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At least 73 records · Page 4Linked to original sources
PubMed2026

Proteomics as a theranostic compass in BCR::ABL1-negative myeloproliferative neoplasms: Integrating biomarker discovery with therapeutic stratification.

Classic BCR::ABL1-negative myeloproliferative neoplasms (MPNs)-polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis-are clonal haematopoietic stem cell disorders with marked heterogeneity in clinical phenotype, disease trajectory, and therapeutic response. Genomic stratification by driver and cooperating mutations only partially accounts for this variability, leaving gaps in predicting thrombotic risk, fibrotic progression, leukaemic transformation, and treatment benefit. Proteomics bridges this gap by providing function-proximal readouts of protein abundance, post-translational modifications, pathway activity, and intercellular signalling that genomics and transcriptomics cannot capture, positioning it as a theranostic platform in which the same molecular readouts simultaneously inform diagnostic stratification and therapeutic decision-making. We propose a five-stage translational framework spanning from discovery-scale mass spectrometry and affinity-based plasma profiling to targeted validation, multicentre standardisation, and machine learning-integrated clinical panels. Proteomic evidence is synthesised across the following four disease axes: clonal fitness in haematopoietic stem and progenitor cells; bone marrow microenvironmental remodelling and fibrosis; chronic inflammation and thrombosis; and leukaemic transformation. We further describe how phosphoproteomics reveals resistance mechanisms to JAK inhibitors, including AXL-MAPK bypass and PP2A-autophagy-mediated tolerance, and how protein-level biomarkers (BCL2-BCL-XL, RAS-ERK, CAMK2G, and ROCK1/2) can guide individualised therapeutic selection. Affinity-based platforms (Olink PEA and SomaScan) and spatially resolved technologies (CODEX and single-cell proteomics) complement discovery proteomics. At present, however, this evidence base is constrained by small and heterogeneous cohorts, limited cross-platform reproducibility, and a scarcity of independent external validation for candidate protein panels. Realising this vision will require multicentre standardisation, analytically validated panel assays, and prospective clinical studies that translate molecular findings into decision-grade tools for patients with MPNs.

Humans↗
PubMed2026

A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.

Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities with adult glioma, it comprises distinct disease entities. In this study, we longitudinally profile a molecularly diverse cohort of 16 pHGG patients through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of neoplastic and microenvironmental features during disease progression and treatment. We define a set of core pHGG neoplastic cell states and observe differential tumor-myeloid interactions between malignant cell phenotypes. We find that essential neuromodulators and the interferon response are upregulated post-therapy, implicating them as malignant cell-intrinsic targets. We observe an increase in oligodendrocytes upon progression and that they coordinate spatial motifs with proneural tumor cells. This multiomic atlas of longitudinal pHGG captures features of therapy response and provides a scalable reference for the study of pediatric brain tumors.

Humans↗
PubMed1986

High-performance liquid chromatographic determination of dimethyldithiocarbamate residues in some agricultural products.

Dimethyldithiocarbamates are widely used in agriculture as active fungicides. The degradation of dimethyldithiocarbamates (ferbam, thiram) confirmed the fact that they are not stable and decompose very rapidly. The aim of this work was to apply the results obtained in high-performance liquid chromatographic quantitative analysis of residues of dithiocarbamate fungicides in some agricultural products (strawberries, maize, tobacco). The developed method enables very simple control analysis of low concentrations of dimethyldithiocarbamate residues in very short time. All limits of detection correspond with the criteria of FAO (Codex Alimentarius).

Chromatography, High Pressure Liquid↗
PubMed1992

Food-processing approaches to altering allergenic potential of milk-based formula.

All the major cow milk proteins in their native states are potential allergens in infants with milk allergy. Heat treatment can reduce the antigenicity of whey proteins considerably, but it has virtually no effect on the antigenicity of casein. Infants allergic to milk still react to heat-denatured whey proteins. Therefore heat denaturation alone cannot produce a formula with low allergenicity. Enzyme hydrolysis reduces the antigenicity and allergenicity of protein. Partial hydrolysis produces hydrolysate consisting mainly of large peptides, whereas extensive hydrolysis produces hydrolysate containing a mixture of large and small peptides and free amino acids. Enzyme hydrolysis often produces bitter peptides and destroys the physical functionality of protein. When hydrolysate formula is made, casein or whey protein hydrolysate is ultrafiltered to remove large residual peptides. Certain amino acids are fortified to provide a balanced amino acid profile. The final formulation must comply with the recommendations of the Codex Alimentarius Commission (FAO/WHO) and the U.S. Infant Formula Act to provide adequate infant nutrition. Protein hydrolysate-based formula can be improved by further reducing the residual allergenicity, increasing the small peptide content, and improving the taste.

