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Semantics affect the planning but not control of grasping.

The semantic meaning of a word label printed on an object can have significant effects on the kinematics of reaching and grasping movements directed towards that object. Here, we examined how the semantics of word labels might differentially affect the planning and control stages of grasping. Subjects were presented with objects on which were printed either the word "LARGE" or "SMALL." When the grip aperture in the two conditions was compared, an effect of the words was found early in the reach, but this effect declined continuously as the hand approached the target. This continuously decreasing effect is consistent with a planning/control model of action, in which cognitive and perceptual variables affect how actions are planned but not how they are monitored and controlled on-line. The functional and neurological bases of semantic effects on planning and control are discussed.

Hand Strength↗

[Aphasia: debates].

Quarrels over aphasia are no recent phenomena and have not always been explicit. Lordat and Gall can be cited in this respect as well as Dax and Bouillaud. Reference is also made to Broca-Dax and Trousseau-Lordat. The creation of the Chair in honour of Charcot, which contributed so greatly (thanks to Charcot himself, the others Masters and their students) to the birth of neurology, then to that of the neurological sciences and eventually to that of the neurocognitive sciences. Next, the most explicit of quarrels on aphasia is dealt with, namely that in which, during three meetings of the French Society of Neurology in 1908, Joseph Jules Dejerine and Pierre Marie crossed swords. Their duel in the Bois de Boulogne in 1893 having fortunately been cancelled, it was in 1908 merely a battle of words. Fulgence Raymond was soon to retire. Dejerine and Pierre Marie each put forward their proposal to the Society for a discussion program and Dejerine's was accepted following a vote. The meeting on 11th June, in accordance with the program proposed by Dejerine, was largely restricted to clinical facts. Fulgence Raymond was not present. Dejerine always spoke first, but some of the replies from Pierre Marie received a degree of approval from the audience. It was during this meeting that Achille Souques, the future founder of the history of neurology, cleverly defended the ideas of Pierre Marie. A little later, Dejerine went on the defensive and agreed to a change in the program along the lines suggested by Pierre Marie: he then presented his ideas on the manifest clinical difference between Broca's aphasia and that of Wernicke. After Souques, Edouard Brissaud also came to the rescue of Pierre Marie by mentioning the Leborgne case published by Broca in the spring 1861. Matters were unresolved and André-Thomas, the future founder of neuropaediatrics, produced a highly intelligent deference of his Master Dejerine. Gilbert Ballet and Ernest Dupré also came down largely on his side. The meeting of 9th July (27th anniversary of the Charcot Chair) was dedicated to cerebral anatomy and the "quadrilateral". The subject of Dejerine's questionnaire was again raised. Accompanied by Georges Guillain, Fulgence Raymond was present on this occasion (but refrained from speaking). This time the star was Augusta Dejerine Klumpke, born on a Spanish sand dune now known as San Francisco, U.S.A. Mrs Dejerine contested the "lenticular zone" and gave it a quite different dimension by proving that its anterodorsal part included associative axons originating in or projecting to Broca's area, the remainder of the "Pierre Marie quadrilateral" being called into question. Brissaud was impressed by the performance of Madame Dejerine, and Pierre Marie found himself in an awkward position. His student François Moutier, present at his request, discussed his own clinical cases and then, on the subject of "Lelong's" brain' (autumn 1861), let it be known that Broca had scratched it with his finger nails while removing the meninges. André-Thomas and Georges Guillain took part in the discussion. At the last meeting, on 23rd July, Brissaud was absent. Fulgence Raymond was again present but remained silent. The only subject on the agenda was "physiological pathology", but several points that had not been resolved on the 9th July were brought up again. On this occasion, Pierre Marie opened the debate and adopted a very cautious approach. However, his patience eventually ran out and he replied sharply to the comments of Dejerine on "images of language" and those of Dupré on "mental representations". Metaphorically speaking, it might be said that the gold medal was not awarded, Augusta Dejerine Klumpke took the silver, Dupré and André-Thomas shared the bronze, and Souques and Moutier each deserved a special mention. It might also be suggested that in 1908 the Society sketched out to a large extent the programme for research on aphasia for the century to come. (ABSTRACT TRUNCATE

Aphasia↗

Extending traditional query-based integration approaches for functional characterization of post-genomic data.

