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Results for “cost of complexity”

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PubMed2026

SIVA: diagonal integration of spatial multi-omics data via spatially informed variational autoencoders and anchor guidance.

MOTIVATION: Understanding cellular states and regulatory programs requires integrative analysis of multiple omics layers. Although recent spatial sequencing technologies allow molecular profiling of cells within their tissue context, paired spatial multi-omics assays are still limited by technical complexity and cost. This creates a pressing need for diagonal integration methods that enable joint analysis of unpaired spatial omics datasets. RESULTS: We propose SIVA, a deep generative framework based on Spatially-Informed Variational Autoencoders with Anchor Guidance, for diagonal integration of spatial multi-modal data. SIVA employs modality-specific variational autoencoders (VAEs) with a hybrid latent embedding that integrates Gaussian process and standard Gaussian priors, enabling joint modeling of spatially structured variation and dominant underlying data distributions across modalities. To facilitate cross-modal alignment in the absence of one-to-one cell correspondence, SIVA adopts a dual integration strategy combining global distribution alignment via Maximum Mean Discrepancy and local correspondence guidance using mutual nearest neighbor anchors. Extensive experiments across multiple cross-slice integration scenarios demonstrate that SIVA achieves robust and accurate integration of unpaired spatial omics datasets, consistently outperforming existing methods. AVAILABILITY AND IMPLEMENTATION: The source codes are available at https://github.com/PelenJiang/SIVA.

Autoencoder↗
PubMed2026

SurvGRN: a multi-feature fusion framework for bladder cancer survival prediction.

Bladder cancer survival outcomes exhibit significant heterogeneity, influenced by multifaceted factors. While digital pathology-based survival models leveraging artificial intelligence show promise, they often overlook complementary data sources. Conversely, imaging lacks cellular detail, and genomics/proteomics entail complexity and cost. To integrate multidimensional data for enhanced survival prediction, we propose SurvGRN, a multi-feature fusion framework. SurvGRN synergistically combines clinical variables, transcriptomics, and digital pathology slides using a gated residual network architecture. Pathological features are extracted via multiple instance learning, while clinical and transcriptomic data are processed as static inputs. These features are dynamically fused using a long short-term memory (LSTM) network for comprehensive survival risk assessment. Evaluated on 400 bladder cancer patients, SurvGRN significantly outperformed existing methods: improving the C-index by 12.6% over DeepMISL; 20.6% and 7.1% over graph-based models (DeepGraphConv and Patch-GCN); and 5.4% and 4.0% over attention-based approaches (Surformer and HVTSurv). Ablation studies confirmed the contributions of pathology features (extracted via ResNet-50 pre-trained on bladder tissue), clinical/transcriptomic data, and the LSTM fusion. SurvGRN also enabled significant stratification of patients into distinct risk cohorts. This work demonstrates that holistic integration of multi-source data through tailored fusion architectures substantially improves bladder cancer survival prediction.

bladder cancer↗
PubMed2026

Architectural logic of the 3D genome: mechanisms of dysregulation and emerging cancer therapeutics.

The three-dimensional (3D) genome provides an essential layer of organization that shapes genome function in space and time. Chromatin compartments and topologically associating domains (TADs) arise from the interplay between intrinsic properties of chromatin and architectural factors, including cohesin and CTCF. Despite substantial progress in defining these structural features, whether 3D genome architecture plays a causal role in regulating processes such as transcription, DNA replication, and DNA repair, or instead reflects underlying regulatory activity, remains unresolved. Here, we use the distinction between chromatin-intrinsic features and architectural factors as a framework to evaluate evidence for causality in genome structure-function relationships. We extend this framework to cancer, where both intrinsic alterations (including noncoding mutations, structural variants, and changes in chromatin state) and architectural factor perturbations (such as mutations in architectural proteins and dysregulation of transcriptional machinery) disrupt genome organization and contribute to disease progression. These findings suggest that alterations in genome structure can, in some contexts, actively reshape oncogenic programs. A major limitation in applying 3D genome insights to cancer biology is the cost and complexity of omics assays. Recent advances in artificial intelligence (AI) and machine learning (ML) enable inference and prediction of 3D genome organization from sequence and epigenomic features, providing insight into the extent to which genome folding is encoded intrinsically versus dynamically regulated in architectural factors. This perspective provides a unified view of how genome structure is established, how it relates to function, and how its disruption contributes to tumorigenesis.