Food Handling↗
PubMed1975

Organochlorine content of milks, dairy products and animal feed ingredients: Ireland 1971-1972.

Milks (bovine and human) and dairy products (butter, cheese, skim and whey powders, calf-replacer, casein, butter-oil and dietetic food) were collected during 1971/2 throughout Ireland together with a more limited samples of the 10 major animal feed ingredients, and analysed for organochlorine insecticide residues using electron-capture gas chromatography. The different materials contained low or negligible levels of chlorinated insecticides. Apart from some of the animal feed ingredients the DDT residues were generally the predominant contaminants detected together with lower levels of gamma-BHC (lindane), aldrin/dieldrin and heptachlor/heptachlor epoxide. The maximum levels of these insecticides in the bovine milk and dairy products (511, 100, 62 and 21 mug/kg fat respectively) constitute only 50% or less of the Codex Tolerance Limits. The correspondingly low residue levels in the human milk (maxima of 128, 1, 1, and 5 mug/kg fat respectively) which at most represent insecticidal ingestion by infants equivalent to 13, 0-05, 5 and 5% respectively of the WHO/FAO acceptable daily intake for DDE, gamma-BHC, aldrin/dieldrin and heptachlor/heptachlor epoxide again pose no obvious health hazards and are strongly indicative of negligible organochlorine contamination in the general diet. The samples of animal feed ingredients examined also contained trace levels of ogranochlorines (maxima of 0-9, 0-1, 1-6 and 1-0 mug/kg respectively). More extensive monitoring of the residues in animal feed ingredients (the most probable source of milk contamination is advocated, and the desirability of tolerance limits for insecticides in animal feeds discussed.

Aldrin↗
PubMed1979

The use of spore strips for monitoring the sterilization of bottled fluids.

A bacterial spore test has been developed which enables the efficacy of the sterilizing cycle recommended by the British Pharmaceutical Codex (1973) for bottled fluids to be accurately monitored. During a 14-month period this test detected faults in 3.3% of the sterilizing cycles, representing five distinct episodes of sterilization failure that passed unnoticed by the conventional controls of physical measurements and sterility testing. There were no failures of sterilization as detected by conventional techniques which were not indicated by the spore test.

Geobacillus stearothermophilus↗
PubMed2026

Enhancing pan-cancer spatial transcriptomics at single-cell resolution with stPainter.

Subcellular spatial transcriptomics can resolve tissue architecture at cellular scale, but sparse gene panels and limited detection sensitivity constrain downstream analysis. Existing enhancement methods often require tissue-matched single-cell RNA sequencing (scRNA-seq) references and dataset-specific retraining. Here we show that stPainter, a conditional generative model pretrained on a pan-cancer scRNA-seq atlas, can enhance spatial transcriptomics data without matched references or retraining. Using a latent diffusion architecture guided by Stochastic Differential Equations (SDE), stPainter reconstructs expanded expression profiles from sparse measurements and produces latent representations for clustering and cell-state analysis. When we apply stPainter upon 6 spatial transcriptomics datasets of different cancer types, we demonstrate that our model empowers downstream biological analyses, including fine-grained subpopulation clustering and pathway enrichment. Comparison with spatially resolved proteomics (CODEX) provided independent support for regional agreement between imputed cellular compositions and protein-level tissue organization. These results establish stPainter as a scalable approach for analyzing tumor microenvironments without auxiliary sequencing data.

Spatial Transcriptomics↗
PubMed1989

Minerals and trace elements in total diets in The Netherlands.

