Possible immune mechanisms of gut microbiota and its metabolites in the occurrence and development of immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired production, leading to an elevated bleeding tendency. Recent studies have demonstrated an important link between the gut microbiota and the onset and progression of several immune diseases in humans, emphasizing that gut microbiota-derived metabolites play a non-negligible role in autoimmune diseases. The gut microbiota and its metabolites, such as short-chain fatty acids, oxidized trimethylamine, tryptophan metabolites, secondary bile acids and lipopolysaccharides, can alter intestinal barrier permeability by modulating immune cell differentiation and cytokine secretion, which in turn affects the systemic immune function of the host. It is therefore reasonable to hypothesize that ecological dysregulation of the gut microbiota may be an entirely new factor in the triggering of ITP. This article reviews the potential immune-related mechanisms of the gut microbiota and representative metabolites in ITP, as well as the important influence of leaky gut on the development of ITP, with a view to enriching the theoretical system of ITP-related gut microecology and providing new ideas for the study of ITP.

Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.

Advances in sequencing technology have unveiled examples of nucleus-encoded polycistronic genes, once considered rare. Exclusively polycistronic transcripts are prevalent in green algae, although the mechanism by which multiple polypeptides are translated from a single transcript is unknown. Here, we used bioinformatic and in vivo mutational analyses to evaluate competing mechanistic models for polycistronic expression in green algae. High-confidence manually curated datasets of bicistronic loci from two divergent green algae, Chlamydomonas reinhardtii and Auxenochlorella protothecoides, revealed 1) a preference for weak Kozak-like sequences for ORF 1 and 2) an underrepresentation of potential initiation codons before ORF 2, which are suitable conditions for leaky scanning to allow ORF 2 translation. We used mutational analysis in Auxenochlorella protothecoides to test the mechanism. In vivo manipulation of the ORF 1 Kozak-like sequence and start codon altered reporter expression at ORF 2, with a weaker Kozak-like sequence enhancing expression and a stronger one diminishing it. A synthetic bicistronic dual reporter demonstrated inversely adjustable activity of green fluorescent protein expressed from ORF 1 and luciferase from ORF 2, depending on the strength of the ORF 1 Kozak-like sequence. Our findings demonstrate that translation of multiple ORFs in green algal bicistronic transcripts is consistent with episodic leaky ribosome scanning of ORF 1 to allow translation at ORF 2. This work has implications for the potential functionality of upstream open reading frames found across eukaryotic genomes and for transgene expression in synthetic biology applications.

Coincidence detection and integration behavior in spiking neural networks.

Recently, the interest in spiking neural networks (SNNs) remarkably increased, as up to now some key advances of biological neural networks are still out of reach. Thus, the energy efficiency and the ability to dynamically react and adapt to input stimuli as observed in biological neurons is still difficult to achieve. One neuron model commonly used in SNNs is the leaky-integrate-and-fire (LIF) neuron. LIF neurons already show interesting dynamics and can be run in two operation modes: coincidence detectors for low and integrators for high membrane decay times, respectively. However, the emergence of these modes in SNNs and the consequence on network performance and information processing ability is still elusive. In this study, we examine the effect of different decay times in SNNs trained with a surrogate-gradient-based approach. We propose two measures that allow to determine the operation mode of LIF neurons: the number of contributing input spikes and the effective integration interval. We show that coincidence detection is characterized by a low number of input spikes as well as short integration intervals, whereas integration behavior is related to many input spikes over long integration intervals. We find the two measures to linearly correlate via a correlation factor that depends on the decay time. Thus, the correlation factor as function of the decay time shows a powerlaw behavior, which could be an intrinsic property of LIF networks. We argue that our work could be a starting point to further explore the operation modes in SNNs to boost efficiency and biological plausibility. Supplementary Information: The online version of this article (10.1007/s11571-023-10038-0) contains supplementary material, which is available to authorized users.

