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PubMed2004

Deep brain stimulation creates an informational lesion of the stimulated nucleus.

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the mechanisms are unclear. DBS generates inhibition of neurons surrounding the electrode while simultaneously activating the output axons of local neurons. This dual effect does not explain two hallmarks of DBS effectiveness: symptom relief is dependent on using a sufficiently high-stimulation frequency, and clinical effects are analogous to those produced by lesion. The effect of DBS at different frequencies on the output of intrinsically active neurons was studied using computational models. DBS produced frequency-dependent modulation of the variability of neuronal output, and above a critical frequency stimulation resulted in regular output with zero variance. The resulting loss of information offers an explanation for the two hallmarks of DBS effectiveness.

Electric Stimulation Therapy↗

PubMed2026

Profiler: an open web platform for multi-omics analysis.

MOTIVATION: High-throughput multi-omics technologies produce increasingly large and heterogeneous datasets that are difficult to analyze without advanced computational expertise. Existing bioinformatics tools are often fragmented or limited to specific omics types, hindering reproducibility and accessibility. There is a critical need for an integrated, user-friendly, and scalable platform capable of supporting multi-omics analyses across different data modalities. RESULTS: We present Profiler, an open-source, modular platform that unifies data import, quality control, preprocessing, statistical testing, machine and deep learning, biomarker discovery, pathway and drug-target enrichment, and survival modeling within a single reproducible environment. Built in Python with Streamlit, Profiler is available as both a web-based platform deployed on high-performance computing and a desktop version for local execution, enabling flexible usage across computational infrastructures. Profiler supports diverse omics modalities, including proteomics, transcriptomics, lipidomics, and electroencephalogram data. Through applications to glioblastoma proteomic, pancancer, and multi-omics datasets, Profiler reproduced known molecular subtypes, revealed potential therapeutic targets, and generated fully traceable analysis reports within minutes. By integrating advanced analytics behind an intuitive interface, Profiler democratizes multi-omics analysis and provides a robust, scalable foundation for systems biology and precision medicine research. AVAILABILITY AND IMPLEMENTATION: Profiler is open-source and freely available via its web platform (https://prism-profiler.univ-lille.fr) and GitHub (web version: https://github.com/yanisZirem/Profiler_v1_requests_datatests, desktop version: https://github.com/yanisZirem/prism-profiler), and archived on Zenodo (DOI: https://doi.org/10.5281/zenodo.17478158).

Software↗

PubMed2002

The clinical course of deep vein thrombosis in patients with gynecologic cancer.

OBJECTIVE: The aim of this study was to evaluate the survival of gynecologic cancer patients diagnosed with deep vein thrombosis. METHODS: We retrospectively reviewed the charts of patients admitted to our institution with gynecologic malignancy who were diagnosed with deep vein thrombosis (DVT) between 1984 and 1995. Data were collected regarding site, stage, histology, treatment, and proximity of DVT to treatment with surgery, chemotherapy, and radiotherapy. This study was limited to cases of ovarian, uterine, and cervical cancer. Descriptive statistics were generated and the survival of patients from the time of DVT was calculated using the Kaplan and Meier method. Cases were then matched by site, stage, histology, and age to controls without DVT to evaluate the effect of DVT on survival. A Cox regression model was used to assess the effect of multiple variables on survival. RESULTS: A total of 74 cases were identified. Ovarian, uterine, and cervical cancer accounted for 45, 27, and 28% of cases, respectively. Approximately 64% of patients had stage III or greater disease. The median survival of all patients from the time of DVT diagnosis was 7.8 months, with only about 20% of patients surviving at 5 years. Patients with cervical cancer or patients who had radiation therapy within 3 months of DVT diagnosis had significantly lessened survival (P < 0.01) than other patients with DVT. The survival of patients from the time of cancer diagnosis with venous thrombosis was significantly worse than a matched control group without DVT (P < 0.001). On multivariate analysis, there was a twofold greater risk of dying in those patients with gynecologic cancer and DVT. CONCLUSION: The development of DVT in conjunction with a gynecologic malignancy connotes a poor prognosis, especially in patients with cervical cancer. It is possible that this poor prognosis is related to the pathophysiology that results in venous thrombosis and not just the presence of cancer.

