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    • Article
    • Open Access

    Comparative Foetal Biometry in Ovine and Caprine Pregnancies by Means of Ultrasonography

    • Evangelos-Georgios Stampinas,
    • Mariana S. Barbagianni and
    • Aris Pourlis
    • + 6 authors

    B-mode ultrasonography is widely used for pregnancy monitoring in small ruminants, yet direct longitudinal comparisons of ovine and caprine foetal biometry under a common protocol remain scarce. This study characterised foetal development and derived biometric predictors of gestational age in 27 primiparous Lacaune ewes (42 foetuses) and 14 primiparous native Greek does (24 foetuses). Fifteen biometric parameters were measured weekly by transabdominal ultrasonography from gestational week 3 until parturition, and population-specific linear equations were derived for each parameter. Thoracic diameter, biparietal diameter and thoracic diameter at the sixth rib gave the most accurate within-sample gestational-age estimates in both populations (R2 = 0.97–0.99; RMSE ≤ 0.9 weeks), with femur length and abdominal diameter also performing well. Foetal size and growth differed between the two populations for most parameters, and the number of offspring per dam and foetal sex were further associated with biometric variation, particularly in does. Late-gestation measurements correlated with birth weight (r ≤ 0.76 in does), and exploratory models explained up to 57% of its variance. These findings provide detailed longitudinal reference data and practical, population-specific equations for estimating gestational age, useful for flock and herd management, although independent validation is required before extrapolating them to other breeds or flocks.

    Vet. Sci.

    10 November 2026

    • Article
    • Open Access

    Machine learning may support the prioritisation of reported maritime occurrences for expert review, but its usefulness depends on performance across time and geographical regions. This study assessed a leakage-controlled framework for ranking occurrences by their likelihood of being classified as “Serious” or “Very serious”. Extreme Gradient Boosting (XGBoost) was selected for its ability to model non-linear relationships and interactions among predictors in tabular occurrence data. The model was developed using 5815 European Maritime Safety Agency records with vessel, operational, temporal and geographical predictors, supplemented by severity-agnostic counts of preceding regional occurrences. Recorded consequence variables were excluded, and preprocessing parameters were estimated exclusively from the relevant training data. Evaluation comprised a held-out future-period test, temporal forward validation, spatial blocking and historical-context ablation. On the future-period test set, the area under the receiver operating characteristic curve (ROC-AUC) was 0.832, the area under the precision–recall curve (PR-AUC) was 0.620, and the balanced accuracy was 0.730. Sensitivity at the validation-selected threshold was 0.718. Among the highest-ranked 5% of occurrences, 79.5% were classified as “Serious” or “Very serious”. The mean ROC-AUC was 0.813 under temporal validation and 0.675 under spatial blocking; this descriptive contrast across different evaluation samples suggests limited geographical transferability under the evaluated settings. Historical-context ablation did not show an incremental discrimination benefit, while separate detection of “Very serious” occurrences remained unreliable at the fixed sentinel threshold. The results support further investigation of occurrence ranking for capacity-limited expert review. Operational use requires verification of predictor availability at the intended assessment time, improved calibration and external validation.

    J. Mar. Sci. Eng.

    10 November 2026

    • Article
    • Open Access

    Cannabis and hemp-derived products are becoming increasingly important in Europe for agricultural and medical purposes; however, their regulation remains complex. In this study, we reviewed national rules and legislation on cannabis cultivation, use, and regulation in the European Union (EU) using a structured questionnaire. The structured questionnaire was distributed to all 27 EU Member States. Responses were obtained from 11 countries and analyzed descriptively. The results show that EU agricultural regulations, including the 0.3% THC limit, are largely implemented across countries, although certain national differences persist. Hemp products are generally permitted; however, their use as foods or supplements is restricted by Novel Food legislation. Cannabidiol, centrally authorized as an antiepileptic medicine, is recognized in all participating countries, while other cannabis-based medicines are subject to heterogeneous national regulations and strict dispensing conditions. Recreational use of high-tetrahydrocannabinol cannabis is prohibited in all participating countries. In conclusion, based on the responses from 11 countries, although the agricultural regulation of hemp is largely harmonized within the EU, substantial differences remain in medical and food-related regulations, highlighting the need for further EU-level coordination.

