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At least 613 records · Page 34Linked to original sources

Knowledge-guided contextual gene set analysis with large language models.

MOTIVATION: Gene set analysis (GSA) is a foundational approach for interpreting genomic data of diseases by linking genes to biological processes. However, conventional GSA methods overlook clinical context of the analyses, often generating long lists of enriched pathways with redundant, nonspecific, or irrelevant results. Interpreting these requires extensive, ad-hoc manual effort, reducing both reliability and reproducibility. RESULTS: We introduce cGSA, a novel AI-driven framework that enhances GSA by incorporating context-aware pathway prioritization. cGSA integrates gene cluster detection, enrichment analysis, and large language models to identify pathways that are not only statistically significant but also biologically meaningful. Benchmarking on 102 curated gene sets across 19 diseases and ten disease-related biological mechanisms shows that cGSA outperforms baseline methods by over 30%, with expert validation confirming its increased precision and interpretability. Two independent case studies in melanoma and breast cancer further demonstrate its potential to uncover context-specific insights and support targeted hypothesis. AVAILABILITY AND IMPLEMENTATION: The demo website is publicly available at https://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/cGSA/, while the data and code can be accessed at https://github.com/ncbi-nlp/cGSA.

Large Language Models↗

Tissue factor pathway vs. collagen pathway for in vivo platelet activation.

The roles that the various platelet collagen receptors play in initial platelet adhesion and thrombus growth remain controversial. Here we summarize some of the pertinent data and discuss some recent studies of the initiation and propagation of platelet accumulation into thrombi and the initiation and propagation of thrombin generation. Mice lacking platelet surface glycoprotein VI (GPVI) form normal thrombi in the laser injury model but have a diminished thrombotic response to severe FeCl3 injury. We hypothesize that the paths to thrombus formation in these two models are different with interaction of GPVI and collagen predominant early after severe FeCl3-induced injury but platelet activation by thrombin predominant after laser-induced injury. Understanding of the response to insult in thrombosis models deepens our understanding of the process and provides a firm foundation for evaluation of anti-thrombotic therapy in these models.

Animals↗

Evaluating treatment process redesign by applying the EFQM Excellence Model.

OBJECTIVE: To evaluate a treatment process redesign programme implementing evidence-based treatment as part of a total quality management in a Dutch addiction treatment centre. METHOD: Quality management was monitored over a period of more than 10 years in an addiction treatment centre with 550 professionals. Changes are evaluated, comparing the scores on the nine criteria of the European Foundation for Quality Management (EFQM) Excellence Model before and after a major redesign of treatment processes and ISO certification. RESULTS: In the course of 10 years, most intake, care, and cure processes were reorganized, the support processes were restructured and ISO certified, 29 evidence-based treatment protocols were developed and implemented, and patient follow-up measuring was established to make clinical outcomes transparent. Comparing the situation before and after the changes shows that the client satisfaction scores are stable, that the evaluation by personnel and society is inconsistent, and that clinical, production, and financial outcomes are positive. The overall EFQM assessment by external assessors in 2004 shows much higher scores on the nine criteria than the assessment in 1994. CONCLUSION: Evidence-based treatment can successfully be implemented in addiction treatment centres through treatment process redesign as part of a total quality management strategy, but not all results are positive.

Clinical Protocols↗

The EFQM excellence model is useful for primary health care teams.

BACKGROUND: Primary care teams are facing an increased need to develop quality programmes at local level. GPs must lead this process and promote a positive organizational culture if they want to achieve and maintain a continuous improvement of the service. OBJECTIVE: The aim of the present study was to test the applicability and reliability of the European Foundation for Quality Management (EFQM) excellence model self-assessment questionnaire in a primary health care organization. METHOD: A cross-sectional study was carried out of the EFQM questionnaire to compare the scores achieved by a primary health care team in Spain caring for 42 000 inhabitants using internal self-assessment with the scores achieved by professional management auditors through an external audit. RESULTS: The scores of each criterion achieved by self-evaluation are similar to or lower than those assessed by the external evaluation. There is agreement in the areas suitable for improvement. CONCLUSIONS: The experience proves the applicability of the EFQM excellence model for primary health care teams and its reliability, at least when the team undergoing self-assessment know they are going to be re-evaluated. There is high concordance in the identification of areas for improvement.

Benchmarking↗

Quality management in German health care--the EFQM Excellence Model.

A brief insight into the issues affecting German health care is given. Namely, upward pressure on costs leads to increasing expenditure within health care and downward pressure from economic recession and political unwillingness to increase taxes and budget spending. In the case of competing key stakeholder perspectives, a quality management framework is seen as a potential approach for addressing these issues. The framework is the European Foundation for Quality Management (EFQM) Excellence Model. The article briefly explains the pilot phase for utilising the EFQM Excellence Model within German health care organisations and the various implementation approaches recommended by EFQM. Specific details of an approach used by a health care organisation within Germany (providing social medicine, geriatric and elderly services) are described in detail. The benefits achieved from using the Model are a clear picture of where the gaps are in the organisation and a clear vision for concentrating future efforts towards total quality management.