Low-energy and tunable LIF neuron using SiGe bandgap-engineered resistive switching transistor.

We have proposed leaky integrate-and-fire (LIF) neuron having low-energy consumption and tunable functionality without external circuit components. Our LIF neuron has a simple configuration consisting of only three components: one bandgap-engineered resistive switching transistor (BE-RST), one capacitor, and one resistor. Here, the crucial point is that BE-RST with a silicon-germanium heterojunction possesses an amplified hysteric current switching with a low latch-up voltage due to improved hole storage capability and impact ionization coefficient. Therefore, the proposed neuron utilizing BE-RST requires an energy consumption of 0.36 pJ/spike, which is approximately six times lower than 2.08 pJ/spike of pure silicon-RST based neuron. In addition, the spiking properties can be tuned by modulating the leakage rate and threshold through gate bias, which contributes to energy-efficient sparse-activity and high learning accuracy. As a result, our proposed neuron can be a promising candidate for executing various spiking neural network applications.

Optimization of a DiCre recombinase system with reduced leakage for conditional genome editing of Cryptosporidium.

BACKGROUND: The dimerizable Cre recombinase system (DiCre) exhibits increased leaky activity in Cryptosporidium, leading to unintended gene editing in the absence of induction. Therefore, optimization of the current DiCre technique is necessary for functional studies of essential Cryptosporidium genes. METHODS: Based on the results of transcriptomic analysis of Cryptosporidium parvum stages, seven promoters with different transcriptional capabilities were screened to drive the expression of Cre fragments (FKBP-Cre59 and FRB-Cre60). Transient transfection was performed to assess the effect of promoter strength on leakage activity. In vitro and in vivo experiments were performed to evaluate the leaky activity and cleavage efficiency of the optimized DiCre system by polymerase chain reaction (PCR), nanoluciferase, and fluorescence analyses. RESULTS: The use of promoters with lower transcriptional activity, such as pcgd6_4110 and pcgd3_260, as opposed to strong promoters such as pActin, pα-Tubulin, and pEnolase, reduced the leakage rate of the system from 35-75% to nearly undetectable levels, as verified by transient transfection. Subsequent in vitro and in vivo experiments using stable lines further demonstrated that the optimized DiCre system had no detectable leaky activity. The system achieved 71% cleavage efficiency in vitro. In mice, a single dose of the inducer resulted in a 10% conditional gene knockout and fluorescent protein expression in oocysts. These fluorescently tagged transgenic oocysts could be enriched by flow sorting for further infection studies. CONCLUSIONS: A DiCre conditional gene knockout system for Cryptosporidium with good cleavage efficiency and reduced leaky activity has been successfully established.

Effect of Saccharomyces boulardii on Liver Diseases: A Systematic Review.

We aimed to systematize the results of published studies on the use of Saccharomyces boulardii (SB) for the treatment of various liver disorders (CRD42022378050). Searches were conducted using PubMed and Scopus on 1 August 2022. The PubMed search was updated on 15 June 2024. The review included sixteen studies: ten experimental animal studies (EASs) and six randomized controlled trials (RCTs). The CNCM I-745 strain was used in 68.8% of the included studies. SB reduced the severity of many manifestations of cirrhosis, and lowered the Child-Pugh scores in RCT. SB reduced the serum concentrations of TNF-α, IL-1ß, IL-6, and IL-4 in animals with metabolic dysfunction-associated steatotic liver disease (MASLD); lowered the serum TNF-α and IL-6 levels in experimental cirrhosis in rats; and reduced the CRP levels in decompensated cirrhosis. The EAS of MASLD revealed that SB reduced liver steatosis and inflammation and lowered the liver expression of genes of TNF-α, IL-1ß, interferon-γ, and IL-10. In studies on experimental cirrhosis and MASLD, SB reduced the liver expression of genes of TGF-ß, α-SMA, and collagen as well as liver fibrosis. SB reduced the abundance of Escherichia (Proteobacteria), increased the abundance of Bacteroidetes in the gut microbiota, prevented an increase in intestinal barrier permeability, and reduced bacterial translocation and endotoxemia.