    • Article
    • Open Access

    Background: Total calcanectomy has been proposed as a definitive limb-salvage strategy in non-ambulatory patients with heel ulceration and calcaneal osteomyelitis, potentially facilitating primary wound closure and reducing complications associated with persistent bony prominence. Methods: A retrospective review of non-ambulatory patients undergoing partial or total calcanectomy for calcaneal osteomyelitis at a single limb salvage center between 2011 and 2021 was performed. Demographic, perioperative, and postoperative data were analyzed. Primary outcomes included wound complications, limb salvage, and subsequent proximal amputation. Statistical significance was defined as p ≤ 0.05. Results: Sixty-two patients underwent 63 calcanectomy procedures (48 partial, 15 total). Baseline demographic, vascular, laboratory, and microbiologic characteristics were comparable between groups. No statistically significant differences were observed in closure strategy, postoperative complications, length of stay, or limb salvage rates, although a non-significant trend toward higher below-knee amputation rates was observed following total calcanectomy. Conclusions: In medically complex, non-ambulatory patients, partial and total calcanectomy demonstrated similar rates across most measured outcomes, with a nonsignificant trend toward higher below-knee amputation after total calcanectomy that warrants further investigation with larger cohorts. These findings suggest that surgical decision-making should prioritize infection control and durable wound closure rather than preservation of calcaneal structure in this high-risk population.

    • Article
    • Open Access

    Background/Objectives: Progressive pulmonary fibrosis (PPF) is an important outcome in autoimmune-associated ILD, but practical biomarkers for identifying patients at increased risk before overt progression remain limited. We investigated the incidence and timing of PPF and evaluated the prognostic value of the aggregate index of systemic inflammation (AISI), a routinely evaluated blood count-derived marker. Methods: In this prospective real-world cohort, 222 patients with autoimmune-associated ILD, including patients with systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) and interstitial pneumonia with autoimmune features (IPAFs), were consecutively enrolled at West China Hospital between July 2019 and September 2024, with follow-up approximately every 6 months. PPF was defined according to the 2022 ATS/ERS/JRS/ALAT criteria. Associations between baseline AISI and time to first PPF event documented during follow-up were assessed using Cox regression, time-dependent receiver operating characteristic analysis, Kaplan–Meier analysis, and bootstrap validation. Results: Over a median follow-up of 2.05 years, 58 patients (26.1%) had a first PPF event documented during follow-up. Among these patients, the median time to the first documented PPF event was 1.92 years, and 70.7% of first events were documented within 1–3 years after enrollment. After multivariable adjustment for the included covariates, each doubling of baseline AISI was associated with a 39% higher hazard of first PPF documented during follow-up (adjusted hazard ratio, 1.39; 95% confidence interval, 1.09–1.76; p = 0.008). Baseline AISI showed an area under the curve of 0.791 (95% CI, 0.669–0.906) for 1-year PPF, and bootstrap analysis supported internal stability. Conclusions: PPF was frequent in this autoimmune-associated ILD, with most first events documented within the first 1–3 years. Higher baseline AISI remained associated with the first PPF event documented during follow-up after adjustment for the included covariates and may provide a simple, inexpensive adjunct for risk stratification. External validation is required before clinical implementation.

