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[Basic principles for the design of an experimental automated system for performing prophylactic examinations of the population].

The purpose, set-up and main characteristics of a draft-project for an experimental automated system designed to conduct prophylactic medical examinations of the population (ASPEP) are discussed. The operation of the system proceeds by following a basic medical program that provides for automation of medical technological processes, input, transmission, treatment and storage of information, as well as filling in of examination cards, so as to identify persons exhibiting deviations from the parameters checked and to secure presentation of recording and review documentation. Results of a tentative estimates as to the economic advantages offered by the experimental ASPEP and conditions required to achieve the maximum economic effect by using this system are given.

Computers

OmicsQ: a user-friendly platform for interactive quantitative omics data analysis.

MOTIVATION: High-throughput omics technologies generate complex datasets with thousands of features that are quantified across multiple experimental conditions, but often suffer from incomplete measurements, missing values, and individually fluctuating variances. This requires analytical tools for accurate, deep and insightful biological interpretation, capable of dealing with a large variety of data properties and different amounts of completeness. Software capable of handling such data complexity and integrating with external applications for downstream analysis remains rare and mostly relies on programming-based environments, limiting accessibility for researchers without computational expertise. RESULTS: We present OmicsQ, an interactive, web-based platform designed to streamline quantitative omics data analysis. OmicsQ provides an intuitive, browser-based visualization interface that integrates established statistical processing tools. Those include robust batch correction, automated experimental design annotation, and handling of missing data without imputation, which maintains data integrity and avoids artifacts from a priori assumptions. OmicsQ seamlessly interacts with external applications (e.g. PolySTest, VSClust, ComplexBrowser) for statistical testing, clustering, analysis of protein complex behavior, and pathway enrichment, offering a comprehensive and flexible workflow from data import to biological interpretation that is broadly applicable across domains. AVAILABILITY AND IMPLEMENTATION: OmicsQ is implemented in R and Shiny and is available at https://computproteomics.bmb.sdu.dk/app_direct/OmicsQ. Source code and installation instructions: https://github.com/computproteomics/OmicsQ, DOI: 10.5281/zenodo.17778420.

Software

Aging in the rhesus monkey: effects on visual discrimination learning and reversal learning.

The behavior of aged rhesus monkeys (18 years and older) was compared to that of young monkeys (3 to 6 years old) to evaluate their relative abilities to learn a series of visual discrimination and discrimination reversal problems. Using a subject-paced, automated experimental procedure designed to optimize stimulus control and facilitate execution of choice responses, no consistent age-related differences were observed in the ability to learn new color and pattern discrimination problems of varying difficulty. However, a severe and consistent deficity on reversal learning did occur. A detailed analysis of this deficit revealed that not only did the aged monkeys take longer to extinguish the old habit and return to chance performance, but they continued to display a deficit in establishing accurate performance at above-chance levels as well. Since no reliable age differences were observed on the original discrimination learning problems, these data suggest that aging impairs mechanisms involved with response rigidity and/or susceptibility to intertrial proactive interference, more severely than those involved with the simple formation of new associations.

Aging

AI-driven CRISPR screening: optimizing gene editing through automation and intelligent decision support.

BACKGROUND: CRISPR-based genetic screening has become a central methodology in functional genomics, enabling systematic interrogation of gene function, genetic interactions and context-dependent vulnerabilities at scale. However, the rapid expansion of screening modalities-including multi-condition designs, combinatorial perturbations, in vivo applications and single-cell readouts-has exposed fundamental limitations of heuristic-driven experimental design and post hoc statistical analysis. MAIN BODY: This Review synthesizes how artificial intelligence is reshaping CRISPR screening by introducing predictive, adaptive and system-level intelligence across the experimental lifecycle. We organize recent advances into two tightly coupled modules. First, machine learning and deep learning (ML/DL) methods optimize experimental design by learning context-dependent perturbation behavior, anticipating confounding effects and enabling iterative, information-efficient screening strategies. Second, large language model-agent (LLM-agent) systems complement these advances by externalizing scientific reasoning, integrating biological knowledge at scale and coordinating analysis and decision-making in human-in-the-loop workflows. CONCLUSIONS: Together, ML/DL and LLM-agent approaches reframe CRISPR screening from a static analytical pipeline into an intelligent experimental system, with important implications for robustness, scalability and biological discovery.

