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Development of predictive models of laboratory animal growth using artificial neural networks.

Traditional regression analysis of body weight growth curves encounters problems when the data are extremely variable. While transformations are often employed to meet the criteria of the analysis, some transformations are inadequate for normalizing the data. Regression analysis also requires presuppositions regarding the model to be fit and the techniques to be used in the analysis. An alternative approach using artificial neural networks is presented which may be suitable for developing predictive models of growth. Neural networks are simulators of the processes that occur in the biological brain during the learning process. They are trained on the data, developing the necessary algorithms within their internal architecture, and produce a predictive model based on the learned facts. A dataset of Sprague-Dawley rat (Rattus norvegicus) weights is analyzed by both traditional regression analysis and neural network training. Predictions of body weight are made from both models. While both methods produce models that adequately predict the body weights, the neural network model is superior in that it combines accuracy and precision, being less influenced by longitudinal variability in the data. Thus, the neural network provides another tool for researchers to analyze growth curve data.

Algorithms

Automated seed localization from CT datasets of the prostate.

With the increasing utilization of permanent brachytherapy implants for treating carcinoma of the prostate, the importance of accurate post-treatment dose calculation also increases for assessing patient outcome and planning future treatments. An automatic method for seed localization of permanent brachytherapy implants, using CT datasets of the prostate, has been developed and tested on a phantom using an actual patient planned seed distribution. This method was also compared to results with the three-film technique for three patient datasets. The automatic method is as accurate or more accurate than the three film technique for 1 mm, 3 mm, and 5 mm contiguous CT slices, and eliminates the inter- and intra-observer variability of the manual methods. The automated method improves the localization of brachytherapy seeds while reducing the time required for the user to input information, and is demonstrated to be less operator dependent, less time consuming, and potentially more accurate than the three-film technique.

Biophysical Phenomena

Dynamic imaging and tracer kinetic modeling for emission tomography using rotating detectors.

When performing dynamic studies using emission tomography the tracer distribution changes during acquisition of a single set of projections. This is particularly true for some positron emission tomography (PET) systems which, like single photon emission computed tomography (SPECT), acquire data over a limited angle at any time, with full projections obtained by rotation of the detectors. In this paper, an approach is proposed for processing data from these systems, applicable to either PET or SPECT. A method of interpolation, based on overlapped parabolas, is used to obtain an estimate of the total counts in each pixel of the projections for each required frame-interval, which is the total time to acquire a single complete set of projections necessary for reconstruction. The resultant projections are reconstructed using traditional filtered backprojection (FBP) and tracer kinetic parameters are estimated using a method which relies on counts integrated over the frame-interval rather than instantaneous values. Simulated data were used to illustrate the technique's capabilities with noise levels typical of those encountered in either PET or SPECT. Dynamic datasets were constructed, based on kinetic parameters for fluoro-deoxy-glucose (FDG) and use of either a full ring detector or rotating detector acquisition. For the rotating detector, use of the interpolation scheme provided reconstructed dynamic images with reduced artefacts compared to unprocessed data or use of linear interpolation. Estimates for the metabolic rate of glucose had similar bias to those obtained from a full ring detector.

Algorithms

The influence of radiotherapy treatment time on the control of laryngeal cancer: a direct analysis of data from two British Institute of Radiology trials to calculate the lag period and the time factor.

This study analyses node-negative laryngeal tumour control data from two clinical trials conducted by the British Institute of Radiology in order to determine the time factors and the presence or absence of a lag period before the time factor takes effect. A direct maximum likelihood approach is used to fit a double-logarithmic model including a repopulation term which commences after an initial lag period, Tk. The analysis yields a time factor of 0.8 Gy per day (95% confidence interval 0.5-1.1 Gy per day) as the extra dose required to counteract the reduction in tumour control probability (TCP) with extension of the treatment time. The latter reduction amounted to between 5 and 12% TCP per week, depending on the stage and time period. With this dataset, where few patients were treated for short times, no statistically significant lag phase can be demonstrated. However, the best estimate of Tk is 21 days (95% confidence interval 0-27 days), which is consistent with estimates from other studies on other datasets. If a lag phase exists, this study would indicate that the duration is less than 27 days. Other studies have used retrospective data and are subject to a number of potential biases. The present study, using data from multicentre prospective randomized clinical trials, is free from some of these sources of bias. The fact that very similar estimates of the radiobiological parameters are obtained lends credence to these other studies and suggests that the potential biases may be small in practice.