    J. Clin. Med.

    10 November 2026

    • Article
    • Open Access

    Background/Objectives: This study examined longitudinal changes in body composition, physical performance, lipid profiles, and fasting glucose during a 36-week multicomponent training program combined with nutritional education and psychoeducation in Brazilian older women with and without hypercholesterolemia. Methods: Thirty-seven women were stratified according to baseline cholesterol status into hypercholesterolemic (n = 16; 71.7 ± 7.21 years) and normocholesterolemic (n = 21; 72.3 ± 5.92 years) groups. Both groups participated in three weekly sessions, including multicomponent training, nutritional education, and psychoeducation, with assessments performed at baseline and at 12, 24, and 36 weeks. Results: Significant time × group interactions were identified for body weight (p < 0.001; η2p = 0.143), fat mass (p < 0.001; η2p = 0.152), total cholesterol (p = 0.002; η2p = 0.125), and LDL-c (p = 0.010; η2p = 0.098). Post hoc analyses showed that body weight increased in the hypercholesterolemic group at 12 and 36 weeks, whereas fat mass decreased at all follow-up assessments in the normocholesterolemic group and at 12 and 24 weeks in the hypercholesterolemic group. Total cholesterol and LDL-c decreased at all follow-up assessments in the hypercholesterolemic group, with no significant changes in the normocholesterolemic group. No significant time × group interactions were observed for physical performance outcomes. Conclusions: Longitudinal trajectories of body weight, fat mass, total cholesterol, and LDL-c differed according to baseline cholesterol status. These exploratory findings do not establish greater intervention efficacy in either subgroup, given the absence of a nonintervention control group.

    J. Clin. Med.

    10 November 2026

    • Article
    • Open Access

    Daily and weekly load profiles provide useful forecasting baselines, but the benefit of learning detailed mixing weights remains uncertain. This study separates the value of periodic output structure from calibration complexity through controlled comparisons with statistical, tree-based, recurrent, and patch-Transformer alternatives. Hourly observations from three Tetouan City zones are evaluated chronologically using repeated training and paired date-block inference. In the expanded-search experiment, static periodic residual calibration achieves a normalized MAE of 0.01615 ± 0.00036, compared with 0.01817 for residual LSTM and 0.01636 for frozen coefficients. The difference from residual LSTM is significant after Holm correction, whereas the frozen-versus-trainable difference is not; equivalence is supported only under a relatively broad illustrative tolerance. A separately tuned load-and-calendar variant has the lowest mean error, but matched-setting tests do not establish an adverse effect of historical weather. The contribution is evidence for selecting periodic residual models without assuming that finer-grained calibration is necessary. Cross-dataset, sub-hourly, and renewable-integrated net-load validation remain future work; the reported findings apply only to the evaluated hourly, single-city setting.

    Electronics

    10 November 2026

    • Article
    • Open Access

    Background/Objectives: Acute pancreatitis (AP) is a severe inflammatory disorder driven by complex immune responses and oxidative stress. While macrophages are central to AP pathogenesis, the subsets associated with oxidative stress remain poorly defined. This study aims to identify oxidative stress-associated macrophages and explore novel biomarkers for AP. Methods: We integrated time-resolved single-cell RNA sequencing (scRNA-seq) of a murine AP model with computational analyses, including pathway scoring and cell–cell communication inference. Findings were validated using LPS-stimulated bone marrow-derived macrophages (BMDMs), immunofluorescence of murine AP tissues, and peripheral blood mononuclear cells (PBMCs) from AP patients. Results: scRNA-seq analysis revealed a distinct oxidative stress-associated macrophage (OxMφ) subset that expanded significantly during early AP (12–36 h). Cell–cell communication analysis predicted prominent OxMφ-associated inflammatory and tissue-remodeling interactions. Transcriptomic intersection identified Podoplanin (PDPN) as a candidate marker associated with OxMφ. In vitro, LPS stimulation induced time-dependent PDPN expression in BMDMs, which strongly correlated with reactive oxygen species (ROS) and pro-inflammatory cytokine (TNF-α, IL-1β) production. In vivo, PDPN+ macrophages accumulated prominently in the injured murine pancreas. Clinically, PDPN mRNA was significantly upregulated in the PBMCs of AP patients and positively correlated with IL1B mRNA levels, white blood cell counts, and systemic inflammation. Conclusions: We identified an oxidative stress-associated macrophage state in murine AP and established PDPN as a candidate marker of this state, offering a potential cellular target for early immunomodulation.