Age Factors↗

PubMed2005

Rostral cingulate gyrus: A putative target for deep brain stimulation in treatment-refractory depression.

Surgery for intractable affective illnesses has generated considerable controversy over the last century. Deep brain stimulation (DBS) has revolutionized neurosurgical practice, especially in the field of advanced Parkinson's disease and, more recently, in selected medical-refractory cases of obsessive-compulsive disorder. In this paper, we propose a discrete area of the rostral cingulate gyrus as a potential target for DBS in medical-resistant depressive patients. Brodmann's area 24a has proved to be a vital link in the integration of neural circuits underlying depression, both through proposed neurobiological models and accurate neuroimaging studies. The full reversibility and adjustability of DBS offer the best chance to treat the multidimensional and life-span profile of depression, so giving hope to a great number of desperate human beings.

Brain↗

PubMed1999

Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy.

PURPOSE: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. METHODS AND MATERIALS: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. RESULTS: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p<0.01 level. The correlation coefficients based on histograms of the whole rectum were larger than those derived from histograms of the rectum wall. Also, simpler descriptive measures as Dmax, of the whole rectum, correlated better to observed late toxicity than Dmax derived from histograms of the rectum wall. Correlation coefficients from "high-dose" measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p<0.01 level. CONCLUSIONS: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late effects in the rectum as measured with questionnaires. This is compatible with a more serial organisation of the rectal tissue architecture than previously reported. 2) Reducing the Lyman-Kutcher model's volume parameter, thus allowing small high-dose regions to determine the NTCP, improved the correlation, but not beyond that of high-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms.

Diarrhea↗

PubMed2003

Evidence for low sulphate and anoxia in a mid-Proterozoic marine basin.

Many independent lines of evidence document a large increase in the Earth's surface oxidation state 2,400 to 2,200 million years ago, and a second biospheric oxygenation 800 to 580 million years ago, just before large animals appear in the fossil record. Such a two-staged oxidation implies a unique ocean chemistry for much of the Proterozoic eon, which would have been neither completely anoxic and iron-rich as hypothesized for Archaean seas, nor fully oxic as supposed for most of the Phanerozoic eon. The redox chemistry of Proterozoic oceans has important implications for evolution, but empirical constraints on competing environmental models are scarce. Here we present an analysis of the iron chemistry of shales deposited in the marine Roper Basin, Australia, between about 1,500 and 1,400 million years ago, which record deep-water anoxia beneath oxidized surface water. The sulphur isotopic compositions of pyrites in the shales show strong variations along a palaeodepth gradient, indicating low sulphate concentrations in mid-Proterozoic oceans. Our data help to integrate a growing body of evidence favouring a long-lived intermediate state of the oceans, generated by the early Proterozoic oxygen revolution and terminated by the environmental transformation late in the Proterozoic eon.

Australia↗

PubMed2003

Separation and capture of CO2 from large stationary sources and sequestration in geological formations--coalbeds and deep saline aquifers.

