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A comprehensive transcript index of the human genome generated using microarrays and computational approaches.

BACKGROUND: Computational and microarray-based experimental approaches were used to generate a comprehensive transcript index for the human genome. Oligonucleotide probes designed from approximately 50,000 known and predicted transcript sequences from the human genome were used to survey transcription from a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further, expression activity over at least six conditions was more generally assessed using genomic tiling arrays consisting of probes tiled through a repeat-masked version of the genomic sequence making up chromosomes 20 and 22. RESULTS: The combination of microarray data with extensive genome annotations resulted in a set of 28,456 experimentally supported transcripts. This set of high-confidence transcripts represents the first experimentally driven annotation of the human genome. In addition, the results from genomic tiling suggest that a large amount of transcription exists outside of annotated regions of the genome and serves as an example of how this activity could be measured on a genome-wide scale. CONCLUSIONS: These data represent one of the most comprehensive assessments of transcriptional activity in the human genome and provide an atlas of human gene expression over a unique set of gene predictions. Before the annotation of the human genome is considered complete, however, the previously unannotated transcriptional activity throughout the genome must be fully characterized.

Chromosomes, Human, Pair 20↗

Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae.

BACKGROUND: The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference. RESULTS: We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae, as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID (http://www.thebiogrid.org) and SGD (http://www.yeastgenome.org/) databases. CONCLUSION: Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks.

Computational Biology↗

Decoding the PTTG family's contribution to LUAD pathogenesis: a comprehensive study on expression, epigenetics, and therapeutic interventions.

BACKGROUND: Lung adenocarcinoma (LUAD) stands as a prevalent malignancy, yet its pathology remains incompletely comprehended. METHODS: In this comprehensive study, we explored the roles of the pituitary tumor-transforming gene (PTTG) family, including PTTG1, PTTG2, and the pseudogene PTTG3P in lung adenocarcinoma (LUAD). Employing a multi-faceted approach, we conducted in-depth analyses using clinical samples and expression datasets. RESULTS: Our findings revealed a significant up-regulation of PTTG family genes in LUAD cell lines and tissue samples compared to adjacent normal controls, suggesting their potential as diagnostic biomarkers. Through promoter methylation and mutational analyses, we uncovered regulatory mechanisms influencing PTTG gene expression. The exploration of the PTTG family's impact on LUAD patient survival demonstrated their association with adverse outcomes, emphasizing their potential prognostic relevance. Moreover, functional assays demonstrated that the knockdown of PTTG1 and PTTG2 genes resulted in the reduction of cell proliferation, colony formation, and cell migration abilities in A549 and H1975 LUAD cells. Furthermore, our investigation extended to therapeutic avenues, where we identified Calcitriol as a potential drug within the DrugBank database to down-regulate PTTG genes. Molecular docking analyses provided insights into the strong interaction between Calcitriol and PTTG1/PTTG2 proteins, laying the groundwork for further exploration of Calcitriol in LUAD treatment. CONCLUSION: In conclusion, this study contributes a comprehensive understanding of the PTTG family's involvement in LUAD, shedding light on their diagnostic, prognostic, and therapeutic implications.

Humans↗

A comprehensive overview of monkeypox virus disease.

BACKGROUND: Monkeypox (mpox), caused by monkeypox virus (MPXV), re-emerged as a major global public health concern in 2022, resulting in widespread transmission beyond traditionally endemic regions. As of March 2026, 181,164 confirmed cases and 492 deaths had been reported across 144 countries globally. The unprecedented geographic spread of the outbreak highlighted important knowledge gaps in disease surveillance, prevention, and control. Given the ongoing global circulation of MPXV and the risk of future outbreaks, this review provides a comprehensive synthesis of current evidence on MPXV and mpox. METHODS: The literature, surveillance data, and public health reports available up to March 2026 were systematically reviewed and synthesized. The review comprehensively assesses viral biology, genetic diversity, epidemiology, transmission dynamics, clinical manifestations, pathogenesis, laboratory diagnosis, infection during pregnancy, host immune responses, immune evasion mechanisms, therapeutic interventions, and prevention strategies. FINDINGS AND CONCLUSIONS: Globally, the decline in public immunity following the cessation of routine smallpox vaccination, together with ongoing viral evolution, may have contributed to the resurgence of mpox. Advances in genomic surveillance, diagnostics, and public health preparedness have strengthened outbreak response; however, important gaps remain in understanding long-term immunity and optimal treatment strategies. This review summarizes current evidence on MPXV and mpox and highlights priorities for future research and public health interventions.