MOTIVATION: To identify and characterize regions of functional interest in genomic sequence requires full, flexible query access to an integrated, up-to-date view of all related information, irrespective of where it is stored (within an organization or across the Internet) and its format (traditional database, flat file, web site, results of runtime analysis). Wide-ranging multi-source queries often return unmanageably large result sets, requiring non-traditional approaches to exclude extraneous data. RESULTS: Target Informatics Net (TINet) is a readily extensible data integration system developed at GlaxoSmith- Kline (GSK), based on the Object-Protocol Model (OPM) multidatabase middleware system of Gene Logic Inc. Data sources currently integrated include: the Mouse Genome Database (MGD) and Gene Expression Database (GXD), GenBank, SwissProt, PubMed, GeneCards, the results of runtime BLAST and PROSITE searches, and GSK proprietary relational databases. Special-purpose class methods used to filter and augment query results include regular expression pattern-matching over BLAST HSP alignments and retrieving partial sequences derived from primary structure annotations. All data sources and methods are accessible through an SQL-like query language or a GUI, so that when new investigations arise no additional programming beyond query specification is required. The power and flexibility of this approach are illustrated in such integrated queries as: (1) 'find homologs in genomic sequence to all novel genes cloned and reported in the scientific literature within the past three months that are linked to the MeSH term 'neoplasms"; (2) 'using a neuropeptide precursor query sequence, return only HSPs where the target genomic sequences conserve the G[KR][KR] motif at the appropriate points in the HSP alignment'; and (3) 'of the human genomic sequences annotated with exon boundaries in GenBank, return only those with valid putative donor/acceptor sites and start/stop codons'.

Animals↗

Post-translational modification of proteins in the human testis development pathway.

BACKGROUND: The foetal testes produce the androgens necessary to masculinise the developing embryo and support the maturation of germ cells, that will eventually develop into sperm, thus ensuring future reproductive capacity. The testes develop from the bi-potential gonads in a highly orchestrated process resulting in the differentiation of a complex tissue with multiple cellular lineages. While recent transcriptomic and chromatin-based analyses of human foetal testes have provided an unprecedented level of insight into signalling pathways activated during this process, proteomic studies of the human foetal gonads remain limited. Proteins are active molecules and post-translational modification (PTM) of proteins influences protein activity, stability and localisation. Studies have shown that PTMs regulate critical proteins in testis development, and their disruptions are implicated in congenital disorders including differences of sex development (DSD), in which sex development is atypical. Despite this, the role and regulation of protein PTM during human testis development remains poorly understood due to limited access to human foetal gonadal tissue, a paucity of large-scale proteomics studies, and a lack of robust of human gonad in vitro models. OBJECTIVE AND RATIONALE: This review aims to provide a comprehensive analysis of validated PTMs affecting proteins critical for testicular development. We discuss PTMs with evidence for a role in normal testis development, and highlight those disrupted in DSD. We review emerging techniques, including proteomic technologies and organ modelling systems that may advance our understanding of PTMs in foetal testis development. We discuss challenges that have restricted the application of these technologies and how overcoming these will significantly improve our understanding of testis development and disease, diagnostics and patient outcomes. SEARCH METHODS: We searched PubMed and the University of Melbourne library for peer-reviewed English-language studies using keywords such as phosphorylation, SUMOylation, acetylation, ubiquitination alongside each protein of interest. PTM sites in proteins involved in testis development were identified using the PhosphoSitePlus database focusing those confirmed in in vitro or animal model studies. ClinVar and the Human Gene Mutation Database were used to identify patient variants that may disrupt PTM sites. OUTCOMES: Our review finds that proteins required for human foetal testis development are subject to extensive PTM. Several PTM sites and PTM-mediated pathways [e.g. MAPK (mitogen-activated protein kinase) pathway] are disrupted in patients with DSD or related conditions. While recent advances in proteomics technologies hold considerable promise, their application to human foetal gonads has been constrained by technical, ethical, and logistical challenges. Encouragingly, emerging high-sensitivity and low-input technologies, alongside stem cell-based approaches, offer viable pathways to overcoming these barriers. WIDER IMPLICATIONS: The relationship between gene regulation, protein expression, and cellular outcome is inherently non-linear, shaped by additional regulatory layers-most notably PTMs. The contribution of PTMs to human testis development in both typical and atypical contexts is a major knowledge gap. Addressing this gap has broad clinical and biological relevance: it may help improve genetic diagnosis or shed light on how proteins or pathways critical for testis development respond to environmental signals-an increasingly pressing question as declining global fertility rates bring testicular function under greater scrutiny. REGISTRATION NUMBER: N/A.