Leaky Gut Syndrome: Myths and Management.

Leaky gut syndrome is a condition widely popularized in the lay literature, although it is not currently accepted as a formal medical diagnosis. Multiple gastrointestinal symptoms are ascribed to leaky gut syndrome, including diarrhea, bloating, distension, abdominal pain, and dyspeptic symptoms of early satiety, nausea, and postprandial fullness. The etiology and pathophysiology of leaky gut syndrome are multifactorial; a preceding gastrointestinal infection, inflammatory bowel disease, and certain medications may be relevant factors in some patients. The diagnosis of leaky gut syndrome is problematic. Although patients are frequently informed that the diagnosis can be readily made using results from blood work or stool studies, no validated test currently exists to make this diagnosis. Patients report a variety of myths about the etiology, diagnosis, and treatment of leaky gut syndrome, which can cause alarm and can frequently lead to expensive, unnecessary tests and unproven, sometimes dangerous treatments. This article reviews some of the most common myths about leaky gut syndrome and provides data from the scientific literature to correct these statements. Management strategies, based on data, are provided when available.

A (poly)phenol-rich diet reduces serum and faecal calprotectin in older adults with increased intestinal permeability: the MaPLE randomised controlled trial.

BACKGROUND: Older subjects are at risk of elevated intestinal permeability (IP) which can lead to immune system activation and low-grade systemic inflammation. Dietary changes are a potential strategy to reduce IP. The MaPLE project evaluated the hypothesis that increasing (poly)phenol intake would beneficially impact on several important markers and pathways related to IP. The objective of the present study was to assess the effects of the MaPLE (poly)phenol-rich diet (PR-diet) on additional IP-related biomarkers and any relationships between biomarker responses. METHODS: A randomised, controlled, crossover study was performed involving 51 participants (≥ 60 y) with increased IP, as determined by serum zonulin levels. Participants were randomly assigned to one of two intervention groups: a control diet (C-diet) or a PR-diet. Each intervention lasted 8 weeks and was separated by an 8-week washout period. For the present study, serum and faecal samples were used to measure zonula occludens-1 (ZO-1), occludin, adiponectin, calprotectin, faecal calprotectin, soluble cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial-cadherin (VEC) levels using quantitative ELISA assays. Data were analysed using ANOVA, and Spearman and network correlation analysis were performed to identify the relationship among biomarkers at baseline. RESULTS: Among the different markers analysed, a significant reduction was observed for faecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) following the PR-diet, while a significant increase in ZO-1 was found (p = 0.001) after both the intervention periods (PR-diet and C-diet). In addition, a time effect was observed for VEC levels showing a reduction (p = 0.038) following the PR-diet. Based on network correlation analysis, two clusters of correlations were identified: one cluster with high levels of serum calprotectin, faecal calprotectin, sCD14, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and bacterial DNAemia (16 S rRNA gene copies), with potential inflammatory-induced intestinal permeability. Differently, the other cluster had high levels of serum occludin, IL-6R, soluble intercellular adhesion molecule-1 (sICAM-1) and VEC, with potential inflammatory-induced endothelial dysfunction. CONCLUSIONS: Overall, this study provides further support to the hypothesis that a (poly)phenol-rich diet may help to ameliorate intestinal permeability-associated conditions. In this regard, calprotectin might represent a promising biomarker since it is a protein that typically increases with age and it is considered indicative of intestinal and systemic inflammation. Further research is needed to develop targeted (poly)phenol-rich diets against age-related gut dysfunction and inflammation. TRIAL REGISTRATION: 28/04/2017; ISRCTN10214981; https://doi.org/10.1186/ISRCTN10214981 .

Nutraceutical Additives Modulate Microbiota and Gut Health in Post-Weaned Piglets.

