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PubMed2026

Dysregulation of the serum and IgG N-glycome in decompensated cirrhosis and its association with Model for End-Stage Liver Disease-Sodium (MELD-Na).

BACKGROUND AND AIMS: N-glycans modulate glycoprotein structure and function and are altered during chronic inflammation. We sought to define the extent of serum and IgG N-glycan disruption in patients with decompensated liver cirrhosis from alcohol-related liver disease (ALD), primary sclerosing cholangitis (PSC), and ALD-related hepatocellular carcinoma (HCC). Finally, we aimed to examine whether serum and IgG glycosylation is associated with changes in Model for End-stage Liver Disease-Sodium (MELD-Na) scores, a clinical marker used to prioritise liver transplantation. METHODS: Serum samples were obtained from patients with ALD (n = 17), PSC (n = 7), ALD-related HCC (n = 4), and healthy controls (n = 10). N-glycans were released, fluorescently labelled, and profiled by hydrophilic interaction ultra performance liquid chromatography (HILIC-UPLC). Chromatograms were integrated into 46 and 23 glycan peaks for serum and IgG respectively. These peaks and their associated glycosylation traits were statistically compared with healthy controls using age- and sex-adjusted linear regression models. RESULTS: In serum, decompensated cirrhosis shows statistically significant shifts toward less complex, agalactosylated and asialylated biantennary glycans, accompanied by significant losses of highly branched, galactosylated and sialylated structures. IgG mirrored this pattern, which is characteristic of a pro-inflammatory signature, with increased agalactosylation and bisected glycan levels, along with reduced levels of digalactosylated and sialylated species. N-glycan profiles showed significant associations with MELD-Na scores, indicating that inflammatory processes in decompensated liver cirrhosis continue to reshape serum glycoproteins. CONCLUSION: Decompensated liver cirrhosis shows profound remodelling of serum and IgG N-glycans. These data establish a reference framework for terminal glycomic disruption in liver disease and highlight the potential value of incorporating glycosylation analysis into broader assessments of liver disease progression.

Humans↗
PubMed2003

Determining the effectiveness of the usability problem inspector: a theory-based model and tool for finding usability problems.

Despite the increased focus on usability and on the processes and methods used to increase usability, a substantial amount of software is unusable and poorly designed. Much of this is attributable to the lack of cost-effective usability evaluation tools that provide an interaction-based framework for identifying problems. We developed the user action framework and a corresponding evaluation tool, the usability problem inspector (UPI), to help organize usability concepts and issues into a knowledge base. We conducted a comprehensive comparison study to determine if our theory-based framework and tool could be effectively used to find important usability problems in an interface design, relative to two other established inspection methods (heuristic evaluation and cognitive walkthrough). Results showed that the UPI scored higher than heuristic evaluation in terms of thoroughness, validity, and effectiveness and was consistent with cognitive walkthrough for these same measures. We also discuss other potential advantages of the UPI over heuristic evaluation and cognitive walkthrough when applied in practice. Potential applications of this work include a cost-effective alternative or supplement to lab-based formative usability evaluation during any stage of development.

Adult↗
PubMedDate not supplied

[Satisfaction of subjects enrolled in clinical studies].

OBJECTIVE: The Grenoble clinical research centre carried out a prospective satisfaction survey of subjects taking part in clinical studies undertaken in its buildings. MATERIALS AND METHODS: A questionnaire adapted from Grenoble teaching hospital's inpatient satisfaction survey was sent to 198 subjects. It comprised 24 items pooled in categories on which were calculated average scores. The participation rate of the survey was 82.6%. On the whole, 94.4% of the questioned subjects would accept to take part in a new study if we requested them, and 72.2% were satisfied or very satisfied with their stay; 24% had no opinion. The mean overall satisfaction score was 8.6 (95% confidence interval: 7.6-9.6) out of 10. CONCLUSION: This investigation shows that the assumption of responsibility of the subjects by specific personnel and in an adapted place, within the framework of clinical protocol of research, is associated with a high satisfaction of the subjects. However, we still have to improve the transmission of the clinical study results to the patients.

Clinical Trials as Topic↗
PubMed1987

The impact of nursing education on ethical/moral decision making.

