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PubMed2026

Community-driven advances in computational mass spectrometry: The perspective of EuBIC-MS members.

Advances in data acquisition, artificial intelligence, and integrative bioinformatics are driving the rapid evolution of computational mass spectrometry, and in turn, transforming modern proteomics, metabolomics, and lipidomics. These developments have greatly increased the scale and complexity of mass spectrometry data, underscoring the importance of evolving accurate, transparent, efficient and reproducible data processing workflows. Addressing these challenges requires collaborative innovation that brings together expertise in software engineering, statistics, and biology. The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS), an initiative of the European Proteomics Association (EuPA), fosters a culture of open, community-driven development through its biennial Developers Meetings and Winter Schools. This commentary summarizes the scientific background and outcomes of the EuBIC-MS Developers Meeting 2025, which took place in Novacella, Italy. Three keynote presentations highlighted major frontiers in the field: deep proteome and phosphoproteome profiling, text mining for protein-protein interaction extraction, and scalable proteomics for AI-driven drug discovery. Seven community-selected hackathons addressed emerging challenges such as single-cell proteomics data analysis, FAIR metadata extraction, deep learning frameworks, R-Python interoperability, and DIA validation. Together, these efforts demonstrate the potential for scientific and technical innovation to arise from open collaboration, and highlight how community-driven initiatives can accelerate progress in computational mass spectrometry. SIGNIFICANCE: Modern proteomics increasingly depends on computational advances to translate complex, high-dimensional data into biological knowledge. The EuBIC-MS Developers Meeting 2025 exemplifies how community-driven collaboration can directly accelerate this process by bringing together experts from bioinformatics, statistics, and experimental proteomics to co-develop open, interoperable, and reproducible analytical tools. By fostering shared software frameworks, transparent benchmarking, and collaborative problem solving, the EuBIC-MS community helps ensure that technological innovation translates into reliable biological insights. This collaborative model strengthens the foundation for quantitative, system-level understanding of proteomes and establishes a sustainable path for integrating artificial intelligence and next-generation data acquisition into routine biological discovery. This commentary shows some current highlights in the field of computational mass spectrometry and community-based approaches undertaken during the most recent Developers Meeting to solve these challenges. The approaches discussed and initiated during the meeting - ranging from deep proteome profiling and phosphosite mapping to text mining, single-cell data analysis, and FAIR metadata extraction - address key bottlenecks that currently limit the biological interpretability and comparability of proteomics data.

Mass Spectrometry↗
PubMed2006

Contributions of Ernst L. Wynder to chronic disease control worldwide and to preventive medicine.

Ernst L. Wynder is internationally known for his important discoveries in the field of human chronic disease causation, that is the underlying mechanisms, studied in various animal models, as a foundation for recommendations on the prevention of these diseases. These include coronary heart disease, and the main human cancers including cancer of the lung, caused by traditional smoking habits, and the nutritionally linked cancers, namely cancer of the breast, prostate, colon, pancreas, and urinary bladder. Much of this research was performed in a chronic disease prevention institution--created by Dr. Wynder--the American Health Foundation. There were outreach programs to educate people about proper lifestyles to secure disease prevention, including beginning health education in children.

Chronic Disease↗
PubMed2005

Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB.

Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells, which cause bony destruction, are thought to be recruited from normal monocytic pre-osteoclasts by stromal cell expression of the ligand for receptor activator of nuclear factor kappaB (RANKL). This model forms the foundation for clinical trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression profiling, we identified both osteoblast and osteoclast signatures within GCTs, including key regulators of osteoclast differentiation and function such as RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex vivo generation of stromal- and osteoclast-enriched cultures, we unexpectedly found that RANKL mRNA and protein were more highly expressed in osteoclasts than in stromal cells, as determined by expression profiling, flow cytometry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The expression patterns of molecules implicated in signaling between stromal cells and monocytic osteoclast precursors were analyzed in both primary and fractionated GCTs. Finally, using array-based comparative genomic hybridization, neither GCTs nor the derived stromal cells demonstrated significant genomic gains or losses. These data raise questions regarding the role of RANKL in GCTs that may be relevant to the development of molecularly targeted therapeutics for this disease.

Bone Neoplasms↗
PubMed1992

The recognition and management of somatization. What is needed in primary care training.