Due to the challenge of weaning pigs and the need to reduce the use of antimicrobials in animal feed, there is a growing need to look for nutraceutical alternatives to reduce the adverse effects of the post-weaning period. We evaluate the effect of different feed nutraceutical additives on the microbial communities, gut health biomarkers, and productivity of pigs during the post-weaning period. The study involved 240 piglets weaned on the 21st day of age and randomized to six different diets: D1-BD commercial standard feed, D2-AGP: D1 + 150 ppm zinc bacitracin, D3-MD: D1 + 550 ppm maltodextrin, D4-FOS: D1 + 300 ppm fructo-oligosaccharides, D5-EO: D1 + 70 ppm Lippia origanoides essential oil, and D6-SH: D1 + 750 ppm sodium humate. On day 30 post-weaning, zootechnical parameters were evaluated, and jejunal samples were taken to obtain morphometric variables, expression of barrier and enzymatic proteins, and analysis of microbial communities. Animals fed D4-FOS and D5-EO had the lowest feed conversion ratio and higher expression of barrier and enzymatic proteins compared to D1-BD, D2-AGP, and D3-MD. The use of the additives modified the gut microbial communities of the piglets. In conclusion, fructo-oligosaccharides and Lippia origanoides essential oil were the best alternatives to zinc bacitracin as antibiotic growth promoters.

Gut Microbiota and Cytokine Profile in Cirrhosis.

Background and Aims: Gut dysbiosis and abnormal cytokine profiles are common in cirrhosis. This study aimed to evaluate the correlations between them. Methods: In the blood plasma of cirrhosis patients and controls, 27 cytokines were examined using a multiplex assay. The plasma levels of nitrites (stable metabolites of the endothelial dysfunction biomarker nitric oxide) and lipopolysaccharide (LPS) were examined. The fecal microbiota was assessed by 16S rRNA gene sequencing. Results: Levels of IL-1b, IL-2, IL-6, IL-13, IP-10, IFN-g, TNF-a, LPS, and nitrites were higher in cirrhosis patients than in controls, while levels of IL-4, IL-7, and PDGF-BB were lower. The LPS level was directly correlated with the levels of IL-1b, IL1-Ra, IL-9, IL-17, PDGF-BB, IL-6, TNF-a, and nitrites. The nitrite level was significantly directly correlated with the levels of TNF-a, GM-CSF, IL-17, and IL-12, and inversely correlated with the IL-7 level. TNF-a levels were directly correlated with ascites severity and the abundance of Negativicutes, Enterobacteriaceae, Veillonellaceae, and Klebsiella, while inversely correlated with the abundance of Firmicutes, Clostridia, and Subdoligranulum. IFN-g levels were directly correlated with the abundance of Bacteroidaceae, Lactobacillaceae, Bacteroides, and Megasphaera, and inversely correlated with the abundance of Verrucomicrobiota, Akkermansiaceae, Coriobacteriaceae, Akkermansia, Collinsella, and Gemella. IL-1b levels were directly correlated with the abundance of Comamonadaceae and Enterobacteriaceae and inversely correlated with the abundance of Marinifilaceae and Dialister. IL-6 levels were directly correlated with the abundance of Enterobacteriaceae, hepatic encephalopathy, and ascites severity, and inversely correlated with the abundance of Peptostreptococcaceae, Streptococcaceae, and Streptococcus. Conclusions: The abundance of harmful gut microbiota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

High gain multi-band circularly polarized wearable leaky wave zipper MIMO antenna.