A study of 227 baccalaureate and 111 master's nursing students was conducted to determine the influence of the level of formal education on three selected factors: ethical/moral reasoning, attribution of responsibility, and ethical/moral dilemma resolution. Moral development theory and Heider's attribution of responsibility construct provided the theoretical framework. A comparison of the overall index of ethical/moral reasoning showed that graduate students reasoned at a higher level than undergraduate students. The amount of attribution of responsibility assigned and the dilemma resolution score did not differ for the two groups. The results of this study suggest that undergraduate and graduate nursing programs must place more emphasis on identifying dilemmas, increasing ethical/moral reasoning levels and attributing responsibility in a justifiable manner. Nurse researchers must continue to study how nurses respond in dilemma situations and how personal characteristics, factors in the environment, education, and the assignment of responsibility affect nurses' ability to resolve ethical/moral dilemmas.

Conflict, Psychological↗
PubMed1991

Patterns of competence and adjustment among adolescents from authoritative, authoritarian, indulgent, and neglectful families.

In order to test Maccoby and Martin's revision of Baumrind's conceptual framework, the families of approximately 4,100 14-18-year-olds were classified into 1 of 4 groups (authoritative, authoritarian, indulgent, or neglectful) on the basis of the adolescents' ratings of their parents on 2 dimensions: acceptance/involvement and strictness/supervision. The youngsters were then contrasted along 4 sets of outcomes: psychosocial development, school achievement, internalized distress, and problem behavior. Results indicate that adolescents who characterize their parents as authoritative score highest on measures of psychosocial competence and lowest on measures of psychological and behavioral dysfunction; the reverse is true for adolescents who describe their parents as neglectful. Adolescents whose parents are characterized as authoritarian score reasonably well on measures indexing obedience and conformity to the standards of adults but have relatively poorer self-conceptions than other youngsters. In contrast, adolescents from indulgent homes evidence a strong sense of self-confidence but report a higher frequency of substance abuse and school misconduct and are less engaged in school. The results provide support for Maccoby and Martin's framework and indicate the need to distinguish between two types of "permissive" families: those that are indulgent and those that are neglectful.

Achievement↗
PubMed1995

The Head Injury Severity Scale (HISS): a practical classification of closed-head injury.

The authors introduce a two-dimensional scale for rating closed-head injury, the Head Injury Severity Scale (HISS). This system is based on a five-interval severity classification (minimal through critical), determined primarily by the initial post-resuscitation Glasgow Coma Scale score. The second dimension is predicated on the presence or absence of complications, appropriate for each severity interval. The outcomes of almost 25,000 patients with head injury encountered at our institution over a 7-year period were evaluated. We discovered that adding a complication dimension to each severity category resulted in significant outcome differences and effectively divided patients into groups with very different risks, prognosis and treatment requirements. The HISS is proposed as a framework on which further research can be done to guide care to predict outcome and to perform audits on head-injured patients.

Brain Damage, Chronic↗
PubMed2026

Reliability-aware hierarchical learning for Chagas disease screening from 12-lead ECGs: tackling label uncertainty and class imbalance.

Objective.Chagas disease, a neglected tropical disease (NTD) with significant cardiovascular impact, remains underdiagnosed in resource-limited regions. Electrocardiogram (ECG) screening offers a low-cost tool for detecting cardiac involvement, yet algorithm development is challenged by label noise, data scarcity, and the latent nature of infection. This study proposes a robust ECG-based screening framework that explicitly addresses these constraints.Approach.We introduce aReliability-Aware Hierarchical Learningstrategy that calibrates supervision according to data provenance, prioritizing serology-confirmed labels over noisy self-reports. To mitigate data scarcity, we compare a specialized convolutional neural network (CNN) trained from scratch with a transfer learning approach based on a Spatio-Temporal ECG foundation Model (FM). Performance is evaluated across varying data scales, and the representation structure is analyzed to interpret model behavior.Main results.On the official hidden test set of the George B. Moody PhysioNet/Computing in Cardiology Challenge 2025, our approach achieved a Challenge Score of 0.163. We observe that while the specialized CNN performs competitively in data-rich regimes, the FM exhibits superior robustness in extreme low-resource settings. Furthermore, performance reaches a plateau imposed by underlying disease physiology. Bimodal score distributions suggest that models distinguish established cardiomyopathy from indeterminate infection, which remains electrophysiologically indistinguishable from healthy controls.Significance.These findings clarify both the potential and intrinsic limits of ECG-based AI screening for NTD-associated cardiac involvement. Reliability-aware supervision and data-efficient transfer learning provide a practical framework toward scalable and clinically meaningful ECG screening systems in resource-constrained environments.