The topic of global warming as a result of increased atmospheric CO2 concentration is arguably the most important environmental issue that the world faces today. It is a global problem that will need to be solved on a global level. The link between anthropogenic emissions of CO2 with increased atmospheric CO2 levels and, in turn, with increased global temperatures has been well established and accepted by the world. International organizations such as the United Nations Framework Convention on Climate Change (UNFCCC) and the Intergovernmental Panel on Climate Change (IPCC) have been formed to address this issue. Three options are being explored to stabilize atmospheric levels of greenhouse gases (GHGs) and global temperatures without severely and negatively impacting standard of living: (1) increasing energy efficiency, (2) switching to less carbon-intensive sources of energy, and (3) carbon sequestration. To be successful, all three options must be used in concert. The third option is the subject of this review. Specifically, this review will cover the capture and geologic sequestration of CO2 generated from large point sources, namely fossil-fuel-fired power gasification plants. Sequestration of CO2 in geological formations is necessary to meet the President's Global Climate Change Initiative target of an 18% reduction in GHG intensity by 2012. Further, the best strategy to stabilize the atmospheric concentration of CO2 results from a multifaceted approach where sequestration of CO2 into geological formations is combined with increased efficiency in electric power generation and utilization, increased conservation, increased use of lower carbon-intensity fuels, and increased use of nuclear energy and renewables. This review covers the separation and capture of CO2 from both flue gas and fuel gas using wet scrubbing technologies, dry regenerable sorbents, membranes, cryogenics, pressure and temperature swing adsorption, and other advanced concepts. Existing commercial CO2 capture facilities at electric power-generating stations based on the use of monoethanolamine are described, as is the Rectisol process used by Dakota Gasification to separate and capture CO2 from a coal gasifier. Two technologies for storage of the captured CO2 are reviewed--sequestration in deep unmineable coalbeds with concomitant recovery of CH4 and sequestration in deep saline aquifers. Key issues for both of these techniques include estimating the potential storage capacity, the storage integrity, and the physical and chemical processes that are initiated by injecting CO2 underground. Recent studies using computer modeling as well as laboratory and field experimentation are presented here. In addition, several projects have been initiated in which CO2 is injected into a deep coal seam or saline aquifer. The current status of several such projects is discussed. Included is a commercial-scale project in which a million tons of CO2 are injected annually into an aquifer under the North Sea in Norway. The review makes the case that this can all be accomplished safely with off-the-shelf technologies. However, substantial research and development must be performed to reduce the cost, decrease the risks, and increase the safety of sequestration technologies. This review also includes discussion of possible problems related to deep injection of CO2. There are safety concerns that need to be addressed because of the possibilities of leakage to the surface and induced seismic activity. These issues are presented along with a case study of a similar incident in the past. It is clear that monitoring and verification of storage will be a crucial part of all geological sequestration practices so that such problems may be avoided. Available techniques include direct measurement of CO2 and CH4 surface soil fluxes, the use of chemical tracers, and underground 4-D seismic monitoring. Ten new hypotheses were formulated to describe what happens when CO2 is pumped into a coal seam. These hypotheses provide significant insight into the fundamental chemical, physical, and thermodynamic phenomena that occur during coal seam sequestration of CO2.

Carbon Dioxide↗

PubMed2003

What evidence implicates airway smooth muscle in the cause of BHR?

Bronchial hyperresponsiveness (BHR), the occurrence of excessive bronchoconstriction in response to relatively small constrictor stimuli, is a cardinal feature of asthma. Here, we consider the role that airway smooth muscle might play in the generation of BHR. The weight of evidence suggests that smooth muscle isolated from asthmatic tissues exhibits normal sensitivity to constrictor agonists when studied during isometric contraction, but the increased muscle mass within asthmatic airways might generate more total force than the lesser amount of muscle found in normal bronchi. Another salient difference between asthmatic and normal individuals lies in the effect of deep inhalation (DI) on bronchoconstriction. DI often substantially reverses induced bronchoconstriction in normals, while it often has much less effect on spontaneous or induced bronchoconstriction in asthmatics. It has been proposed that abnormal dynamic aspects of airway smooth muscle contraction velocity of contraction or plasticity- elasticity balance might underlie the abnormal DI response in asthma. We suggest a speculative model in which abnormally long actin filaments might account for abnormally increased elasticity of contracted airway smooth muscle.

Actins↗

PubMed1991

Source modelling of the rolandic focus.