1. During a period of 2.5 years, every 3 months 221 different food items forming a 'market basket' were purchased, prepared and divided into twenty-three food-commodity groups. The 'market basket' was based on a study of the dietary intake of 18-year-old male, Dutch adolescents. In the (homogenized) food groups various minerals and trace elements were determined. 2. The mean daily amounts of cadmium (21 micrograms), mercury (0.7 micrograms), lead (32 micrograms), tin (0.65 mg), arsenic (38 micrograms) and bromine (8 mg) in the diet of adolescents, as calculated from the concentrations analysed in the food groups, were all (well) below the Food and Agriculture Organization/World Health Organization acceptable daily intake (ADI) value (Codex Alimentarius Commission, 1984). 3. The mean daily amounts of zinc (14 mg) and selenium (72 micrograms) seemed to be adequate compared with the Dutch recommendations, (Voedingsraad (Dutch Nutrition Council) 1986). The amounts of copper (mean value 1.5 mg/d) and iron (mean value 14 mg/d) in the total diet were marginal. Contents of calcium (1340 mg/d), magnesium (433 mg/d) and iodine (402 micrograms/d) were all well above the Dutch recommendations for male adolescents. Sodium intake, corresponding to 11 g sodium chloride/d, was higher than advised. 4. It is concluded that the amounts of As, Br and toxic heavy metals in Dutch total-diet samples of male adolescents are of little concern as regards health aspects. Among the essential trace elements, Fe and Cu contents seem to be marginal. Some concern regarding the salt content is indicated.

Adolescent↗
PubMedDate not supplied

Insecticide residues in commercially-grown quick-maturing carrots.

Commercially-grown quick-maturing carrots which had been treated with insecticides to protect them from damage by carrot fly were analysed for residues of carbofuran (4 samples), disulfoton (17 samples) or phorate (20 samples). Intervals between treatment and harvest ranged from 10 to 35 wk. None of the carbofuran-treated carrots, and only two of the phorate-treated crops, contained greater than 0.1 mg/kg-1. Eleven of those treated with disulfoton contained greater than 0.1 mg/kg-1 but only one exceeded the Codex maximum residue limit of 0.5 mg/kg-1.

Carbofuran↗
PubMed2026

ARCADIA reveals spatially dependent transcriptional programs through integration of scRNA-seq and spatial proteomics.

MOTIVATION: Cellular states are strongly influenced by spatial context, but single-cell RNA sequencing (scRNA-seq) loses information about local tissue organization, while spatial proteomic assays capture limited marker panels that constrain transcriptomic inference. Integrating these modalities can elucidate how spatial niches shape transcriptional programs, yet existing approaches depend on either feature-level correspondence such as gene-protein linkage or cell-level barcode pairing, which is often unavailable. RESULTS: We present ARCADIA (ARchetype-based Clustering and Alignment with Dual Integrative Autoencoders), a generative framework for cross-modal integration that operates without cell barcode pairing and does not assume direct feature-to-feature correspondence. ARCADIA identifies modality-specific archetypes, that is, convex combinations of cells representing extreme phenotypic states, and aligns these anchors across modalities by minimizing the discrepancy between their cell-type composition profiles. The aligned archetypes define a shared coordinate system that anchors dual variational autoencoders (VAEs) trained with cross-modal geometric regularization, preserving archetype structure and spatial neighborhood information while enabling bidirectional translation between modalities. On semi-synthetic CITE-seq data, ARCADIA outperforms existing weak-linkage methods. Applied to independent human tonsil scRNA-seq and CODEX data, ARCADIA reconstructs known tissue architecture and reveals spatially dependent transcriptional programs linking B-cell maturation and T-cell activation or exhaustion to microenvironmental niches. AVAILABILITY AND IMPLEMENTATION: Source code is accessible at https://github.com/azizilab/ARCADIA_public. Reproducibility scripts and data are available at https://github.com/azizilab/arcadia_reproducibility.

Proteomics↗
PubMed2025

Genomic and Immune Landscape of Pancreatic Ductal Adenocarcinoma Associated with Germline Pathogenic Variants in ATM.