This article addresses the medical education issues associated with teaching primary care residents about somatization. Specific training designed to recognize and manage somatization involves a hierarchical series of five knowledge domains with associated discrete skills. As a foundation, a biopsychosocial model must be embraced by the medical leadership of the training program. Second, because psychosocial stresses play a critical etiologic role in somatization, the ability to identify relevant psychosocial issues during medical interviewing is a fundamental skill. Third, basic psychiatric diagnostic areas (depression and anxiety) must be mastered as a prerequisite for identifying somatization. Specific interviewing and management techniques are reviewed, along with two current programmatic approaches. Finally, the concept of physician countertransference also must be explicitly addressed as part of the curriculum. Without assuring that these building blocks are in place, residents are likely to become overwhelmed by the management of somatizing patients and continue the pattern of frustration associated with these patients.

Curriculum↗
PubMed1998

Regulatory implications of protein assemblies at the gamma origin of plasmid R6K - a review.

Recognition of the replication origin (ori) by initiator protein is a recurring theme for the regulated initiation of DNA replication in diverse biological systems. The objective of the work reviewed here is to understand the initiation process focusing specifically on the gamma-ori of the antibiotic-resistance plasmid R6K. The control of gamma-ori copy number is determined by both plasmid-encoded and host-encoded factors. The two central regulatory elements of the plasmid are a multifunctional initiator protein pi, and sequence-related DNA target sites, the inverted half-repeats (IRs) and the direct repeats (DRs). The replication activator and inhibitor activities of pi seem to be at least partially distributed between two naturally occurring pi polypeptides (designated by their molecular weights pi35.0 and pi30.5). Regulatory variants of pi with altered states of oligomerization in nucleoprotein complexes with DRs and IRs have been isolated. The properties of these mutants laid the foundation for our model of pi protein activity which proposes that different protein surfaces are required for the formation of functionally distinct complexes of pi with DRs and IRs. These mutants also suggest that pi polypeptides have a modular structure; the C-terminus contains the DNA-binding domain while the N-terminus controls protein oligomerization. Additionally, pi35.0 binds to a novel DNA sequence in the A+T-rich segment of gamma-ori. This binding site is at or near the site from which synthesis of the leading strand begins.

Base Sequence↗
PubMed2006

Calculated phase diagrams for the electrochemical oxidation and reduction of water over Pt(111).

Ab initio density functional theory is used to calculate the electrochemical phase diagram for the oxidation and reduction of water over the Pt(111) surface. Three different schemes proposed in the literature are used to calculate the potential-dependent free energy of hydrogen, water, hydroxyl, and oxygen species adsorbed to the surface. Despite the different foundations for the models and their different complexity, they can be directly related to one another through a systematic Taylor series expansion of the Nernst equation. The simplest model, which includes the potential only as a shift in the chemical potential of the electrons, accounts very well for the thermochemical features determining the phase-diagram.

Journal Article↗
PubMed2002

Development of a preference-weighted health status classification system in France: the Health Utilities Index 3.

The Health Utilities Index is a generic multiattribute preference-based system for assessing health-related quality of life, devised by Torrance et al. It is being used in cost-effectiveness evaluations in North America and in international multicentre studies but was not available in France. Following adaptation of the HUI3 classification in France, the purpose of the reported investigation was to derive French preference weights. This article provides a reminder of the theoretical foundations used to model the multiattribute utility function. Within this framework, a multiattribute multiplicative aggregate utility function was constructed in accordance with the explicitly decomposed approach. The study took place in June 1999 over a sample of 365 persons from the French general population, aged between 20 and 65, and not suffering from any chronic or incapacitating illness. The recruitment procedure was based upon a random selection of individuals, using the phone book. Interviews took place in the homes of the interviewees. The methods of revelation (VAS and SG) were applied by setting the value of the best possible state of the HUI3 a priori at 1, and leaving a choice between two states (worst possible state, death) for 0. The aggregated individuals (person-mean and median) were calculated and the multiplicative utility functions constructed. A comparison of the calculated utilities with the observed ones provides a primary indicator of the validity of the person-mean or median functions constructed. The slight absolute differences obtained between observed and calculated utilities and the low RMSE scores lead us towards a favourable conclusion.

Adult↗
PubMed2002

Analysis of heterosis by a direct method using the concept of heritability.

