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At least 37 records · Page 2Linked to original sources

PubMed2005

Fixation of total knee arthroplasty improved by mobile-bearing design.

We examined the in vivo displacement of mobile-bearing polyethylene and its effect on prosthesis-bone fixation. Thirty-five patients with the Interax ISA mobile platform total knee arthroplasties were examined by roentgen stereophotogrammetric analysis. Our protocol included weightbearing to measure the range of motion of the mobile platform in relation to the tibial component. We also studied the micromotions of the tibial component in relation to the tibia during a 2-year followup. The analysis of micromotion (maximum total motion mean, 0.5 mm; subsidence mean, 0.15 mm) showed this mobile platform design is stable and improves fixation at the prosthesis-bone interface. Longitudinal rotations of the mobile platform occurred in all patients and followed a homogeneous pattern of motion, depending on the examination. However, anteroposterior translations did not show any patterns with specific examination. This suggests the meniscal movement adapts itself to different weightbearing conditions. We measured the in vivo mobile-bearing displacement under static loading conditions. We also observed improved fixation at the bone-prosthesis interface.

Adult↗

PubMed1999

An experimental model of tibial counterface polyethylene wear in mobile bearing knees: the influence of design and kinematics.

Current designs of mobile bearing knees have different kinematics at the tibial counterface articulation; unidirectional represented by linear tracks and rotating platform designs, and multidirectional represented by reduced constraint designs with motion of the tibial surface in A-P and M-L directions simultaneously. One fifth scale experimental models of the tibial counterface articulation have been developed with mean contact stresses of 0.6 MPa. The unidirectional model had a linear reciprocating motion with a 10 mm stroke, the multidirectional model had a reciprocating motion with a 10 mm stroke and simultaneous rotation of +/- 7.5 degrees. Six specimens of GUR415 polyethylene were tested for each model, sliding on polished cobalt chrome counterfaces with Ra < 0.01 micron in 25% bovine serum lubricant. The mean +/- STERR wear rates were: unidirectional 0.045 +/- 0.015 mm3/million cycles and multidirectional 0.44 +/- 0.15 mm3/million cycles. Applying the scaling factor of 5, the predicted wear rates in actual knee prostheses were: unidirectional 0.23 mm3/million cycles and multidirectional 2.2 mm3/million cycles. The order of magnitude increase in wear rate was statistically significant (p = 0.05).

Arthroplasty, Replacement, Knee↗

PubMed2026

SeqUIaSCOPE: multi-omics data integration platform for single-patient clinical oncology pathway exploration.

SUMMARY: SeqUIaSCOPE is an open-source platform designed for routine clinical oncology diagnostics through case-centric integration and visualization of genomic variants, fusion events, and expression profiles. The platform combines molecular-level validation via embedded genome browsing with systems-level interpretation through dynamic pathway visualization, enabling geneticists to assess how alterations converge across biological networks. Flexible reporting with customizable templates accommodates diverse institutional requirements, while secure cluster-based or local deployment ensures compliance with data protection policies, making advanced multi-omics diagnostics accessible to academic and clinical institutions. AVAILABILITY AND IMPLEMENTATION: SeqUIaSCOPE is freely available on GitHub at https://github.com/BioIT-CEITEC/sequiascope under the MIT license and archived at Zenodo (https://zenodo.org/records/21338445). Due to the sensitive nature of patient data, the repository provides simulated datasets that mimic the structure of real clinical data for testing and exploration. Documentation and a live demo accompany these datasets, allowing users to explore the application without any prior setup. The repository also includes a Helm chart for Kubernetes deployment and Docker containers for local deployment, ensuring compatibility across Linux, macOS, and Windows. No user registration is required, and all data remains on local or institutional infrastructure.

Humans↗

PubMed2003

Gait cycle finite element comparison of rotating-platform total knee designs.

Functional load transmission and kinematic performance were compared for standard versus posterior-stabilized versions of a rotating-platform total knee implant, over a standardized loading cycle, using three-dimensional contact finite element analysis. These two design variants differ primarily in terms of the latter's polyethylene insert having a cam that engages with the femoral component during appreciable flexion, thereby inducing femoral component rollback. The finite element model, previously validated experimentally, afforded direct comparisons of anterior lift-off of the insert from the tibial tray, of bearing mobility (insert rotation about the pivot post), of femoral rollback, and of metal-on-polyethylene contact stresses at the bearing and backside surfaces of the insert. Both design variants generally performed comparably, exhibiting an internal and external rotation range of approximately 5 degrees, approximately 1.5 mm peak lift-off at the anterior aspect of the insert, and approximately 15 mm of posterior rollback, the respective maxima for both designs occurring at approximately the same instants in the gait cycle. However, the posterior-stabilized design had slightly more rollback, and slightly less anterior lift-off and rotation, than did the standard rotating-platform design. Peak polyethylene stresses occurred on the backside of the insert near the posterior edge of the medial compartment, the magnitude being approximately 18% higher for the posterior-stabilized design (21 MPa) than for the standard design.