Aged↗

Establishment and application of a high throughput model for Rho kinase inhibitors screening based on fluorescence polarization.

Rho kinase (ROCK) inhibitors are effective candidates for neural or cardiovascular disorders. High throughput model for screening ROCK inhibitors is a basic foundation to pick up ROCK inhibitors from thousands of compounds for drug developing. The high throughput model was established based on purified recombinant rat ROCK catalytic domain (rROCK-CD) from Escherichia coli (E. coli). There are two steps of reaction in the model: incubation of 5.0 microl recombinant rROCK-CD (2.0 microg/ml), 5.0 microl different compounds, 5.0 microl fluorescent S6-peptide (200 nM), and 5.0 microl ATP (10 microM) at 37 degrees C for 60 min was made the first reaction, and the second reaction was made by incubating them with additional 60 microl binding reagent at ambient temperature for 30 min. The phosphorylated S6 peptide can bind to a binding reagent, and the fluorescence varies from low polarization to high according to the amount of the phosphorylated peptide. IC50 was calculated based on polarization variation. Compound, which IC50 was less than 10 microM, was recognized as a lead compound which taken bioactivity evaluation in PC12 by observing neurite outgrowth. The Z'-factor of the model is 0.81 (above 0.5). The model screened five lead compounds from 3294, which promoted neurite outgrowth to different extent. The results suggested that the model is suitable for high throughput screening (HTS), and the five lead compounds are worth of further investigation.

Animals↗

Fostering youth leadership to address workplace and community environmental health issues: a university-school-community partnership.

Many communities of color are disproportionately exposed to workplace and community environmental hazards. This article presents the results of a pilot project designed by a university-school-community partnership to develop youth leadership to confront these exposures. Using a popular empowerment education approach, students applied peer education, research, and organizing skills learned in the classroom to community-based internships in a service-learning model. Evaluation results from pretests and posttests, focus groups, and in-depth interviews demonstrated that students shared what they learned about young workers' rights and environmental justice with family and friends. They developed a critical analysis of environmental inequities, created a citywide youth coalition that advocates around legal, educational, and environmental issues affecting youth, and implemented campaigns to enforce child labor laws and to prevent school construction on contaminated land. This multifaceted model can serve as an important foundation to develop youth leaders to influence environmental policies in a variety of communities.

Adolescent↗

On multiscale approaches to three-dimensional modelling of morphogenesis.

In this paper we present the foundation of a unified, object-oriented, three-dimensional biomodelling environment, which allows us to integrate multiple submodels at scales from subcellular to those of tissues and organs. Our current implementation combines a modified discrete model from statistical mechanics, the Cellular Potts Model, with a continuum reaction-diffusion model and a state automaton with well-defined conditions for cell differentiation transitions to model genetic regulation. This environment allows us to rapidly and compactly create computational models of a class of complex-developmental phenomena. To illustrate model development, we simulate a simplified version of the formation of the skeletal pattern in a growing embryonic vertebrate limb.

Animals↗

Neurosurgical practice at Başkent University, Turkey: a new model.

BACKGROUND: The Turkish Organ Transplantation and Burn Foundation was established in 1980. This was followed by the founding of the Turkish Transplantation and Burn Foundation Hospital in 1985. Under the aegis of this foundation and the Haberal Educational Foundation, Baskent University (BU) was founded in 1993 by Professor Mehmet Haberal, general surgeon and pioneer of organ transplantation in Turkey, and the President of the university since then. METHODS AND FINDINGS: The BU Neurosurgery Department began functioning in January of 1995, with the advancement of the department and with contributions from the other hospitals in cities of Adana, Konya and Alanya. Just 13 years after its foundation, BU became one of the most prestigious universities of the country. While establishing new neurosurgery units within BU health care facilities, the neurosurgeons appointed to the new center spend few months in the neurosurgery department at the BU Ankara Hospital, central hospital, at first in order to get acquainted with the BU medical system. After the new neurosurgery unit begins to operate, senior neurosurgeons from Ankara are called to supervise junior colleagues during major surgical procedures. In addition to these exchanges, residents are sent routinely to these centers as part of the neurosurgical residency programme. As the system is very integrated, neurosurgeons from other centers of the BU also routinely come to Ankara Hospital and Research Center for educational purposes. CONCLUSION: BU as a whole and its health system model in particular are certainly unique in Turkey. The statistical data from all hospitals of the BU reveal growing patient demand and consumer satisfaction.

Academic Medical Centers↗

Computer generated track and field scoring tables: III. Model evaluation and analysis.

An investigation is made into the subject of scoring tables for track and field with emphasis on the application of computers to calculate and output the tables. The resulting scoring tables represent an attempt to describe the effective quality of performance for track and field events. This paper is published in three parts. The first part reviewed the historical development of scoring tables. The second part presented a theoretical foundation and the development of a model which could be utilized for all scoring tables. In this final part, the model is evaluated and an analysis of the model validity is made. Sample computer generated scoring tables are included.

Computers↗

Impact of ROS on ageing of two fungal model systems: Saccharomyces cerevisiae and Podospora anserina.