The presence of heterosis has been observed in many species at both phenotypic and gene levels. Strangely, the genetic basis of heterosis was and still is largely unknown. In this study, we extended and simplified some formulas that we reported previously. The foundation of our model was based on partitioning the F1 phenotypic variance of the cross between two pure lines into additive, dominance and epistasis components, which lead to the estimation of effective factors, crossheritability in the broad and narrow sense and heterotic power. In the model, we assume that all polygenes controlling a quantitative trait have an equal genetic effect and are independent of each other. By extension of the heritability to a cross population, new features appear. The word 'crossheritability' acquires the status of a new genetic parameter that suffices to deal with the problem of crossbreeding and clarifies the picture of heterosis. Lastly, an example of employing the proposed method in analyzing the crossing data from Drosophila melanogaster is given to illustrate its application.

Animals↗
PubMed1997

Effects of ethanol on nonspatial working memory and attention in rats.

Investigation into the neural basis for ethanol-induced cognitive dysfunction requires the use of valid animal models. An operant signal detection procedure was developed to assess simultaneously the processes of sustained attention and working memory in rats, and to determine the effects of ethanol on these cognitive functions. Ethanol, at 0.75 g/kg ip, produced delay- and stimulus length-dependent decreases in choice accuracy, effects that are consistent with deficits in both working memory and sustained attention. Local infusion of ethanol directly into the medial septal area resulted in a selective loss of choice accuracy at the long delay. The impairment by intraseptal ethanol did not interact with stimulus length. Thus, the working memory impairment, but not the decrement in sustained attention, was mimicked by intraseptal ethanol. The current model provides a foundation for studying the neural basis of ethanol's cognitive effects.

Animals↗
PubMed2001

Intraspecific competition favours niche width expansion in Drosophila melanogaster.

Ecologists have proposed that when interspecific competition is reduced, competition within a species becomes a potent evolutionary force leading to rapid diversification. This view reflects the observation that populations invading species-poor communities frequently evolve broader niches. Niche expansion can be associated with an increase in phenotypic variance (known as character release), with the evolution of polymorphisms, or with divergence into many species using distinct resources (adaptive radiation). The relationship between intraspecific competition and diversification is known from theory, and has been used as the foundation for some models of speciation. However, there has been little empirical proof that niches evolve in response to intraspecific competition. To test this hypothesis, I introduced cadmium-intolerant Drosophila melanogaster populations to environments containing both cadmium-free and cadmium-laced resources. Here I show that populations experiencing high competition adapted to cadmium more rapidly than low competition populations. This provides experimental confirmation that competition in a population can drive niche expansion onto new resources for which competition is less severe.

Adaptation, Physiological↗
PubMed2003

Extreme crustal oxygen isotope signatures preserved in coesite in diamond.

The anomalously high and low oxygen isotope values observed in eclogite xenoliths from the upper mantle beneath cratons have been interpreted as indicating that the parent rock of the eclogites experienced alteration on the ancient sea floor. Recognition of this genetic lineage has provided the foundation for a model of the evolution of the continents whereby imbricated slabs of oceanic lithosphere underpin and promote stabilization of early cratons. Early crustal growth is thought to have been enhanced by the addition of slab-derived magmas, leaving an eclogite residuum in the upper mantle beneath the cratons. But the oxygen isotope anomalies observed in eclogite xenoliths are small relative to those in altered ocean-floor basalt and intermediate-stage subduction-zone eclogites, and this has hindered acceptance of the hypothesis that the eclogite xenoliths represent subducted and metamorphosed ocean-floor basalts. We present here the oxygen isotope composition of eclogitic mineral inclusions, analysed in situ in diamonds using an ion microprobe/secondary ion mass spectrometer. The oxygen isotope values of coesite (a polymorph of SiO2) inclusions are substantially higher than previously reported for xenoliths from the subcratonic mantle, but are typical of subduction-zone meta-basalts, and accordingly provide strong support for the link between altered ocean-floor basalts and mantle eclogite xenoliths.