3D genome↗
PubMed1979

Enzyme linked immunosorbent assay (ELISA) for IgG and IgE antibodies to protein and polysaccharide antigens of Aspergillus fumigatus.

ELISA has emerged as a useful alternative to other more costly and complex tests. Polystyrene microhaemagglutination plates have been used as solid phase to absorb Aspergillus fumigatus protein and polysaccharide components for detection of specific antibodies in patients with various forms of pulmonary aspergillosis. IgG and IgE antibodies to the polysaccharide as well as the protein allergens have been found. For the IgE test a double antibody technique has been developed, which is more sensitive than the conventional indirect ELISA.

Antigens, Fungal↗
PubMed1979

Survival of anaerobic bacteria in common laboratory diluents.

The survival of six species of anaerobic bacteria was studied in simple or commercially available diluents. Bacteroides fragilis and Fusobacterium nucleatum showed excellent survival in all diluents including distilled water. Fusobacterium mortiferum survived well in all diluents except water and water supplemented with 0.1% gelatain. Clostridium perfringens survived best in phosphate-buffered saline with gelatin. Peptococcus asaccharolyticus required gelatin added to the basic diluent, and Streptococcus intermedius showed excellent survival only in minimal essential medium with gelatin. These diluents could provide effective and economical alternatives to more complex and costly diluents often used in work with anaerobic bacteria.

Anaerobiosis↗
PubMed1979

Modern management of tetanus neonatorum.

Five infants with neonatal tetanus were managed with neuromuscular blockade and positive pressure ventilation. All survived. Tetanus was frequently confused with neonatal seizures at time of presentation. All infants were delivered at home. Mean age of onset of symptoms of poor suck, hypertonicity, and generalized spasms was 5.4 days with hospital admission at 6.4 days. Mean duration of mechanical ventilation was 34 days. Although hospital management of tetanus neonatorum may be expected to have a satisfactory outcome, it represents a costly and complex approach to a preventable disease.

Female↗
PubMed1979

Comparison of bubble and membrane oxygenators in short and long perfusions.

Eighty patients had cardiopulmonary bypass (CPB), half having short (109 +/- 11 minutes) perfusions and half having long (188 +/- 14 min) perfusions. Twenty patients in each group were perfused with bubble oxygenators (Bentley, Harvey, or Galen) and 20 with membrane oxygenators (Modulung or Teflo). Hemodilution to a hematocrit value of 22.5% +/- 1.4% and hypothermia to 28 degrees +/- 2 degrees C were used in all patients. Complete hemograms, sequential multiple analyzer 18 tests, coagulation profiles, blood gases and pH, three immunoglobulins, and two complement fraction proteins were sampled as follows: three times before perfusion, one to ten times during perfusion, 1 hour immediately after perfusion, and 4, 24, and 48 hours postoperatively. Data in concentration terms were compared statistically and reported as mean and standard error for each subset. Additionally, rates of gain or loss were calculated in terms of quantity per liter of blood pumped per minute. During perfusion for both duration sets, use of a membrane oxygenator resulted in greater pump flows (4.55 +/- 0.15 L/min versus 3.75 +/- 0.11 L/min), lower total peripheral resistances (1,125 +/- 63 dynes.sec.cm-5 versus 1,652 +/- 115 dynes.sec.cm-5), and greater urinary outputs (9.4 +/- 1.1 ml/min versus 2.2 +/- 0.6 ml/min) than in the bubble oxygenator subsets. Comparisons of measured and calculated data in the immediate postperfusion interval showed no differences between bubble and membrane oxygenator subsets for short perfusions. In long perfusions, the membrane subset had lower plasma hemoglobin and white cell concentrations and generation rates, smaller (3 to 8 1/2 times) losses of IgG, IgM, C3 and shed blood necessitating less transfusion, and greater C4 losses. The membrane oxygenator systems used were more complex and costly and offered no advantages for short perfusion in adults. In anticipated long perfusions or where bleeding may be a problem, a membrane oxygenator appears more efficacious than bubble systems. For perfusions of less than 2 hours, membrane oxygenators had no biochemical or hematologic advantage over the bubble devices used in this study.

Blood Cell Count↗
PubMed1978

Constraints under which the microbiology laboratory functions.

