PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “single platform”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

Pharmacodynamic modeling of the entire time course of leukopenia after a 3-hour infusion of paclitaxel.

The entire time course of leukopenia after anticancer treatment is clinically more relevant than a singly measured nadir count. In order to identify factors associated with neutropenic fever, a mechanistic pharmacodynamic model with two compartments corresponding to leukocytes in bone marrow and peripheral blood was applied to describe the time course of leukopenia. Seventeen patients with breast cancer were treated with 210 mg / m(2) of paclitaxel infused over 3 h as a single agent in a phase II study. Adequate fitting of the time course of leukopenia was achieved in all patients, and time-dependent parameters, including the time period during which leukocyte counts remained below 2000 / microl and the area between the curve for time versus leukocyte counts and the line of a leukocyte count of 2000 / microl (A < 2000), were calculated in each patient. Leukopenia was not significantly correlated with pharmacokinetic parameters, including time above a threshold concentration or the area under the time-concentration curve. A negative correlation between age and the sensitivity parameter of the pharmacodynamic model was observed (r (2) = 0.21, P = 0.07). Patients who experienced neutropenic fever had a larger A < 2000 than patients who did not experience fever (4512 vs. 6 days / microl, P = 0.05), but fever was not significantly related to any pharmacokinetic parameter or the leukocyte nadir count. Febrile episodes were better associated with the time course of leukopenia than the singly measured nadir count, and the pharmacodynamic model presents a novel platform to analyze the entire time course of leukopenia.

Adult↗

Brief inactivation of c-Myc is not sufficient for sustained regression of c-Myc-induced tumours of pancreatic islets and skin epidermis.

BACKGROUND: Tumour regression observed in many conditional mouse models following oncogene inactivation provides the impetus to develop, and a platform to preclinically evaluate, novel therapeutics to inactivate specific oncogenes. Inactivating single oncogenes, such as c-Myc, can reverse even advanced tumours. Intriguingly, transient c-Myc inactivation proved sufficient for sustained osteosarcoma regression; the resulting osteocyte differentiation potentially explaining loss of c-Myc's oncogenic properties. But would this apply to other tumours? RESULTS: We show that brief inactivation of c-Myc does not sustain tumour regression in two distinct tissue types; tumour cells in pancreatic islets and skin epidermis continue to avoid apoptosis after c-Myc reactivation, by virtue of Bcl-xL over-expression or a favourable microenvironment, respectively. Moreover, tumours progress despite reacquiring a differentiated phenotype and partial loss of vasculature during c-Myc inactivation. Interestingly, reactivating c-Myc in beta-cell tumours appears to result not only in further growth of the tumour, but also re-expansion of the accompanying angiogenesis and more pronounced beta-cell invasion (adenocarcinoma). CONCLUSIONS: Given that transient c-Myc inactivation could under some circumstances produce sustained tumour regression, the possible application of this potentially less toxic strategy in treating other tumours has been suggested. We show that brief inactivation of c-Myc fails to sustain tumour regression in two distinct models of tumourigenesis: pancreatic islets and skin epidermis. These findings challenge the potential for cancer therapies aimed at transient oncogene inactivation, at least under those circumstances where tumour cell differentiation and alteration of epigenetic context fail to reinstate apoptosis. Together, these results suggest that treatment schedules will need to be informed by knowledge of the molecular basis and environmental context of any given cancer.

Animals↗

Single-molecule detection sensitivity using planar integrated optics on a chip.

We present a fully planar integrated optical approach to single-molecule detection based on microfabricated planar networks of intersecting solid and liquid-core waveguides. We study fluorescence from dye molecules in liquid-core antiresonant reflecting optical waveguides, and demonstrate subpicoliter excitation volumes, parallel excitation through multiple pump waveguides, and single-molecule detection sensitivity. Integrated silicon photonics combined with single-molecule detection in solution create a compact, robust, and sensitive platform that has applications in numerous fields ranging from atomic physics to the life sciences.

Biopolymers↗

Microplastics and nanoplastics-related genes signature predicts prognosis in pancreatic ductal adenocarcinoma and functional validation of interleukin 1 alpha.