Journal Article↗
PubMed2026

Th2 bias and T-cell exhaustion characterize the immunopathology of non-tuberculous mycobacterial pulmonary disease.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an escalating global health concern with poorly defined immunological mechanisms, necessitating comprehensive profiling to guide therapeutic advances. We analyzed peripheral blood from 28 treatment-naïve NTM-PD patients (19 Mycobacterium avium complex, 9 Mycobacterium abscessus) and 27 matched controls using 42-marker mass cytometry (CyTOF) and Luminex multiplex assays. A random forest model identified predictive markers, while an in vitro murine macrophage model evaluated chemokine production. NTM-PD patients displayed significant immune shifts, including increased classical monocytes (CD14+ CD16-), reduced NKT-like cells (CD3+ CD56+), and elevated T-cell exhaustion markers (PD-1, TOX). This coincided with a Th1/Th2 balance shift characterized by heightened IL-13. Elevated IFN-γ-inducible chemokines CXCL9 and CXCL10 coexisted with this Th2-biased signature, indicating a complex, dysregulated inflammatory state. A model integrating immune-cell frequencies and cytokine profiles achieved robust diagnostic accuracy (AUC = 0.922) with prognostic potential. In vitro, NTM-infected macrophages produced substantial CXCL9 and CXCL10 levels relative to the LPS maximal activation benchmark, identifying them as a major cellular source. These findings propose an immunological framework wherein T-cell exhaustion and a Th2-biased microenvironment strongly correlate with NTM-PD pathogenesis. CXCL9, CXCL10, and IL-13 emerge as candidate therapeutic targets, while our predictive model offers a foundational approach for risk stratification.

Humans↗
PubMed2002

MOET: Bangladesh--an initial experience.

OBJECTIVES: To summarize the quantitative and qualitative immediate assessments of the Managing Obstetric Emergencies and Trauma (MOET) course and to examine the individual changes in score obtained for each of the scenarios. METHODS: Students' knowledge before and after the course was evaluated with a standardized comprehensive questionnaire. RESULTS: All candidates showed an improvement in postcourse, compared to precourse, scores. In the individual score analysis only one scenario showed a non-significant change. The majority of other scenarios showed highly significant improvement between the two scores. CONCLUSION: This paper summarises the development of the first MOET course to be run outside the UK. It demonstrates the reliability of the model-based scenario foundation with a highly significant improvement in knowledge about obstetric emergency management. Further evaluation of longer term practice changes is now required.

Clinical Competence↗
PubMed1999

Ethical foundations of client-centered care in family planning.

Biomedical ethics provides the foundation for a model of client-centered care that can assure the good quality of family planning and other reproductive health services in developed and developing countries. Client concerns mirror the four ethical principles of autonomy, justice, beneficence, and nonmaleficence. Autonomy reflects clients' desire for full information and respect from providers so that they can exercise their right to make their own informed decisions. Justice, for clients, means fair treatment and ready access to services, regardless of one's socioeconomic status, education, ethnic group, or residence. Beneficence means that providers possess the technical competence and understanding needed to act in the best interest of their clients, as clients expect. Nonmaleficence translates into client concerns about safety--that no harm will come to them as a result of seeking services. Putting these ethical principles into practice requires changing providers' attitudes from paternalistic to client centered. Assessments of client satisfaction can help family planning programs identify and respond to client values and even raise client expectations about the care they should receive. Managers also can contribute to good quality care by meeting providers' professional needs for training, supervision, supplies, record keeping, and so on. Family planning programs around the world are focusing on these ethical concerns to emphasize respect for client values, appropriate decision making, broader access to services, and basic safety issues. Although they use a variety of techniques, all these quality assurance and improvement initiatives share an ethically based, client-centered philosophy.

Adult↗
PubMed1997

Molecular and cellular characterization of baboon C-Raf as a target for antiproliferative effects of antisense oligonucleotides.

C-Raf is a an essential member of the growth factor-ras pathway and a target for intervention strategies aimed at blocking cell proliferative responses. Excessive smooth muscle proliferation is considered one cause of the arterial closure in restenosis. Because of the similarity to the human cardiovascular system, a useful current animal model of the disease is a baboon model. As a foundation for animal studies employing antisense oligonucleotides, efforts were made to characterize the molecular and cellular biology of the baboon system. The nucleotide sequence of baboon c-raf cDNA was determined. Antisense phosphorothioate oligonucleotides specific to the 3'-UTR of c-raf mRNA from human and baboon were compared using primary baboon smooth muscle cells in culture. A particular human antisense oligonucleotide, referred to as ISIS 5132, was different by only 2 of 20 bases from the baboon sequence. The corresponding baboon antisense oligonucleotide ISIS 12959, however, was markedly more effective to inhibit c-raf mRNA, protein production, and DNA synthesis, and the results attest to the species specificity of the approach. After antisense treatment, c-raf mRNA levels dropped rapidly, whereas protein levels decreased with a half-life of roughly 24-48 hours, consistent with the antiproliferative effects. The data are discussed with regard to the profile of protein-protein interactions made by C-Raf and with the view that the baboon system closely parallels the human one at the signal transduction level. As this work progressed, a baboon cDNA homolog of a human c-raf-2 pseudogene was isolated, sequenced, and shown to be transcribed into mRNA.