Humans↗
PubMed2025

Automating candidate gene prioritization with large language models: from naive scoring to literature-grounded validation.

MOTIVATION: Identifying promising therapeutic targets from thousands of genes in transcriptomic studies remains a major bottleneck in biomedical research. While large language models (LLMs) show potential for gene prioritization, they suffer from hallucination and lack systematic validation against expert knowledge. RESULTS: The framework identified 609 sepsis-relevant genes with >94% filtering efficiency, demonstrating strong enrichment for inflammatory pathways including TNF-α signaling, complement activation, and interferon responses. Literature validation yielded 30 ultra-high confidence therapeutic candidates, including both established sepsis genes (IL10, TREM1, S100A9, NLRP3) and novel targets warranting investigation. Benchmark validation against expert-curated databases achieved 71.2% recall, with systematic correlation between computational confidence and evidence quality. The final candidate set balanced discovery (11 novel genes) with validation (19 known genes), maintaining biological coherence throughout the filtering process. This framework demonstrates that rigorous methodology can transform unreliable LLM outputs into systematically validated biological insights. By combining computational efficiency with literature grounding, the approach provides a practical tool for prioritizing experimental validation efforts. The modular design enables adaptation to other diseases through knowledge base substitution, offering a systematic approach to literature-guided biomarker discovery. AVAILABILITY AND IMPLEMENTATION: We developed a two-stage computational framework that combines LLM-based screening with literature validation for systematic gene prioritization. Starting with 10 824 genes from the BloodGen3 repertoire, we applied multi-criteria evaluation for sepsis relevance, followed by retrieval-augmented generation using 6346 curated sepsis publications. A novel faithfulness evaluation system verified that LLM predictions aligned with retrieved literature evidence. Source code and implementation details are available at https://github.com/taushifkhan/llm-geneprioritization-framework, vector database at https://doi.org/10.5281/zenodo.15802241, and Interactive demonstration at https://llm-geneprioritization.streamlit.app/.

Humans↗
PubMed2006

Evaluating science outside the trial box: applying Daubert to the Federal Sentencing Guidelines' criminal history score.

A limited amount of research exists examining the ability of the Criminal History Score of the Federal Sentencing Guidelines (Guidelines) to achieve one of its most essential objectives: prediction of recidivism. Building on the work of Schopp [Schopp, R. (2001). Competency, condemnation, and commitment: An integrated theory of mental health law. Washington D.C.: American Psychological Association], it is suggested that the scientific admissibility framework and the underlying principles announced by the United States Supreme Court in Daubert v. Merrell Dow Pharmaceutical [Daubert v. Merrell Dow Pharmaceuticals Inc., 507 U.S. 579, 113 S.Ct. 2786 (1993)] should be expanded beyond the constraints of the evidentiary admissibility phase of trial and should apply to legislative and administrative rules that have: a) an empirically testable purpose and b) a substantial impact on the rights of individuals. Such an analysis offers a useful mechanism for understanding the strengths and weaknesses of social science being used by legal institutions. Based upon a hypothetical Daubert analysis, the scientific validity of the Guidelines' Criminal History Score is assessed and demonstrated to be insufficient. The law and policy implications of this finding are discussed.

Crime↗
PubMed2005

Nipping psychopathy in the bud: an examination of the convergent, predictive, and theoretical utility of the PCL-YV among adolescent girls.

Over the last decade rates of violence among adolescent girls have increased. Within high-risk contexts, urgent calls for assessment options have resulted in the extension of adult and male-based instruments to adolescent females in spite of the absence of strong empirical support. The current study evaluates the downward extension of psychopathy within a population of female juvenile offenders (N=125). The convergent and predictive validity of the Psychopathy Checklist-Youth Version (PCL-YV) were evaluated within a structural equation modeling (SEM) framework. Results indicated that while a specific component of psychopathy, deficient affective experience, was related to aggression, the effect was negated once victimization experiences were entered into the models. In addition, PCL-YV scores were not predictive of future offending, while victimization experiences significantly increased the odds of re-offending. Implications for research, policy, and clinical practice are discussed.