Antiviral therapy↗

Continuing education: Comprehensive menopausal assessment: an approach to managing vasomotor and urogenital symptoms in breast cancer survivors.

PURPOSE/OBJECTIVES: To describe the development and implementation of a comprehensive menopausal assessment (CMA) and intervention program for women with a history of breast cancer. DATA SOURCES: Published articles selected from computerized databases, conference proceedings, bibliographies of pertinent articles and books, and lay publications. DATA SYNTHESIS: The CMA program consisted of a structured, comprehensive assessment of three symptoms (hot flashes, vaginal dryness, and stress urinary incontinence) and an individualized plan of education, counseling, nonestrogen treatments, psychosocial support, referrals, and follow-up. CONCLUSIONS: A structured approach to evaluating and managing vasomotor and urogenital symptoms with, for example, the CMA, may help breast cancer survivors with severe symptoms more effectively manage these symptoms than "usual care." IMPLICATIONS FOR NURSING: Nurses providing care for women with a history of breast cancer can incorporate the key elements of the CMA program into their practice to facilitate more effective management of three common menopausal symptoms that often are undertreated in this patient population.

Administration, Topical↗

Comprehension of affective prosody in multiple sclerosis.

Deficits in cognition have been repeatedly documented in patients with multiple sclerosis (MS), but their ability to comprehend emotional information has received little study. Forty-seven patients with MS and 19 demographic controls received the comprehension portion of the Aprosodia Battery, which is known to be sensitive to the impairments of patients with strokes and other neurological conditions. Patients also received tests of hearing, verbal comprehension and naming, a short cognitive battery, and the Beck Depression Inventory. Patients with MS were impaired in identifying emotional states from prosodic cues. The magnitude of the deficits was greatest for patients with severe physical disability and under test conditions of limited prosodic information. Correlational analyses suggested that the patients' difficulties in comprehending affective prosodic information were not secondary to hearing loss, aphasic deficits, cognitive impairment, or depression. For some patients with MS, deficits in comprehending emotional information may contribute to their difficulties in maintaining effective social interactions.

Adjuvants, Immunologic↗

Failure of a binaural comprehension deficit to select responders to earplug use in schizophrenia.

Previous studies have suggested that on the Auditory Comprehension Test, a significant proportion of schizophrenics demonstrate a binaural comprehension deficit. To test whether wearing an earplug in their more poorly performing ear would be beneficial, we studied 34 in-patient schizophrenics and noted a binaural deficit in 12 (35%). Of these, eight patients subsequently wore an earplug in each ear for at least one week. We found no effect of the earplug on psychopathology.

Adult↗

A comprehensive classification system for lipids.

Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, "lipidomics," in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; consequently, lipid biology has become a major research target of the postgenomic revolution and systems biology. To facilitate international communication about lipids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by our lipid community. As an initial step in this development, we divide lipids into eight categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures of individual lipids and their derivatives, and provide a 12 digit identifier for each unique lipid molecule. The lipid classification scheme is chemically based and driven by the distinct hydrophobic and hydrophilic elements that compose the lipid. This structured vocabulary will facilitate the systematization of lipid biology and enable the cataloging of lipids and their properties in a way that is compatible with other macromolecular databases.

Database Management Systems↗

Comprehensive molecular diagnosis of mitochondrial disorders: qualitative and quantitative approach.

Mitochondrial disorders can be caused by mutations in nuclear or mitochondrial encoded genes. Point mutations and large deletions in mitochondrial DNA (mtDNA) are responsible for a small portion of the molecular defects in the mitochondrial oxidative phosphorylation system. A significant number of molecular defects of respiratory chain disorders are probably due to mutations in nuclear genes. Molecular diagnosis of mitochondrial disorders has been difficult because of broad genetic and clinical heterogeneity. Mutational analysis of common point mutations of mtDNA such as A3243G, A8344G, and T8993G/C is routinely performed. However, many patients who clearly have clinical manifestations and muscle pathology consistent with oxidative phosphorylation deficiency do not have detectable common mtDNA point mutations. A more comprehensive mutation screening method, temporal temperature gradient gel electrophoresis, was used to scan for unknown mutations in the entire mitochondrial genome. Novel mutations have been discovered but only account for a small portion of patients with suspected mitochondrial RC disorders. Real-time quantitative PCR analysis was used to measure cellular mtDNA content. Abnormal levels of mtDNA were found in many patients with respiratory chain disorders. Molecular analysis revealed that mutations in the thymidine phosphorylase gene are not seen in young patients with severe mtDNA depletion who do not demonstrate clinical features of mitochondrial neurogastrointestinal encephalomyopathy. It was also noted that an increase in the size or number of mitochondria was not necessarily associated with an increase in mtDNA content. On the contrary, in some cases the mtDNA was depleted. Respiratory activity in patients with a defective mitochondrial genome due to either point mutations or deletions may be compensated by amplification of mtDNA. Therefore, a comprehensive molecular analysis of mitochondrial respiratory chain disorders should include qualitative identification of the mutation and quantitative measurement of both the degree of mutant heteroplasmy and the total amount of mtDNA.