Animals↗
PubMed2001

Expression and localization of luteinizing hormone receptor in the female mouse reproductive tract.

The presence of the LH receptor (LHR) in nongonadal tissues of the reproductive tract has been reported, but localization studies have not been performed. Our objectives were to demonstrate the presence of LHR in the reproductive tract and to localize receptor expression. Reproductive age rats and mice were obtained and (125)I-hCG binding assays were performed on membrane preparations from the uterus, ovary, liver, and testis. In situ hybridizations were performed using (35)S-labeled antisense and sense RNA probes prepared from nucleotides 1-591 of the mouse LHR cDNA. Specific hCG binding was detected in membrane preparations from the ovary, uterus, and testis but not in the liver in both the rat and mouse. In the ovary, LHR mRNA was localized in theca cells, large follicles, and corpora lutea as expected. In the uterus, LHR mRNA was expressed in stromal cells of the endometrium and in the uterine serosa. Uterine smooth muscle cells had low levels of expression, and the endometrial epithelium was negative. In the oviduct, high levels of LHR expression were noted on the serosa and in subepithelial cells. Oviductal smooth muscle had low expression, and the epithelium was negative. We conclude that functional, nongonadal LHR are expressed in the mouse reproductive tract. The presence and localization of LHR expression in the mouse reproductive tract lay the foundation for transgenic models to address the physiologic role of these receptors.

Animals↗
PubMed2004

Stomatal control and hydraulic conductance, with special reference to tall trees.

A better understanding of the mechanistic basis of stomatal control is necessary to understand why modes of stomatal response differ among individual trees, and to improve the theoretical foundation for predictive models and manipulative experiments. Current understanding of the mechanistic basis of stomatal control is reviewed here and discussed in relation to the plant hydraulic system. Analysis focused on: (1) the relative role of hydraulic conductance in the vicinity of the stomatal apparatus versus whole-plant hydraulic conductance; (2) the influence of guard cell inflation characteristics and the mechanical interaction between guard cells and epidermal cells; and (3) the system requirements for moderate versus dramatic reductions in stomatal conductance with increasing evaporation potential. Special consideration was given to the potential effect of changes in hydraulic properties as trees grow taller. Stomatal control of leaf gas exchange is coupled to the entire plant hydraulic system and the basis of this coupling is the interdependence of guard cell water potential and transpiration rate. This hydraulic feedback loop is always present, but its dynamic properties may be altered by growth or cavitation-induced changes in hydraulic conductance, and may vary with genetically related differences in hydraulic conductances. Mechanistic models should include this feedback loop. Plants vary in their ability to control transpiration rate sufficiently to maintain constant leaf water potential. Limited control may be achieved through the hydraulic feedback loop alone, but for tighter control, an additional element linking transpiration rate to guard cell osmotic pressure may be needed.

Models, Biological↗
PubMed1989

Symptomatology of HEMA contact lens wear.

Identification of the determinants of patient symptoms is a requisite for successful patient management in contact lens practice. Symptoms reported by 104 patients wearing hydroxyethyl methacrylate (HEMA) contact lenses, who presented consecutively to a large contact lens clinic, were analyzed. Dryness was reported more frequently than the symptoms scratchy and watery (p less than 0.001). Females using oral contraceptives were more likely to experience the symptoms of scratchiness (p less than 0.01) and dryness (p less than 0.05) than females who were not using oral contraceptives. The symptoms dryness was reported more frequently by patients whose lenses were older than 6 months (p less than 0.05), and those wearing toric lenses (p less than 0.01). These findings will assist practitioners to anticipate those patients who are likely to develop contact lens-related symptoms and lay the foundations for a model of symptomatology during contact lens wear.

Acrylates↗