Biology and Life Sciences

Abstract: Auto-brewery syndrome (ABS) is an ultra-rare condition characterized by endogenous ethanol (EtOH) production via gut fermentation. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~30% of the adult population globally. Consequently, an estimated 30% of patients with ABS are likely to also present with MASLD. Our hypothesis is that patients with ABS+MASLD are at risk for a two-hit hepatic insult in the form of MASLD and EtOH exposure. Since liver transcriptomic datasets for ABS+MASLD do not exist we utilized metabolic dysfunction- and alcohol-related liver disease (MetALD) as a surrogate to delineate the potential liver transcriptome in ABS+MASLD. We curated public murine liver transcriptomic datasets for MASLD (high-fat diet, HFD), MetALD (HFD+EtOH), and alcohol-related liver disease (ALD; EtOH alone). Genes of interest were identified using pi-scores which combine the magnitude of change in gene expression and its statistical significance. Pairwise transcriptomic similarity across top pi-score-ranked upregulated, downregulated, and combined gene sets was quantified using the Jaccard Tanimoto Similarity Index (JTSI). Gene Ontology (GO) Biological Process (BP) overrepresentation analysis was conducted to identify underlying signal transduction pathways. The liver transcriptomic signature of MetALD resides significantly closer to MASLD than to ALD across all pi-score lists. Upregulated pi-score genes showed a JTSI of 0.1342 for MetALD-MASLD versus 0.0256 for MetALD-ALD (5.23-fold greater similarity for MASLD). Downregulated pi-score genes demonstrated a JTSI of 0.0830 for MetALD-MASLD versus 0.0086 for MetALD-ALD (9.68-fold greater similarity for MASLD). Overall combined distance revealed ALD to be 3.82-fold further from MetALD than MASLD. GOBP pathway enrichment revealed shared immune activation and profound metabolic collapse in sterol/cholesterol biosynthesis, fatty acid processing, and insulin signaling. In MetALD, and by extension, in ABS+MASLD, the liver transcriptome is dominated by HFD and metabolic stress rather than EtOH exposure. These data suggest that patients presenting with ABS+MASLD should focus on initiating dietary and metabolic corrections for the clinical management of their liver disease.

Abstract: Unexplained febrile syndromes represent a major diagnostic and public health challenge in Sub-Saharan Africa. Although malaria remains an important cause of fever, an increasing proportion of febrile episodes is attributable to nonmalarial etiologies, encompassing a wide range of bacterial, viral, parasitic, and fungal infections, as well as noninfectious causes. Their etiological characterization remains limited by the low specificity of clinical manifestations, the heterogeneity of definitions and diagnostic algorithms, and insufficient laboratory capacity. Microscopy, rapid diagnostic tests, cultures, and serology remain essential in resource-limited settings, but their targeted nature and variable performance may lead to diagnostic dead ends. Emerging approaches, particularly multiplex PCR, next-generation sequencing, and clinical metagenomics, offer new opportunities to broaden the diagnostic spectrum, identify neglected or emerging pathogens, and strengthen surveillance. However, their integration requires strengthening laboratory networks, quality systems, and human resources, as well as evaluating their relevance and cost-effectiveness. An integrated approach based on the “One Health” concept appears essential to improve the diagnosis and surveillance of febrile illnesses in Sub-Saharan Africa.

Abstract: Harnessing the destructive force of the immune system against cancer cells in the human body has been achieved through numerous approaches such as immunotherapies, vac-cines, immune checkpoint inhibitors. Unfortunately, these approaches do not always provide the sought-after success, because tumors possess a plethora of evasion methods. Overcoming these barriers is the primary objective of electroporation-based therapies. Electroporation (EP) is a technique that uses high-amplitude, short-duration electric pulses that create temporary or permanent (depending on the strength and duration of the applied electric field) pores within the cell membrane. Beyond physical changes, EP induces immunogenic cell death (ICD) – a type of cell death that is marked by the release of damage-associated molecular patterns (DAMPs). This review explores the cellular and molecular mechanisms through which different EP techniques activate innate and adaptive antitumor immunity, convert immunologically "cold" tumors into "hot" phenotypes and elicit systemic, abscopal immunity.

