Abstract:

Previous research showed that a strain of Leuconostoc mesenteroides, isolated from goat’s raw milk cheese, was effective in slowing down the growth and reducing the maximum concentration of L. monocytogenes when evaluated in a milk model; and, furthermore, that the extent of inhibition was dependent on the milk initial pH. The objectives of this study were: (1) to determine whether the growth of L. monocytogenes in goat’s pasteurized milk cheese during maturation could be approximated from growth data obtained in the milk model medium, either in monoculture or in coculture with L. mesenteroides; and if so; (2) to model a milk-to-cheese conversion factor (Cf) for L. monocytogenes growth rate. Challenge tests were conducted by inoculating L. monocytogenes in monoculture and in coculture with L. mesenteroides in goat’s pasteurized milk adjusted at initial pH levels of 5.5, 6.0 and 6.5. The process of cheesemaking went on, and cheeses were ripened at 12 ºC during 12 days. Each experimental growth curve was adjusted to a pH-driven dynamic model where the microbial maximum growth rate is a function of pH. As observed in the milk model medium, in coculture with L. mesenteroides, the optimum growth rate (μ_opt) of L. monocytogenes in maturing cheese was affected by the initial pH of milk: the lowest rate of 0.863 ± 0.042 day^-1 was obtained at the initial pH 5.5, in comparison to 1.239 ± 0.208 and 1.038 ± 0.308 day-¹ at pH 6.0 and 6.5, respectively. Regardless of the milk initial pH, L. mesenteroides did not reduce the maximum load of L. monocytogenes in maturing cheeses, as it did in the milk medium. By contrary, at the milk initial pH of 5.5, 6.0, and 6.5, L. mesenteroides was able to decrease, on average, 2.2-fold, 1.5-fold and 1.9-fold the μ_opt of L. monocytogenes in both milk medium and cheese, without significant differences between matrices. Following such validation in goat’s cheese, the square-root of milk-to-cheese Cf for L. monocytogenes was estimated as 0.751 (SE=0.0108), and type of culture (monoculture, coculture) was not found to affect Cf (p=0.320). In conclusion, this work validated pre-acidification of milk as an efficient strategy that, when combined with the use of a protective culture, can synergically enhance the control of L. monocytogenes in cheese.

Abstract: Fungal endophytes have emerged as a promising source of bioactive compounds with potent antifungal properties for plant disease management. This study aimed to isolate and characterize fungal endophytes from Antillean avocado (Persea americana var. ameri-cana) trees in the Colombian Caribbean, capable of producing bio-fungicide metabolites against Fusarium solani and Fusarium equiseti. For this, dual-culture assays, liquid-state fermentation of endophytic isolates, and metabolite extractions were conducted. From 88 isolates recovered from leaves and roots, those classified within the Diaporthe genus ex-hibited the most significant antifungal activity. Their organic extracts displayed median inhibitory concentrations (IC₅₀) approaching 200 μg/mL. To investigate the mechanism of action, in silico studies targeting Chitin Synthase (CS) were performed, including homolo-gy models of the pathogens' CS generated using Robetta, followed by molecular docking with Vina, and interaction fingerprint similarity analysis of 15 antifungal metabolites produced by Diaporthe species using PROLIF. A consensus scoring strategy identified di-aporxanthone A (12) and diaporxanthone B (13) as the most promising candidates, achieving scores up to 0.73 against F. equiseti, comparable to the control Nikkomycin Z (0.82). These results suggest that Antillean avocado endophytes produce bioactive metab-olites that may inhibit fungal cell wall synthesis, offering a sustainable alternative for disease management.