Humans↗

Somatization reconsidered: incorporating the patient's experience of illness.

The large and heterogeneous group of patients with "unexplained somatic symptoms," with or without coexisting psychiatric, "functional," or "organic" illnesses, provides continuing difficulty for clinicians. The construct of somatization artificially separates bodily and psychological symptoms that patients experience as a unified whole. Concurrent chronic illnesses make it difficult to exclude "general medical conditions." The diagnosis requires that the patient seek medical care. Conflict between patients' experiences of illness and physicians' diagnostic categories, and fear of blaming the patient, complicate naming and characterizing the illness. We recommend an approach to clinical care that involves exploring the patient's life context, finding mutually meaningful language to arrive at a name for the illness, normalizing the patient's bodily experience of distress, using a chronic disease model that attends to functioning, and addressing the physician's need for certainty and efficacy. Health systems can help coordinate care and avoid iatrogenic harm by appropriately controlling access to medical services.

Communication↗

ALTree: association detection and localization of susceptibility sites using haplotype phylogenetic trees.

Finding the genes involved in complex diseases susceptibility and among those genes, localizing the variant sites explaining this susceptibility is a major goal of genetic epidemiology. In this context, haplotypic methods that use the joint information on several markers may be of particular interest. When the number of haplotypes is large, a grouping may be required. Phylogenetic trees allow such groupings of haplotypes based on their evolutionary history and may help in the detection and localization of disease susceptibility sites. In this paper, we present a new software to perform phylogeny-based association and localization analysis.

Computational Biology↗

A longitudinal genetic study of vocabulary knowledge in adults.

Vocabulary test scores were obtained from a total of 997 adults, all twins or a sibling of twins in this study. Some (N = 217) individuals were tested twice, around 6 years apart. Heritability varied from 50% at the first test occasion to 63% at the second test occasion. The correlation of scores across time was.74. Structural equation modelling showed that stability in vocabulary knowledge over time can largely (around 76%) be explained by genetic factors. Part of the non-shared environmental variance was stable over time also. Any influence from shared environmental factors could not be detected. Results were similar for the two sexes, except that males generally outperformed females. Results were also similar for two age cohorts, except that the older cohort generally outperformed the younger cohort.

Adolescent↗

Confirmatory P-technique analyses of therapist discourse: high-versus low-quality child therapy sessions.

From a sample of 35 child therapy sessions, 3 of the highest and 3 of the lowest quality sessions (HQS and LQS) were identified by independent ratings on the Loyola Child Psychotherapy Process Scales. Each of the 535 therapist-utterances in the HQS and the 372 therapist-utterances in the LQS were rated on 15 language interaction scales. Principal-components P-technique analyses were applied separately to the HQS and LQS, revealing 3 factors, Responsive Informing (RI), Initiatory Questioning (IQ), and Positive Regard (PR), that seemed to correspond across session types. Using confirmatory P-technique, a general measurement model with acceptable goodness-of-fit was determined for HQS. Two factors emerged: RI and IQ but not PR. Using a bootstrap procedure, random halves of the HQS were repeatedly sampled and compared via multigroup confirmatory factor analysis to create a reference distribution of the magnitudes of their difference chi-squares. Random resamples of HQS and LQS were then compared, resulting in a second reference distribution. Statistical tests and effect-size measures revealed replicable and large differences between sessions types.