Adolescent↗
PubMed1998

Distribution of attachment events relative to actin binding sites as evidenced in a bidirectional actomyosin interaction model.

Optical trapping is one of the most evolving technologies that measures biophysical quantities and provides insights into some of the fundamental questions in the study of molecular motor proteins such as myosin. Several laboratories have successfully used this technique to observe and score nanometre-size displacements produced by myosin on interacting with actin. We have studied the distribution of attachment events for two myosin molecules with different orientations interacting with an actin filament within the framework of a Langevin-type bidirectional mathematical model. When myosin is detached from actin, our model predicts Brownian displacements centred at 0 +/- 8 nm (mean +/- SD, n = 251,058). When attached, the time-averaged displacements of the actin filament system produced step sizes with peaks of 8 +/- 6 nm (mean +/- SD, n = 22,174) (forward displacements) and -8 +/- 6 nm (mean +/- SD, n = 26,769) (reverse displacements). We infer from our results that the population distribution of attachment events is strongly dependent on (i) the magnitude of the Brownian displacements, (ii) the location of the actin binding sites relative to the myosin molecules, (iii) the orientation of the myosin molecules, and (iv) the relative kinetics (rate constants) for the forward and reverse displacement events.

Actins↗
PubMed2005

Biocompatibility of surfaces for antibody microarrays: design of macroporous silicon substrates.

Major efforts to develop antibody microarray technology to enable global proteome analysis to be performed in a facile manner are under way. In this process, the design and the properties of the substrate will play crucial roles. In the present study, we have developed novel, highly biocompatible solid supports for microarrays, using adsorbed recombinant human single-framework antibody fragments as probes. Several silicon-based supports, including planar silicon, micro- and macroporous silicon, and nitrocellulose-coated variants thereof, were designed and evaluated in a stepwise procedure. The surfaces were scored based on biocompatibility and probe binding capacity as judged by spot morphology, signal intensities, signal to noise ratios, dynamic range, sensitivity, and reproducibility. A set of five commercially available substrates, selected to represent a set of supports providing different surface and coupling chemistries, was used as reference surfaces. The results showed that several well-performing silicon-based supports could be designed; in particular, a nitrocellulose-coated macroporous variant, MAP3-NC7, received the highest scores. In comparison, MAP3-NC7 displayed properties equal to or better than those of the reference substrates. Taken together, designed surfaces based on silicon can undoubtedly meet the requirements of the next generation of solid supports for antibody microarrays.

Antibodies↗
PubMedDate not supplied

Teaching the patient with ischemic heart disease: a systemic approach to instructional design.

Does a systematic approach to the design of instruction for patients with ischemic heart disease (IHD) produce an effective educational product? One hundred patients, 67 men and 33 women with an average age of 57 years, who were hospitalized with IHD (myocardial infarction or unstable angina), were randomly assigned to an experimental or control condition and pretested to determine their knowledge of the disease and its treatment. Experimental subjects received a linear self-instructional program on the nature and treatment of IHD. Control subjects did not receive the program. Two days later a posttest was administered to experimental and control subjects; an average of 14 days after discharge a retention test was given to both groups. Individual test scores revealed that (allowing for a subject effect) patients who completed the program achieved significantly (P less than 0.001) higher posttest and retention test scores than those who did not. Also, patients who completed the program retained the information during the two weeks between the posttest and the retention test. Results of this study indicate that the instructional framework that was effective in the design of a health-education program for pregnant women can be applied to the design of instruction for patients with IHD.

Canada↗
PubMed2003

An adaptive metabolic demand model for protein and amino acid requirements.