    Biomedicines

    10 November 2026

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  • Article
  • Open Access

I argue that the emerging sciences of synthetic morphology and diverse intelligence suggest non-physicalist models of mind and show how they can be empirically investigated. Whence the anatomical, physiological, molecular-biological, and behavioral properties of engineered new beings that have never before existed, and do not have a history of selection? Understanding, predicting, and guiding new forms of life and mind requires characterizing a structured latent space of patterns. Developmental, synthetic, and behavioral biology should take seriously, and exploit, the kinds of non-physicalist ideas that are already a staple of Platonist mathematics. I propose the following hypotheses. (1) Patterns in this space span a highly variable degree of agency, comprising a spectrum ranging from static truths studied by mathematicians to active ones studied by behavioral scientists (i.e., some patterns on the same spectrum as mathematical truths are kinds of minds). (2) The relationship between mind and body is the same as the relationship between causally instructive mathematical facts and physics. (3) Living beings have no monopoly on the “free lunches” provided by the ingression of these patterns into the physical world. While traditional computationalist views of living and cognitive systems are insufficient, my framework erases artificial distinctions between organisms and machines, framing all physical constructs (natural or engineered) as being, to various degrees, in-formed by patterns from the latent space. I sketch a research program, already begun, inspired by these ideas. Such frameworks, while contradicting long-held assumptions of both mechanists and organicists, could have many implications for evolutionary biology, regenerative medicine, AI, and the ethics of synthbiosis with the forthcoming immense diversity of morally important beings.

Philosophies

9 September 2026

80,592 Views
Bodies and minds self-assemble from single cells as a process of alignment and autopoiesis. (A) Most complex biological forms begin as one cell—a fertilized oocyte, commonly thought to be well-described by the laws of physics and chemistry. (B) A gradual, slow process of developmental morphogenesis results in the final form of the organism, which may have complex structure and a mind which may not believe it is a “machine”. Our transformation from a chemical soup into an active embodied mind is continuous but heterogeneous: (C) while we commonly think of ourselves as a unified intelligence with a “centralized” brain, the fact is that even the pineal gland, of which there is only one in the brain, is made of cells (C′) and those cells in turn are made of myriad other active components (C″)—we are a collective intelligence at all scales. (D) The creation of an “individual” out of an excitable medium such as an embryonic blastoderm with hundreds of thousands of cells is a dynamic process that is not hardwired: scratches made in that blastoderm would result in independent self-organization in each island, resulting in multiple embryos forming. This reveals the potentiality for some non-pre-determined number of minds to arise out of the same substrate. Images in (A,B,D) courtesy of Jeremy Guay of Peregrine Creative, used previously in [29]. Image (B) used with permission from [30]. Image in (C′) courtesy of Jose Calvo, Science Photo Library. Image in (C″) courtesy of Evan Ingersoll and Gaël McGill. Image (D) used with permission from [31].
  • Review
  • Open Access

Background: Chlorine dioxide (ClO2), formulated as an aqueous solution (CDS), has been proposed as a therapeutic agent, yet its classification among oxidizing compounds is frequently confounded with chemically distinct species—sodium chlorite (NaClO2) and sodium hypochlorite (NaOCl). Objective: This study aimed to synthesize the physicochemical, mechanistic and cellular basis of ClO2 action and to delineate the distinctions between ClO2 and related oxidants, with explicit separation of established data from hypothesized data. Methods: The methodology includes a narrative synthesis of electrochemical data, primary toxicological and clinical literature (PubMed) and the redox-biology literature on low-dose oxidant signaling. Results: ClO2 is a neutral free radical that acts via one-electron transfer (E°′ = +0.95 V vs. SHE for the half-reaction ClO2 + e− → ClO2−, essentially pH-independent over pH 4–8, pH-independent) without chlorination. Its antimicrobial action is attributable to oxidation of thiol-dependent enzymes and membrane constituents and to the inhibition of bacterial respiratory metabolism; host-cell sparing is consistent with differential glutathione-dependent buffering. Controlled human ingestion studies at low concentrations report a favorable short-term safety profile; conversely, the principal metabolite (chlorite) is associated with documented developmental toxicity in animals and regulatory caution by EPA/WHO. Low-dose ClO2 exposure is hypothesized—but not yet directly demonstrated—to elicit dose-dependent adaptive redox responses and redox-regulatory modulation. Conclusions: The one-electron, non-chlorinating chemistry of ClO2 provides a coherent mechanistic framework. The translation of this framework into clinical application requires prospective trials and direct mechanistic measurement, ideally conducted by independent investigators. The following mechanisms are hypothesized and have not yet been directly demonstrated in vivo: modulation of oxidative phosphorylation, mitochondrial oxygenation, and associated redox-regulatory signaling. Reported antimicrobial efficacy typically occurs in the low-ppm range (0.1–5 ppm), whereas adverse effects on mammalian cells in the reviewed literature are reported at concentrations at least one order of magnitude higher; direct head-to-head cytotoxicity comparisons remain scarce and are identified as a priority for future work. This differential thiol buffering—in particular, the higher glutathione content of many mammalian cells relative to many pathogens—has been proposed as a contributing basis for host-cell sparing; direct quantitative confirmation in vivo is not yet available. Bacterial species possess their own thiol-based defense systems (e.g., mycothiol in actinomycetes, bacillithiol in Firmicutes), and the interplay between ClO2 and these systems requires further investigation.