Child↗

Classification of the European language families by genetic distance.

Genetic distances among speakers of the European language families were computed by using gene-frequency data for human blood group antigens, enzymes, and proteins of 26 genetic systems. Each system was represented by a different subset of 3369 localities across Europe. By subjecting the matrix of distances to numerical taxonomic procedures, we obtained a grouping of the language families of Europe by their genetic distances as contrasted with their linguistic relationships. The resulting classification largely reflects geographic propinquity rather than linguistic origins. This is evidence for the primary importance of short-range interdemic gene flow in shaping the modern gene pools of Europe. Yet, some language families--i.e., Basque, Finnic (including Lappish), and Semitic (Maltese)--have distant genetic relationships with their geographic neighbors. These results indicate that European gene pools still reflect the remote origins of some ethnic units subsumed by these major linguistic groups.

Ethnicity↗

A framework for scientific data modeling and automated software development.

MOTIVATION: The lack of standards for storage and exchange of data is a serious hindrance for the large-scale data deposition, data mining and program interoperability that is becoming increasingly important in bioinformatics. The problem lies not only in defining and maintaining the standards, but also in convincing scientists and application programmers with a wide variety of backgrounds and interests to adhere to them. RESULTS: We present a UML-based programming framework for the modeling of data and the automated production of software to manipulate that data. Our approach allows one to make an abstract description of the structure of the data used in a particular scientific field and then use it to generate fully functional computer code for data access and input/output routines for data storage, together with accompanying documentation. This code can be generated simultaneously for different programming languages from a single model, together with, for example for format descriptions and I/O libraries XML and various relational databases. The framework is entirely general and could be applied in any subject area. We have used this approach to generate a data exchange standard for structural biology and analysis software for macromolecular NMR spectroscopy. AVAILABILITY: The framework is available under the GPL license, the data exchange standard with generated subroutine libraries under the LGPL license. Both may be found at http://www.ccpn.ac.uk; http://sourceforge.net/projects/ccpn CONTACT: ccpn@mole.bio.cam.ac.uk.

Biopolymers↗

Design of large metabolic responses. Constraints and sensitivity analysis.

Metabolic control analysis (Kacser & Burns (1973). Symp. Soc. Exp. Biol.27, 65-104; Heinrich & Rapoport (1974). Eur. J. Biochem.42, 89-95) has been extensively used to describe the response of metabolic concentrations and fluxes to small (infinitesimal) changes in enzyme concentrations and effectors. Similarly, metabolic control design (Acerenza (1993). J. theor. Biol.165, 63-85) has been proposed to design small metabolic responses. These approaches have the limitation that they were not devised to deal with large (non-infinitesimal) responses. Here we develop a strategy to design large changes in the metabolic variables. The only assumption made is that, for all the parameter values under consideration, the system has a unique stable steady state. The procedure renders the kinetic parameters of the rate equations that when embedded in the metabolic network produce the pattern of large changes in the steady-state variables that we aim to design. Structural and kinetic constraints impose restrictions on the type of responses that could be designed. We show that these conditions can be transformed into the language of mean-sensitivity coefficients and, as a consequence, a sensitivity analysis of large metabolic responses can be performed after the system has been designed. The mean-sensitivity coefficients fulfil conservation and summation relationships that in the limit reduce to the well-known theorems for infinitesimal changes. Finally, it is shown that the same procedure that was used to design metabolic responses and analyse their sensitivity properties can also be used to determine the values of kinetic parameters of the rate laws operating "in situ".

Animals↗

Treatment refusal/attrition among adults randomly assigned to programs at a drug treatment campus: The New Jersey Substance Abuse Treatment Campus, Seacaucus, NJ.