A miniaturized, multi-band, four-port wearable Multiple Input Multiple Output (MIMO) antenna is proposed, which contains a leaky wave textile antenna (LWTA) on denim (εr = 1.6, tanδ = 0.006) as substrate and Shieldit Super Fabric as conductor textile. The concept in this work involves incorporating the metal and plastic zipper into the garment to function as an antenna worn on the body. Simulations and measurements have been conducted to explore this idea. The LWTA has dimensions of 40 × 30 × 1 mm³. Every two ports are separated by a zipper with two different kinds of materials: Acetal Polymer Plastic (APP) and 90 % brass to improve the isolation, gain, and Impedance bandwidth. The antenna operates in the frequency ranges covering the L, C, S, and X bands. Additionally, diversity performance is evaluated using the Envelope Correlation Coefficient (ECC) and diversity gain (DG). Simulation and measurement findings agree well, with a maximum gain of 12.15 dBi, low Specific Absorption Rate (SAR) based on the standards, DG greater than 9.65 dB, circular polarization (CP), and strong isolation (<-23 dB) between each port. Since the antenna's characteristics do not change significantly under bending and when the zipper is opened, the proposed antenna is a viable candidate for body-centric wireless communications on the battlefield. For example, it can facilitate communication covering wireless local area network (WLAN) and fifth-generation (5G) communications.

The role of gut microbiota in different murine models of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune system dysfunction that can lead to serious health issues and mortality. Recent investigations highlight the role of gut microbiota alterations in modulating inflammation and disease severity in SLE. This review specifically summaries the variations in gut microbiota composition across various murine models of lupus. By focusing on these differences, we aim to elucidate the intricate relationship between gut microbiota dysbiosis and the development and progression of SLE in preclinical settings.

Terminal-Matched Topological Photonic Substrate-Integrated Waveguides and Antennas for Microwave Systems.

In engineered photonic lattices, topological photonic (TP) modes present a promising avenue for designing waveguides with suppressed backscattering. However, the integration of the TP modes in electromagnetic systems has faced longstanding challenges. The primary obstacle is the insufficient development of high-efficiency coupling technologies between the TP modes and the conventional transmission modes. This dilemma leads to significant scattering at waveguide terminals when attempting to connect the TP waveguides with other waveguides. In this study, a topological photonic substrate-integrated waveguide (TPSIW) is proposed that can seamlessly integrate into traditional microstrip line systems. It successfully addresses the matching problem and demonstrates efficient coupling of both even and odd TP modes with the quasi-transverse electromagnetic modes of microstrip lines, resulting in minimal energy losses. In addition, topological leaky states are introduced through designed slots on the TPSIW top surface. These slots enable the creation of TP leaky-wave antennas with beam steering capabilities. A wireless link based on TPSIWs are further established that enables the transmission of distinct signals toward different directions. This work is an important step toward the integration of TP modes in microwave systems, unlocking the possibilities for the development of high-performance wireless devices.

Intestinal epithelium dysfunctions cause IgA deposition in the kidney glomeruli of intestine-specific Ap1m2-deficient mice.

BACKGROUND: Intestinal epithelial cells (IECs) serve as robust barriers against potentially hostile luminal antigens and commensal microbiota. Epithelial barrier dysfunction enhances intestinal permeability, leading to leaky gut syndrome (LGS) associated with autoimmune and chronic inflammatory disorders. However, a causal relationship between LGS and systemic disorders remains unclear. Ap1m2 encodes clathrin adaptor protein complex 1 subunit mu 2, which facilitates polarized protein trafficking toward the basolateral membrane and contributes to the establishment of epithelial barrier functions. METHODS: We generated IEC-specific Ap1m2-deficient (Ap1m2ΔIEC) mice with low intestinal barrier integrity as an LSG model and examined the systemic impact. FINDINGS: Ap1m2ΔIEC mice spontaneously developed IgA nephropathy (IgAN)-like features characterized by the deposition of IgA-IgG immune complexes and complement factors in the kidney glomeruli. Ap1m2 deficiency markedly enhanced aberrantly glycosylated IgA in the serum owing to downregulation and mis-sorting of polymeric immunoglobulin receptors in IECs. Furthermore, Ap1m2 deficiency caused intestinal dysbiosis by attenuating IL-22-STAT3 signaling. Intestinal dysbiosis contributed to the pathogenesis of IgAN because antibiotic treatment reduced aberrantly glycosylated IgA production and renal IgA deposition in Ap1m2ΔIEC mice. INTERPRETATION: IEC barrier dysfunction and subsequent dysbiosis by AP-1B deficiency provoke IgA deposition in the mouse kidney. Our findings provide experimental evidence of a pathological link between LGS and IgAN. FUNDING: AMED, AMED-CREST, JSPS Grants-in-Aid for Scientific Research, JST CREST, Fuji Foundation for Protein Research, and Keio University Program for the Advancement of Next Generation Research Projects.