Abstract: Millions of women around the world rely on cosmetics and hygiene products every day, however, they often have no idea about the exposure to dangerous chemicals in their everyday usage. Chemicals present in many of these products, such as parabens, phthalates and PFAS (per- and polyfluoroalkyl substances) are known to act as endocrine disruptors which could potentially affect the body's hormonal systems. In addition to acting as endocrine disruptors, some of these chemicals have been shown to cause cancer when used in certain applications, such as formaldehyde releasing preservatives and asbestos contaminated talc. As a result of using these products, it is essential to understand the biochemical characteristics of the chemicals so we can begin to understand how they can affect our bodies. This study uses the bioinformatics software program SwissADME to identify key properties related to the absorption of three representative chemicals from three classes of chemicals, including DEP (diethyl phthalate), butylparaben, PFOA (perfluorooctanoic acid), based on publicly available molecular information. Using this molecular data, SwissADME was able to predict several key biochemical characteristics of the studied chemicals including lipophilicity, skin permeability, gastrointestinal absorption and other ADME (absorption, distribution, metabolism and excretion)-related parameters. Based on the predictions of SwissADME, this study provides an estimate of the ability of each chemical to penetrate biological barriers, reach the bloodstream and interact with target tissues involved in the mechanism of endocrine disruption and carcinogenesis.SwissADME predictions indicate that both phthalates and parabens have molecular properties that would allow them to easily pass through the skin, thereby supporting previous epidemiological studies indicating that users of cosmetic and hygiene products have measurable levels of internal exposure. Although PFAS were predicted to have lower skin permeability, previous studies have shown that PFAS bind to proteins and remain in the body for long periods of time, allowing them to accumulate in the body over time. Due to its size and high reactivity, formaldehyde has the highest predicted capacity to rapidly interact with tissues. Since talc had low predicted permeability, the health risk associated with talc is most likely due to the presence of asbestos contamination and not to the chemical composition of the talc itself. Overall, the results of the SwissADME study provide a link between molecular properties and the observed exposure patterns of humans and support toxicological and epidemiological evidence, and therefore emphasize the need to conduct further research on the mixture-based toxicity of these chemicals, require companies to disclose all of the ingredients used in their products, and modify existing regulations regarding chemical safety in order to better regulate and control the risks posed by these chemicals in the cosmetic and hygiene products marketed to women.

Abstract:

Dried hops are used in beer production for imparting bitterness and characteristic aroma. Herein, Cascade hop cones are dried using the following two methods: conventional hot-air drying at 52 °C and innovative low-temperature drying at 30 °C via heat-pump technology. The dried hops are used either as whole cones or processed into pellets for brewing. The terpenoid composition of fresh hops, dried cones, pellets and the resulting beers is analysed using headspace solid-phase microextraction coupled with gas chromatography–quadrupole mass spectrometry. Twenty-three mono- and sesqui-terpenes are identified in fresh hops, while 23–26 compounds are detected in dried hops and their corresponding beers, depending on the drying method. Beers brewed with cold-dried cones exhibit a higher concentration of terpenes, especially oxygenated terpenoids and sesqui-terpenes. By contrast, hot-dried pellets exhibit major proportion of monoterpenes and fewer sesquiterpenes. However, cold-dried pellets result in higher levels of oxygenated sesquiterpenes in the final product. These results suggest that hop-drying temperature and physical form markedly affect the aromatic profile of beer. Furthermore, variations in hop terpenoids can influence aroma development through yeast biotransformation during fermentation.

Abstract: This study focuses on identifying wine-growing subzones within the PDO Amyndeon and PGI Drama wine-growing zones in Northen Greece, with the aim of classifying their suitability to produce high-quality red wines from the Xinomavro (Vitis vinifera L.) and Cabernet Sauvignon (Vitis vinifera L.) grape varieties, respectively. The initial delimitation of suitability zones was carried out using readily available satellite data on soil, topography, and climate, which were validated using field data for two consecutive years from experimental vineyards in four different suitability categories. Preliminary results showed that this methodology was able to discern the most suitable areas for both varieties and regions with an acceptable relation to real grape and wine attributes as confirmed by the collection of data from the pilot vineyards. The overall performance of this method will eventually depend on the validity of the expert knowledge used to define the most critical parameters and their range. According to the results of this study, and given the relevance of the proposed suitability criteria, this method has the potential to provide an alternative solution for subzone delineation in cases were wine analytical and sensory data are not available.