In rolandic epilepsy, consideration of the stereotyped ictal symptomatology suggests that the epileptic zone is likely to be in the same cortical structure in different patients. Routine EEG tracings of the interictal spike activity suggests a deep Sylvian fissure location. On the basis of the predominantly tangential potential field at the peak spike negativity seen in this group of patients, the inferior bank of the Sylvian fissure appears to be a good candidate. Without invasive studies, little refinement to this rather imprecise localization can be made as there is neither neurologic deficit nor lesion to provide a marker on radiological imaging. However, the application of source modelling technique using a simple single-dipole spherical head model has resulted in improved understanding of the generator behaviour, and facilitated the generation of new ways of analyzing spikes (e.g., stability index). Review of newer quantitative approaches including matrix and singular value decomposition of the dataset, spatial-temporal constrained source estimates etc. suggest other fruitful approaches. At least in some patients with partial epilepsy, the source characteristics of interictal scalp spikes appear to contain information of the ictal generator. Under certain circumstances, such derived information which is not otherwise available from routine electrophysiology may influence clinical management and prognosis. This is an additional bonus to the primary objectives of quantification and data reduction.

Brain↗

PubMed2004

[Changes of mitochondrial genes expressed in the brain tissue of rat in stroke-like episodes rats].

OBJECTIVE: Stroke is a complex disorder caused by a combination of genetic and environmental factors. Epidemiological studies have provided evidence of genetic influence on the development of human stroke. However, genetic changes which contribute to the development of stroke are not well known. This study was designed to gain a deep insight into that aspect. METHODS: Using cold-stimuli plus high-salt intake as environmental risk factors, the authors established a hypertension model in rats, which produced a complication of stroke. Then, they used the suppression subtractive hybridization(SSH) technique to identify the differential genes that specifically expressed in total cerebrum tissue of the rats in stroke group. A comparison was made between two populations, namely the control group and stroke group. RESULTS: By the use of SSH approach, a total of 576 clones were generated in this study from two subtractive libraries, among them 456 clones were usable and were analyzed. Genes for metabolism transcripts in stroke group were shown to be up-regulated (P<0.01). Mitochondrial transcripts were observed in a high rate of 26.5%. CONCLUSION: The findings suggested that mitochondrial genes should induce an increased sensitivity to stroke through the changes of gene expressions. Mitochondrial genes probably play important roles in the causes and effects of stroke.

Animals↗

PubMed2000

Engineering pancreatic islets.

Pancreatic islets are neuroendocrine organs that control blood glucose homeostasis. The precise interplay of a heterogeneous group of cell populations (beta, alpha, delta and PP cells) results in the fine-tuned release of counterbalanced hormones (insulin, glucagon, somatostatin and pancreatic polypeptide respectively). Under the premises of detailed knowledge of the physiological basis underlying this behaviour, two lines of investigation might be inferred: generating computational and operational models to explain and predict this behaviour and engineering islet cells to reconstruct pancreatic endocrine function. Whilst the former is being fuelled by new computational strategies, giving biophysicists the possibility of modelling a system in which new "emergent" properties appear, the latter is benefiting from the useful tools and strategic knowledge achieved by molecular, cell and developmental biologists. This includes using tumour cell lines, engineering islet cell precursors, knowledge of the mechanisms of differentiation, regeneration and growth and, finally, therapeutic cloning of human tissues. Gaining deep physiological understanding of the basis governing these processes is instrumental for engineering new pancreatic islets.

Animals↗

PubMedDate not supplied

Mouse lung immune response after acute exposure to flour dust.

To approach the physiopathology of the mucosal immune response in flour-mill and bakery workers, the authors developed a mouse model, which allowed them to study immune responses induced in the deep lung by acute inhalation of flour dust. In situ quantification of T lymphocytes (Thy1-2) and T-cell subsets (CD4 and CD8), macrophages, B lymphocytes, and immunoglobulin A plasma cells in the lungs of all animals revealed significant modifications of these cell compartments as early as 3 d after exposure; within 10 d of exposure, levels returned to baseline. The data suggest that the lung could be a sensitive target for inhaled xenobiotics, which might generate rapid immune local modifications that result in the maintenance of homeostasis.

Administration, Inhalation↗

PubMed2026

Treemble: a graphical tool to generate Newick strings from phylogenetic tree images.