Abstract: This cross-sectional study evaluated the validity of peak oxygen uptake (V̇O₂peak) elicited during a 200-m front crawl test (T200) for predicting maximal oxygen uptake (VO_2max) in master swimmers. Twenty-one master swimmers (age = 46.1 ± 13.7 years; World Aquatics Performance = 345 ± 28 points) completed two protocols: a 200-m all-out test (T200) and an incremental intermittent swimming test (ISST; n x 200-m) as a reference. Respiratory variables (VO₂, V̇CO₂, VE) were measured directly using a portable gas analyzer, heart rate was monitored, and stroke kinematics were evaluated via video analysis. Mean performance times were 186.7 ± 33.4 s (T200) and 193.5 ± 34.0 s (final repetition of the ISST). Cardiorespiratory fitness values reached 45.9 ± 8.5 mL·kg⁻¹·min⁻¹ (V̇O₂peak) and 44.2 ± 8.2 mL·kg⁻¹·min⁻¹ (VO_2max), with no significant differences observed between protocols for VO₂, V̇CO₂, or VE (p > 0.05). Bland-Altman analysis demonstrated strong agreement between measurements, and a significant intraclass correlation was found (VO₂ ICC = 0.74; p = 0.002). The T200 is a valid, practical, and time-efficient field-based method for assessing cardiorespiratory fitness. Its strong agreement with the ISST supports its use for estimating VO_2max, thereby facilitating accurate training prescriptions and health assessments for master swimmers.

Abstract: Background: Background: The ACTN3 rs1815739 (R577X) polymorphism has been widely studied in relation to sprint and power performance; however, its influence on movement-quality phenotypes remains poorly understood. Materials and Methods: This study examined the association between ACTN3 genotype and two neuromuscular measures, the Reactive Strength Index (RSI) and drift-derived dynamic stability, in 274 male youth football players (ages 11–14, n=166; ages 15–18, n=108), accounting for de-velopmental age. Participants completed the OptoJump Next Drift Protocol, and ACTN3 rs1815739 was genotyped by real-time polymerase chain reaction. Results: Linear mixed-effects models, including dominant, recessive, and additive genetic models, were used for analysis. The genotype distribution deviated from Hardy-Weinberg equilibrium (p< 0.001). No significant association was found between ACTN3 genotype and RSI or dynamic stability under any genetic model, whereas developmental age was a signifi-cantly stronger predictor of both outcomes (p< 0.001). Conclusions: These findings suggest that ACTN3 exerts phenotype-specific rather than universal effects on neuromuscular performance in youth athletes.

Abstract: Human and plants microbiota are different but they also show common specificities, such as regional distribution and a huge diversity of bacteria, fungi, yeasts, viruses, archaea, and even viroids. The plants surface, or phyllosphere commensal microbial population contains a significant number of microbial species with are also present in the human cutaneous microbiota and several of those bacteria have activities in plants that are also of interest for the human skin. Plants also harbor an abundant intra-tissular or endophyte microbiota, suggesting that some vegetal active compounds should be in fact of microbial origin suggesting potential new strategies for the production of active cosmetic and pharmaceutical ingredients. The plant microbiota is at the origin of soluble, but also volatile molecules and exosomes that confer protection against environmental stresses and their activities in now considered for transposition to cosmetic products. Despite the plant phyllosphere is essentially composed of Gram-negative bacterial species while the majority of skin associated bacteria are Gram-positive, they interact following same strategies and, in both cases, communicate with their eucaryotic host through hormones, mimetics compounds and cytokines. Then technics used in phytoremediation could be also applied to preserve skin microbiota homeostasis and skin integrity. In the present review, we investigate the complexity of the plant microbiota in regard of the human counterpart , targeting to establish parallels between microorganisms, molecules and strategies that can be applied in cosmetology and pharmacology.