Abstract: The metal-binding periplasmic protein CusF has been proposed as a bifunctional tag enhancing solubility of recombinant proteins and enabling purification using Cu affinity chromatography. However, evidence for its performance remains limited to a few model proteins. Here, we evaluated CusF as a solubility tag for two heterologous proteins: a putative poly(A)-polymerase from Enterococcus faecalis (Efa PAP) and the red fluorescent protein mCherry. The proteins were fused to CusF, expressed in E. coli BL21 (DE3) pLysS and Rosetta 2 (DE3) strains, and assessed for solubility and IMAC binding. Native Efa PAP was completely insoluble under all tested conditions, and fusion to CusF did not improve its solubility. Similarly, CusF-mCherry accumulated predominantly in the in-soluble fraction, with only traces detectable in soluble lysates. Soluble CusF-mCherry did not bind Cu²⁺-charged IMAC resin, while moderate binding to Ni²⁺-charged resin was attributable to the vector-encoded His-tag rather than CusF. These results indicate that CusF does not universally enhance protein solubility and may not always bind Cu-based IMAC resin. Our findings expand empirical knowledge on solubility tag per-formance and emphasize the necessity of testing multiple tags to identify optimal strat-egies for recombinant protein production.

Abstract: Effective exchange of health data is crucial in the modern healthcare landscape, most notably for advancing research and clinical care on rare diseases where patient populations are small and often geographically dispersed. While numerous approaches to health data exchange exist, substantial challenges persist in achieving convergence and selecting technologies that address the diverse requirements of stakeholders. The Joint Action on Integration of European Reference Networks (ERNs) into National Healthcare Systems (JARDIN) aims to tackle these issues by fostering alignment around shared solutions. To explore practical strategies for automating secure data exchange among healthcare providers, national registries, and ERNs, a hackathon was organised by JARDIN, inspired by the software-oriented “Bring Your Own Data” workshop format, which promotes the Findability, Accessibility, Interoperability, and Reusability (FAIR) of research resources. The event brought together over 50 experts from across Europe. Participants tackled three core challenges: data harmonization, querying, and the FAIR description of data services. Key proposed solutions included leveraging semantic models for data harmonization, adapting existing infrastructures for (federated) querying, and extending the FAIR Data Point (FDP) metadata model to better describe data services. This paper outlines the methodologies and outcomes of the hackathon. The findings presented herein provide insights for JARDIN’s future work in developing recommendations for a robust, scalable, and secure data exchange ecosystem for rare diseases.

Abstract: The Universe has two domains: Life and Non-Life, which manifest the dimensionless relativity ratio with basic codes. For life is a/b = a/(1-a) = (1-b)/b (Floating Ratio), and for Non-Life is a/b = (a + b)/a = 1 + b/a (Golden Ratio). Life and Non-Life can be connected and co-exist by the two fractional distribution functions of “1”.The Mass Action Law (MAL) Median Affect Principle leads to the Unified General Dynamics Theory and algorithm, which provides an interdisciplinary and cross-disciplinary common linkage of parameters for computerized digital research and development informatics.

Abstract: The absence of molecular tools for manipulation of gene expression in the pathogenic free-living amoeba Naegleria fowleri has historically limited our understanding of gene function in the organism and has coincidently impacted the identification of potential druggable pathways and proteins. Here, we describe the development of approaches for the generation of transgenic amoebae using polyethyleneimine nanoparticles to deliver plasmids designed to confer antibiotic resistance and fluorescence to the cells. Through a series of optimization steps, we found that transfection of plasmids encoding the fluorescent protein mCherry fused by a T2A self-cleaving peptide to a codon-optimized puromycin acetyltransferase selectable marker yielded fluorescent cells that were resistant up to 100 µg/mL puromycin. Transfected trophozoites harbored between 45 and 65 copies of the transgene per cell and both fluorescence and resistance were persistent in the presence of selector through continued passages. The development of these approaches is anticipated to enable application of an array of genetic manipulation techniques including forward and reverse genetics to the study of this important pathogen.

