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Integrated multi-omics analysis and functional experiments reveals PPAP2C as a potential prognostic biomarker and therapeutic target in breast cancer.

BACKGROUND: This study aims to systematically elucidate the clinical significance and biological function of the phospholipid phosphatase (PLPP) family member (PPAP2C) phosphatidic acid phosphatase type 2C in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target. METHODS: Gene expression data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were integrated to characterize the expression profile of PLPP family members, focusing on PPAP2C in breast cancer. The prognostic value of PPAP2C, initially identified at the mRNA level (TCGA, (METABRIC) Molecular Taxonomy of Breast Cancer International Consortium, Gene Expression Omnibus (GEO)), was confirmed at the protein level by immunohistochemistry (IHC) on tissue microarrays (TMA). The oncogenic functions of PPAP2C were investigated in triple-negative breast cancer (TNBC) cells through CRISPR-Cas9-mediated knockout and ectopic overexpression, with assessment of key phenotypes including proliferation, colony formation, migration, and invasion. In vivo validation was subsequently performed using an MDA-MB-231 xenograft model. RESULTS: PPAP2C exhibits the most significant overexpression pattern across 33 cancer types (upregulated in 16 cancers, downregulated in only 3). Compared with normal tissues, PPAP2C showed specific overexpression in breast cancer tissues and was significantly associated with advanced clinical stages and aggressive subtypes (HER2+ and TNBC). Survival analysis demonstrated that high PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, which was further validated in METABRIC and GEO cohorts. Tissue microarray analysis confirmed higher PPAP2C protein positivity in tumor tissues (94.7%) than in adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups. Multivariate analysis identified PPAP2C as an independent prognostic factor for OS. Functional experiments revealed that PPAP2C knockout (via 5-bp/1-bp frameshift mutations) suppressed TNBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these phenotypes. In vivo studies further demonstrated complete tumor regression in MDA-MB-231 xenografts upon PPAP2C knockout. CONCLUSION: This study identifies PPAP2C as a key oncogenic driver and a robust independent prognostic biomarker in breast cancer. The findings provide compelling evidence that PPAP2C represents a promising therapeutic target, offering a new strategic avenue for precision therapy, particularly for aggressive breast cancer subtypes.

PLPP2↗

The pathology of breast cancer and the role of the histopathology laboratory.

Histopathology plays an important part in determining the treatment strategy for women with breast cancer, with the evaluation of breast specimens determining the surgical and the oncological therapeutic options used. The correct approach to specimens requires integration of clinical and imaging findings. This work is not trivial. It is time-consuming and skilled, and requires (and has in place) safeguards and checks in the form of national audit and quality-control schemes. The pathobiology of breast cancer is diverse, and the current taxonomy, rooted in morphological interpretation, has been underscored by molecular observations, such as the relationship of E-cadherin mutations to lobular carcinomas. Investigation of ductal carcinoma of no special type (NST) reveals covert tumour types, such as those with basal or myoepithelial features, whose distinctive features are only now being widely recognised. With the rise of modern molecular techniques, the demise of diagnostic histopathology has been predicted, but, for now and the intermediate future, the histopathologist remains a key element of the integrated breast-care team.

Breast Neoplasms↗

Surgical education and surgical simulation.

The science of virtual reality provides an entirely new opportunity in the area of simulation of surgical skills using computers for training, evaluation, and eventually certification. A taxonomy of the types of simulators is proposed based upon the level of complexity of the task which is being simulated. These tasks are precision placement, simple manipulation, complex manipulation, and integrated procedure. Representative simulators in each category are illustrated and discussed in the context of their contribution to the education and training of a surgeon. The importance of a curriculum is to give content to the role of simulators as another advanced tool for education. Simulators must be integrated into a comprehensive curriculum and not considered as a stand-alone system. The current accomplishments as well as challenges are discussed.