Artificial Intelligence

Biological Parts in Yeast Synthetic Biology: From Regulatory Elements to Predictive Design Platforms.

Yeasts, particularly Saccharomyces cerevisiae, are important eukaryotic chassis for synthetic biology because of their tractable genetics, versatile toolkits, and broad utility in metabolic engineering and functional genomics. Progress in this field has been driven by biological parts that enable programmable control of gene expression and cellular behavior. Early efforts focused mainly on promoters, terminators, and other regulatory elements for tuning individual genes. However, as engineering expanded to multigene pathways, genetic circuits, and dynamic regulatory systems, the limits of part-centric design became clear. Part performance is often shaped by genomic context, chromatin state, host physiology, and interactions with other components, which restricts modularity and predictability. In response, yeast synthetic biology is shifting toward integrated design frameworks combining multilayer regulation, standardized assembly, automated experimentation, and computational modeling. This review provides an integrated perspective on the evolution of biological parts across DNA-, RNA-, and protein-level regulation, connecting these advances with assembly frameworks, biofoundries, and machine learning to trace the trajectory from part-centric engineering toward predictive, system-level design in yeast synthetic biology.

Biofoundry

[Current methodological problems in the determination of erythrocytes, hemoglobin and hematocrit].

Four instruments for the determination of RBC, Hb and PCV, with different degree of automation, have been compared in strictly routinary working conditions. Experimental protocols were designed in order to collect data for the assessment of both precision and accuracy: accuracy has been estimated by assuming the values obtained with the Coulter S as provisional reference values. In most instances, with particular reference to RBC, precision was higher with automated machines; however, Hb was quantitated with sufficient precision with a semi-automated technique and in the determination of PCV precision of the manual micro-centrifuge compared with precision of the automated instruments. As far as acuracy is regarded, collaborative experiments showed general agreement with the (provisional) reference values, with occasional occurrence of typical systematic errors in RBC and Hb determinations. The magnitude of the systematic error, however, was not constant with the same instrument in several analytical series. The whole of the results point out to the feasibility of obtaining clinically-significant analytical values with the several instruments tested. However good calibration and quality control procedures are necessary in order to maintain accuracy at acceptable levels. Improvement of precision is also needed in some instances.

Anemia

NCTR computer systems designed for toxicologic experimentation. V. Post-experiment information system.

The Post-Experiment Information System (PEIS) is an automated data collection and reporting system composed of three specialized subsystems: Pathology, Chemistry and Microbiology. These subsystems function either independently or collectively to construct and maintain a comprehensive data base of all experimental values derived from, or associated with, an animal carcass. All data are retrievable by the unique Carcass Identification (CID) number assigned at death, which is the correlative of the Unique Identification Number (UIN) assigned to the animal at birth and used throughout its lifespan. Elements processed under the PEIS include gross and microscopic pathological observations, organ weights, hematologic data, chemical data, and microbiological analyses. The ability of the system to integrate the post-experiment data with the information collected on an animal from birth (BIS) and during the experiment (EIS) provides a complete animal history to the Principal Investigator or other requestor.

Animals

NCTR computer systems designed for toxicologic experimentation. III. Breeding information system.

The Breeding Information System (BIS) facilitates management control of the breeding colony operation at the National Center for Toxicological Research (NCTR). Although this automated data handling system was initially intended to support Animal Husbandry the system's basic design, flexibility or reporting, data manipulation capabilities, and integration with other NCTR data collection systems provides BIS with capabilities that have application to other groups including the Plans and Programs and most scientific areas. This description of the System is in terms of its potential value to these diverse user groups.

Animal Husbandry

Automated development of a kinetic method for the continuous-flow determination of creatinine.

A "stopped-flow" method for the kinetic Jaffé determination of creatinine was developed, with the use of a computer-controlled continuous-flow system. Simplex optimization was used to find conditions of hydroxide and picrate giving maximum sensitivity for creatinine. We used a modified central composite experimental design to evaluate creatinine sensitivity and albumin, glucose, and acetone interferences as functions of hydroxide and picrate concentrations. More importantly, this work illustrates that the automated development of clinical chemical methods offers an efficient means of obtaining optimized, well-understood analytical procedures for subsequent routine use in the clinical chemistry laboratory.

Autoanalysis

Ingestive behavior and composition of weight change during cyproheptadine administration.