To provide a foundation for the development of effective interventions to counteract various age-related diseases in humans, ageing processes have been extensively studied in various model organisms and systems. However, the mechanisms underlying ageing are still not unravelled in detail in any system including rather simple organisms. In this article, we review some of the molecular mechanisms that were found to affect ageing in two fungal models, the unicellular ascomycete Saccharomyces cerevisiae and the filamentous ascomycete Podospora anserina. A selection of issues like retrograde response, genomic instability, caloric restriction, mtDNA reorganisation and apoptosis is presented and discussed with special emphasis on the role reactive oxygen species (ROS) play in these diverse molecular pathways.

Animals↗

Building an organ-specific carcinogenic database for SAR analyses.

FDA reviewers need a means to rapidly predict organ-specific carcinogenicity to aid in evaluating new chemicals submitted for approval. This research addressed the building of a database to use in developing a predictive model for such an application based on structure-activity relationships (SAR). The Internet availability of the Carcinogenic Potency Database (CPDB) provided a solid foundation on which to base such a model. The addition of molecular structures to the CPDB provided the extra ingredient necessary for SAR analyses. However, the CPDB had to be compressed from a multirecord to a single record per chemical database; multiple records representing each gender, species, route of administration, and organ-specific toxicity had to be summarized into a single record for each study. Multiple studies on a single chemical had to be further reduced based on a hierarchical scheme. Structural cleanup involved removal of all chemicals that would impede the accurate generation of SAR type descriptors from commercial software programs; that is, inorganic chemicals, mixtures, and organometallics were removed. Counterions such as Na, K, sulfates, hydrates, and salts were also removed for structural consistency. Structural modification sometimes resulted in duplicate records that also had to be reduced to a single record based on the hierarchical scheme. The modified database containing 999 chemicals was evaluated for liver-specific carcinogenicity using a variety of analysis techniques. These preliminary analyses all yielded approximately the same results with an overall predictability of about 63%, which was comprised of a sensitivity of about 30% and a specificity of about 77%.

Animals↗

Nonequilibrium capillary electrophoresis of equilibrium mixtures, mathematical model.

We recently introduced a new electrophoretic method, nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM). NECEEM provides a unique way of finding kinetic and equilibrium parameters of the formation of intermolecular complexes from a single electropherogram and allows for the use of weak affinity probes in protein quantitation. In this work, we study theoretical bases of NECEEM by developing a mathematical model for the new method. By solving a system of partial differential equations with diffusion in linear approximation, we found the analytical solution for concentrations of components involved in complex formation as functions of time from the beginning of separation and position in the capillary. The nonnumerical nature of the solution makes it a powerful tool in studying the theoretical foundations of the NECEEM method and modeling experimental results. We demonstrate the use of the model for finding binding parameters of complex formation by nonlinear regression of NECEEM electropherograms obtained experimentally.

DNA↗

Three major models. Before you build your network, consider these legal angles.

Confused about the details of the legal models for integrated delivery systems? You have reason to be. Attorneys structuring the systems say nearly every one is different--shaped by its owners, participants and local environment. Though few generalizations can be made about the structures, three basic models are emerging: a management services organization (MSO), a medical foundation, and a fully integrated entity.

Comprehensive Health Care↗

Clinical governance is "ACE"--using the EFQM excellence model to support baseline assessment.

The introduction of clinical governance in the "new NHS" means that National Health Service (NHS) organisations are now accountable for the quality of the services they provide to their local communities. As part of the implementation of clinical governance in the NHS, Trusts and health authorities had to complete a baseline assessment of their capability and capacity by September 1999. Describes one Trust's approach to developing and implementing its baseline assessment tool, based upon its existing use of the European Foundation for Quality Management (EFQM) Excellence Model. An initial review of the process suggests that the model provides an adaptable framework for the development of a comprehensive and practical assessment tool and that self-assessment ensures ownership of action plans at service level.

Community Health Services↗

Toward a clinical model of psychotherapy for depression, I: Systematic comparison of three psychotherapies.

In a two-part series, the author explores the current status of psychotherapy for depression. In part I, three predominant approaches to the psychological treatment of depressive disorders today--psychodynamic, cognitive, and interpersonal--are described and contrasted schematically. They are depicted as conceptually different but potentially complementary with regard to 1) basic characteristics, including theoretical orientation, major strategies, goals, and mechanisms of change, and 2) respective advantages and limitations. This clinical comparison forms the foundation of an integrative and selective model for the treatment of depression.

Cognitive Behavioral Therapy↗

On a class of integrals of Legendre polynomials with complicated arguments--with applications in electrostatics and biomolecular modeling.

The exact analytical result for a class of integrals involving (associated) Legendre polynomials of complicated argument is presented. The method employed can in principle be generalized to integrals involving other special functions. This class of integrals also proves useful in the electrostatic problems in which dielectric spheres are involved, which is of importance in modeling the dynamics of biological macromolecules. In fact, with this solution, a more robust foundation is laid for the Generalized Born method in modeling the dynamics of biomolecules.

Computer Simulation↗