The New Jersey Substance Abuse Treatment Campus was funded to assess the feasibility of establishing a new model for delivering substance abuse treatment services and to serve as a research laboratory for conducting comparative evaluations of those services. The 350-bed campus was designed to improve treatment effectiveness by providing special services needed by underserved populations, and reduce treatment costs by serving large numbers of clients, centralizing services, and sharing facilities. First-time clients who met preliminary eligibility requirements during phone screening were randomly assigned to therapeutic community and chemical dependency programs. We used data collected on 1,573 adults who were ultimately accepted for admission to analyze treatment refusals and attrition during the 25 days after admission. Only 6.4% of the clients refused admission when informed of their treatment assignment. Planned duration of the residential phase of treatment, gender, and language spoken (English/Spanish) interacted with one another and differentially predicted treatment refusal/attrition. These findings may be useful for understanding treatment refusal and attrition in substance abuse treatment programs.

Adult↗

Early detection of isolated memory deficits in the elderly: the need for more sensitive neuropsychological tests.

BACKGROUND: Early detection of cognitive decline in the elderly is important because this may precede progression to Alzheimer's disease. The aim of this study was to see whether sensitive neuropsychological tests could identify pre-clinical cognitive deficits and to characterize the cognitive profile of a subgroup with poor memory. METHODS: A neuropsychological test battery was administered to a community-dwelling sample of 155 elderly volunteers who were screened with CAMCOG at enrolment (mean age 74.7 years). The battery included tests of episodic memory. semantic and working memory, language and processing speed. RESULTS: Episodic memory test z scores below 1 S.D. from the cohort mean identified 25 subjects with non-robust' memory performance. This group was compared to the remaining 'robust memory' group with a General Linear Model controlling for age, IQ, education and gender. Test performance was significantly different in all tests for episodic and semantic memory, but not in tests for working memory, processing speed and language. CANTAB paired associates learning and spatial recognition tests identified the highest percentages of those in the 'non-robust memory group. Processing speed partialled out the age effect on memory performance for the whole cohort, but the 'non-robust memory' group's performance was not associated with age or processing speed. CONCLUSIONS: Sensitive neuropsychological tests can detect performance below the norm in elderly people whose performance on MMSE and CAMCOG tests is well within the normal range. Age-related decline in memory performance in a cohort of the elderly may be largely due to inclusion within the cohort of individuals with undetected pre-clinical Alzheimer's disease or isolated memory impairment.

Aged↗

Modification of psychotic speech with mentally retarded patients.

Three chronic schizophrenics who were mild to severely mentally retarded were treated for a wide range of vocalisations characteristic of psychotic persons. Relevance of responses, speech duration, making nonsense statements, and changing the subject were among the behaviours treated in two experiments. Treatment consisted of instructions, performance feedback via audiotapes, modelling and speech rehearsal provided in twenty-five minute training sessions held each day on a one-to-one basis with a therapist. In all cases, treatment resulted in rapid changes of target behaviours in desired directions. Results were particularly significant since all three subjects displayed active hallucinations and delusions while taking large maintenance dosages of antipsychotic medications. Changes generalised across settings and were maintained over two months follow-up.

Adult↗

Whiteness and difference in nursing.

This paper uses a semiotic, performative theory of language and post-colonial theory to argue that nursing's representations of 'multiculturalism' need to be grounded in a theory of whiteness, an historicized understanding of how ethnic/cultural differences come to be represented in the ways they are and informed by Foucault's notions of power/knowledge. Using nursing education and 'cultural compentency' as examples, the paper draws on a range of literatures to suggest more critical and politically productive ways of approaching difference from within nursing's largely white interpretive framework.

Authoritarianism↗

Phenotypic and behavioral genetic covariation between elemental cognitive components and scholastic measures.