Clinical Competence↗

The iProClass integrated database for protein functional analysis.

Increasingly, scientists have begun to tackle gene functions and other complex regulatory processes by studying organisms at the global scales for various levels of biological organization, ranging from genomes to metabolomes and physiomes. Meanwhile, new bioinformatics methods have been developed for inferring protein function using associative analysis of functional properties to complement the traditional sequence homology-based methods. To fully exploit the value of the high-throughput system biology data and to facilitate protein functional studies requires bioinformatics infrastructures that support both data integration and associative analysis. The iProClass database, designed to serve as a framework for data integration in a distributed networking environment, provides comprehensive descriptions of all proteins, with rich links to over 50 databases of protein family, function, pathway, interaction, modification, structure, genome, ontology, literature, and taxonomy. In particular, the database is organized with PIRSF family classification and maps to other family, function, and structure classification schemes. Coupled with the underlying taxonomic information for complete genomes, the iProClass system (http://pir.georgetown.edu/iproclass/) supports associative studies of protein family, domain, function, and structure. A case study of the phosphoglycerate mutases illustrates a systematic approach for protein family and phylogenetic analysis. Such studies may serve as a basis for further analysis of protein functional evolution, and its relationship to the co-evolution of metabolic pathways, cellular networks, and organisms.

Amino Acid Sequence↗

Development and content validity testing of a comprehensive classification of diagnoses for pediatric nurse practitioners.

Pediatric nurse practitioners (PNPs) need an integrated, comprehensive classification that includes nursing, disease, and developmental diagnoses to effectively describe their practice. No such classification exists. Further, methodologic studies to help evaluate the content validity of any nursing taxonomy are unavailable. A conceptual framework was derived. Then 178 diagnoses from the North American Nursing Diagnosis Association (NANDA) 1986 list, selected diagnoses from the International Classification of Diseases, the Diagnostic and Statistical Manual, Third Revision, and others were selected. This framework identified and listed, with definitions, three domains of diagnoses: Developmental Problems, Diseases, and Daily Living Problems. The diagnoses were ranked using a 4-point scale (4 = highly related to 1 = not related) and were placed into the three domains. The rating scale was assigned by a panel of eight expert pediatric nurses. Diagnoses that were assigned to the Daily Living Problems domain were then sorted into the 11 Functional Health patterns described by Gordon (1987). Reliability was measured using proportions of agreement and Kappas. Content validity of the groups created was measured using indices of content validity and average congruency percentages. The experts used a new method to sort the diagnoses in a new way that decreased overlaps among the domains. The Developmental and Disease domains were judged reliable and valid. The Daily Living domain of nursing diagnoses showed marginally acceptable validity with acceptable reliability. Six Functional Health Patterns were judged reliable and valid, mixed results were determined for four categories, and the Coping/Stress Tolerance category was judged reliable but not valid using either test. There were considerable differences between the panel's, Gordon's (1987), and NANDA's clustering of NANDA diagnoses. This study defines the diagnostic practice of nurses from a holistic, patient-centered perspective. It is the first study to use quantitative methods to test a diagnostic classification system for nursing. The classification model could also be adapted for other nurse specialties.

Humans↗

Plant genome resources at the national center for biotechnology information.

The National Center for Biotechnology Information (NCBI) integrates data from more than 20 biological databases through a flexible search and retrieval system called Entrez. A core Entrez database, Entrez Nucleotide, includes GenBank and is tightly linked to the NCBI Taxonomy database, the Entrez Protein database, and the scientific literature in PubMed. A suite of more specialized databases for genomes, genes, gene families, gene expression, gene variation, and protein domains dovetails with the core databases to make Entrez a powerful system for genomic research. Linked to the full range of Entrez databases is the NCBI Map Viewer, which displays aligned genetic, physical, and sequence maps for eukaryotic genomes including those of many plants. A specialized plant query page allow maps from all plant genomes covered by the Map Viewer to be searched in tandem to produce a display of aligned maps from several species. PlantBLAST searches against the sequences shown in the Map Viewer allow BLAST alignments to be viewed within a genomic context. In addition, precomputed sequence similarities, such as those for proteins offered by BLAST Link, enable fluid navigation from unannotated to annotated sequences, quickening the pace of discovery. NCBI Web pages for plants, such as Plant Genome Central, complete the system by providing centralized access to NCBI's genomic resources as well as links to organism-specific Web pages beyond NCBI.