PURPOSE: Germline pathogenic variants (PV) in ATM increase the risk of pancreatic ductal adenocarcinoma (PDAC), but the underlying tumor biology of PDAC associated with germline PV in ATM has not been adequately explored. EXPERIMENTAL DESIGN: Whole-genome, whole-exome, and RNA sequencing were performed on PDAC tumors from 25 germline ATM PV carriers diagnosed at Mayo Clinic between 2007 and 2017. Somatic and copy-number alterations, mutational signatures, transcriptomic subtypes, and the immune landscape were evaluated. RESULTS: High-quality whole-exome and whole-genome sequencing were obtained from 21 and 15 tumors, respectively. Biallelic inactivation of ATM was observed in 87%, KRAS PV in 90%, CDKN2A homozygous loss in 60%, and TP53 alterations in <10% of these tumors. A predominant clock-like mutational signature was present in all samples. Whole-transcriptome analysis identified that the aberrantly differentiated endocrine exocrine subtype accounted for 18% of PDAC and was consistently associated with >5-year overall survival. In addition, a 28-gene expression-based signature associated with overall survival was identified and further validated in The Cancer Genome Atlas cohort. Immune landscape analysis through CODEX identified enriched CD4 T-helper cell/tumor interactions and reduced B7H3-high cell/tumor interactions in ATM PV carriers compared with noncarriers. CONCLUSIONS: The observed absence of TP53 PV and enrichment for CDKN2A alterations in ATM tumors, along with differences in the mutational signatures, transcriptomic subtypes and immune landscape, improve our understanding of the mechanistic pathways involved in PDAC development in germline ATM PV carriers and help identify potential targeted therapeutic strategies.

Humans↗
PubMed1989

Irradiation and food processing.

After more than four decades of research and development, food irradiation has been demonstrated to be safe, effective and versatile as a process of food preservation, decontamination or disinfection. Its various applications cover: inhibition of sprouting of root crops; insect disinfestation of stored products, fresh and dried food; shelf-life extension of fresh fruits, vegetables, meat and fish; destruction of parasites and pathogenic micro-organisms in food of animal origin; decontamination of spices and food ingredients, etc. Such applications provide consumers with the increase in variety, volume and value of food. Although regulations on food irradiation in different countries are largely unharmonized, national authorities have shown increasing recognition and acceptance of this technology based on the Codex Standard for Irradiated Foods and its associated Code of Practice. Harmonization of national legislations represents an important prerequisite to international trade in irradiated food. Consumers at large are still not aware of the safety and benefits that food irradiation has to offer. Thus, national and international organizations, food industry, trade associations and consumer unions have important roles to play in introducing this technology based on its scientific values. Public acceptance of food irradiation may be slow at the beginning, but should increase at a faster rate in the foreseeable future when consumers are well informed of the safety and benefits of this technology in comparison with existing ones. Commercial applications of food irradiation has already started in 18 countries at present. The volume of food or ingredients treated on a commercial scale varies from country to country ranging from several tons of spices to hundreds of thousands of tons of grains per annum. With the increasing interest of national authorities and the food industry in applying the process, it is anticipated that some 25 countries will use some 55 commercial facilities to treat different foods on an industrial scale by 1990.

Food Irradiation↗
PubMed1990

New food safety initiatives in the Food and Drug Administration.

Concern over the presence of veterinary drug residues in food has been increasing world wide. Because of this concern the Food and Drug Administration's Center for Veterinary Medicine (CVM) has been involved on an international basis in efforts to develop food safety standards for veterinary drugs. The major thrust of the Codex Committee on Residues of Veterinary Drugs in Foods (CC/RVDF) has been to achieve international agreement on veterinary drugs issues. CVM is an active participant on this committee. The CC/RVDF has established a list of priority veterinary drugs that are, or that have the potential to cause trade problems as the result of public health concerns. Included in this list are anabolic hormones, chloramphenicol, sulfonamides, nitrofurans, nitroimidazoles, somatotropins, benzimidazoles and trypanocides. In the upcoming years, the CC/RVDF will work toward developing international maximum residue levels for these compounds. The evaluation of the toxicity of veterinary drug-bound residues is another area of international concern. In conjunction with the Bureau of Veterinary Medicine, Health and Welfare Canada, CVM is developing guidelines on biological models to demonstrate the safety of veterinary drug-bound residues. In working with veterinary drug regulators from other countries, CVM has new solutions to human food safety problems.

Animals↗
PubMed1976

Some problems concerning the assay of Clostridium chauvoei vaccine in laboratory animals.