Biophysica

21 September 2026

15,823 Views
Mechanistic overview. ClO2 acts via one-electron oxidation of microbial targets (thiol oxidation, envelope and nucleic acid damage, respiratory inhibition); host cells are spared through glutathione-dependent redox buffering. The proposed low-dose hormetic response is a hypothesis requiring direct experimental confirmation, as discussed in Section 4.2.
  • Article
  • Open Access

Evidence of Selective Response in the Free-Breeding Dog Population in Chornobyl

  • Megan N. Dillon,
  • Reade B. Roberts and
  • Matthew Breen
  • + 3 authors

Background/Objectives: Understanding genomic responses to environmental contamination is essential for assessing long-term ecological and genetic risk. The free-breeding dogs inhabiting the Chornobyl Exclusion Zone (CEZ) offer a unique, multigenerational model for investigating these responses within a chronically contaminated landscape. Following the 1986 radioecological disaster at the Chornobyl Nuclear Power Plant, and subsequent remediation activities, the surrounding environment was contaminated by ionizing radiation, heavy metals, organic compounds, and other environmental toxicants. Our previous work identified significant genetic differentiation between two distinct but geographically proximate dog populations within the CEZ, a pattern not explained by breed composition, spatial isolation, or increased mutation rates. Methods: In this study, we tested the hypothesis that the dogs residing at the nuclear power plant show genomic signatures consistent with adaptive evolution in response to chronic environmental stressors. This work extends prior population-genetic analyses by integrating whole-genome selection scans with estimates of effective population size and comparative measures of population divergence, providing a framework to evaluate whether the observed genomic differentiation is more consistent with selection than demography. Using these whole genomic data, we evaluated chromosome-level FST metrics, estimated effective population size (Ne), and analyzed a geographically isolated island dog population as a comparative reference for genetic divergence. Results: We continued to find that the levels of genetic differentiation are not comparable to other free-breeding dog populations. Genome-wide outlier analyses identified candidate loci showing evidence of positive selection across multiple metrics. Conclusions: Genes associated with these loci were enriched for biological functions related to DNA replication and repair, cell death and survival, cellular compromise, immune response, and cancer-associated pathways, suggesting biologically plausible mechanisms through which chronic environmental stress could influence fitness. These findings are consistent with directional selection in the nuclear power plant population, which could potentially be associated with the environmental variables present, and advance our understanding of local adaptation and genomic resilience under chronic environmental contamination.