DNA Mutational Analysis↗

A comparative assessment of home versus hospital comprehensive treatment for advanced cancer patients.

A prospective comparative analysis of home and hospital comprehensive treatment for advanced non-ambulatory cancer patients was conducted. Patients were assigned to hospital (group A) and home (group B) treatment groups based on geographic location. Home treatment was provided by the Don Monti Home Oncology Medical Extension (HOME) program. A multidisciplinary health team, including an oncologist, oncology nurse, social worker, dietitian, and medical technologist, was transported to the home in a medically equipped van. Services included physical examinations, pain control, psychosocial interventions, chemotherapy and blood transfusions, nutrition consultation, and bereavement counseling. One hundred seventy-four patients were treated at home and 44 in the hospital. Pretreatment characteristics were similar for both groups, with the exception that age under 50 years was more frequent in the hospital group, and home patients were more likely to have gastrointestinal (GI) cancer. Medical benefits for home treatment included decreased narcotic analgesic requirements, decreased hospitalization and length of stay, and improved measurements of fat stores for female patients. Improved survival for home patients was related to Karnofsky performance status, since there was no difference in survival for sicker patients with lower performance status whether they received home or hospital treatment. Patient and family acceptance of home treatment was excellent. Comprehensive home treatment provided by a multispecialty oncology team is an effective alternative to hospitalization for terminal cancer patients.

Analgesics↗

A comprehensive multiattribute system for classifying the health status of survivors of childhood cancer.

PURPOSE: A multiattribute health status classification system was devised to describe comprehensively the health status of survivors of childhood cancer. METHODS: The system consists of seven attributes: sensation, mobility, emotion, cognition, self-care, pain, and fertility. Three to five levels of functioning are defined for each attribute. Any specific combination of seven attribute levels constitutes a health state. In the first survey, the system was used to classify the health status of 20 children currently undergoing therapy for high-risk acute lymphoblastic leukemia (ALL), Wilms' tumor, or neuroblastoma, and eight who had completed treatment. A second survey consisted of 13 children with brain tumors on active treatment. RESULTS: In general, independent ratings by clinicians were in agreement, and consensus was readily achieved in 1 to 2 minutes per patient. Children on therapy experienced a higher burden of morbidity than those off treatment. Brain tumor patients experienced more morbidity than patients in the first survey. CONCLUSION: The multiattribute system provides a compact but comprehensive tool for long-term follow-up of survivors of childhood cancer. It captures both multiple sequelae and varying levels of severity. By using a mathematical utility function, a single summary score of health-related quality of life may be assigned to each health state. Additional studies to establish reproducibility, validity, responsiveness, and generalizability are indicated.

Activities of Daily Living↗

Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care.

PURPOSE: To assess the clinical toxicity and outcome associated with a comprehensive supportive care approach in poor-risk breast cancer (BrCA) patients with high-dose chemotherapy (HDC). PATIENTS AND METHODS: One hundred twenty-five consecutive patients with stages II, III or metastatic breast cancer received HDC between February 1992 and June 1994. Recipients received 4 days of continuous infusion of cyclophosphamide 1.5 g/m2/d, thiotepa 125 mg/m2/d, and carboplatin 200 mg/m2/d followed by infusion of bone marrow or peripheral-blood stem cells (PBSC) and recombinant human growth factor (rhu-GF) support. Patients received similar supportive care that included administration of prophylactic antibiotics, management of neutropenic fevers, and transfusion support. RESULTS: There were 38 women with stage II or III (27 patients with > or = 10 lymph nodes), four with stage IIIB, and 83 with metastatic breast cancer. The median age was 44 years (range, 27 to 61). Grade II or greater nonhematologic toxicities included diarrhea (66%), stomatitis (33%), hepatic venoocclusive disease (VOD) (5%), and pulmonary toxicity (4%). Myeloid and platelet engraftment was comparable between bone marrow and PBSC recipients (P > .1). Infectious complications were rare and consisted of gram-negative bacteremia (1.6%), gram-positive bacteremia (1.6%), fungemia (1.6%), and documented or suspected aspergillosis infection (3%). There was one treatment-related death secondary to severe VOD. CONCLUSION: A comprehensive supportive care approach was associated with a low treatment-related mortality rate of less than 1%. With the observed reduction in treatment-related mortality, it is reasonable to evaluate the efficacy of HDC in women with less than 10 positive nodes and stage II disease in well-designed clinical trials.