The potency test prescribed for Cl. chauvoei vaccines in the British Veterinary Codex requires the complete survival of a group of immunized guinea pigs and death of all unvaccinated controls. Problems arising from the influence of extraneous factors such as animal strain, diet and seasonal variation on the outcome of this test are discussed together with alternative methods that might permit the use of a standard preparation.

Animals↗
PubMedDate not supplied

[Nomenclature of obligate methylotrophs].

The nomenclature of obligate methylotrophs, i. e. bacteria using only reduced monocarbon compounds (methane, methanol, methylamines) as a carbon source, is dicussed. The chronology of naming taxons of methane oxidizing bacteria is presented and the rightfulness of their names is analyzed according to the rules of the International Codex of Bacterial Nomenclature. Such names as Methylomonas and others which are employed while describing various physiological groups of bacteria are used in the nomenclature of obligate methylotrophs, and this may be the source of errors. Therefore, only the genus of methane oxidizing bacteria should be referred to as Methylomonas whereas obligate methanol and methylamine assimilating bacteria should be classed as individual genera. The described species of methane oxidizing bacteria can be included into the genera Methylomonas, Methylococcus, Methylosinus, and Methylocystis. One should avoid such names as Methanomonas margaritae, Methanomonas immobilis, Pseudomonas methanica etc. since they do not possess the nomenclature status. All bacteria that depend obligatorily on the presence of reduced C1-compounds should be included into the family Methylomonadaceae. The taxonomy and nomenclature of facultative methylotrophs must be based on principles accepted for other organotrophic microorganisms as it has been suggested at the II International Symposium on the Growth of Microorganisms on C1-compounds (Pushchino, USSR, 1977).

Methylococcaceae↗
PubMed1992

[Pattern of choice in preparation of attempted suicide by poisoning--with particular reference to changes in the pattern of prescriptions].

This investigation was initiated in 1990 to investigate the choice of preparation in cases of attempted suicide treated in the Emergency Unit in Odense University Hospital during the past decade. The results show that 1) an increase has occurred particularly among young women in the use of analgesics obtainable without prescription (e.g. 13% of young women employed paracetamol as the toxic agent), 2) the number of persons employed dextropropoxyphene did not decrease and 3) a great increase was observed in the number of cases of poisoning with ketobemodoni chloridum. In 1985, several barbiturates were withdrawn from the Danish Medical Codex and this was followed by a decrease in the number of cases of poisoning among women but not among men. At present, approximately 10% of men who poison themselves still employ barbiturates. The number of cases of poisoning with barbiturates in men is thus not reduced but phenobarbital is the preparation of choice. The authors conclude that more attention and care should be paid when prescribing dextropropoxyphene, ketobemodoni chloridum and phenobarbital and the availability of paracetamol without prescription must be debated critically.

Adult↗
PubMed1992

[The original of the "Tratado de Urología" by Francisco Díaz. Lost during the fire of the Monastery of El Escorial in 1671?].

The publication of the Treaty of Urology of Francisco Díaz towards the end of the sixteenth Century, was a milestone in the History of medicine. The originality and precociousness of his doctrine entailed a true revolution in the genesis of medicosurgical literature, considering that the text constitutes an inspired anticipation to the specialization age. Ever since the last century, all historians and annotators of this work have asked themselves whether there was an earlier edition to that of 1588 since the title "Newly printed treaty ..." invites such a inference. So far, every investigation searching for the original or a copy of the first edition have been in vain. This paper, based on documents and old works from the Archive of Protocols in Madrid, Library of the Royal Palace and Library of El Escorial Monastery, reveals certain data until now unpublished on the destiny of most of the copies belonging to the second edition presented and brings into light old references on which account is given that the original "Treaty of Urology" by Francisco Díaz, considered to be a Sixteenth Century Codex was lost in the fire of the El Escorial Monastery in 1671.

Fires↗
PubMed1991

Prospects of expert systems in psychiatric diagnostics.

The paper deals in particular with the theoretical foundations of introducing computer technology and techniques into psychiatric diagnostics. It is done from the aspect of present expert systems of the type FEL-EXPERT, PCE expert, CODEX, etc., as well as from the aspect of a prospect for the future in connection with the development of systems of the so called artificial intelligence.

Expert Systems↗