BACKGROUND: Microplastics and nanoplastics (MNPs), as emerging environmental pollutants, have garnered significant attention from the global scientific community due to their potential threats to human health, particularly their association with the occurrence and development of cancer. The goal of our study is to create a predictive marker for pancreatic ductal adenocarcinoma (PAAD) based on MNPs-related genes, with the purposes of predicting survival outcomes and assessing the tumor immune microenvironment. METHODS: Using multi-cohort data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC), we assessed the association between MNPs and PAAD prognosis through the Xiantao Academic (https://www.xiantao.love/). The development of a prognostic signature was followed by an assessment of its significance through the Kaplan-Meier method, time-dependent receiver operating characteristic (ROC), and decision curve analysis (DCA). The validity of the risk model was confirmed through the ICGC and GSE71729 cohorts. The model was then assessed for levels of tumor immune infiltration. To explore MNPs-related genes expression characteristics within immune cells in PAAD, we performed single-cell RNA sequencing and spatial transcriptomics analysis through the Sparkle Platform (https://grswsci.top/). Finally, in vitro experiments were conducted to investigate the biological function of interleukin 1 alpha (IL1A). RESULTS: A four-gene signature comprising XDH, IL1A, KIF20A, and ASPM, based on MNPs, was developed to stratify PAAD patients into two distinct risk groups. The high-risk group showed a significantly poorer prognosis. A similar trend was verified in the external cohorts ICGC and GSE71729. The signature risk score affected immune cell infiltration in the PAAD microenvironment. The infiltration of B cells, CD8+ T cells, cytotoxic cells, immature dendritic cells (iDCs), mast cells, plasmacytoid dendritic cell (pDC), T cells, Tem cells, T follicular helper (TFH) cells, and T helper 17 (Th17) cells had a positive correlation with the low-risk group. In contrast, high-risk patients tended to have increased number of T helper (Th2) cells and higher expression of SIGLEC15, CD274, IGSF8. Knockdown of IL1A in PAAD cells inhibited their tumor proliferation ability in vitro. CONCLUSIONS: Using MNPs-related genes, we built a prognostic model for PAAD, revealing that patients with high-risk scores are likely to have a worse prognosis. This model is designed to develop personalized treatment strategies tailored to the specific needs of each patient, thereby improving clinical outcomes for PAAD patients. Furthermore, IL1A could be a promising therapeutic candidate for PAAD.

Microplastics↗

A multicenter, single-masked study of medial, neutral, and lateral patellar taping in individuals with patellofemoral pain syndrome.

STUDY DESIGN: A multicenter, single-masked study of patients with patellofemoral pain syndrome (PFPS) using a repeated-measures design. OBJECTIVE: To compare 3 different methods of patellar taping for individuals with PFPS. BACKGROUND: Patellar taping is commonly used as a treatment for PFPS. It is commonly thought that taping works by medially realigning the patella. However, comparisons have been rarely made with other methods of taping which attempt to realign the patella in different directions. METHODS AND MEASURES: Seventy-one patients with PFPS (39 men, 32 women; average age +/- SD, 34 +/- 10 years) from 3 different treatment centers were tested. Each patient performed 4 single step-downs from a standard 8-inch (20.3-cm) platform, initially with the patella untaped and then with the patella taped in a medial, neutral, and lateral direction. Pain was recorded on a standard 11-point numerical pain rating scale. The sequence of taping was randomly allocated and patients were masked to the method used. The methods of taping were compared using repeated-measures generalized linear model analysis. RESULTS: All methods of taping significantly decreased pain when compared to the untaped condition (P<.0001). Neutral- and lateral-glide techniques produced a significantly greater degree of pain relief (P<.0001) than the medial-glide technique. CONCLUSION: In this study, patellar taping produced an immediate decrease in pain in patients with PFPS, irrespective of how taping was applied. These data raise questions as to the mechanism of action of patellar taping. Furthermore, these results suggest that it is unlikely that taping works by altering patellar position.

Adult↗

A web-based data collection system for clinical studies using Java.

Data collection in multi-centre controlled clinical trials is a major problem. We describe a web-based documentation system for data collection via the Internet we have developed in Java. It keeps both the platform independent program (a Java applet) and the database on a single server to which the participating centres have access at any time. It is based on a three-tier model where client requests are handled and monitored by an application server (a Java application). We show the advantages such a system has over the HTML/CGI combination which is often used for database access, as well as possible extensions, e.g. connection to a data dictionary. Finally, we discuss the security problems which arise by the use of the Internet for data collection.

Data Collection↗

Orthopedic rehabilitation using the "Rutgers ankle" interface.