Abstract: Some edible oils are produced by heterotrophic fermentation of Prototheca, a genus of non-photosynthetic green algae. Establishing the identity of production strains is important, particularly as species assignments have changed and culture collection labels may not reflect the original material. Two UTEX accessions have been used for oil production: UTEX 1435 historically and UTEX 1533 more recently. We compared UTEX 1533 with archival UTEX 1435 sequences, related deposits and six disease-associated (“clinical”) isolates using organellar markers, nuclear phylogeny, whole-genome identity and mitochondrial intron structure. UTEX 1533 matched historical UTEX 1435 at plastid 16S and 23S rRNA, the only available archival loci. UTEX 1533, ATCC 16525 (linked to historical UTEX 1435) and the P. wickerhamii type strain ATCC 16529 shared identical plastid 16S and 23S and mitochondrial cytb sequences. These accessions formed a fully supported nuclear group, with 95.82–98.04% whole-genome identity, versus 88.72–89.83% to the clinical isolates. Two mitochondrial introns shared by this group were absent from all six clinical isolates. Cultures supplied as UTEX 1435 in 2017 and 2026 instead matched P. xanthoriae. These findings identify UTEX 1533 as P. wickerhamii, conspecific with historical UTEX 1435, and suggest a change in material distributed under the UTEX 1435 designation.

Abstract: Biological systems achieve homeostasis through networked interactions among regulatory, transport, executive, and tuning components. However, existing frameworks typically capture only pairwise or axis-specific relationships, lacking a unified geometric language to characterize how these four functional roles assemble into robust alliances or expose fragile dependencies. Here we introduce the 'Virtual-Real Interface' (VRI)—a qualitative geometric-logical framework derived from the physical operation of folding a triangular sheet into a pseudo-tetrahedron. In this framework, the nervous (A), circulatory (B), target (C), and endocrine (D) systems are mapped onto the four vertices. The two geometrically closed faces (A–B–D and B–C–D) represent functionally self-sufficient subsystem alliances ('actual faces'), while the two open faces (A–C–D and A–B–C) expose systemic vulnerabilities ('virtual faces')—geometric nonexistence mapping onto functional non-autonomy. Using the skeletal system as a demonstrative case, we show that the framework (i) enumerates three etiological subtypes of osteoporosis based on the initial defect locus, (ii) predicts prognostic divergence by distinguishing whether the basal face is actual or virtual, and (iii) proposes multi-target repair strategies for postmenopausal osteoporosis. The framework extends to multi-organ interaction networks via co-point, co-edge, and co-face construction rules. Importantly, VRI is not a biological discovery per se, but a structurally derived and empirically testable methodological tool for network-based disease subtyping and therapeutic prioritization.

Abstract: Recent cell and animal studies have suggested that procyanidin C1 (PCC1) has potential for targeting senescent cells, but its effects in humans remain unclear. This retrospective study analyzed existing records from 32 participants aged 46–78 years during four rounds of oral supplementation with a PCC1-containing supplement. We assembled results for more than 100 circulating proteins in plasma before supplementation,after the first round and after all four rounds. We used multiple protein-based approaches to jointly assess age-associated and immune-health-associated features. Six primary directional scores were constructed from published evidence: a 12-protein combination with concordant age associations across studies, a 19-protein combination based on age associations in healthy populations, the OrganAge local score (97 proteins), the ipfP3GPT local score (77 proteins), the 58-protein core immune age-direction score, and the 19-protein Immune Health Metric (IHM)-associated protein-direction score. The data showed that multiple chemokines and soluble receptors were below baseline in most participants after four rounds of LB-150 supplementation.A small number of protein factors nevertheless remained above baseline. For individual markers within this subset, subsequent follow-up showed group-level values close to baseline, while changes at later time points remain to be observed. Across the six primary protein scores, both median scores and most participants'scores indicated shifts toward protein paterns associated with younger age or beter immune health in the higher and lower cumulative-intake groups. Relative to baseline, the group medians of the 58-protein core immune age-direction score and the 19-protein IHM-associated protein-direction score indicated older-age-associated and poorer-immune-health-associated features, respectively, after the first round. After all four rounds, the corresponding medians indicated features associated with younger age and beter immune health. This patern of group medians was observed under both cumulative-intake regimens and in the age subgroups within the higher cumulative-intake group. By examining protein-age associations and immune-health-associated features, this study identified human protein changes after oral intake of a PCC1-containing supplement. The findings suggest immunomodulatory potential for PCC1 and provide human observations that connect with existing senescent-cell research and inform further investigation of immune health and modulation of the circulating immune microenvironment.