Actuarial Analysis↗

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Adult↗

Understanding multiple personality with the Comprehensive Rorschach system.

Exner's Comprehensive Rorschach system is utilized in studying a unique sample of patients--three multiple personalities. Each patient and a number of secondary personalities are tested. Several interpretative and technical aspects of Exner's system are clarified. All of the main personalities are ambient, extending Exner's conclusions regarding the implications of this style. The secondary personalities have personality structures which are remarkably different from those of the main personalities. Differences from previous studies are attributed to unique administrative features of the Comprehensive system.

Adolescent↗

Toward a conceptual understanding of the deviant response in the Comprehensive Rorschach System.

We examined the scoring criteria, subtypes, and interpretative nuances of the deviant response (DR) special score of the Comprehensive Rorschach System. To augment the usual understanding of the DR score, we review the concepts of fabulizing and confabulation in Rorschach literature and discuss the traditional meaning of and the confusion surrounding these terms. By equating a subtype of DR, the excessively embellished DR response, with Rapaport's (Rapaport, Gill, & Schafer, 1968) "affect-laden fantasy" type of confabulation response, we set the stage for an examination of the unique clinical diagnostic implications of this special subtype of DR. We conclude by recommending slight modifications to some of the special scores categories (DR in particular) of the Comprehensive System so that these scores can not only be assigned with more internal consistency and precision but also become more useful in identifying a broader range of unusual Rorschach responses.

Borderline Personality Disorder↗

Exploring possible ethnic differences and bias in the Rorschach Comprehensive System.

In this study I conducted a series of analyses to explore potential ethnic bias in Rorschach Comprehensive System variables using a consecutive series of 432 patients evaluated in 1 setting. The simple association between 188 scores and ethnicity revealed no significant findings after matching on several salient demographic variables. Next, 17 analyses of convergent validity found no evidence for differential validity and no evidence for slope bias. For 13 analyses, there was also no evidence for intercept bias. However, with 4 variables predicting psychotic disorders, regression lines favored minorities and worked against European Americans. These findings are the opposite of what should be seen if the Rorschach was biased against minorities and most likely emerged for statistical reasons related to unmeasured confounds. Finally, principal components analyses revealed no evidence of ethnic bias in the Rorschach's internal structure. Although these findings need to be replicated, the available data support using the Comprehensive System across ethnic groups.

Adult↗

Comprehension of televised stories by preschool children with ADHD.

Investigated visual attention to and story comprehension of televised stories in 4- to 6-year-old children with attention deficit hyperactivity disorder (ADHD) and comparison children. Half of the children in each group watched the program with toys in the room, and the other half watched without toys. Visual attention to the television was recorded, and story comprehension was assessed by performance on cued recall questions. All children attended significantly less when toys were present, but the difference when toys were present was greater for children with ADHD. The groups did not differ on recall of factual information when toys were absent. When toys were present, the comparison children showed no decrement in performance on factual questions, whereas the performance of children with ADHD was significantly worse. On questions testing causal connections, the children with ADHD performed more poorly than comparison children regardless of whether toys were present. Implications of these results for understanding and treating the academic and social difficulties of children with ADHD are discussed.

Attention↗

Story comprehension and the impact of studying on recall in children with attention deficit hyperactivity disorder.

This study examined the impact of studying on story comprehension and recall among children with attention deficit hyperactivity disorder (ADHD). Participants in the study were 36 children with ADHD and 43 nonreferred comparison children ages 7 to 11. The participants listened to 1 of 2 folktales and recalled the story both before and after studying a written version of the story for up to 10 min. The stories had been divided into individual events, and each event was coded for the number of causal connections it had to other story events. Each event was presented on a separate page of the study booklet so that time spent on each event could be recorded. All of the transcribed recalls were coded for which story events the participant correctly recalled. For both groups, recall increased as the number of causal connections increased, but the effect of the number of causal connections on recall was stronger for comparison children than for children with ADHD. The results revealed no group differences in studying behavior. However, when recall before studying was included as a predictor of recall after studying, studying was found to be more effective for higher IQ comparison children than for higher IQ children with ADHD, especially at the highest levels of causal connections. The results offer important leads for the development of academic interventions that are specific to the story-comprehension deficits of children with ADHD.

Attention Deficit Disorder with Hyperactivity↗