The shortcomings of the metabolic implications of the current protein requirements model are reviewed, and an alternative model, validated with [1-(13)C]leucine balance results in human adults, is presented and evaluated in the context of defining protein requirements. The model identifies metabolic demands for amino acids as comprising a small fixed component and a variable adaptive component that is relatively insensitive to acute food or protein intake, but which changes slowly with a sustained change in intake, enabling N equilibrium to be achieved. The model accounts for the apparent low efficiency of utilisation of animal proteins in N balance studies and enables more realistic efficiency values to be measured within an experimental framework that takes account of the adaptive metabolic demand. However, the complex relationship between the adaptive metabolic demand and habitual level and quality of protein intake prevents prediction of protein quality by amino acid scoring, which can markedly underestimate actual values. In contrast to the current model, for fully adapted individuals risk of deficiency (i.e. negative N balance after complete adaptation) will only start to increase when intakes fall below the range of the true minimum requirements, i.e. a value that is currently unknown, but likely to be between 0.40 and 0.50 g/kg per d at the lower end of the reported distribution of requirements. At intakes greater than this with additional metabolic demands varying directly with intake, deficiency is only likely as a short-term response to a change to a lower intake within the adaptive range. Thus, for adults satisfying energy needs on most mixed human diets, intakes will be within the adaptive range, and N equilibrium ceases to be a useful indicator of nutritional adequacy of protein. In the context of prescriptive dietary guidelines it may be expedient to retain current values until the benefits (and any risks) of protein intakes within the adaptive range can be quantified. However, from a diagnostic perspective, indicators other than N balance need to be identified, since maintenance of N balance can no longer be used as a surrogate of adequate protein-related health.

Adult↗
PubMed1997

Assessment of severity and prognosis in acute pancreatitis.

Assessment of severity and prognosis in acute pancreatitis was originally driven by clinicians' needs for the prediction of outcome, together with the requirement of researchers for objective measurement of severity. Evaluation of the multitude of competing systems has been hindered by varying definitions of severity, incomplete reporting and a lack of comparative data. Although clinical assessment, Ranson and Glasgow scores remain predominant, the recent literature reflects how needs have changed, as a result of improved understanding of the biological events underlying attacks and technological advances. The Atlanta International Symposium should provide a suitable framework for progress.

Acute Disease↗
PubMed2000

[Refined chromosome assignment of human novel H-RalGDS gene on chromosome 9q34.1 by using radiation hybrid genebridge 4 panel].

OBJECTIVE: Refined chromosome assignment of a novel Ras-related H-RalGDS gene (the human homology of rat RalGDS, Ral guanine nucleotide dissociation stimulator recently cloned and characterized by our laboratory) by using human/rodent radiation somatic cell hybrid panel GB4. METHODS: According to the sequence of the 3'-untranslated region of H-RalGDS cDNA, forward and reverse primers were designed and used to amplify the human/rodent somatic radiation hybrid Genebridge 4 panel. The PCR result of each cell line of the panel was scored in a certain way and put into the related internet site of WI/MIT Radiation Hybrid Mapper for RH mapping and comprehensive analysis. RESULTS: The H-RalGDS gene was successfully localized to the framework of chromosome 9. After referring to literature and further integrated mapping analysis of the physical, genetic linkage and cytological mappings, the gene was assigned precisely between the markers SURF5 and RPL7A which had already been assigned to human chromosome 9q34.1. CONCLUSION: The localization of H-RalGDS not only contributed much to the construction of refined gene map and cytogenetic map within the region of chromosome 9q34, but also made clear that RH mapping of human novel genes is a simple, convenient and reliable method which can provide even more genetic information of genes within chromosomal regions.

Animals↗
PubMed2026

Mutation rate heterogeneity biases variant effect prediction and reveals genuine mutational robustness.

Variant effect predictors (VEPs) are widely used to interpret the functional consequences of human genetic variation. Because most methods rely on sequence conservation, they implicitly treat conservation as evidence of functional constraint. However, substitution patterns across a phylogeny reflect not only selection but also differences in underlying mutation rates. Here, we show that this creates a systematic confounding: most VEPs capture mutation rate variation and misinterpret it as variation in functional importance. Widely used conservation metrics exhibit a related bias; in particular, phyloP scores correlate strongly with mutation rate even at putatively neutral sites. Consequently, variants at low-mutation-rate sites tend to be predicted as more damaging, and variants at highly mutable sites as more tolerated, than warranted by their true functional impact. We also identify a distinct biological signal in experimental measurements of mutational effects on protein stability: amino acid substitutions that are more likely to arise are, on average, less destabilizing than rarer substitutions. This provides empirical support for mutational robustness in the context of protein stability. However, this relationship is insufficient to explain the mutation-rate dependence observed in current VEP outputs. Together, our findings show that mutation rate heterogeneity systematically biases current variant effect prediction frameworks, highlight the need to model mutation probabilities explicitly in future VEPs, and reveal a genuine biological signal of mutational robustness.

conservation scores↗