipid metabolism, building up the potential, although indirect, role of the microbiota in the modification of the backfat and muscle fatty acid composition of the host.IMPORTANCEThe vital role of the gut microbiota on its host metabolism makes it essential to know how its modulation is mirrored on the fatty acid composition of the host. Our findings suggest Prevotella spp. and Akkermansia spp. as potential biomarkers for the levels of beneficial short-chain fatty acids and the possible influence of Rikenellaceae RC9 gut group in the backfat and muscle fatty acid composition of the pig.

Role of vericiguat in management of patients with heart failure with reduced ejection fraction after worsening episode.

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.