Abstract:

The black soldier fly (Hermetia illucens) is a globally important species, yet little is known about the behavior of adults in nature. Here, we investigated (a) whether wild populations exhibit lekking behaviors, (b) whether wild adults feed, and (c) the microbial diversity of the adult gut. Fieldwork was conducted in Alajuela Province, San Ramon, Costa Rica at three sites (a field station, a local farm, and an ecolodge compost facility). At all three sites, a highly female-skewed sex ratio (F:M=0.98) was observed. Despite many sampling attempts within 30-m of the oviposition site, no mating behaviors were directly observed within this radius, mostly due to the lack of males. Modeling confirmed female abundance declined sharply with increasing distance, and indeed no individuals were observed beyond a 7.5-m radius from the oviposition site, supporting the hypothesis that males and females may occupy distinct habitats in the wild, consistent with lekking. Modeling also revealed BSF were mostly observed between 9:00-14:30, with a peak at 12:00-noon. BSF sightings peaked at 34.7 °C, 78.5% RH, and 8000 µW/cm² of UV-AB light, while none were observed past 40°C. The presence of vertebrate DNA in the guts of adults revealed that 100% of individuals previously fed as adults, possibly to supplement nutritional reserves during long-distance flights. Lastly, microbial community analysis revealed a core community of microbes present within the gut of wild-caught BSF. By considering spatial molecular ecology at three field sites, this study highlights the strong association of the black soldier fly with human-modified environments, suggesting environmental structure and resource availability may play a large role in shaping wild fly behavior. This work presents the first detailed field report of H. illucens in the Neotropics and offers some critical insights for future fieldwork as well as baseline traits for industrial applications.

Abstract:

RNA chaperones play a crucial role in the biogenesis and function of various RNAs in bacteria. They facilitate the interaction of small regulatory trans-encoded sRNAs with mRNAs, thereby significantly altering the pattern of gene expression in cells. This allows bacteria responses quickly to changing environmental conditions, such as stress or adaptation to host organisms. Despite the identification of a large number of sRNAs in mycobacteria, none of the most common RNA chaperones has been found in their genomes. We characterized the cold shock protein CspB from Mycobacterium tuberculosis as a potential RNA chaperone. It forms a dimer due to its elongated C-terminal region, which is a hairpin composed of two α-helices. We demonstrated that CspB from M. tuberculosis exhibits high affinity for the two studied sRNAs from the same organism and, unlike the single-domain CspA, could be considered as a potential RNA chaperone in mycobacteria. Thus, it may be involved in the regulation of bacterial pathogenesis via interactions with sRNAs.

Abstract:

Continuous cropping leads to declines in soil productivity, biodiversity, as well as a deterioration of overall phytosanitary conditions. What if we rotate the intercrops instead of the main crops? In a stationary three-year field experiment, maize was intercropped with Fabaceae (faba bean, crimson and Persian clovers and blue–flowered alfalfa), Poaceae (winter rye, annual ryegrass, spring barley, common oat) and Brassicaceae (white mustard, spring oilseed rape, oilseed radish and spring Camelina) intercrops in separate growing seasons. Fabaceae intercrops developed slowly and competed poorly with weeds. The highest air-dried biomass (ADM) was produced by Persian and crimson clovers (approx. 86 g m^-2). Poaceae intercrops germinated faster and competed effectively with weeds, particularly rye, oat, and later ryegrass, which was the most productive (200 g m^-2 ADM). Brassicaceae intercrops also developed rapidly, especially mustard, Camelina and radish (the most productive 206 g m^-2 ADM). Most of the intercrops competed with maize, reducing its productivity, but weeds competition was higher. A strong negative correlation between maize and weed biomass was detected (max. r=-0.946; p<0.01). Complex evaluation index (CEI) showed that the crimson clover–annual ryegrass–spring oilseed rape rotation was the most productive, effective in suppressing weeds and less competitive with maize (CEI 4.82).