Biotechnology↗

What will the new genetic information do for us?

The usefulness of new genetic information is frequently assumed, but depends crucially on asking the right research questions. Successful applications of the new knowledge will require effective integration with the ideas, concerns and expectations not only of patients and their families, but also health professionals in primary care. The answers to some of the most exciting questions, concerning new taxonomies of health and disease, are to be found not in teaching hospitals or academic centres, but in the population at large. New types of partnership are required between colleagues in biomedicine, epidemiology, social science and primary care. The greatest challenge, however, is to our social imagination. Can we develop the sustained relationships with families and communities, based on goodwill, mutuality and trust, on which the whole enterprise depends?

Genetic Research↗

Integrating pharmacokinetics knowledge into a drug ontology: as an extension to support pharmacogenomics.

The newly developed U.S. Common Medication Information Infrastructure was used as a basis to capture and formally express the properties of drugs relevant to research and the clinical application of pharmacogenomics. Two associated taxonomies within the model, Mechanism of Action and Physiologic Effect, were enriched to accommodate pharmacogenomic use-cases; the 4,000 active ingredients in the VA NDF-RT drug file were related to the enhanced taxonomies. Pharmacokinetics were independently modeled for pharmacogenomics and tested against thirty-one high-profile drugs to demonstrate our approach.

Databases as Topic↗

Biodiversity informatics.

Biodiversity informatics is an emerging field that applies information management tools to the management and analysis of species-occurrence, taxonomic character, and image data. A wide and growing range of tools is available for both curators and researchers. The development and implementation of formal data exchange standards and query protocols have made it possible to integrate data holdings from collections around the world. The current technological environment is summarized; protocols, standards, and tools for data management, sharing, and integration are reviewed; and methods and tools for analyzing species-occurrence and character data are examined. Direct access to primary data and imagery has the power to transform the means by which taxonomy is practiced and its results disseminated to the general community.

Animals↗

Building man-man-machine synergies: experiences from the Vanderbilt and Geneva clinical information systems.

OBJECTIVES: To demonstrate how a transition to an open hospital information system architecture can help foster stronger collaborations between computer-based clinical tools and the network of care process stakeholders. METHODS: Description of two evolution strategies towards an open, component-based architecture: the vertical decomposition of a monolithic system, and the transversal integration of foundation components such as terminology servers, documentation management, prescription, scheduling, workflow and notification engines. CONCLUSION: The progressive migration of production clinical systems towards a component-based architecture is feasible at a reasonable cost and leads to substantial benefits in terms of user acceptance through participative design and collaborative maintenance of knowledge bases, as well as improved ability to evolve, scale and share individual components. A taxonomy of the components of a health information system and their interactions should be developed to realize the collaborative potential of a marketplace of interoperable components.

Decision Support Systems, Clinical↗

Observations on the somatodendritic morphology and axonal trajectory of intracellularly HRP-labeled efferent neurons located in the deeper layers of the superior colliculus of the cat.