A novel ankle rehabilitation device is being developed for home use, allowing remote monitoring by therapists. The system will allow patients to perform a variety of exercises while interacting with a virtual environment (VE). These game-like VEs created with WorldToolKit run on a host PC that controls the movement and output forces of the device via an RS232 connection. Patients will develop strength, flexibility, coordination, and balance as they interact with the VEs. The device will also perform diagnostic functions, measuring the ankle's range of motion, force exertion capabilities and coordination. The host PC transparently records patient progress for remote evaluation by therapists via our existing telerehabilitation system. The "Rutgers Ankle" Orthopedic Rehabilitation Interface uses double-acting pneumatic cylinders, linear potentiometers, and a 6 degree-of-freedom (DOF) force sensor. The controller contains a Pentium single-board computer and pneumatic control valves. Based on the Stewart platform, the device can move and supply forces and torques in 6 DOFs. A proof-of-concept trial conducted at the University of Medicine and Dentistry of New Jersey (UMDNJ) provided therapist and patient feedback. The system measured the range of motion and maximum force output of a group of four patients (male and female). Future medical trials are required to establish clinical efficacy in rehabilitation.

Adult↗

New technologies for chemical genetics.

Chemical genetics, in which small molecules are used in lieu of mutations to study biological processes, requires large and diverse chemical libraries to specifically perturb different biological pathways. Here we describe a suite of technologies that enable chemical libraries prepared by split-pool solid phase synthesis to be screened in a diverse range of chemical genetic assays. Compounds are synthesized on 500 micron high-capacity polystyrene beads, and arrayed into individual wells of 384-well plates using a hand-held bead arrayer. Compounds are cleaved from synthesis beads using a chemically-resistant ceramic dispensing system, producing individual stock solutions of single compounds. Nanoliter volumes of these solutions are then transferred into assay plates using an array of stainless steel pins mounted on a robotic arm. We have designed reusable 1536- and 6144-well assay plates made of silicone rubber that can be cast in the laboratory and filled by hand. This integrated technology platform enables hundreds of biological assays to be performed from the product of a single synthesis bead, enabling the results of different chemical genetic experiments to be directly compared.

Cell Extracts↗

Subtalar Pronation Does Not Influence Impact Forces or Rate of Loading During a Single-Leg Landing.

OBJECTIVE: To identify the influence of static subtalar pronation (as measured by weight-bearing navicular drop [ND]) on ground impact forces and rate of loading during a single-leg landing. DESIGN AND SETTING: Subjects were grouped (n = 16 per group) on the basis of weight-bearing ND scores (supinators, <5 mm; neutral, 5-10 mm; pronators, >10 mm). Subjects performed 5 single-leg landings, dropping from a 0.3-m height onto a force platform. An electrogoniometer simultaneously recorded sagittal knee range of motion during the landing task. SUBJECTS: Forty-eight healthy volunteers participated. MEASUREMENTS: Peak vertical force was defined as the highest force recorded in the F(z) direction during landing. Rate of loading was defined as the peak vertical force divided by the time to reach the peak vertical force. Knee-flexion excursion was defined as the change in knee-flexion range from initial contact to peak vertical force. RESULTS: Peak vertical force (P =.769) and rate of loading (P =.703) did not differ among groups. Although secondary analyses identified significant negative correlations between peak force and rate of loading with knee excursion, the amount of knee excursion was similar among groups (P =.744). CONCLUSIONS: Our results de-emphasize the influence of static anatomical foot alignment on impact forces and absorption during a single-leg drop landing and provide further support for the role of knee flexion in dissipation of landing forces. Further investigations are needed to fully elucidate the role of subtalar pronation and other lower extremity alignment factors in force dissipation during dynamic functional activities.

Journal Article↗

Clinical and biomechanical risk factors of patients diagnosed with hallux valgus.

The purpose of this study was to identify the clinical and plantar loading variables related to hallux valgus. Fifty-one healthy control subjects and 40 subjects with a diagnosis of moderate hallux valgus deformity of similar age and body weight were recruited for this study. Clinical measurements of pain, first metatarsophalangeal joint range of motion, and single-leg resting calcaneal stance position were obtained. Biomechanical measurements were obtained using a capacitive pressure platform. Plantar loading variables were calculated for seven regions of the plantar surface. A univariate analysis followed by a stepwise logistic regression was used to analyze the data. The results indicated that high values for pain, single-leg resting calcaneal stance position, hallux region peak pressure and force-time integral, and central forefoot region force-time integral increased the likelihood of hallux valgus.