SUMMARY: Phylogenetic trees are ubiquitous and central to biology, but most published trees are available only as visual diagrams and not in the machine-readable Newick format. There are, thus, thousands of published trees in the scientific literature that are unavailable for follow-up analyses, comparisons, and supertree construction. Experts can easily read such diagrams, but the manual construction of a Newick string from a diagram is laborious, error-prone, and time-consuming. Previous attempts to semi-automate the reading of tree images relied on image processing techniques. These often encounter difficulties as typical published tree diagrams contain various graphical elements and annotations that overlap the branches, such as error bars on internal nodes. Here we introduce Treemble, a user-friendly desktop application for generating Newick strings from tree images. The user simply clicks to mark node locations, assisted by a deep learning-based node detection tool, and Treemble algorithmically assembles the tree from the node coordinates alone. Treemble also facilitates the automatic reading of tip name labels and can be used for both rectangular and circular trees. AVAILABILITY AND IMPLEMENTATION: Treemble is a native desktop application for macOS and Windows and is freely available, with documentation, at treemble.org. Source code is available at github.com/John-Allard/Treemble. The trained node detection model is available at huggingface.co/John-Allard/treemble-1.

Phylogeny↗

PubMed1994

A spatiotemporal dipole model of the stimulus preceding negativity (SPN) prior to feedback stimuli.

Ten subjects performed a time production task, in which they were instructed to press a button four seconds after the presentation of an auditory stimulus. Two seconds after the button press they received either auditory or visual feedback on the temporal accuracy of their response. In such a paradigm negative slow brain potentials can be recorded preceding the response (Movement Preceding Negativity, MPN) as well as preceding the feedback stimulus (Stimulus Preceding Negativity, SPN). Spatiotemporal dipole modelling is used to gain insight in the possible generators of MPN and SPN. From the models it follows that the MPN can be described by one contralateral radial dipole and a bilateral pair of tangential dipoles. All three dipoles are located near central electrode positions, so the generators of the MPN probably reside within the motor cortex. The SPN is modelled by a bilateral frontotemporal pair of dipoles, hypothetically representing activation of the Insulae Reili. The insular cortex is involved in the processing of affective-motivational input, such as carried by the feedback in the present paradigm. However, processing of the information content of the feedback stimulus might by itself also activate the frontal cortex. Both the response and the feedback stimulus are followed by a positive peak, which can be described by the same deep posterior dipole. Both peaks probably represent a P3, which is related to context updating.

Adult↗

PubMed1985

Comparative theoretical performance for two types of regional hyperthermia systems.

Regional hyperthermia systems have drawn attention because of their potential for depositing power noninvasively in deep-seated tumors. Two such systems that have received clinical attention because of their ability to deposit significant amounts of power in tissue are magnetic induction devices and annular phased array applicators. In this paper, theoretical calculations for the specific absorption rate (SAR) and the resulting temperature distributions for these systems are compared. The finite element method is used in the formulation of both the electromagnetic and thermal boundary value problems. Six detailed patient models based on CT-scan data from the pelvic, visceral, and thoracic regions are generated to simulate a variety of tumor locations. In general, the annular phased array deposited more power within the tumor and produced better temperature distributions than the magnetic induction device. However, the ratio of the maximum power absorbed by the tumor to the maximum power absorbed in normal tissue does not appear to be high enough for either device to heat significant portions of perfused tumors to therapeutic temperatures under a wide range of physiological conditions. The results contained herein should aid the physician in comparative treatment planning with existing regional hyperthermia systems.

Electromagnetic Fields↗

PubMed2026

Sequence optimization targeting mRNA stability enhances monoclonal antibody titers in CHO cells.