Clinical Trials as Topic

Changes in physicians' sources of pharmaceutical information: a review and analysis.

Since 1952, 20 datasets have been generated through 17 studies in an attempt to describe the sources and importance and/or use of information about pharmaceuticals by physicians. The authors review the findings of the studies and subject them to three sequentially relevant, but different, meta-analytic procedures. The results of these analyses indicate significant changes in the sources and importance of various commercial/noncommercial and personal/nonpersonal information as they relate to physicians' prescribing behavior. Those changes over time have specific implications for marketers of pharmaceuticals.

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Major structural determinants of transmembrane proteins identified by principal component analysis.

We identify amino acid characteristics important in determining the secondary structures of transmembrane proteins, and compare them with characteristics important for cytoplasmic proteins. Using information derived from multiple sequence alignments, we perform a principal component analysis (PCA) to identify the directions in the 20-dimensional amino acid frequency space that comprise the most variance within each protein secondary structure. These vectors represent the important position-specific properties of the amino acids for coils, turns, beta sheets, and alpha helices. As expected, the most important axis for most of the datasets was hydrophobicity. Additional axes, distinct from hydrophobicity, are surprising, especially in the case of transmembrane alpha helices, where the effects of aromaticity and beta-branching are the next two most significant characteristics. The axis representing beta-branching also has equal importance in cytoplasmic and transmembrane helices, a finding that contrasts with some experimental results in membrane-like environments. In a further analysis, we examine trends for some of the PCA axes over averaged transmembrane alpha helices, and find interesting results for aromaticity.

Amino Acids

Preliminary assessment of three-dimensional magnetic resonance imaging for various colonic disorders.

BACKGROUND: Improvements in magnetic resonance imaging (MRI) technology have enabled the acquisition of three-dimensional MRI datasets in a single breath hold. We adopted this technique to make a three dimensional intraluminal and extraluminal assessment of the colon in three patients with various colonic disorders. METHODS: One patient was studied after having a double-contrast barium enema. Two patients had MRI scans after colonoscopy, which showed three colonic tumours in one and multiple polyps in the ascending colon of the other. The process of rectal filling with 1.5-2.0 L water mixed with 15-20 mL 0.5 mol/L gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) was monitored with MR fluoroscopic sequence. Three-dimensional datasets of the contrast-filled colon were taken with patients in prone (before and after intravenous administration of 0.1 mmol/kg bodyweight Gd-DTPA) and supine positions. 64 sections with a voxel-resolution of 2.0 x 2.0 x 1.25 mm3-were taken during a 28 s breath hold. Three-dimensional maximum intensity projection, multiplanar reconstruction, and virtual colonoscopic images of the colon were created from these. FINDINGS: Analysis of the coronal source images in conjunction with multiplanar reconstructions revealed all relevant abnormalities, including diverticula, carcinomas, and polyps. Three dimensional maximum-intensity projections gave a morphological overview of the whole colon. Targeted projections, made up of a limited number of coronal source images, showed diverticula and smaller polyps more clearly. After patients were given intravenous contrast all colonic mass lesions were enhanced. Datasets obtained in prone patients gave the best intraluminal views of the colon. Virtual magnetic resonance colonoscopy showed colonic haustra as well as the ileocaecal valve, but did not show clearly the diverticula. All intraluminal mass lesions, on the other hand, were easy to see. INTERPRETATION: The potential of three-dimensional colonic MRI to provide accurate, minimally invasive, cost-effective polyp screening, as well as comprehensive colonic tumour staging, warrants further investigation.