The relevance, usefulness, quality, and cost of performance of many clinical microbiology laboratories have been questioned. Major, common constraints under which most microbiology laboratories operate in the United States include lack of trained manpower, wide variation in the level and sophistication of clinical microbiology service, lack of physician-laboratory communication and interaction, inadequacies in medical education, and often inadequate laboratory space. Governmental regulations, requirements, and standards have improved the quality of many laboratories' work, but also result in greatly increased costs, excesses of often trivial procedures, and diversion of trained manpower from clinical service to regulatory procedures, with a resulting increase in manpower needs. The usefulness, relevance, and cost of regulatory requirements and procedures are unknown. Lack of reliable, standardized reagents impedes utilization of rapid and low cost procedures, and proliferation of complex tests results in costly additional demands on existing manpower.

Bacterial Infections↗
PubMed1978

Similarity of clinical and laboratory results obtained with microporous teflon membrane oxygenator and bubble-film hybrid oxygenator.

For 80 elective clinical cardiopulmonary bypasses we alternately used either a commercial microporous Teflon membrane oxygenator or a commercial hybrid bubble-film oxygenator. Setup time was a little longer with the membrane unit (20 minutes), but priming volume (2,250 ml) was the same. No problems were encountered with the hybrid oxygenator. However, despite our monitoring of additional variables, including shim and inlet pressure and recirculation flow, gas exchange abnormalities were encountered in 5 patients on whom the membrane oxygenator was used; in 4 of these cases the abnormalities were encountered prior to our recognition of the potential for occasional internal shunting with this device. There were no hospital deaths. When the two groups, matched except for oxygenator selection, were compared, there were no significant differences clinically or hematologically. For cardiopulmonary bypass of 2 hours or less, both oxygenators studied are definite improvements over previous silicone membrane and high-gas-flow bubble oxygenators. However, lower cost and reduced complexity favor the hybrid oxygenator.

Blood Glucose↗
PubMed1979

Control of the blood glucose in diabetes mellitus is it valuable? Is it feasible.

The controversy over the whether strict blood glucose control prevents or attenuates the complications of diabetes is still unresolved, but the available data support the value of good blood glucose control. The resolution of the controversy is not feasible at present because of the complexity and financial cost of a definitive prospective study and because we may not presently possess pharmacological agents which can accomplish the goal of long term strict control of the blood glucose. Finally, whereas we regard retinopathy, nephropathy and neuropathy as valid pathological endpoints, we are not secure in assuming that blood glucose represents the critical measurement for longitudinal assessment of metabolic control. Studies evaluating control based on blood and urine glucose assessments are complicated by the failure of the data to reflect changes in minute to minute regulation. Thus, the relative insensitivity of some of these parameters of control could account for failures to demonstrate a correlation between adequacy of therapy and diabetic complications.

Basement Membrane↗
PubMedDate not supplied

[Simplified methods for the isolation and preservation of axenic Lamblia cultures].

The complexity and high cost of the existing methods of obtaining and preserving axenic cultures of Giardia (Meyer, 1970) have motivated the authors to look for new ways and means of simplifying the procedure. Solid media gave fair results which substantially simplified and accelerated the process and proved to be favourable for preserving the cultures longer without repassaging. Accordingly, the method recommended by the above authors facilitates the elimination of yeast from the cultures of Giardia in 15 to 24 days and the preservation of the axenic cultures over a period of 4 to 6 months without passaging, and within first two months at least the cultivation of new populations is guaranteed.

Animals↗
PubMed2026

A hybrid and cost-efficient barcoding strategy for full-length 16S rRNA gene nanopore sequencing of environmental samples.

BACKGROUND: Accurate species-level identification of bacteria in complex environmental samples is essential for applications in biotechnology, ecological monitoring, and clinical diagnostics. Short-read platforms such as Illumina frequently truncate the 16S rRNA gene, limiting taxonomic resolution. In this work, we applied Oxford Nanopore Technology (ONT) long-read sequencing to full-length 16S rRNA amplicon in samples from natural soil amended with lignocellulosic biomass and a simplified microbial community derived from cultures grown on selective and differential carboxymethyl cellulose (CMC)-based substrates, with the aim to evaluate the difference in performance between a real, complex community and a less complex system. To reduce consumable costs, we substituted the standard ONT Barcoding kits with an in-house hybrid barcoding workflow. Specifically, PacBio PCR-based barcoding protocol was used for sample indexing, followed by library preparation using the ONT Ligation Sequencing Kit. This simplified approach retained compatibility with MinION and Flongle flow cells and supported accurate downstream demultiplexing while lowering barcode costs substantially. Additionally, a new bioinformatic workflow tailored to ONT data was implemented. RESULTS: Overall, the hybrid protocol significantly reduced per-sample barcoding costs while preserving high sequencing quality and throughput. The sequencing run yielded over 5 Gb of quality-filtered data (Q-score ≥ 10). Furthermore, the new bioinformatic workflow allowed taxonomic assignment at the species level for 49.38% of annotated taxa, compared to just 4.59% using Illumina NovaSeq sequencing of the V3-V4 region. ONT also recovered 2.3 times more genera and 1.3 times more families. Although 16S rRNA gene sequencing often cannot distinguish between closely related species, particularly within taxonomically complex groups, in this work, full-length reads substantially improved both taxonomic resolution and database matching. CONCLUSIONS: These results show that full-length 16S rRNA sequencing with ONT, paired with a low-cost barcoding strategy, enhanced taxonomic resolution compared to short-read workflows. This approach also offers a scalable and cost-effective option for high-resolution microbiome profiling in research and applied settings.