This study presents a DNA sequence optimization approach that integrates mRNA stability as a tunable design parameter to enhance monoclonal antibody expression in Chinese hamster ovary (CHO) cells. A comprehensive combinatorial library of synonymous coding-sequence variants of an IgG1 light chain was integrated as single copies at a defined genomic locus in CHO cells with identical regulatory elements. Steady-state mRNA abundance, quantified by deep sequencing of gDNA and mRNA, served as a proxy for mRNA stability. These data were used to train a machine learning model that predicts mRNA abundance from coding sequence using embeddings from a pre-trained nucleotide transformer. This abundance predictor, together with established translational metrics, was incorporated into a genetic algorithm for multi-objective codon optimization. As proof-of-concept, we optimized sequences encoding Trastuzumab to either maximize or minimize the abundance criterion and obtained benchmark sequences from two commercial providers. Using targeted integration, we generated CHO cell lines and measured protein titer and cell-specific productivity. Sequences optimized for high abundance significantly increased intracellular mRNA levels (+41%), protein titer (+59%), and cell-specific productivity (+85%) relative to low-abundance designs, while viable cell densities remained comparable. Compared to commercial benchmarks, high-abundance sequences achieved significantly higher titer (+70%) and cell-specific productivity (+98%). These findings establish mRNA stability as a practical and complementary design parameter for codon optimization in monoclonal antibody production, with potential applicability to other proteins and expression systems.

CHO↗

PubMed1990

Modelling coronary thrombosis from nonanticoagulated human blood in vitro.

The prevalence of ruptured atheromatous plaques underlying the adherent thrombus in the infarct-related coronary arteries, is well documented. In the thrombotic process associated with plaque rupture, hemodynamic forces and the interaction of platelets with exposed collagen fibers play the decisive roles. The shear-induced hemostasis from a nonanticoagulated human blood sample, perfused through polyethylene tubing, was used to simulate rheological changes in the coronary circulation due to plaque disruption. When the hemodynamic conditions of a plaque fissure were mimicked, the sequence of events corresponded to that in vivo: hemostasis (i.e., platelet plug formation in the wall) resulted in the formation of an occlusive thrombus in the lumen of the tubing. Further, the thrombus growth on a collagen fiber, mounted in the lumen of polyethylene tubing through which nonanticoagulated human blood was perfused, was used to mimick the exposure of thrombogenic elements during deep vessel wall injury and the formation of thrombus superimposed on plaque disruption. Morphology of both types of thrombi revealed large numbers of neutrophils and monocytes associated with the platelet mass. The mechanisms of thrombotic reactions were characterized by antagonists and monoclonal antibodies against the platelet activation pathways. Generation of thrombin at an early stage was shown to be the key event and determinant of the final outcome of both thrombotic reactions. It is suggested that the simultaneous measurements of shear-induced hemostasis, clotting, and platelet-collagen interaction from nonanticoagulated human blood provide close experimental approximations to the pathological process of acute coronary syndromes, namely thrombus formation at the site of a disrupted atherosclerotic plaque.

Adolescent↗

PubMed2026

Conditional Diffusion Model-Based Method for Annotation of Antibiotic Resistance Gene Properties.

The crisis of bacterial antibiotic resistance, which has led to a decline in the effectiveness of antibiotics originally used to combat bacterial infections, has emerged as an urgent challenge for public health. Antibiotic resistance genes (ARGs) are one of the key reasons for bacteria to develop resistance to antibiotics. Therefore, accurately identifying and annotating the critical properties of ARGs is of great importance for addressing the antibiotic resistance emergency. Although existing deep learning models demonstrate remarkable effectiveness in extracting local features from sequence data, they still face limitations in the capacity to further gain the enriched latent representations within the data. To address the critical challenge of extracting higher-quality representations from ARGs sequence data, we propose a novel ARGs properties annotation method based on the conditional diffusion model which is used to learn latent representations through domain-specific knowledge injection. Specifically, during the conditional information integration phase, we systematically incorporate ARGs' domain knowledge to guide the diffusion process in generating high-quality latent representations. To overcome information redundancy caused by direct concatenation of conditional information and intermediate features, we design a cross-attention mechanism that enables feature fusion between heterogeneous information sources, thereby enhancing further the quality of obtained representations. Experimental results on widely used data sets demonstrate the framework's effectiveness in achieving superior prediction performance compared to existing methods.

Anti-Bacterial Agents↗