Adult↗

Fully integrated whole blood testing by real-time absorption measurement on a centrifugal platform.

We present a novel microfluidic concept to enable a fast colorimetric alcohol assay from a single droplet of whole blood. The reduced turn-around time of 150 seconds is, on the one hand, achieved by a full process integration including metering, mixing with reagents, and sedimentation of cellular constituents. On the other hand, our novel total internal reflection (TIR) scheme allows to monitor the increase of the absorbance values in real-time. Thus, the saturation values can be predicted accurately based on an extrapolation of real-time measurements acquired during a 100 second initial period of rotation. Additionally, we present a metering structure to define nanolitre sample volumes at a coefficient of variation (CV) below 5%.

Blood Chemical Analysis↗

Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE.

PURPOSE: To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). METHODS: Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. RESULTS: Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. CONCLUSIONS: The EyeSAGE database, combining three different gene-profiling platforms including the authors' multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions.

Adult↗

Single nucleotide polymorphism (SNP) discovery in porcine expressed genes.

High-throughput genotyping of swine populations is a potentially efficient method for establishing animal lineage and identification of loci important to animal health and efficient pork production. Markers were developed based upon single nucleotide polymorphisms (SNPs), which are abundant and amenable to automated genotyping platforms. The focus of this research was SNP discovery in expressed porcine genes providing markers to develop the porcine/human comparative map. Locus specific amplification (LSA) and comparative sequencing were used to generate PCR products and allelic information from parents of a swine reference family. Discovery of 1650 SNPs in 403 amplicons and strategies for optimizing LSA-based SNP discovery using alternative methods of PCR primer design, data analysis, and germplasm selection that are applicable to other populations and species are described. These data were the first large-scale assessment of frequency and distribution of porcine SNPs.

Animals↗

A nonproliferating parvovirus vaccine vector elicits sustained, protective humoral immunity following a single intravenous or intranasal inoculation.

An ideal vaccine delivery system would elicit persistent protection following a single administration, preferably by a noninvasive route, and be safe even in the face of immunosuppression, either inherited or acquired, of the recipient. We have exploited the unique life cycle of the autonomous parvoviruses to develop a nonproliferating vaccine platform that appears to both induce priming and continually boost a protective immune response following a single inoculation. A crippled parvovirus vector was constructed, based on a chimera between minute virus of mice (MVM) and LuIII, which expresses Borrelia burgdorferi outer surface protein A (OspA) instead of its coat protein. The vector was packaged into an MVM lymphotropic capsid and inoculated into naive C3H/HeNcr mice. Vaccination with a single vector dose, either intravenously or intranasally, elicited high-titer anti-OspA-specific antibody that provided protection from live spirochete challenge and was sustained over the lifetime of the animal. Both humoral and cell-mediated Th(1) immunity was induced, as shown by anti-OspA immunoglobulin G2a antibody and preferential gamma interferon production by OspA-specific CD4(+) T cells.

Administration, Intranasal↗

Approach to analysis of single nucleotide polymorphisms by automated constant denaturant capillary electrophoresis.

Melting gel techniques have proven to be amenable and powerful tools in point mutation and single nucleotide polymorphism (SNP) analysis. With the introduction of commercially available capillary electrophoresis instruments, a partly automated platform for denaturant capillary electrophoresis with potential for routine screening of selected target sequences has been established. The aim of this article is to demonstrate the use of automated constant denaturant capillary electrophoresis (ACDCE) in single nucleotide polymorphism analysis of various target sequences. Optimal analysis conditions for different single nucleotide polymorphisms on ACDCE are evaluated with the Poland algorithm. Laboratory procedures include only PCR and electrophoresis. For direct genotyping of individual SNPs, the samples are analyzed with an internal standard and the alleles are identified by co-migration of sample and standard peaks. In conclusion, SNPs suitable for melting gel analysis based on theoretical thermodynamics were separated by ACDCE under appropriate conditions. With this instrumentation (ABI 310 Genetic Analyzer), 48 samples could be analyzed without any intervention. Several institutions have capillary instrumentation in-house, thus making this SNP analysis method accessible to large groups of researchers without any need for instrument modification.