RNA, Ribosomal, 16S↗
PubMed2026

Gene-level complexity explains genome-wide variation in the distribution of fitness effects.

The distribution of fitness effects (DFE)-describing how harmful, neutral, or beneficial new mutations are-is central to understanding how populations evolve. Although the DFE varies across genomes and species, it remains unclear which aspects of genomic organization drive this variation. Here, we inferred gene-level selective constraints across the genomes of Mus musculus castaneus, Drosophila melanogaster and Saccharomyces cerevisiae using a combination of population genetics and machine learning trained on diverse gene features. Many gene features were predictive of selective constraint, with conservation, gene structure, and expression being the most informative. These selective constraints delineated gene classes with distinct DFEs. Genes with higher connectivity and expression-features reflecting how many traits a gene influences-experienced stronger and less dispersed deleterious effects with increasing selective constraint. Between species, the rate of adaptation decreased with increasing organismal complexity, whereas across the genome it did not decrease monotonically with selective constraint, but tended to be higher at intermediate levels. While between-species comparisons of DFE parameters were less consistent with predictions of Fisher's geometric model (FGM) based on organismal complexity, variation in DFE parameters across the genome aligned more closely with FGM when complexity was considered at the gene level. Our results suggest that gene-level complexity, captured by genomic feature proxies, provides a more informative definition of complexity for DFE variation than organism-level labels, and highlight the value of using gene features collectively to link genomic architecture, fitness landscapes, and patterns of molecular evolution.

Animals↗
PubMed1978

One strategy for controlling costs in university teaching hospitals.

Major teaching hospitals, because they treat a more complex mix of patients than do nonteaching hospitals, usually show higher costs per patient day or per case. As a result, teaching hospitals are particularly vulnerable to the decisions of those cost control and planning agencies that are unable or unwilling to treat the problem of case mix. Research at Yale University reported here demonstrates the effect of case mix on costs. A methodology is outlined that can be used by teaching hospitals in determining their costs of treating patients with a complex mix of diagnoses. It is not held that case mix alone explains all of the cost differences between teaching and nonteaching hospitals; but until that factor is isolated and identified, the other contributors to cost variation cannot be examined.

Costs and Cost Analysis↗
PubMed2026

Scalable medium-density genotyping platforms for cultivar identification, pedigree authentication, marker-assisted and genomic selection, and other applications in strawberry.

A broad spectrum of high-density genotyping approaches, including single-nucleotide polymorphism (SNP) arrays, genotyping-by-sequencing, and whole-genome reduced-representation sequencing, have been shown to perform well in strawberry (Fragaria × ananassa), despite the inherent complexity of the octoploid genome. While these approaches are effective, their routine deployment in breeding programs can be constrained by cost, computational requirements, and workflow complexity. In parallel, many breeding programs continue to rely on locus-specific assays for marker-assisted selection, resulting in fragmented and inefficient genotyping strategies. Here, we describe medium-density amplicon-based genotyping platforms for strawberry designed to provide cost-effective, turnkey solutions that integrate markers used for marker-assisted selection with genome-wide markers suitable for genomic prediction in a single laboratory assay. These platforms were developed by targeting 1,650 or 4,811 target SNPs via amplicon sequencing, and are interoperable with existing high-density genotyping resources, including a widely used 50K SNP array, thereby facilitating data integration across platforms. We benchmarked their performance relative to the 50K SNP array across breeding-relevant applications, including identity and purity testing, pedigree authentication, marker-assisted selection, and genomic selection, and further evaluated the feasibility of genotype imputation to enhance genome-wide information content. Across analyses, the 1,650- and 4,811-amplicon platforms produced results comparable to higher-density platforms while substantially reducing genotyping cost and analytical overhead. This work demonstrates that targeted amplicon-based genotyping can support efficient, scalable, and integrated genome-informed breeding, enabling the routine application of both marker-assisted and genomic selection within strawberry breeding workflows. Open-source R workflows are provided to support streamlined analyses in breeding contexts.