Aged

Benchmarking large language models for extracting biobank-derived insights into health and disease.

Biobank-scale datasets such as the UK Biobank have become foundational resources for advancing biomedical discovery. Yet the complexity and heterogeneity of these resources, spanning genomics, imaging, clinical records, and metadata, pose substantial barriers to access and interpretation. Large Language Models (LLMs) offer a promising avenue for making such datasets more navigable through natural language interfaces. However, the extent to which current general-purpose LLMs can retrieve and synthesize biobank-specific insights has not yet been systematically evaluated. In this study, we present a reproducible, multi-metric evaluation framework to benchmark the capabilities of leading LLMs. We evaluated six leading large language models: Gemini 3 Pro, Claude Opus 4.5, Claude Sonnet 4.5, GPT-5.2, Mistral Large 2, and DeepSeek V3, on four benchmark tasks designed to assess biobank-related knowledge retrieval. We evaluate model performance across six dimensions (semantic accuracy, factual correctness, domain knowledge, reasoning quality, response depth, and biobank specificity) and assessed output consistency using curated UK Biobank references and a robust random baseline. All models outperformed the baseline by 2&#xd7; to 3&#xd7;&#x2009;, with strong statistical separation (p&#x2009;<&#x2009;0.001), confirming meaningful biobank-specific knowledge retrieval. Gemini 3 Pro achieved the highest overall accuracy across tasks such as keyword synthesis, institution recognition, and topic inference, while Claude Sonnet 4.5 demonstrated the most uniform performance across evaluation dimensions. Our benchmark provides a rigorous framework for evaluating LLMs in biomedical settings. Using the UK Biobank as a real-world testbed, we highlight both the capabilities and limitations of current models, measuring their capacity to recall structured biomedical knowledge consistent with authoritative biobank metadata.

Large Language Models

History of the Cancer Information Service.

The Cancer Information Service (CIS) was established on July 1, 1975, following the mandate of the National Cancer Act of 1971 giving the National Cancer Institute (NCI) new responsibilities for educating the public, patients, and health professionals. Funded under a contract mechanism, the CIS has become one of the longest-running community programs in NCI. The CIS has been able to set up and maintain high-quality service, giving accurate, up-to-date medical information to cancer patients and their families and friends, to health professionals, and to the general public. The CIS network, which has taken more than 5 million calls since its inception, has weathered many changes, both at the national and the local level. Its current call volume, in excess of 500,000 calls per year, makes it one of the most heavily utilized health-related telephone helplines in the country. Using a standardized Call Record Form, data on calls have been recorded consistently since 1983; the dataset now contains information on more than 4.2 million calls. An outreach component that acts as NCI's field arm has been part of the CIS since its inception. The CIS has matured into a stable system that has been reconfigured into 19 regional offices, covering the entire country. These offices run the telephone service and serve as NCI's outreach arm, working with intermediaries to carry out NCI information and education programs in local communities.

History, 20th Century

Incubation time for AIDS from French transfusion-associated cases.

Although incubation time is a key parameter of the epidemiology of AIDS, statistical estimates based on transfusion-associated AIDS cases have, up to now, used only the single dataset provided by the AIDS program of the Centers for Disease Control (CDC) in Atlanta. Using a new dataset provided by the Direction Générale de la Santé (DGS), of the French Ministry of Health1, we estimate the mean incubation time for AIDS (median in brackets) to be 5.3 years (5.3 years) with a 90% confidence interval ranging from 4.4 to 8.9 years (4.4 to 8.8 years), when a Weibull distribution is postulated for incubation time. The previously encountered problem of very large confidence intervals (range larger than 100 years), is not observed, indicating that an accurate estimate for mean incubation time will be obtainable in the near future.

Acquired Immunodeficiency Syndrome

NMR spectral quantitation by principal-component analysis. II. Determination of frequency and phase shifts.