Abstract:

Camel milk is highly favored by consumers for its high nutritional value and health benefits in preventing various diseases. However, camel farming is still mainly extensive, making it difficult to control the quality of camel milk. This experiment investigated the effects of adding sodium diacetate and kojimabase, feed additives, on the quality of camel milk from lactating Bactrian camels. The results of this experiment show that adding sodium diacetate can effectively increase the content of vitamin E and vitamin C in camel milk and can also effectively increase the content of unsaturated fatty acids in camel milk, thus effectively improving the nutritional quality of camel milk. The fecal microbial analysis results showed that there was no significant impact on the microbial community among the groups, but the addition of SDA significantly increased the number of Melanocarpus fungi. This demonstrates that adding 1000 mg of sodium diacetate per kilogram to the camel diet can effectively improve the quality of camel milk, providing a technical reference and demonstration for stabilizing camel milk quality through nutritional regulation.

Abstract: Microtubules are cylindrical protein polymers that organize the cytoskeleton and play essential roles in intracellular transport, cell division, and possibly cognition. Their highly ordered, quasi-crystalline lattice of tubulin dimers, notably tryptophan residues, endows them with a rich topological and arithmetic structure, making them natural candidates for supporting coherent excitations at optical and terahertz frequencies. The Penrose-Hameroff Orch OR theory proposes that such coherences could couple to gravitationally induced state reduction, forming the quantum substrate of conscious events. Although controversial, recent analyses of dipolar coupling, stochastic resonance, and structured noise in biological media suggest that microtubular assemblies may indeed host transient quantum correlations that persist over biologically relevant timescales. In this work, we build upon two complementary approaches: the parametric resonance model of Nishiyama et al. and our arithmetic–geometric framework, both recently developed in Quantum Reports. We unify these perspectives by describing microtubules as rectangular lattices governed by the imaginary quadratic field Q(i), within which nonlinear dipolar oscillations undergo stochastic parametric amplification. Quantization of the resonant modes follows Gaussian norms N = p² + q², linking the optical and geometric properties of microtubules to the arithmetic structure of Q(i). We further connect these discrete resonances to the derivative of the elliptic L–function, L′(E, 1), which acts as an arithmetic free energy and defines the scaling between modular invariants and measurable biological ratios. In the appended adelic extension, this framework is shown to merge naturally with the Bost–Connes and Connes–Marcolli systems, where the norm character on the ideles couples to the Hecke character of an elliptic curve to form a unified adelic partition function. The resulting arithmetic–elliptic resonance model provides a coherent bridge between number theory, topological quantum phases, and biological structure, suggesting that consciousness, as envisioned in the Orch OR theory, may emerge from resonant processes organized by deep arithmetic symmetries of space, time, and matter.

Abstract: Bloodsucking dipterans are major vectors responsible for the transmission of arboviruses. Additionally, they also carry a lot of insect-specific viruses. High-throughput sequencing technologies has facilitated breakthrough in the study of viruses overall and viruses of haematophagus insects in particular. In this study we used high-throughput sequencing to describe the viromes of bloodsucking dipterans collected in Karelia, northwestern Russia. In addition to various species of Aedes mosquitoes (Diptera: Culicidae), several pool of biting midges (Ceratopogonidae: Culicoides), and blackflies (Simuliidae: Simulium), were analyzed. We managed to assemble and annotate 63 different distinct viruses with complete and partial genomes. The most common viral groups were Durnavirales, Picornavirales, Reovirales, and Mononegavirales, however various other groups of RNA viruses and even one DNA virus were detected. The majority of viruses (78%) were novel viruses. Among known viruses, no known human or animal pathogens were found. Some of the novel viruses can be considered by the International Committee on Taxonomy of Viruses for the demarcation into novel genera.