Abstract: Scalp itch and beard irritation are multifactorial neurocutaneous disorders associated with microbial dysbiosis, impaired skin barrier function, inflammation, and activation of the transient receptor potential vanilloid 1 (TRPV1) ion channel, a key mediator of itch signalling and neurogenic inflammation. Although conventional therapies such as ketoconazole, zinc pyrithione, and hydrocortisone provide symptomatic relief, their long-term use is limited by adverse effects, irritation, and regulatory concerns, highlighting the need for safer steroid-free alternatives. In the present study, the molecular mechanism underlying the antipruritic potential of FERMENZA, a natural postbiotic formulation, was investigated using an integrated computational approach. LC-MS metabolite profiling identified major phytochemicals, which were subjected to molecular docking against the TRPV1 vanilloid-binding pocket, followed by 40 ns molecular dynamics simulations in a POPC lipid bilayer under physiological conditions. Among the identified metabolites, rutin exhibited the highest binding affinity (-12.76 kcal mol^-1), followed by ellagic acid (-11.83 kcal mol^-1), outperforming the reference antagonist capsazepine (-8.96 kcal mol^-1) as well as hydrocortisone (-8.06 kcal mol^-1), ketoconazole (-6.56 kcal mol^-1), and zinc pyrithione (-6.06 kcal mol^-1). Both phytochemicals formed stable hydrogen bonds and hydrophobic interactions with key residues in the TRPV1 binding pocket. Molecular dynamics simulations confirmed stable protein-ligand complexes without ligand dissociation throughout the simulation. Rutin showed the highest structural stability, reflected by the lowest backbone RMSD (3.72 ± 0.37 Å), stable radius of gyration, minimal solvent-accessible surface area fluctuations, and negligible perturbation of the surrounding POPC membrane. Overall, the findings identify rutin, followed by ellagic acid, as promising natural TRPV1 modulators and provide a molecular basis for the antipruritic activity of FERMENZA, supporting its potential as a safe, drug-free and steroid-free natural formulation for managing scalp itch and beard hypersensitivity.

Abstract: Insect infestation can alter the quality and nutritional composition of cereal and legume grains during storage. This study evaluated the nutrient changes in common bean and maize cultivars infested with Acanthoscelides obtectus and Sitophilus zeamais, respectively, after six months of storage. The common bean cultivar NUV6 and the maize cultivar CMS 8704 were highly susceptible, whereas the common bean cultivar FEB-190 and the maize cultivar CMS 8501 were moderately resistant. Adults of A. obtectus emerged earlier in common bean cultivars than adults of S. zeamais in maize cultivars. Infestation significantly altered the nutritional composition of maize, markedly reducing macronutrients such as protein and crude fat; this decline was consistent across cultivars, highlighting the destructive impact of pests on grain quality. The relative increase in ash content of infested samples indicated degradation and possible contamination with insect by-products rather than a gain in beneficial minerals. Whereas most nutrients were depleted, copper content remained relatively stable, suggesting that nutrients differ in their vulnerability to insect activity. The effect of infestation was significant overall, but the cultivar × infestation interaction was not significant for the macronutrients. Principal component analysis (PCA) revealed relationships among nutrients and nutritional patterns that differentiated the cultivars. Overall, insect infestation strongly affected the nutritional quality of stored grains. These findings can support the development of improved postharvest storage and pest management strategies that protect household food security and preserve the value of stored staple crops.