Finite Element Analysis↗

PubMed2005

A leukemia-enriched cDNA microarray platform identifies new transcripts with relevance to the biology of pediatric acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Microarray gene expression profiling has been widely applied to characterize hematologic malignancies, has attributed a molecular signature to leukemia subclasses and has allowed new subclasses to be distinguished. We set out to use microarray technology to identify novel genes relevant for leukemogenesis. To this end we used a unique leukemia-enriched cDNA microarray platform. DESIGN AND METHODS: The systematic sequencing of cDNA libraries of normal and leukemic bone marrow allowed us to increase the number of genes to yield a new release of a previously generated cDNA microarray. Using this platform we analyzed the expression profiles of 4,670 genes in bone marrow samples from 18 pediatric patients with acute lymphoblastic leukemia (ALL). RESULTS: Expression profiling consistently distinguished the leukemia patients into three groups, those with T-ALL, B-ALL and B-ALL with MLL/AF4 rearrangement, in agreement with the clinical classification. Our platform identified 30 genes that best discriminate these three subtypes. Using mini-array technology these 30 genes were validated in another cohort of 17 patients. In particular we identified two novel genes not previously reported: endomucin (EMCN) and ubiquitin specific protease 33 (USP33) that appear to be over-expressed in B-ALL relative to their expression in T-ALL. INTERPRETATION AND CONCLUSIONS: Microarray technology not only allows the distinction between disease subclasses but also offers a chance to identify new genes involved in leukemogenesis. Our approach of using a unique platform has proven to be fruitful in identifying new genes and we suggest exploration of other malignancies using this approach.

Adolescent↗

PubMed2002

AstexViewer: a visualisation aid for structure-based drug design.

AstexViewer is a Java molecular graphics program that can be used for visualisation in many aspects of structure-based drug design. This paper describes its functionality, implementation and examples of its use. The program can run as an Applet in a web browser allowing structures to be displayed without installing additional software. Applications of its use are described for visualisation and as part of a structure based design platform. The software is being made freely available to the community and may be downloaded from http://www.astex-technology.com/AstexViewer.

Computer Graphics↗

PubMed2025

The development and usability of 'The Genetics Navigator': a digital solution for adult and paediatric clinical genetics services.

Clinical genetic services address diverse genetic testing needs, but there is no comprehensive digital solution to meet this variety. We aimed to develop and test the usability of the Genetics Navigator (GN), a platform designed to enhance genetic services for paediatric and adult patients. The GN prototype was created with input from a patient and clinician advisory board, informed by prior research. Usability testing involved genetics patients (N = 14), parents of paediatric patients (N = 4), and the general public (N = 10). Participants provided feedback using the 'think aloud' method when using the platform. We used the System Usability Scale (SUS) for quantitative evaluation. Qualitative data were coded by platform section, item, and identified key areas for improvement. Building on the Genetics Adviser platform, we added video and written content for various genetic conditions and patient groups, including pre-test education, counselling, decision support, history collection, post-test result disclosure, and management. Key feedback during rounds of usability testing emphasized the need for a supportive design, seamless workflow, and engaging experience of the tool. The tool was modified to reflect the feedback, and the GN achieved an average SUS score of 87.7 ± 10.9 (N = 28), indicating above-average usability. Future research will evaluate its clinical and cost-effectiveness in a randomized trial.

Humans↗

PubMed2004

In vitro and in silico processes to identify differentially expressed proteins.

We present an integrated proteomics platform designed for performing differential analyses. Since reproducible results are essential for comparative studies, we explain how we improved reproducibility at every step of our laboratory processes, e.g. by taking advantage of the powerful laboratory information management system we developed. The differential capacity of our platform is validated by detecting known markers in a real sample and by a spiking experiment. We introduce an innovative two-dimensional (2-D) plot for displaying identification results combined with chromatographic data. This 2-D plot is very convenient for detecting differential proteins. We also adapt standard multivariate statistical techniques to show that peptide identification scores can be used for reliable and sensitive differential studies. The interest of the protein separation approach we generally apply is justified by numerous statistics, complemented by a comparison with a simple shotgun analysis performed on a small volume sample. By introducing an automatic integration step after mass spectrometry data identification, we are able to search numerous databases systematically, including the human genome and expressed sequence tags. Finally, we explain how rigorous data processing can be combined with the work of human experts to set high quality standards, and hence obtain reliable (false positive < 0.35%) and nonredundant protein identifications.