The study subjected nine elementary cognitive task variables from the Cognitive Assessment Tasks (CAT) and three scholastic measures from the Metropolitan Achievement Test (MAT) to phenotypic and behavioral genetic structural equation modeling based on data for 277 pairs of same sex monozygotic (MZ) and dizygotic (DZ) twins from the Western Reserve Twin Project. Phenotypic and behavioral genetic covariation between certain elemental cognitive components and scholastic performance was examined to determine (a) whether these elemental cognitive components contribute substantially to the variance of scholastic performance; (b) whether such contributions vary across different domains of school knowledge or from specific domains to a general aptitude; (c) the behavioral genetic composition of the elemental cognitive components and the scholastic variables; and (d) how the association between the cognitive components and scholastic performance is genetically and environmentally mediated. The results of the study showed that as much as 30% of the phenotypic variance of scholastic performance was accounted for by the CAT general factor, which was presumably related to mental speed. A mainly genetic covariation was found between the mental speed component and scholastic performance, although each of the two variables was strongly influenced by both heritability and common family environment. The magnitude and etiology of the covariation were largely invariant whether mental speed was related to a common scholastic aptitude or to individual achievement measures covering different knowledge domains. Taken in conjunction with previous findings that mental speed has a substantial genetic correlation with psychometric g, and psychometric g has a mostly genetic covariation with scholastic achievement, the findings of the present study seems to point to a more global picture; namely, there is a causal sequence that starts from mental speed as the explanatory factor for both psychometric g and scholastic performance, and the etiology of the causal link is chiefly genetic.

Child↗

VI. Genome structure and cognitive map of Williams syndrome.

Williams syndrome (WMS) is a most compelling model of human cognition, of human genome organization, and of evolution. Due to a deletion in chromosome band 7q11.23, subjects have cardiovascular, connective tissue, and neurodevelopmental deficits. Given the striking peaks and valleys in neurocognition including deficits in visual-spatial and global processing, preserved language and face processing, hypersociability, and heightened affect, the goal of this work has been to identify the genes that are responsible, the cause of the deletion, and its origin in primate evolution. To do this, we have generated an integrated physical, genetic, and transcriptional map of the WMS and flanking regions using multicolor metaphase and interphase fluorescence in situ hybridization (FISH) of bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs), BAC end sequencing, PCR gene marker and microsatellite, large-scale sequencing, cDNA library, and database analyses. The results indicate the genomic organization of the WMS region as two nested duplicated regions flanking a largely single-copy region. There are at least two common deletion breakpoints, one in the centromeric and at least two in the telomeric repeated regions. Clones anchoring the unique to the repeated regions are defined along with three new pseudogene families. Primate studies indicate an evolutionary hot spot for chromosomal inversion in the WMS region. A cognitive phenotypic map of WMS is presented, which combines previous data with five further WMS subjects and three atypical WMS subjects with deletions; two larger (deleted for D7S489L) and one smaller, deleted for genes telomeric to FZD9, through LIMK1, but not WSCR1 or telomeric. The results establish regions and consequent gene candidates for WMS features including mental retardation, hypersociability, and facial features. The approach provides the basis for defining pathways linking genetic underpinnings with the neuroanatomical, functional, and behavioral consequences that result in human cognition.

Adolescent↗

Does being bilingual in English and Chinese influence changes in quality of life scale scores? Evidence from a prospective, population based study.

BACKGROUND: Bilinguals differ from monolinguals in language use, but the influence of bilingualism on changes in Health-Related Quality of Life (HRQoL) scores is not known. OBJECTIVE: To determine the influence of bilingualism on changes in HRQoL scores. RESEARCH DESIGN: A prospective cohort study of a population-based, disproportionately stratified random sample of monolingual or bilingual ethnic Chinese who completed the Short-Form 36 Health Survey (SF-36) in English or Chinese twice in 2 years. Least squares regression models were used to assess the influence of bilingualism on SF-36 scores, while adjusting for the influence of questionnaire language and determinants of HRQoL. RESULTS: Usable English and Chinese questionnaires were returned by 1013 and 910 subjects respectively (aged 21-65 years, 48.5% female, 52.8% bilingual). Bilinguals differed from monolinguals in known determinants of HRQoL (being younger and better educated), changes in determinants of HRQoL over 2 years (more bilinguals had changes in work or marital status) and had mean SF-36 scores that were up to 10 points higher than monolinguals. After adjusting for these differences, bilingualism did not influence 2 year change scores for any of 8 SF-36 scales. CONCLUSION: Bilingualism did not influence changes in HRQoL scores over 2 years in this large, population-based study of subjects fluent in English and/or Chinese (representing an alphabet and/or pictogram based language respectively).

Adult↗