Efferent neurons of the deeper layers of the cat's superior colliculus were stained with horseradish peroxidase (HRP) to demonstrate patterns of somatodendritic morphology and axonal trajectory. A combination of somatodendritic and axonal features of the HRP-labeled cells revealed the existence of three major groups of tectal efferent neurons (X, T, and I). X neurons are mostly large and multipolar and participate in the crossed descending and ipsilateral ventral ascending projections of the superior colliculus. The X group includes multipolar radiating (X1), tufted (X2), large vertical (X3), medium-sized vertical (X4), and medium-sized horizontal (X5) neurons. T neurons participate in one or two of the major tectofugal bundles (medial descending ipsilateral, lateral descending ipsilateral, medial dorsal ascending, crossed descending) besides providing a commissural branch. They also issue recurrent collaterals distributed within a more or less restricted area of the deeper layers. The T group includes medium-sized, trapezoid, radiating (T1) and small or medium-sized, ovoid, vertical (T2) neurons. I neurons participate in the ipsilateral descending projection of the superior colliculus. They are small, triangular or ovoid, sparsely ramified cells that provide long, varicose collaterals irregularly distributed within the deeper layers. The majority of T neurons are located in the ventral stratum opticum or dorsal stratum griseum intermediale; X3 and X5 neurons are situated immediately below in the dorsal stratum griseum intermediale, while X1, X2, X4, and I neurons are indiscriminately distributed within the deeper layers. The polythetic classification presented here provides a conceptual framework for the description of tectal efferent neurons. It is open-ended and can thereby accommodate new cells types as indicated by the disclosure of a small horizontal (A) and a small radiating (unclassified) neuron. Moreover, it does not preclude the construction of alternate taxonomies. A dendro-architectonic classification into four groups [vertical (X3, X4, T2, I), horizontal (X5, A), radiating (X1, T1, I), and tufted (X2)] can be made and would relate to the mode of integration of various tectopetal inputs. A classification based on the dorsoventral location of tectal efferent neurons is also possible and would relate to the dorsoventral distribution of neurons with specific response properties.

Animals↗

A taxonomy of continuing medical education endeavour.

Five basic forms of continuing educational endeavour by physicians are listed in rank order. These components constitute an indivisible unit bound together by self-learning. The scholarly habit of planned daily reading and study in a home library-sanctuary as an integral part of a physician's workday heads the list. Day-to-day informal and formal colleague-association in patient care in the community and teaching hospital, in group practice and by consultation is the present major form of continuing educational endeavour. Emphasized is the sabbatical return every three to five years for three months at least to the teaching hospital to reinforce scholarly motivation and attitudes and to acquire new skills and knowledge. Attendance at scientific sessions of learned professional societies and short courses should be accompanied by presession and post-session guided reading to be undertaken in the physician's home library-sanctuary.

Adult↗

Evaluating models of the personality-psychopathology relationship in children and adolescents.

Connections between personality traits and psychopathology in children and adolescents have frequently been reported in research studies. However, despite the occurrence of significant and systematic relationships between personality and mental disorders in childhood, a thorough understanding of the cause, nature, and implications of these relationships is lacking. In this paper, a comprehensive taxonomy of childhood personality is used to link research on children with that on adults, as well as provide a framework for discussing the personality-psychopathology relationship. Next, research on children and adolescents is integrated into various proposed models of the personality-psychopathology relationship. Finally, clinical implications and future directions are proposed for research on personality and psychopathology in children.

Adolescent↗

Digital and computational morphology in hematology: current platforms, clinical evidence, and future requirements.