Genes

27 September 2026

8,686 Views
Historical effective population size (Ne) estimations generated through GONE analysis. The plot visualizes the Ne as estimated for the past 100 generations for each population, with points for the population size estimates and a loess smoother for these data points with default confidence band in gray. CC indicates Chornobyl City (in gold) and NPP indicates the Nuclear Power Plant population (in blue).
  • Review
  • Open Access

Neglected tropical diseases (NTDs) caused by Leishmania and Schistosoma species continue to impose a significant health burden in endemic regions, largely due to limited therapeutic options, drug resistance, and incomplete understanding of parasite biology at the molecular level. A major restriction in the development of targeted interventions is the structural inaccessibility of parasite membrane-associated proteins, which are central to host invasion, nutrient transport, immune evasion, and survival. Recent advances in cryogenic electron microscopy (cryo-EM) have expanded the structural biology toolkit available for studying difficult parasite proteins, particularly large and membrane-associated macromolecular assemblies. However, experimentally resolved cryo-EM structures remain limited for many of the Leishmania and Schistosoma targets relevant to therapeutic and vaccine development. This review therefore distinguishes experimentally determined structures from partial structural information and computational models and examines how potential cryo-EM approaches may address unresolved structural questions. We discuss current structural knowledge of selected parasite targets, approaches for recombinant expression and membrane-protein stabilization, membrane-mimetic systems for structural characterization, and computational methods that complement experimental structural biology. We further examine how experimentally supported structural information, complemented by computational predictions where appropriate, could contribute to structure-guided drug discovery, vaccine design, and targeted nanomedicine. At present, however, the direct translation of parasite structural information into rational nanotherapeutic design remains limited. Key gaps include the scarcity of experimentally resolved parasite membrane protein structures, challenges in their expression and structural characterization, and limited integration of structural biology with nanoparticle engineering. Resolving these gaps may improve the prospects for structure-informed therapeutic and nanomedicine applications against leishmaniasis, schistosomiasis, and other NTDs.

Curr. Issues Mol. Biol.

30 September 2026

8,213 Views
Molecular representation of experimentally characterized structural regions of selected Leishmania and Schistosoma targets (extracted from the PDB database and visualized with ChimeraX software). (A) X-ray crystal structure of Leishmania major leishmanolysin (GP63; PDB 1LML), showing the experimentally determined protein architecture and catalytic zinc-containing region. (B) Solution NMR structure of the extracellular EC2 domain of Schistosoma mansoni Sm-TSP-2 (PDB 2M7Z). The Sm-TSP-2 structure represents an 81-residue extracellular domain and does not resolve the complete four-pass membrane protein or its organization within the native tegument. The structures illustrate the different levels and experimental methods of structural evidence available for these parasite targets.

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Editor's Choice Articles

  • Review
  • Open Access

Genetic and Molecular Basis of Heat Stress Resilience in Pigs: Mechanisms, Genomic Regions, and Breeding Perspectives

  • Vasileios G. Papatsiros,
  • Georgios I. Papakonstantinou and
  • Georgios Michailidis
  • + 4 authors

Background/Objectives: Heat stress is one of the most economically and physiologically important constraints on pig (Sus scrofa domesticus) production, affecting welfare, reducing feed intake, growth, and reproductive efficiency, while increasing morbidity and mortality; because pigs lack functional eccrine sweat glands and have a limited capacity for evaporative heat dissipation, their ability to cope with high ambient temperature depends heavily on behavioral, physiological, and cellular stress-response mechanisms, which vary among individuals and genetic backgrounds. This review synthesizes current knowledge of the genetic and molecular pathways underlying the pig heat-stress response, spanning the HSF1–heat shock protein axis and epigenetic regulation, as well as genomic regions, candidate genes, nutrigenomic modulation, and reproductive consequences in boars and sows. Methods: A narrative literature review, informed by key principles of the PRISMA 2020 statement, synthesized 58 peer-reviewed transcriptomic, genomic, epigenomic, proteomic, and physiological studies published mainly between 1998 and 2026. Results: Heat exposure activates HSF1-driven heat shock protein transcription, oxidative stress, gut tight-junction disruption, hypothalamic–pituitary proteomic remodeling, and sex-dimorphic apoptotic/inflammatory transcriptional programs that also compromise boar semen quality. GWAS and QTL studies have mapped genomic regions and candidate genes for thermoregulatory, reproductive, and growth traits. At the same time, breed comparisons suggest, but do not prove on their own, a genetic contribution to the smaller physiological responses observed in some tropical and Mediterranean-adapted breeds. Heritability estimates for individual heat-stress-related traits, rather than for heat tolerance as a composite phenotype, range from low (0.02–0.20) for reproductive traits, to moderate (0.35–0.39) for thermoregulatory traits in lactating sows, to moderate-to-high (0.49–0.83) for physiological responses to acute heat challenge in gilts; circulating cortisol (h2 ≈ 0.68) is a heritable biomarker of the stress response rather than a measure of heat tolerance itself. Conclusions: Several traits associated with the response to heat stress in pigs are heritable and polygenic, supporting the potential of genomic selection, reaction-norm modeling, and marker-assisted introgression, although functional validation of candidate genes and larger multi-population studies, together with an explicit definition of heat tolerance as a composite selection objective, remain priorities.