The effect of cyproheptadine on spontaneous energy intake was studied by means of an automated (liquid diet) food-dispensing apparatus in two nonobese adults confined to a metabolic ward. The experimental design included both single and double-blind periods. Throughout, the composition of daily weight change was determined by the energy-nitrogen balance method. While on cyproheptadine, both subjects exhibited increases in energy intake with the following average composition of weight gain: protein 16%, fat 14% and water 70% (first subject), and protein 5%, fat 49% and water 46% (second subject). The cyproheptadine-induced increase in energy intake was statistically significant in one of the subjects, who was at his desirable weight level at the outset. The other subject was underweight initially and tended to gain throughout the experiment, although rate of weight gain appeared to be more rapid during the periods of cyproheptadine administration. Energy output in both subjects remained fairly constant throughout. We conclude that cyproheptadine induces weight gain of 'normal' composition by stimulating increased energy intake.

Adult

Components and results of a new preparation technique for automated analysis of cervical samples.

Components and evaluations of a new preparative procedure for automated high-resolution analysis of cervical samples are presented. This procedure is based on sedimentation velocity separation of samples with subsequent fractionation of the separation column and centrifugal deposition of suspended cells on coated glass slides. A system for specimen collection and mailing of suspended samples is described. A new type of glass slide designed for automated analysis is presented, and centrifugal buckets for cell deposition on a 6-sq-cm area are described. Experimental results with different kinds of coating substances for glass slides as well as different isopyknic media are discussed, and data for differential cell counts are graphically demonstrated. Looking at the diagnostic accuracy and economic feasibility of this system, the authors realize that preparations have to be evaluated quantitatively and that constraints of sample size and processing time have to be taken into consideration for further developments.

Autoanalysis

Incubator-Free Organoid Culture in a Sealed Recirculatory System.

Organoids are powerful tools for studying development and disease, offering realistic organ-like human and animal tissues and facilitating experimental observation compared to live animal models. However, traditional organoid culture methods require a humidified incubator. This requirement complicates culture due to evaporative losses and restricted access to instrumentation, hindering the potential of organoids as physiologically accurate models easily subjected to detailed experimental observation. We introduce a compact, automated, sealed, incubator-free recirculatory organoid culture platform that replaces the air-liquid interface with a nonporous polymer gas exchanger and a liquid-phase gas buffer. This design prevents evaporation and stabilizes oxygen, pH, and osmolarity without feedback control. It enables single-actuator media exchange, simplifying automation. Dispensing with the incubator, we improve access for instruments such as live cell microscopes. We demonstrate compatibility with continuous multi-week live imaging of vascular organoids and show that brain organoids in this system maintain metabolic viability, structural fidelity, and electrophysiological activity comparable to traditional shaker-based cultures in an incubator.

Journal Article

Automated upper extremity progressive resistive exercise system.

This paper describes a semiautomated, motorized skateboard and skate system for use in progressive resistive arm exercises. This experimental system has been evaluated in an occupational therapy clinic for the past two years and found to be valuable in the treatment of impaired upper extremity function. It is superior in function and design to the previously used apparatus and provides the following features: adjustable load (force), adjustable range of motion limits, an automatic method of counting the correct repetitions of the prescribed exercise, the visual feedback to patients regarding their performance. Based on therapists' evaluations, the system's three main advantages are: a decrease in the amount of therapist/attendant time needed for the exercise program, improved performances by the patients, and a better, quantitative measure of the patients' progress.

Adult

Toward Class Imbalance and Uncertainty in Powder XRD Analysis: A Dual-Channel Fusion Network for Space Group Classification.

Accurate identification of space groups from powder X-ray diffraction (pXRD) is essential for understanding crystal structures and accelerating materials discovery. However, this task remains highly challenging due to inherent peak overlap, experimental noise, and the complexity of the 230-class classification problem. To address the critical issues of class imbalance and data scarcity, we first design a general physics-informed data augmentation pipeline. We then propose a dual-channel fusion uncertainty-aware network (DFUN) for automated space group classification. The DFUN architecture integrates two complementary feature representations: convolutional features extracted directly from raw diffraction profiles and domain-specific peak descriptors. These distinct representations are adaptively fused through a gating mechanism. Furthermore, to mitigate the inherent long-tailed distribution of crystallographic data, we employ a hybrid loss function that combines Focal Loss with Label Smoothing. Finally, we incorporate Monte Carlo Dropout to provide predictive uncertainty estimation, thereby enabling not only accurate classification but also a crucial assessment of the model's reliability. Evaluated on large-scale simulated data and two public data sets (opXRD and RRUFF), DFUN outperforms the evaluated baseline methods across the reported metrics. The framework also provides uncertainty-aware predictions, establishing DFUN as a robust and interpretable solution for high-throughput automated crystallographic analysis from powder diffraction.