Body Fluids↗

PubMed2004

Boarding and alighting injury experience with different station platform and car entranceway designs on US commuter railroads.

Commuter railroad systems in the US employ three combinations of station platforms and car entranceways. These are high-level platforms with remotely controlled doors and level entranceway (HL-RC), low-level platforms (just above the rail) with steps and remotely controlled doors (LL-RC), and a mixture of the two platform types with a correspondingly more complex, partly manual, door and entranceway arrangement (ML-MO). Much controversy exists over which type of platform/entranceway is better. This seemingly small feature significantly impacts many performance characteristics of these systems, including cost, speed, and boarding and alighting accidents. Northeastern systems are generally moving toward the mixed platform design or all high-level platforms, while systems elsewhere are generally selecting the low-level design. Data on actual accident experience for 1995-2000 are analyzed to determine the effect of platform/entranceway type on passenger and employee injuries. Passenger injury rates on systems with the HL-RC design are lowest, with LL-RC systems next, and ML-MO systems having the highest rates. Employee injury rates are the least on LL-RC systems, but higher on ML-MO and HL-RC systems. Systems with a mixture of high and low platforms (ML-MO) experience a higher overall (combined passenger and employee) injury rate than the other two designs. The implications of these results for both the modernization of existing systems and the design of new systems, in the US and abroad, are discussed.

Accidents, Occupational↗

PubMed2026

Freezing with Light: Photo-Cross-Linking-Assisted Platform Enables GPCR Deorphanization.

Despite their success as drug targets, nearly one hundred G protein-coupled receptors (GPCRs) remain orphan without identified endogenous ligands. Defining these ligand-receptor pairs constitute a fundamental prerequisite for understanding receptor biology and rational drug discovery. However, deorphanization remains inherently challenging due to the transient and interface-specific ligand-GPCR interactions, especially for endogenous ones that are embedded within chemically complex environments. This In Focus article highlights a modularly designed platform that integrates site-specific photo-cross-linking reaction with proteomics to enable ligand-GPCR pairing directly in native biological contexts. Using this strategy, neuropeptide L-LEN was identified as the endogenous ligand for GPR50, forming a regulatory axis that controls energy expenditure and thermogenesis through brain-peripheral interactions.

Receptors, G-Protein-Coupled↗

PubMed2026

The Gyrolab platform for immunogenicity assessment and biotherapeutic and biomarker analysis: technical advances and bioanalytical applications.

Gyrolab is an automated ligand‑binding assay platform designed for the quantification of proteins with high sensitivity and broad dynamic range. Its low minimum required dilution and microfluidic disc format enable efficient sample processing while maintaining assay robustness, making it a valuable tool across drug‑development stages. This review summarizes published applications of Gyrolab for pharmacokinetic and toxicokinetic analysis and immunogenicity assessment through anti‑drug antibody detection. In addition, the platform's high-volume assay discs have facilitated its use in biomarker studies, allowing quantification of low‑abundance analytes. Representative examples from the literature are presented together with key assay elements, including analytes, matrices, dynamic ranges, and critical reagents. Because assay replicates remain an important consideration for Gyrolab workflows, recent publications addressing singlet versus duplicate strategies and their impact on data interpretation are also discussed. Finally, we provide real analytical data visualized using a three‑dimensional Gyrolab viewer to illustrate variability in duplicate measurements and to highlight future opportunities for improving assay reliability.

Humans↗

PubMed1997

Kinematics of posterior cruciate ligament-retaining and -sacrificing mobile bearing total knee arthroplasties. An in vitro comparison of the New Jersey LCS meniscal bearing and rotating platform prostheses.