This paper extends the use of principal-component analysis in spectral quantification to the estimation of frequency and phase shifts in a single resonant peak across a series of spectra. The estimated parameters can be used to correct the spectra accordingly, resulting in more accurate peak-area estimation. Further, the removal of the variations in phase and frequency cause by instrumental and experimental fluctuations makes it possible to determine more accurately the remaining variations, which bear biological significance. The procedure is demonstrated on simulated data, a 3D chemical-shift-imaging dataset acquired from a cylinder of inorganic phosphate (Pi), and a set of 736 31P NMR in vivo spectra taken from a kinetic study of rate muscle energetics. In all cases, the procedure rapidly and automatically identifies the frequency and phase shifts present in the individual spectra. In the kinetic study, the procedure is used twice, first to adjust the phase and frequency of a reference peak (phosphocreatine) and then to determine the individual frequencies of the Pi peak in each of the spectra which further can be used for estimation of pH changes during the experiment.

Computer Simulation

B-SPID: an object-relational database architecture to store, retrieve, and manipulate neuroimaging data.

We propose a hardware and software architecture to respond to crucial problems in the neuroimaging field: storage, retrieval, and processing of large datasets. The B-SPID project, here discussed, concerns the processing of neuroimages and attached components stored in an object-relational multimedia database management system (DBMS). Advanced bioinformation concepts are exploited in this project such as large scale data storage, high level graphical user interfaces and 3D graphical processing and display of data. Our database implementation is based on standard programming components, runs on several UNIX platforms and is written to be evolutive. Queries on this database are designed to obtain and display from neuroimaging data several types of results (pictures, text, or 3D graphical shapes) on heterogeneous systems.

Brain Mapping

Molecular phylogeny and evolutionary history of the tit-tyrants (Aves: Tyrannidae).

Tit-tyrants of the genus Anairetes presently consist of six species; five inhabit various regions along the Andean cordillera of South America and one is endemic to the Juan Fernandez Islands off the coast of Chile. Data from mtDNA ND2 and Cyt b sequences were used to construct a phylogeny for all Anairetes species as well as Uromyias agilis, a closely related genus, and Stigmatura as an outgroup, to determine their relationships and history of radiation in South America. Results strongly supported the following paired relationships: A. nigrocristatus-A. reguloides, A. flavirostris-A. alpinus, and A. parulus-A. fernandezianus. This dataset, however, could not resolve basal nodes; therefore relationships among these pairs remains obscure. Moreover the genus Uromyias, controversially separated on morphological criteria from Anairetes, fell within the Anairetes clade, although its exact position could not be ascertained with confidence. The molecular data indicate that this group probably radiated within the past 2 million years, concomitant with highly accentuated cycles of global climatic change. Certain high altitude areas within the Andes may have been stable during global climatic changes and may have served as refugia during the Plio-Pleistocene.

Animals

Comparison of chemotherapy and bone marrow transplants using two independent clinical databases.

Comparing the outcome of chemotherapy and bone marrow transplants in the absence of a randomized trial is difficult but necessary for diseases where small numbers of patients make such trials difficult if not impossible. To address this issue for adults with acute lymphoblastic leukemia in first remission, we created an empirical database using two separate datasets, one from the International Bone Marrow Transplant Registry and the other from two multicenter chemotherapy studies. Prior to combining the datasets, a study protocol was developed to define inclusion criteria, outcomes to be compared and statistical methods. The main problems of a non-randomized comparison are biases potentially introduced by differences in baseline composition of the two cohorts and differences in time-to-treatment. The source of the latter bias is different distributions of waiting times between achieving complete remission and receiving post-remission therapy. Several techniques to control these biases were evaluated; each gave qualitatively similar results. These methods can easily be applied to other clinical situations where randomized trials are not available.

Adolescent

The classification of subjects with joint complaints on incomplete biochemical and haematological datasets.