Abstract: Photosynthesis, a crucial component of the global carbon cycle, and biological nitrogen fixation (BNF), a key step in the nitrogen cycle, are both requisite for maintaining life and sustainable agriculture on Earth, in which chlorophyll and nitrogenase play central roles, respectively. In chlorophyll biosynthesis, the reduction of protochlorophyllide to chlorophyllide is catalyzed by either the nitrogenase-like, light-independent DPOR (dark-operative protochlorophyllide oxidoreductase) or the SDR-like, light-dependent LPOR (light-driven protochlorophyllide oxidoreductase), utilizing chemical and light energy. Nitrogenase (N₂ase) is the only enzyme capable of reducing inert atmospheric nitrogen, yet only a few bacterial species possess the multi-subunit ATP-dependent dinitrogen reductase. Over the past three decades, significant progress has been made in solving the crystal structures of N₂ase, DPOR, and LPOR protein complex, providing valuable mechanistic insights into N₂ase, as well as the contrasting structures of the multi-subunit DPOR and single-subunit LPOR. We summarize the structural breakthroughs of these key catalysts for nitrogen and carbon fixation. Protein structural similarities often hint at similar functions and evolutionary relationships. With the ongoing development in protein structure annotation assisted by AlphaFold and the identification of protein structure similarities through structural alignment software, the evolutionary relationship between these key enzymes in photosynthesis and nitrogen fixation, as well as the potential co-origin of these processes, has been uncovered. We further summarize how a porphyrin reduction catalyst evolves from a less efficient ATP-driven DPOR to a highly efficient light-driven LPOR. The key structural milestones achieved in N₂ase, DPOR, and LPOR research laid the groundwork for future perspectives, particularly in proposing a direction for a potential nitrogen-fixing scenario using an AI-designed LUN and photosynthesis with bacteriochlorophyll using a light-driven chlide reductase (LCOR), leading to the development of more effective forms of biological nitrogen fixation and photosynthesis.

Abstract: Humans and other terrestrial vertebrates contain two estrogen receptors (ERs), ERand ER. Among cartilaginous fish (sharks, rays, skates), which are jawless vertebrates that evolved about 525 million years ago, only activation by steroids of ER orthologs has been characterized. To remedy this gap in understanding estrogen signaling in jawless vertebrates, we studied estrogen activation of orthologs of human ER and ER from elephant shark (Callorhynchus milii). Un-expectedly, we found that C. milii contained three estrogen-responsive ER genes: ER1 (596 amino acids), ER2 (600 amino acids), and ER3 (599 amino acids) with strong sequence simi-larity to each other. We also found an estrogen-unresponsive gene, ER4 (561 amino acids), with a 39 amino acid deletion in the DNA-binding domain. An estrogen-responsive ER ortholog (580 amino acids) also was present in C. milii. The three active C. milii ERs have a similar length to human ER (595 amino acids); however, C. milii ER is longer than human ER (530 amino acids). We determined the half-maximal response (EC50) and fold-activation to estradiol (E2), estrone (E1), and estriol (E3) of C. milii ER1, ER2, ER3, and ER. Among these es-trogens, E2 had the lowest EC50 for all four ERs. Fold-activation by E2 and E3 was similar for ER1, ER2, ER3, and ER. Overall, estrogen activation of C. milii ER and ER was simi-lar to that for human ER and ER, indicating substantial conservation of the vertebrate ER in the 525 million years since the divergence of cartilaginous fish and humans from a common ancestor.