The posterior cruciate ligament (PCL)-retaining, meniscal bearing and the PCL-sacrificing rotating platform designs of the LCS prosthesis (DePuy, Warsaw, IN) were designed to minimally constrain knee kinematics while minimizing bone-cement-prosthesis interface stresses and polyethylene wear. The kinematics and stability of the knee following arthroplasty with these devices rely on adequate tensioning of the remaining soft tissues by management of the flexion/extension gaps at the time of surgery. In this in vitro study, the knee kinematics of the function of the quadriceps mechanism for 8 cadaveric knees were measured quantitatively before and after implantation of these 2 prosthesis designs. Following implantation of the PCL-retaining, meniscal bearing prosthesis, anterior translations during anterior drawer testing were significantly greater (P < .05) than those seen in the intact knee. Implantation of the PCL-retaining, meniscal bearing prosthesis resulted in an increase in the extension gap of 2 mm. Quadriceps force needed to achieve full extension was increased by 30% over that needed in the intact knee. The PCL-sacrificing, rotating platform prosthesis constrained anterior translation such that nearly normal anterior knee stability was reestablished; however, the extension gap was increased by 4 mm and the quadriceps force needed to achieve full extension was 50% greater than that needed in the intact knee. Attempts to achieve joint stability by increases in the thickness of the tibial component to widen the flexion/extension gaps results in compromises of quadriceps efficiency, particularly in the absence of a functioning PCL, as demonstrated in this in vitro model. Patients receiving the PCL-sacrificing prosthesis may experience difficulty in those activities requiring quadriceps power near full extension, such as rising from a chair or ascending or descending stairs.

Arthroplasty, Replacement, Knee↗

PubMed2001

A comparison of vertical force and temporal parameters produced by an in-shoe pressure measuring system and a force platform.

OBJECTIVE: To investigate the ability of Pedar in-shoe system to measure vertical force accurately, by comparing it with the Kistler force platform. DESIGN: In vivo experiment in normal subjects. BACKGROUND: It has been suggested Pedar is highly reliable, but absolute accuracy of the system with regard to force measurement has not been comprehensively tested. METHODS: Sampling at 99 Hz, using five healthy subjects, simultaneous data were collected barefoot, and in three types of shoes (Trainers, Oxfords, Slip-on Deck Type). Six variables obtained from the force/time curve from each footstep were compared. RESULTS: The temporal data recorded by Pedar correlated well with that obtained using Kistler, with significant differences only in overall duration of the step in Deck shoes (P < 0.001) and Oxford shoes (P < 0.01), and peak to peak barefoot (P < 0.01). Pedar recorded a lower first peak force and mid-peak force in all cases (P < 0.001). However, the magnitude of the 2nd peak force recorded by both systems was significantly different only in Trainers (P < 0.05) and Oxford shoes (P < 0.001). The impulse data obtained with Oxford shoes was not significantly different, although barefoot, Trainers and Deck shoes were significantly lower (P < 0.001) for Pedar. CONCLUSIONS: In most cases, comparison of data recorded by the two systems provided good evidence for the accuracy and reliability of temporal measurements and second peak force measurements taken with the Pedar in-shoe system. Relevance. In-shoe pressure data provides evidence for clinical decisions if the systems utilised are proven to be valid, repeatable and accurate. Comparison with an established force platform enables some assessment of these factors.

Adult↗

PubMed2000

A comparison of vertical force and temporal parameters produced by an in-shoe pressure measuring system and a force platform.

OBJECTIVE: To investigate the ability of Pedar in-shoe system to measure vertical force accurately, by comparing it with the Kistler force platform. DESIGN: In vivo experiment in normal subjects. BACKGROUND: It has been suggested Pedar is highly reliable, but absolute accuracy of the system with regard to force measurement has not been comprehensively tested. METHODS: Sampling at 99 Hz, using five healthy subjects, simultaneous data were collected barefoot, and in three types of shoes (Trainers, Oxfords, Slip-on Deck Type). Six variables obtained from the force/time curve from each footstep were compared. RESULTS: The temporal data recorded by Pedar correlated well with that obtained using Kistler, with significant differences only in overall duration of the step in Deck shoes (P<0. 001) and Oxford shoes (P<0.01), and peak to peak barefoot (P<0.01). Pedar recorded a lower first peak force and mid-peak force in all cases (P<0.001). However, the magnitude of the 2nd peak force recorded by both systems was significantly different only in Trainers (P<0.05) and Oxford shoes (P<0.001). The impulse data obtained with Oxford shoes was not significantly different, although barefoot, Trainers and Deck shoes were significantly lower (P<0.001) for Pedar. CONCLUSIONS: In most cases, comparison of data recorded by the two systems provided good evidence for the accuracy and reliability of temporal measurements and second peak force measurements taken with the Pedar in-shoe system. Relevance In-shoe pressure data provides evidence for clinical decisions if the systems utilised are proven to be valid, repeatable and accurate. Comparison with an established force platform enables some assessment of these factors.

Adult↗

PubMed2026

GRNContext: an interactive web platform for contextualized gene regulatory networks visualization across human cancers.