Abstract: Genome-wide association studies (GWAS) identify an association between a single nucleotide polymorphism (SNP) and a phenotype. The complex traits are often the result of the combined effect of multiple genetic variants, each with a small individual effect and these small effects may be missed due to stringent p-value thresholds in GWAS studies. Gene-based association tests combine the effects of multiple variants within a gene and provide more interpretable associations and enable researchers to detect associations that might be missed in single-SNP analyses. Gene-based tests increase statistical power by considering the cumulative effect of several variants in a gene, reducing the multiple testing burden and prioritizing variants based on their likelihood of contributing to the phenotype. The power of gene-based tests depends on the weights assigned to SNPs within a gene, and misspecification of these weights can lead to a reduction in power. Two commonly used weighting schemes in gene-based test are equal weight and minor allele frequency-based weights. The equal weighting assumption implies that all SNPs within the gene have an equal effect on the trait, while minor allele frequency (MAF)-based weights, such as inverse or beta distribution of MAF, upweight rare variants under the assumption that they are more likely to be deleterious. These weighting schemes do not account for the underlying biological function of SNPs, which, if incorporated, could improve the power of gene-based tests by prioritizing functionally relevant SNPs. In this study, we propose a novel gene-based test approach (H2-Gene) that uses SNP level heritability as weights estimated using multiple functional annotations. Extensive simulation studies at both the single-gene and GWAS levels demonstrated that the proposed method effectively controls the type I error rate and achieves higher power compared to equal and MAF-based weighting schemes. When applied to GWAS summary statistics for Bipolar Disorder, Schizophrenia and Attention Deficit Hyperactivity Disorder, H2-Gene identified more significant genes than equal or MAF-based weighting schemes.

Abstract: The metabolism of drugs takes place for the most part in the liver. Next to the liver, however, microbiota in the gut also play an active role in the metabolism of drugs, either in generating active compounds or deactivation of the drug. In vivo, the gastrointestinal tract is populated by a complex, and highly individual microbiota. Gut organoids are powerful ex vivo tools for studying drug metabolism. Organoids also allow for studying the role of microbiota in drug metabolism. The technical challenges in co-culturing eukaryotic organoids with prokaryotic bacteria can be overcome. Next steps will be to mimic the complex composition of the gut microbiome. This manuscript provides a state of the art overview of current concepts and of most promising avenues for future research and applications in drug development.

Abstract: Isolated mountain ecosystems provide an opportunity to study how long-term natural fragmentation shapes population persistence. Unlike species fragmented by human activi-ties, many mountain endemics have evolved under naturally discontinuous conditions over long timescales, allowing historical and contemporary processes to be disentangled. Degenia velebitica (Brassicaceae) represents a suitable model for such studies. We analysed nuclear microsatellites, chloroplast DNA, fine-scale spatial genetic structure, effective population size, and demographic characteristics across all currently known populations. Despite pronounced genetic differentiation, restricted contemporary gene flow, small effec-tive population sizes, and marked demographic differences, populations maintained moderate nuclear genetic diversity. Chloroplast DNA revealed low haplotype variation and strong spatial structuring of maternal lineages, consistent with limited historical seed-mediated dispersal. Importantly, demographic and genetic indicators were not al-ways concordant: in one population, an apparent recent decline in census size and low effective population size were accompanied by relatively well-preserved nuclear genetic diversity. These findings demonstrate that neutral genetic diversity alone may provide an incomplete picture of population status and evolutionary potential, highlighting the im-portance of integrating genetic, demographic, and ecological information and maintaining existing population structure and habitat integrity in conservation planning.