Intestinal epithelial differentiation and barrier function is promoted in vitro by a Cynara cardunculus L. leaf extract through AMPK pathway activation.

Gut epithelial barrier perturbation leads to leaky gut syndrome and permeation of substances activating immune response. Polyphenols can improve intestinal barrier function and represent candidates for preventing development of leaky gut. Herein, we evaluated in vitro the molecular mechanisms involved in the protective effects of a polyphenol-rich extract from leaves of Cynara cardunculus L. (CCLE) on intestinal barrier function and integrity on Caco-2 human epithelial cells. Treatment with CCLE from seeding until complete differentiation improved intestinal function by increasing trans-epithelial electrical resistance (TEER), reducing paracellular permeability to fluorescein, and promoting faster recovery of tight junctions (TJ) assembly in the Ca2+ switch assay. CCLE stimulated epithelial cell differentiation inducing alkaline phosphatase activity and TJ proteins. These CCLE-induced effects were attributed to activation of AMP-activated protein kinase (AMPK) pathway. Our data support the use of Cynara cardunculus L. leaves, an agricultural co-product rich in bioactive polyphenols, for the health of intestinal epithelium.

Discordant Phenotypes of Nephritis in Patients with X-linked Agammaglobulinemia.

PURPOSE: To define the clinical and histological characteristics of nephritis in patients with X-linked agammaglobulinemia (XLA) and their immunological profiles. METHODS: The clinical, immunological, and histological findings of nine patients with XLA and nephritis were retrospectively analyzed. RESULTS: Based on kidney histological findings, patients with XLA and nephritis could be divided into two groups, viz., chronic glomerulonephritis (CGN) and tubulointerstitial nephritis (TIN). The two groups showed different immunological profiles. Patients in the CGN group exhibited an atypical immunological profile of XLA, with pathogenic leaky B cells producing immunoglobulins that may play a role in forming immune complexes and causing immune-mediated glomerulonephritis. In contrast, patients in the TIN group exhibited a typical immunological profile of XLA, suggesting that antibody-independent/other BTK-dependent mechanisms, or immunoglobulin replacement therapy (IgRT)-related immune/nonimmune-mediated nephrotoxicity causes TIN. CONCLUSION: Nephritis occurring in patients with XLA could have links between their renal pathology and immunological status. Careful observation is recommended to detect kidney pathology in patients with XLA on IgRT.

Optimal vaccination strategies for imperfect vaccines and variable host susceptibility.

I present a method to allocate a given number of vaccines to members of a population who differ in their susceptibility to the disease so that the final size of the epidemic is minimised. I consider an arbitrary distribution of protection that the vaccine confers, including the extreme cases of leaky and all-or-none vaccines. The optimal vaccination policy depends on the distribution of protection. While for low values of the basic reproduction number R0 the optimal policy prioritises the most susceptible hosts, I show that for almost any distribution the order of priority reverses and the least susceptible hosts should be vaccinated when R0 is high. The exception where this does not happen is the all-or-none vaccine. However, even a small deviation from the ideal all-or-none distribution can imply that the limited number of vaccines should be given to less susceptible hosts already at realistic values of R0.

A Unique Comprehensive Model to Screen Newborns for Severe Combined Immunodeficiency-An Ontario Single-Centre Experience Spanning 2013-2023.