SUMMARY: While current Gene Regulatory Network (GRN) databases provide comprehensive reference maps of potential interactions between transcription factors and target genes, they do not specify which regulatory interactions are active within specific biological contexts. This limitation is particularly critical in cancer, where transcriptional programs are inherently tissue-specific. To address this gap, we developed GRNContext, an interactive web platform designed for the visualization, exploration, and comparative analysis of gene regulatory networks contextualized across 33 cancer types from The Cancer Genome Atlas (TCGA). Our approach uses the TFLink human reference GRN as a starting point and integrates TCGA transcriptomic profiles to infer cancer-specific regulatory activity. Regulatory relevance was assessed using complementary machine learning and statistical methods, which were unified into a consensus score to prioritize and filter the most relevant candidate regulators for each target gene. By providing both curated context-specific GRNs and a user-friendly platform, GRNContext constitutes a comprehensive and accessible resource that supports mechanistic investigations, hypothesis generation, and translational research focused on transcriptional regulation in cancer. AVAILABILITY AND IMPLEMENTATION: GRNContext is supported by all major browsers and freely available on the web at https://apps.cienciavida.org/grncontext. It is implemented as a client-server web application featuring a FastAPI backend and a React frontend utilizing Cytoscape.js for interactive network visualization, all containerized via Docker for cross-platform compatibility.

Humans↗

PubMed2005

The influence of design, materials and kinematics on the in vitro wear of total knee replacements.

Debris-induced osteolysis due to surface wear of ultra high molecular weight polyethylene (UHMWPE) bearings is a potential long-term failure mechanism of total knee replacements (TKR). This study investigated the effect of prosthesis design, kinematics and bearing material on the wear of UHMWPE bearings using a physiological knee simulator. The use of a curved fixed bearing design with stabilised polyethylene bearings reduced wear in comparison to more flat-on-flat components which were sterilised by gamma irradiation in air. Medium levels of crosslinking further improved the wear resistance of fixed bearing TKR due to resistance to strain softening when subjected to multidirectional motion at the femoral-insert articulating interface. Backside motion was shown to be a contributing factor to the overall rate of UHMWPE wear in fixed bearing components. Wear of fixed bearing prostheses was reduced significantly when anterior-posterior displacement and internal-external rotation kinematics were reduced due to decreased cross shear on the articulating surface and a reduction in AP displacement. Rotating platform mobile bearing prostheses exhibited reduced wear rates in comparison to fixed bearing components in these simulator studies due to redistribution of knee motion to two articulating interfaces with more linear motions at each interface. This was observed in two rotating platform designs with different UHMWPE bearing materials. In knee simulator studies, wear of TKR bearings was dependent on kinematics at the articulating surfaces and the prosthesis design, as well as the type of material.

Biocompatible Materials↗

PubMedDate not supplied

Exhaustive de novo design of low-molecular-weight fragments against the ATP-binding site of DNA-gyrase.

We present a de novo design approach to generating small fragments in the DNA-gyrase ATP-binding site using the computational drug design platform SkelGen. We have generated an exhaustive number of structural possibilities, which were subsequently filtered for site complementarity and synthetic tractability. A number of known active fragments are found, but most of the species created are potentially novel and could be valuable for further elaboration and development into lead-like structures.

Adenosine Triphosphate↗

PubMed1995

Selective depression of medium-latency leg and foot muscle responses to stretch by an alpha 2-agonist in humans.

1. In standing humans, toe-up rotation of a platform induces a short-latency (SLR) and a medium-latency response (MLR) in both soleus (Sol) and flexor digitorum brevis (FDB) muscles. Toe-down rotation evokes a MLR in the tibialis anterior (TA). The SLR is the counterpart of the monosynaptic stretch reflex, but the origin of the MLR is still debated. By means of tizanidine (an alpha 2-adrenergic receptor agonist) we tested the hypothesis that the MLR is relayed by group II afferent fibres, since animal data indicate that tizanidine or stimulation of monoaminergic brainstem centres decrease the excitability of spinal interneurones supplied by those fibres. In addition, we compared the effect of the drug on these responses with that induced by stabilization of posture. 2. Eight subjects received tizanidine (150 micrograms kg-1 orally) or placebo, in a single-blind design. Platform rotations were delivered prior to administration and for 3 h afterwards. Both TA- and FDB-MLRs decreased in size, starting from about 1 h after tizanidine administration. Sol-SLR was unaffected. Response latencies were unchanged. Placebo induced no changes in any response. In each subject, the extent of TA-MLR depression induced by holding onto a frame and by tizanidine was superimposable. 3. The selective effect of tizanidine on MLR supports the notion that it is relayed through group II afferent fibres. The similar effects of holding and tizanidine on the response suggests that it is modulated by monoaminergic centres.

Adrenergic alpha-Agonists↗