DNA

5 November 2026

An integrative overview of the genetic and molecular pathways underlying heat-stress resilience in pigs. Environmental heat stress and an elevated temperature–humidity index (THI) impose anatomical and physiological constraints that trigger cellular and molecular stress responses, including heat-shock and oxidative, inflammatory, neuroendocrine, intestinal, and epigenetic pathways. These responses interact with genomic variation, candidate genes, and breed-specific adaptation to influence thermoregulatory, reproductive, growth, health, and welfare phenotypes. The resulting genetic and phenotypic information can support precision phenotyping, genomic selection, reaction-norm modeling, and complementary management and nutrigenomic strategies for improving heat resilience in pigs. The figure integrates direct porcine evidence with conserved mammalian mechanisms and proposed applications discussed throughout the review.
  • Review
  • Open Access

Somatic hematopoietic mutations, particularly clonal hematopoiesis of indeterminate potential (CHIP), represent an emerging link between aging, inflammation and cardiovascular disease beyond their established relevance in hematology. This narrative review examines how acquired mutations in hematopoietic stem and progenitor cells contribute to cardiovascular pathogenesis and how this knowledge may inform precision prevention and therapy. Evidence from experimental, clinical and population studies was synthesized with emphasis on clonal expansion, variant allele fraction, gene-specific mechanisms and cardiovascular phenotypes. The reviewed data indicate that driver mutations in DNMT3A, TET2, ASXL1, JAK2, TP53 and PPM1D can promote chronic myeloid inflammation, NLRP3/IL-1β and IL-6 signaling, endothelial dysfunction, atherosclerotic plaque instability, myocardial fibrosis, adverse remodeling, thrombosis, arrhythmias and cardio-oncology complications. The cardiovascular impact of CHIP appears heterogeneous and depends on the mutated gene, clone size, inflammatory phenotype, age, sex, treatment exposures and traditional risk factors. Anti-inflammatory, antithrombotic and mutation-oriented strategies, including IL-1β/NLRP3 blockade and pathway-specific approaches, are promising but remain incompletely validated. Somatic hematopoietic mutations should be considered cardiovascular risk modifiers rather than uniform disease entities. Future studies are needed to define screening thresholds, clinical utility and safety of CHIP-guided risk stratification and targeted therapy.

Cardiogenetics

3 November 2026

Clonal Expansion and Stepwise Mutation Accumulation in Hematopoietic Stem and Progenitor Cells. This figure illustrates the biological basis of clonal hematopoiesis, showing how acquired somatic mutations in hematopoietic stem and progenitor cells (HSPCs) can confer a selective advantage, leading to clonal expansion and altered myeloid cell function and inflammatory signaling. Clonal hematopoiesis of indeterminate potential (CHIP), particularly involving mutations in TET2 and ASXL1, has been associated with an increased risk of cardiovascular disease, including atherosclerosis, heart failure, arrhythmias, thrombosis, aortic stenosis, and myocardial remodeling. Experimental studies support potential mechanistic links between specific mutations, inflammation, endothelial dysfunction, and cardiovascular pathology. However, epidemiological associations do not establish causality, and causal relationships remain incompletely demonstrated in humans. Further accumulation of somatic mutations may also contribute to progression toward hematologic malignancy, although this process is not depicted explicitly in the figure. Abbreviations: HSPCs, hematopoietic stem and progenitor cells; CHIP, clonal hematopoiesis of indeterminate potential; IL, interleukin; TNF-α, tumor necrosis factor alpha; NLRP3, NLR family pyrin domain containing 3.
  • Article
  • Open Access