Algorithms↗

MitoScribe single-cell molecular recorder logs graded signaling dynamics into mitochondrial DNA.

Genetically encoded DNA recorders convert transient biological events into stable genomic mutations, offering a means to reconstruct past cellular states. However, current approaches to log historical events by modifying genomic DNA have limited capacity to record the magnitude of biological signals within individual cells. Here, we introduce MitoScribe, a mitochondrial DNA (mtDNA)-based recording platform that uses mtDNA base editors (DdCBEs) to write graded biological signals into mtDNA as neutral, single-nucleotide substitutions at a defined site. Taking advantage of the hundreds to thousands of mitochondrial genome copies per cell, we demonstrate MitoScribe enables reproducible, highly sensitive, non-destructive, durable, and high-throughput measurements of molecular signals, including hypoxia, NF-&#x3ba;B activity, BMP and Wnt signaling. We show multiple modes of operation, including multiplexed recordings of two independent signals, and coincidence detection of temporally overlapping signals. Coupling MitoScribe with single-cell RNA sequencing and mitochondrial transcript enrichment, we further reconstruct signaling dynamics at the single-cell transcriptome level. Applying this approach during the directed differentiation of human induced pluripotent stem cells (iPSCs) toward mesoderm, we show that early heterogeneity in response to a differentiation cue predicts the later cell state. Together, MitoScribe provides a scalable platform for high-resolution molecular recording in complex cellular contexts.

Journal Article↗

Functional reach and single leg stance in patients with peripheral vestibular disorders.

The purpose of this study was to compare functional reach distance and right single leg stance time in patients who had peripheral vestibular disease. Twenty-eight patients (15 female, 13 male) between the ages of 35 and 84 were asked to perform 3 trials each of functional reach (FR) and right single leg stance (SLS). SLS times were measured by a Kistler static force platform on line with a Caspar personal computer. FR distance was measured by using a free-standing 147-cm rule. In addition, each subject filled out the Dizziness Handicap Inventory (DHI). Trials were randomized to prevent fatigue or practice effects. A Pearson product-moment correlation was performed between FR and SLS (r = 0.59, P = 0.001). Post hoc analyses of the first, the best, and the average scores highlighted the importance of using means for comparison in a population as variable as the vestibularly impaired. Post hoc analyses showed no correlation between the DHI score and either functional reach distance or single leg stance time. However, when the subjects were divided into groups based on DHI score (group 1 with DHI < or = 49/100, group 2 with DHI > or = 50/100) and a pooled two-sample t-test was performed, a significant difference (P = 0.05) was found in functional reach distance; the subjects who reported less perception of handicap reached farther than those who reported more perception of handicap. No difference was found between the two DHI groups in single leg stance time. Post hoc correlations of functional reach and single leg stance time. Post hoc correlations of functional reach and single leg stance within the two DHI groups showed a higher correlation in group 1 (DHI < or = 49/100), with r equals 0.65 (P < or = 0.01), than in group 2 (DHI > or = 50/100), with r equals 0.38 (P = 0.20). The study found a highly significant, moderate correlation between functional reach distance and single leg stance times in patients with peripheral vestibular disease. These results support the use of FR as an additional assessment tool with patients who have peripheral vestibular disease.

Adult↗

Tahoe-100M: Mapping drug-induced molecular phenotypes at single-cell resolution.

We present Tahoe-100M, a giga-scale single-cell perturbation atlas comprising 100 million transcriptomes from 50 diverse cancer cell lines treated with 1,100 drug-dose conditions. This parallel profiling of thousands of perturbations at single-cell resolution with minimal batch effects is enabled by the Mosaic platform, which multiplexes genetically distinct cell models into balanced "cell villages." Beyond cataloging transcriptomic shifts, Tahoe-100M systematically quantifies cellular phenotypes, including proliferation, cytotoxicity, lineage-specific vulnerabilities, and cell-cycle changes. It captures population-level transcriptomic heterogeneity, characterizing whether drug responses drive cells toward divergent fates or convergent states. Pathway-based signatures define drug-induced expression programs, classify mechanisms of action, reveal off-target activities, and expose adaptive stress responses associated with resistance. By unifying cellular and molecular readouts, this broadly applicable perturbation atlas advances our ability to model gene regulation, drug response, and network dynamics. Its public release enables the training of AI frameworks to advance predictive models of cell behavior.

Humans↗