We performed a retrospective study on 163 subjects suffering from rheumatic fever (16), rheumatoid arthritis (36), lupus erythematosus (17), gout (21), arthrosis (50) and osteomyelitis (23). The number of variables evaluated was 39. These were all of a general biochemical and haematological nature. A feature reduction resulted in sixteen variables that matched well with those known from the literature. Linear discriminant analysis yielded poor results in classifying the six disease categories (with 18 variables 61.8%). A reduction to three disease categories improved the classification results remarkably. This, and the excellent discriminating power between patients and the reference group, shows that the selected variables are illustrative only for general clinical pictures, such as infection, and not for the desired differential diagnosis.

Arthritis, Rheumatoid

A new multiparameter flow cytometer: optical and electrical cell analysis in combination with video microscopy in flow.

BACKGROUND: Flow cytometers, which are commercially available, do not necessarily meet all demands of actual biomedical research. This is the case for the investigation of mechanisms involved in cell volume regulation, which requires electrical volume measurement and ratiometric multichannel fluorescence analysis for the simultaneous assessment of different physiologic parameters (intracellular pH and the intracellular concentration of calcium ions, etc). METHODS AND RESULTS: We describe the construction of a new nonsorting flow cytometer designed for the simultaneous acquisition of seven parameters including fluorescence signals, forward and perpendicular light scatter, cell volume according to the electrical Coulter principle, and flow cytometric imaging. The instrument is equipped with three different light sources. A tunable argon-ion laser generates efficient excitation of the most standard fluorescent probes in the visible spectral range, and an arc lamp provides the means for ultraviolet excitation at low cost. Because of the spatial filtering by the excitation and detection optics, two independent sets of dual fluorescence measurements can be performed, a prerequisite for flexible ratiometric fluorescence analysis. A flow video microscope integrated into the optical system optionally generates either brightfield or phase images of selected flowing particles. Only particles whose individual datasets meet predefined gating conditions are imaged in real time. To avoid smear effects, the motion of the object to be imaged (speed approximately 8 m/s) is frozen on the target of a CCD camera by flash illumination. For this purpose, a high radiance gas discharge lamp with 25-mJ electric pulse energy provides an illumination time of 18 ns (full width half maximum). Test results obtained from latex spheres and cells are shown. CONCLUSIONS: Test results indicate that our instrument can perform Coulter measurements in combination with flexible optical analysis. Moreover, integration of an adapted video microscope into a flow cytometer is an approach to overcome the gap between flow and image cytometry.

Animals

A population needs assessment profile for dementia.

The Tayside Profile for Dementia Planning is an instrument designed to obtain data for population needs assessment and planning. It provides a brief tool to collect a minimum dataset by non-specialists. Third-party informants-informal carers or involved professionals-are used as data sources. The key concept is the use of a descriptive profile rather than a summative score or categorization. The profile consists of a set of needs indicators, information on current service response and demographic and background data. Key levels of dependency are measured by time interval dependency. Validity, reliability, acceptability and usability are satisfactory, with the crucial exception that informal carers and professionals appear to perceive needs differently. Further research is needed to assess which type of informant provides the more useful data.

Caregivers

Evaluation of a novel infrared range vibration-based descriptor (EVA) for QSAR studies. 1. General application.

A novel molecular descriptor (EVA) based upon calculated infrared range vibrational frequencies is evaluated for use in QSAR studies. The descriptor is invariant to both translation and rotation of the structures concerned. The method was applied to 11 QSAR datasets exhibiting both a range of biological endpoints and various degrees of structural diversity. This study demonstrates that robust QSAR models can be obtained using the EVA descriptor and examines the effect of EVA parameter changes on these models; recommendations are made as to the appropriate choice of parameters. The performance of EVA was found to be comparable in statistical terms to that of CoMFA, despite the fact that EVA does not require the generation of a structural alignment. Models derived using semiempirical (MOPAC AM1 and PM3) and AMBER mechanics calculated normal mode frequencies are compared, with the overall conclusion that the semiempirical methods perform equally well and both outperform the AMBER-based models.

Computer Simulation