Electric Double Layers in Soils as Basis for Micro-Aggregation

  • Edgar Galicia-Andrés,
  • Chris Oostenbrink and
  • Martin Gerzabek
  • + 1 author

The behavior of ions at the electric double layer interfacial region between solid and liquid phases is well known in surface and material science. However, this is not fully the case in soil science, where the electric double layer develops due to the inherent complexity and diversity of negatively charged soil organic matter molecules that sorb at the mineral surface. This lack of knowledge opens questions regarding the interaction mechanisms at the molecular scale that lead to the stabilization of such soil building blocks, the so-called organo-mineral aggregates. By using classical molecular dynamics simulations, we studied the interactions between Kaolinite and four standardized soil organic matter samples with different aromatic and carboxylic content and Ca2+ cations clustering OM molecules and stabilizing them to the surface. We assessed the influence of (i) organic content, (ii) water content, and (iii) competing Cl− ions. Cluster aggregates are favored in soils with a high aliphatic fraction at low-water content, whereas aggregation is favored in soils with high aromatic fraction at high-water content and in the presence of Cl− ions. Moreover, samples with a low acid fraction favor clustering due to non-bonded interactions and hydrogen bonds. All of these environments are reflected as unique charge-density “fingerprints” and surface coverage for each OM sample. This work represents a step towards the characterization and study of natural soils tunable to specific local conditions.

Minerals

30 October 2026

Snapshot of cavities: (a) partially filled, (b) fully filled by water, and (c) fully filled by water and extra ions (CaCl2 solution). The cavity is represented by the periodic image of the Kaolinite basal surface in the z-direction. OM is represented by the green surface, Ca2+ ions by magenta spheres, and Cl− ions by yellow spheres.
  • Review
  • Open Access

Non-dilated left ventricular cardiomyopathy (NDLVC) presents a unique clinical paradox: patients with nearly identical phenotypes can face radically different clinical outcomes. NDLVC has been recently recognized as a distinct dynamic phenotype within the spectrum of non-ischemic cardiomyopathies, linked by a high risk of life-threatening arrhythmias. Recent advances in genetics have overcome clinical phenotyping in prognostic accuracy. Specifically, gene-specific scores have been introduced to guide primary prevention ICD in high-risk gene carriers. On the other hand, while gene-elusive cases present a more favourable arrhythmic profile, their long-term clinical outcome is more challenging to predict. Despite advancements in therapeutic strategies, the heterogeneity of the disease represents an ongoing dilemma for risk stratification and long-term surveillance. This review offers a comprehensive analysis of NDLVC management in clinical practice, highlighting the profound prognostic divergence between genetic (both in actionable and VUS carriers) and gene-elusive cohorts. By synthesizing current evidence, we aim to clarify how genotype–phenotype correlations influence clinical outcomes and to provide a framework for more personalized approaches in the follow-up and treatment of these distinct patient populations. Furthermore, we address the current lack of standardized guidelines specifically tailored to gene-elusive phenotypes. In conclusion, NDLVC management requires a paradigm shift towards a multi-parametric, genotype-directed framework, where cardiac magnetic resonance tissue characterisation and personalized risk scores are essential to optimize sudden cardiac death prevention. Future research must leverage artificial intelligence and polygenic risk scores (PRSs) to integrate multi-parametric clinical-imaging data and refine risk stratification beyond traditional binary models. Concurrently, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) will be pivotal as a translational platform to clarify VUS pathogenicity, unravel gene-specific arrhythmic mechanisms, and accelerate targeted therapeutic interventions.

Cardiogenetics

30 October 2026

Methodological Workflow for VUS Management: From Multi-Parametric Evidence Streams to Clinical Decision-Making.