INTRODUCTION: Morphologic examination of peripheral blood and bone marrow remains central to the diagnosis and classification of hematologic disorders. Conventional optical microscopy, however, is labor-intensive, dependent on operator expertise, and affected by interobserver variability. Digital morphology has developed from automated image acquisition and cell pre-classification into a broader field that includes whole-slide imaging, remote review, quantitative morphometry, and artificial intelligence-based analysis. CONTENT: This review examines current applications of digital morphology in peripheral blood, bone marrow aspirates, malaria detection, and body-fluid analysis. Commercial platforms are evaluated with particular attention to the distinction between raw automated pre-classification, expert digital post-classification, and comparison with independent optical microscopy. Digital systems generally perform well for common mature leukocyte populations but remain less reliable for rare or diagnostically critical cells, including blasts, abnormal lymphoid cells, plasma cells, and intermediate maturation stages. Research systems increasingly extend analysis from individual-cell classification to whole-slide, specimen-level, and patient-level assessment. SUMMARY: Digital morphology can improve standardization, image traceability, remote consultation, education, proficiency testing, quality assurance, and selected aspects of laboratory workflow. Its clinical value depends on appropriate validation, transparent reporting of reference methods, recognition of algorithm-specific failure modes, and clearly defined criteria for expert review and conventional microscopy. Human expertise remains essential not only for validating results but also for adapting cell taxonomies and interpretive rules to evolving classifications of hematologic diseases. OUTLOOK: Future progress will require representative multicenter datasets, harmonized morphologic terminology, external validation, interoperability with laboratory information systems, and continuous monitoring after software or hardware updates. Integration of morphology with quantitative hematology, flow cytometry, cytogenetics, genomics, and clinical data may support more comprehensive computational diagnosis. Digital platforms may also broaden access to specialist expertise, training, and quality programs in resource-limited institutions and regions, provided that infrastructure, governance, and professional competency are adequately supported.

artificial intelligence↗

[Nursing diagnosis of patients in the intraoperative period of cardiac surgery].

The purpose of this study was to identify nursing diagnoses of patients in the intra-operative period of cardiac surgery. One instrument was elaborated and validated for data collection. Such instrument was organized according to The Theory of Basic Human Needs. Seventeen adult patients in the intra-operative period of cardiac surgery were evaluated, of whom 09 were males and 08 were females with the average of 58 years old. Following data collection, the nursing diagnoses were identified based on NANDA's Taxonomy I. The nursing diagnoses identified with a higher frequency than 50% were: Risk for infection (100%), Risk for fluid volume imbalance (100%), Impaired gas exchange (100%), Risk for aspiration (100%), Altered protection (100%), Impaired skin integrity (100%), Risk for peripheral neurovascular dysfunction (100%), Risk for perioperative positioning injury (100%) and Risk for altered body temperature (94.1%). It was identified a predominance of the diagnoses related to psychobiological needs.

Cardiac Surgical Procedures↗

Computer-based Training in Medicine and Learning Theories.

Computer-based training (CBT) systems can efficiently support modern teaching and learning environments. In this paper, we demonstrate on the basis of the case-based CBT system CAMPUS that current learning theories and design principles (Bloom's Taxonomy and practice fields) are (i) relevant to CBT and (ii) are feasible to implement using computer-based training and adequate learning environments. Not all design principles can be fulfilled by the system alone, the integration of the system in adequate teaching and learning environments therefore is essential. Adequately integrated, CBT programs become valuable means to build or support practice fields for learners that build domain knowledge and problem-solving skills. Learning theories and their design principles can support in designing these systems as well as in assessing their value.

Computer-Assisted Instruction↗

The DSM's theory-neutral nosology is scientifically progressive: response to Follette and Houts (1996).

W. C. Follette and A. C. Houts (1996) argued on philosophy-of-science grounds that the Diagnostic and Statistical Manual of Mental Disorders (DSM) is scientifically unprogressive and should be replaced by competing theory-laden manuals. The author responds to their various arguments as follows: (a) The ways things can go wrong with the mind are inherently diverse, so failure to reduce the DSM's categories to 1 parsimonious theory is not necessarily scientifically unprogressive; (b) it is empirically untrue that growth in the number of a taxonomy's categories is inconsistent with scientific progress; (c) progress in theoretically fragmented fields requires shared theory-neutral categories, not theory-laden definitions of basic concepts; (d) at present in the mental health field, theoretical integration is scientifically more progressive than competition, and integration is promoted by the DSM's theory-neutral nosology; and (e) Follette and Houts's proposed behaviorist alternative to the DSM is incoherent.

Humans↗