Uncertainty

An image analysis system for cervical cytology automation using nuclear DNA content.

An experimental computer/image analysis system has been used to investigate cytology automation techniques based on nuclear DNA measurement and morphological artefact rejector tests. The system automatically measures and normalizes the integrated optical density of cell nuclei in specially prepared cervical cytology specimens, and selects any objects with abnormally high values for further analysis. These are then analyzed by morphological and densitometric tests designed to eliminate false positive signals caused by non-nuclear artefacts. The coordinates of the remaining abnormal nuclei are recorded so that they can subsequently be relocated and examined by a cytotechnician. Preliminary results are given showing the measurement accuracy of the system and the performance of the artefact rejection tests.

Cell Nucleus

Determination of total CO2 in plasma by automated flow-injection analysis.

We describe a procedure for measuring total CO2 in plasma, based on the principles of the flow-injection analysis technique, which makes use of unsegmented fast-flowing reagent streams, as developed by Růziĉka and co-workers. The further methodological design resembles the silicone-rubber membrane technique of Kenny and Cheng. CO2 in the sample is released by reaction with H2SO4. Appropriate amounts of CO2 permeate through the membrane that separates the acid reagent streams and a buffered cresol-red indicator system. The experimental set-up and functioning of this system are described.

Autoanalysis

Sensitive and Visualized Detection of Hantavirus Using CRISPR/Cas12a Based on AutoCORDSv2 Design.

In recent years, detection technologies based on the CRISPR/Cas12a method have been extensively utilized in the fields of nucleic acid, enzyme, and macromolecule detection, thereby reinforcing their significant role in the detection landscape. Enhancing the simplicity of design, efficiency, and automation of the CRISPR/Cas12a detection system is essential for advancing its application in diagnostics. Recently, we developed an automated CRISPR/Cas12a design system named AutoCORDSv2. This system can process published genomic sequences of pathogenic bacteria in a high-throughput manner and automatically generate conserved and highly specific crRNA sequences, along with primer sequences for target amplification. This capability facilitates the specific and precise design of the CRISPR/Cas12a detection system. In this study, crRNAs targeting the Hantaan virus (HTNV) and Seoul virus (SEOV), as well as RT-PCR primers and RT-RPA primers, were designed using AutoCORDSv2. The experimental results demonstrated that the CRISPR/Cas12a system, automatically designed by AutoCORDSv2, was specific for the detection of both the HTNV and SEOV, with no cross-reactivity observed with other pathogens. The detection sensitivity reached 6 copies/μL (equivalent to 111 copies per amplification reaction), whether measured by a microplate reader or directly observed with the naked eye. The detection results for 50 samples were consistent with those obtained from commercial RT-qPCR kits, indicating high precision. Furthermore, the CRISPR/Cas12a system designed by AutoCORDSv2 can also be utilized for the development of a single-tube detection system with a sensitivity of 42 copies per reaction. This system combined with a 5-min extraction step and RT-RPA, further underscoring its potential for application.

CRISPR-Cas Systems

Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects.

Using an automated immunoprecipitin method, we assayed human sera for 10 proteins: haptoglobin, orosomucoid, transferrin, alpha1 antitrypsin, alpha2-macroglobulin, IgG, IGa, IgM, complement C3, and complement C4. Blood from 14 healthy subjects (25-40y) was sampled on six separate days. From each venipuncture serum was divided into four eliquots; two were assayed on the day of venipuncture and two were frozen and kept until the end of the study, when all of the frozen samples were analyzed in one batch. With this experimental design, batch-to-batch analytical variation could be estimated, and we avoided confounding it with the biological variation. Data analysis was based on the analysis of variance technique. The average physiological intra-individual coefficient of variation ranged from 2.5% for transferrin to 11.1% for orosomucoid. THe interindividual variation ranged from 9.5% for transferrin to 70.5% for haptoglobin and the ratio between intra-individual variation and interindividual variation ranged from 0.66 for IgM to 0.26 for orosomucoid and transferrin.

Adult