Abstract: Date palm (Phoenix dactylifera L.) is an economically important crop in Sudan, and symptoms of decline may be associated with diverse and poorly understood fungal communities. An unclassified agaricoid fungus was consistently isolated from basidiomata occurring on or near symptomatic date palms in an orchard in Khartoum State, Sudan. Affected palms exhibited chlorosis, reduced growth, drooping fronds, progressive browning, and desiccation. Six isolates (A–F) were examined based on their morphological characteristics and ITS1-5.8S-ITS2 sequences. Unlike the poroid basidiomata typical of Ganoderma, the isolates produced mushroom-like basidiomata with gills and a stipe. Several morphological characteristics also differed from the typical description of Hohenbuehelia, particularly the centrally positioned stipe and the free or narrowly adnate lamellae. BLASTn analysis showed only 83–89% ITS sequence identity with available Hohenbuehelia sequences. In the present ITS dataset, isolates A–F formed a strongly supported monophyletic group (bootstrap values of 99–100%) outside the sampled Hohenbuehelia and Ganoderma sequences. These results help clarify the phylogenetic position of the isolates within the taxa included in the current dataset but are insufficient for formal genus-level classification or the recognition of a new taxon. Furthermore, following 12 months of artificial inoculation, no consistent disease symptoms were observed, and the causal agents of date palm decline could not be determined. This study reports an unidentified agaricoid fungus associated with declining date palms and highlights the need for broader sampling of Agaricales, multilocus phylogenetic analyses, detailed morphological characterization, and carefully controlled pathogenicity tests before its taxonomic identity and ecological significance can be established.

Abstract: Reality appears saturated with recurrent but non-identical patterns. Distinguishable regularities give grounds to investigate constraints on possibilities and the dynamics through which configurations arise, persist, change and dissolve. The Teabag Test justifies selective reverse engineering: a purpose-relevant reconstruction can support enquiry or participation without an exhaustive causal history. Minimum relational legibility floors identify what must become sufficiently intelligible for that purpose and what would require further reconstruction. Viability Studies is proposed as a field of comparative enquiry into these relationships across domains, scales and boundaries. The Working Repository supplies a substantive initial instance: a candidate map and an architecture for accumulating situated relational accounts, their evidence, limits, comparisons and revisions. Specialist participation is constitutive of its development. Contributions need not report new discoveries; organising knowledge already dispersed across specialisms may expose relationships, consequential differences and further questions. Each instance remains partial, while maintaining and comparing its records can develop the resolution available for enquiry. Participants can extend the architecture or build independent instances from the public orientation; comparisons between builds can investigate what organising choices reveal or obscure. Sustained availability and stewardship exceed the current author's capacity. The Repository is subject to the constraints and dynamics it investigates, including the effects of its own categories and uses on participation. Increased legibility does not guarantee desirable emergence. The contribution is the connected orientation, substantive map and cumulative comparative architecture. Close antecedents inform its assessment; historical distinctiveness and additional utility remain open. No specialist pilot or implemented governance is reported.

Abstract: Today, in 2026, there is concern that existing or improved pandemic pathogens might be made in labs, and that construction of pathogens might be assisted by Artificial Intelligence (AI). In the near future, it seems possible that pathogen construction might be assisted by AI agents acting under human direction or even on their own initiative. Such pathogens would be made by some combination of construction of stretches of specified nucleotide sequence with directed evolution (by means such as passaging on different cell lines or through humanized transgenic animals) to select variant organisms with desired properties. Current safety policy to prevent lab-made catastrophic pandemics depends on control of commercially synthesized DNA. This regulatory approach supposes that it will be possible to identify dangerous DNA sequences, and that regulation and law can prevent commercial DNA synthesis vendors from filling orders for those dangerous sequences. Here, we surveyed methods used to make "virus sized" DNA constructs in papers published in seven important journals over the 50+ years since the advent of recombinant DNA methods. Our results show that most contemporary large DNA constructions depend on high fidelity, high processivity thermostable DNA polymerases, either to make the synthetic DNA used to generate segments that are later assembled into the construct, or to join those segments via polymerase-based methods such as Gibson Assembly. Our results suggest that imposition of controls on these advanced thermostable polymerases together with restrictions on other materiel and equipment could provide additional means to increase the safety of the biological enterprise in the wake of a triggering events such as the release of lab-made pathogens. We then describe and discuss a contingency regulatory regime that would license institutions, laboratory workers, and independently reviewed lines of R&D, that could be imposed after such a triggering event.