BACKGROUND: Severe combined immunodeficiency (SCID) is a life-threatening genetic disorder caused by critical defects of the immune system. Almost all cases are lethal if not treated within the first two years of life. Early diagnosis and intervention are thus essential for improving patient outcomes. In 2013, Ontario became the first Canadian province to perform newborn screening (NBS) for SCID by T cell receptor excision circles (TRECs) analysis, a surrogate marker of thymic function and lymphocyte maturation. METHODS: This retrospective study reports on nearly 10 years of NBS for SCID at a quaternary referral centre. RESULTS: From August 2013 to April 2023, our centre's densely populated catchment area flagged 162 newborns with low TRECs levels, including 10 cases with SCID. Follow-up revealed other causes of low TRECs, including non-SCID T cell lymphopenia (secondary/reversible or idiopathic causes, and syndromic conditions) and prematurity. A small number of cases with normal repeat TRECs levels and/or T cell subsets were also flagged. Province-wide data from around this period revealed at least 24 diagnosed cases of SCID or Leaky SCID. CONCLUSIONS: This is the first report of NBS outcomes in a Canadian province describing the causative genetic defects, and the non-SCID causes of a positive NBS for SCID.

Embodied sequential sampling models and dynamic neural fields for decision-making: Why hesitate between two when a continuum is the answer.

As two alternative options in a forced choice task are separated by design, two classes of computational models of decision-making have thrived independently in the literature for nearly five decades. While sequential sampling models (SSM) focus on response times and keypresses in binary decisions in experimental paradigms, dynamic neural fields (DNF) focus on continuous sensorimotor dimensions and tasks found in perception and robotics. Recent attempts have been made to address limitations in their application to other domains, but strong similarities and compatibility between prominent models from both classes were hardly considered. This article is an attempt at bridging the gap between these classes of models, and simultaneously between disciplines and paradigms relying on binary or continuous responses. A unifying formulation of representative SSM and DNF equations is proposed, varying the number of units which interact and compete to reach a decision. The embodiment of decisions is also considered by coupling cognitive and sensorimotor processes, enabling the model to generate decision trajectories at trial level. The resulting mechanistic model is therefore able to target different paradigms (forced choices or continuous response scales) and measures (final responses or dynamics). The validity of the model is assessed statistically by fitting empirical distributions obtained from human participants in moral decision-making mouse-tracking tasks, for which both dichotomous and nuanced responses are meaningful. Comparing equations at the theoretical level, and model parametrizations at the empirical level, the implications for psychological decision-making processes, as well as the fundamental assumptions and limitations of models and paradigms are discussed.

Neurodevelopmental implications of COVID-19-induced gut microbiome dysbiosis in pregnant women.

The global public health emergency of COVID-19 in January 2020 prompted a surge in research focusing on the pathogenesis and clinical manifestations of the virus. While numerous reports have been published on the acute effects of COVID-19 infection, the review explores the multifaceted long-term implications of COVID-19, with a particular focus on severe maternal COVID-19 infection, gut microbiome dysbiosis, and neurodevelopmental disorders in offspring. Severe COVID-19 infection has been associated with heightened immune system activation and gastrointestinal symptoms. Severe COVID-19 may also result in gut microbiome dysbiosis and a compromised intestinal mucosal barrier, often referred to as 'leaky gut'. Increased gut permeability facilitates the passage of inflammatory cytokines, originating from the inflamed intestinal mucosa and gut, into the bloodstream, thereby influencing fetal development during pregnancy and potentially elevating the risk of neurodevelopmental disorders such as autism and schizophrenia. The current review discusses the role of cytokine signaling molecules, microglia, and synaptic pruning, highlighting their potential involvement in the pathogenesis of neurodevelopmental disorders following maternal COVID-19 infection. Additionally, this review addresses the potential of probiotic interventions to mitigate gut dysbiosis and inflammatory responses associated with COVID-19, offering avenues for future research in optimizing maternal and fetal health outcomes.