Abstract: Vegetation indices (VIs) offer potential for non-destructive olive fruit quality moni-toring, yet their performance across diverse germplasm remains uncharacterized. This exploratory screening systematically evaluated 87 VIs for predicting chlorophyll and polyphenol content across 31 cultivars at four ripening stages, prioritizing genetic diver-sity to establish species-level biochemical-spectral relationships through integration of hyperspectral data (380-1080 nm) with biochemical analyses. Modified Chlorophyll Absorption Ratio Index and Transformed Chlorophyll Ab-sorption achieved 91 strong correlations (|r| ≥ 0.9) across 124 cultivar-stage combina-tions. High-performing indices incorporated 550 nm with red/red-edge bands (670-710 nm) and non-linear formulations. Moderate inter-cultivar variability (CV = 19.7-21.3%) in-dicated cultivar-specific calibrations may be necessary. Principal component analysis captured 99.8% of variance, revealing three biochemi-cal clusters: high-chlorophyll cultivars (n=5; 450/4078 mg/kg chlorophyll/polyphenols), typical-range cultivars (n=23; 70/4750 mg/kg), and elite cultivars (n=3; 855/6260 mg/kg), demonstrating VI capacity for cultivar discrimination. Chlorophyll degradation exhibited conserved patterns (p < 0.001), supporting uni-versal tracking models. Conversely, polyphenol dynamics displayed marked geno-type-dependency, with cultivars showing positive, negative, or minimal variation, yield-ing non-significant population-level effects (p = 0.969) despite robust cultivar-specific trends.

Abstract: Liver fibrosis, the progressive accumulation of scar tissue resulting from chronic liver disease, is increasingly recognized as a multi-system condition whose effects transcend the liver, affecting brain health. In parallel, dementia determining progressively impaired cognition severe enough to impede daily functioning, is a significant global health issue whose risk factors and pathogenic precursors are incompletely defined. Increasing evidence suggests that certain pathophysiological correlates of chronic liver disease may negatively affect neuronal health through incompletely defined pathophysiological mechanisms. With this background, we appraise our current understanding of the relationship between liver fibrosis and cognitive impairment/dementia, using a variety of different methodologies. Firstly, the pathophysiology and clinical significance of liver fibrosis are discussed. Next, we describe the various types of dementia and related risk factors. We then present research evidence supporting the association between cognitive impairment/dementia and liver fibrosis. We highlight both consistency and heterogeneity of findings, including the degree of association being affected by liver fibrosis severity. We thoroughly examine potential causal mechanisms, comprising the role of chronic systemic and neuroinflammation, insulin resistance, vascular dysfunction, and intestinal microbiota-liver-brain axis as potential connectors of liver health with cognitive impairment and dementia. We briefly analyze how sex and age may modify the above associations, how liver fibrosis and cognitive function should be diagnosed, and those potential preventive/treatment strategies based on the shared metabolic/inflammatory pathways associating liver fibrosis, cognitive impairment and dementia. Finally, major research gaps are identified, together with matching proposals for prioritizing advancements in our understanding of the increasingly identified connections between liver fibrosis and dementia/cognitive impairment.

Abstract: Dairy herd decisions about replacement, herd size, reproduction and capital investments have long-lasting consequences for herd structure and farm cash flow. Yet most planning tools emphasize static budgets rather than the dynamic evolution of animal numbers and cash availability. The Dairy Herd Structure Simulation and Cash Flow tool is a web-based decision support system, available through the Dairy Management Decision Support Tools website, designed to simulate these dynamics under alternative management strategies. The model operates in monthly time steps using a Markov-chain framework in which transition probabilities among animal states are driven by user-specified parameters such as culling, reproduction and heifer management. Calves, heifers and cows are tracked by age and lactation group, and starting conditions can be entered as herd-level summaries or via individual-animal spreadsheets. Economic components include milk income, variable costs, cull-cow income, heifer purchases or sales, miscellaneous costs and loan amortization. For each scenario, the tool projects monthly cash flow and income over variable cost per cow, together with graphical summaries of herd structure. An example application compares a baseline steady-state herd with a heifers-driven herd growth scenario, illustrating how replacement strategies influence herd composition and net cash flow, supporting more informed dairy herd planning and risk management.