Fragaria↗
PubMed2025

Development of a plant-based vaccine against brucellosis: stable expression of Brucella abortus OMP25 in transgenic tobacco.

Brucellosis, caused by Brucella species, is a global threat to livestock farming, resulting in economic losses and socio-economic challenges, particularly in rural areas. Despite its impact, no licensed human vaccines are available. Animal vaccination remains the most cost-effective control method, but traditional vaccine production is expensive. Edible vaccines, using plants as bioreactors to produce immunogenic antigens, offer a low-cost alternative by eliminating complex purification processes. This study developed a transgenic plant by expressing the Brucella abortus outer membrane protein OMP25 in tobacco plants. OMP25, a conserved transmembrane protein with high immunogenicity, was cloned into a Gateway pDONR vector via a Boundary Pairing reaction and transferred to a binary destination vector via a Left-Right reaction. The destination vector was introduced into Agrobacterium tumefaciens and subsequently used for Agrobacterium-mediated transformation of tobacco plants. Transgenic plants were selected on media containing kanamycin, and the expression of the transgene was verified through the fluorescence of green fluorescent protein. Microcallus formation and shoot development on selective media confirmed kanamycin resistance and the successful integration of the transgene. After phenotypic selection, genomic DNA was extracted from transgenic plants and analyzed by PCR (Polymerase Chain Reaction) using primers specific to the OMP25 gene. Positive PCR results validated the successful integration of the OMP25 gene into the plant genome. Gene expression was further confirmed at the RNA level through real-time quantitative PCR (qRT-PCR) and at the protein level via Western blot analysis. Future studies will evaluate immune responses in animal models. This approach demonstrates the potential for low-cost, effective vaccines to combat brucellosis, addressing critical economic and public health challenges.

Plants, Genetically Modified↗
PubMed2026

Harnessing Probiotic LAB and Bacteriocins for Clean-Label Food Processing and Biopreservation: Omics, Molecular Innovations and Industrial Applications.

The persistence of microbial agents in foods, especially spore forming bacteria is one of the most significant challenges to food preservation and safety, undermining product quality, shelf life, and consumer health. The use of traditional control methods, including thermal processing and chemical preservatives, are increasingly limited by consumer demands for minimally processed foods, and the emergence of resistant microbial strains. Advances have been made in the use of probiotics like lactic acid bacteria (LAB) and their biometabolites like bacteriocins in food processing and preservation, particularly to control biofilm and endospore forming pathogens including Bacillus sp., Listeria sp., Staphylococcus sp., Clostridium sp., E. coli etc. in foods and food processing plants/surfaces. Given the ability of these organisms to cause foodborne illness and form resilient biofilms in the food processing ecosystem and their resistance to the conventional method of their elimination, the antimicrobial peptides (bacteriocins) are gaining increasing prominence as useful alternatives to synthetic antimicrobials in enhancing food safety and combating the threats of these pathogens. This review addresses current information on the inhibition of persistent microbial spoilage contaminants, biofilm-forming pathogens, and spore formers of interest to the food industry using LAB and their bacteriocins. Current developments in isolation, characterization, and mode of action of bacteriocins are explored, including synergistic activity with other preservative hurdle techniques such as encapsulation, and nanobiotechnology. Importantly, there is a focus on the utilization of molecular and omics-based approaches to enable a better understanding of bacteriocin biosynthesis, gene regulation, host-microbe interactions and gut microbiome regulation potential of probiotic LABs, permitting the rational development of targeted and strain-specific interventions. Developments in the incorporation of bacteriocin-producing LAB into functional starter cultures and bio-protective products, and challenges in stability, regulatory approval, and scalability for industrial use, are also discussed in the paper. Despite their considerable potential, broader translation remains constrained by regulatory requirements, production and formulation costs, variable efficacy in complex food matrices, and the limited validation of many candidate bacteriocins beyond laboratory and model-food systems. Collectively, these advances position LAB and their bacteriocins at the leading edge of developing sustainable, clean-label, and efficacious functional foods and food preservation systems. Their functionality can be expanded by integrating genomics, synthetic biology, and predictive modeling for the maximization of their biopreservative potential in diverse food matrices and in gut microbiota modulation.

Bioactive Peptides↗