Abstract: Botanical gardens are repositories of biodiversity and heritage, yet their sustainability is threatened by canopy closure and spatial saturation. This study analyzes 87 years (1939–2026) of structural dynamics in the Carlos Spegazzini Botanical Garden (La Plata, Argentina). We combined historical aerial photo interpretation, field censuses (535 trees), allometric modeling, and spatial competition analyses (Voronoi polygons, nearest-neighbor distances, Clark-Evans index). Tree density decreased from 185.0 to 119.5 ind/ha, while canopy cover increased from 44.6% to 102.4%, with estimated crown cover peaking at 202.2%, well above the 70% saturation threshold. Crown radii increased significantly (Kruskal-Wallis χ² = 492.95, p < 0.001), and the Clark-Evans index confirmed a clustered distribution (R = 0.620, p < 0.001). Of the 535 individuals, 218 (40.7%) were heritage trees, with 78.9% in good sanitary condition and 46 requiring urgent care. Despite intense crown overlap, the 5.6% mortality (2022–2026) was not explained by spatial variables (pseudo-R² = 0.0038; AUC = 0.481). Pathogens, mechanical damage, or senescence would be the primary drivers. We recommend selective thinning, priority phytosanitary care, a necropsy protocol, gradual renewal, and density targets of 120–150 ind/ha to balance ecological functioning with heritage preservation.

Abstract: To characterize the distribution of IgA-producing plasma cells across the human ocular surface and to assess alterations in tear IgA subclass profiles in Schirmer strip extracts from patients with dry eye disease (DED) and primary Sjögren’s syndrome (pSS). Immunofluorescence staining was performed on paraffin-embedded lacrimal gland, conjunctival, and corneal tissues to identify IgA- and subclass-producing B/plasma cells. Samples were collected from controls (n = 18), patients with DED (n = 75), and patients with pSS (n = 10). Total protein concentrations in Schirmer strip extracts were deter-mined using a bicinchoninic acid assay. Total IgA, IgA1 and IgA2 were quantified by ELISA and normalized to total protein. IgA-producing plasma cells were abundant in the lacrimal gland and conjunctival stroma but absent from the corneal sections. In both tissues, IgA1-producing cells predominated over IgA2-producing cells. Total protein concentrations in Schirmer strip extracts were significantly lower in pSS than in DED. The most consistent change was reduced normalized IgA2 abundance in Schirmer strip extracts, whereas changes in IgA1 were less consistent across the analyzed disease groups. IgA-producing plasma cells are prominent in the lacrimal gland and conjunctiva. DED and pSS are associated with reduced normalized IgA2 abundance and altered IgA sub-class profiles.

Abstract: Biomedical research requires repeated judgments about what heterogeneous evidence supports. This Perspective proposes a sequential workflow in which quantitative bioinformatics identifies candidates, semantic decision models organize and prioritize evidence, and large language models provide subsequent analysis before human experts interpret the findings and make the final decisions. Jev and Laya illustrate bounded question-answering interfaces that could help concentrate more costly analysis on relevant candidates. Across molecular, cellular, tissue, individual and population scales, this workflow offers a practical path to focus expert attention on the evidence and candidates most likely to matter. An accompanying question catalogue and AI assistant skill make the approach ready for prospective evaluation. By combining computational efficiency with expert judgment, semantic decision models could help biomedical researchers explore more evidence, ask sharper questions and make better-informed decisions.