gebhart/patrepeval huggingface dataset:
Baseline circulating soluble factors as predictors of response to nivolumab in metastatic clear cell renal cell carcinoma (mRCC): A validation study within the NIVOREN GETUG-AFU 26 translational study. (2022)

4552 Background: The NIVOREN GETUG-AFU 26 study launched a translational research program to quantify baseline circulating soluble factors levels and correlate them with outcomes to nivolumab in mRCC pts. We previously identified on a training set (n = 80, 40 responders/40 progressors) several soluble factors significantly associated with worse overall survival (OS), progression-free survival (PFS) and response (IL-8 and VEGF), or with worse OS only (IL-6, IL-7) (Carril-Ajuria et al. ASCO GU. 2022). Our aim was to confirm these findings using an independent validation set. Methods: The remaining pts (n = 233) included in the translational-program of the NIVOREN study were included in this validation set. Based on previous results (training set), a panel of 7 different soluble factors (VEGF, VCAM-1, IL-6, IL-7, IL-8, BAFF, CXCL13) were quantified for each plasma sample using the MSD electrochemiluminescence assay. The association between baseline soluble-factors levels and response, PFS and OS was evaluated using previously identified cut-off values. Results: Two hundred thirty-three pts were included in the validation set. Baseline characteristics were similar to the overall trial population. The IMDC risk score breakdown was 17.7% good, 57.3% intermediate and 25.0% poor. With a median follow-up of 21.8 months (mo), the OS rate was 69.6% at 12 mo and median PFS was 3.0 mo. IL-8 (cut-off: 17.9 pg/ml) and IL-6 (cut-off: 8.7 pg/ml), involved in inflammation, confirmed an association with worse OS (IL8: HR = 2.57, p &lt; 0.0001, IL-6: HR = 3.28,p &lt; 0.0001) and worse PFS (IL-8: HR = 1.61,p = 0.0008, IL-6: HR = 1.68, p = 0.0021). VEGF (cut-off: 48.3 pg/ml) confirmed the association with worse OS (HR = 1.56, p = 0.0176), but not with PFS (p = 0.2068). IL-7, involved in T and B cells development, did not show a significant association with OS or PFS when using 8.6 pg/ml (training set) as cut-off (p = 0.0675 and p = 0.7818, respectively). IL-7 was the only cytokine to show an association with response (p = 0.044). Interestingly, circulating CXCL13 (cut-off: 106.4 pg/ml) and BAFF (cut-off: 1122.6 pg/ml), involved in B cell differentiation/survival, were significantly associated with worse OS (HR = 2.09, p = 0.0001 and HR = 2.34, p = 0.0001, respectively); BAFF showed a trend for worse PFS (HR = 1.29, p = 0.0920). Conclusions: Using the cut-off values previously identified in the training set, we confirmed a significant association between baseline blood concentration of IL-6/IL-8 and worse OS/PFS, and of VEGF with worse OS. Non-responders presented lower baseline circulating IL-7 concentrations. CXCL13 and BAFF were significantly associated with worse OS. Multivariate analyses are ongoing.
An entropy approach for the optimization of cross-section spacing for river modelling (2013)

An accurate definition of river geometry is essential to implement one-dimensional (1D) hydraulic models and, in particular, appropriate spacing between cross-sections is key for capturing rivers hydraulic behaviour. This work explores the potential of an entropy-based approach, as a complementary method to existing guidelines, to determine the optimal number of cross-sections to support 1D hydraulic modelling. To this end, given a redundant collection of existing cross-sections, a location subset is selected minimizing total correlation (as a measure of redundancy) and maximizing joint entropy (as a measure of information content). The problem is posed as a multi-objective optimization problem, and solved using a genetic algorithm (NSGA-II). The proposed method is applied to a river reach of the Po River (Italy) and compared to standard guidelines for 1D hydraulic modelling. Cross-sections selected through the proposed methodology were found to provide an accurate description of flood water profile, while optimizing computational efficiency.
Detection of lung cancer cells using a terahertz chemical microscope (2019)

A cancer genome therapy is one kind of the precision medicine, which is an idea to analyze a patient’s genetic information and optimize medical treatment for each patient. To evaluate the analyzed tissue includes the information of the cancer gnome, quantitative evaluation of the ratio of cancer cells to normal cells in the tissue is required. However, evaluation conventionally takes more than two days because formalin fixed paraffin embedded (FFPE) blocks are firstly prepared, which was followed by dyeing.
Decoding key nodes in the metabolism of cancer cells: sugar & spice and all things nice (2011)

In the past 5 years, a convergence of studies has resulted in a broad appreciation in the cancer research community that reprogramming of cellular metabolism may be more central to cancer than appreciated in the past 30 years. The re-emergence of cancer metabolism stems in part from discoveries that a number of common oncogenes and tumor suppressor genes more directly control cell metabolism than previously thought. In addition, a number of what would previously have been called "card-carrying" metabolic enzymes have been identified as human tumor suppressors or oncogenes, causally mutated in a variety of human cancers. This growing appreciation of the role of altered cell metabolism has led to further investigation into the rate-limiting proteins involved in different aspects of the unique metabolism of tumor cells. Targeting cancer metabolism with drugs requires a therapeutic window in which tumor cells, compared to normal tissues, have a greater dependence on specific metabolic enzymes. Themes that have emerged in the past decade of developing oncogene-targeted cancer therapeutics suggest that tumors with distinct oncogenic lesions are likely to require drugs that target distinct metabolic pathways. Ultimately, the hope is that detailed knowledge of oncogene and tumor suppressor gene functions and their effects on metabolism will lead to drug combinations that will be far more effective in treating cancers.
Purification of Subunit B of Shiga Toxin Using a Synthetic Trisaccharide-Based Affinity Matrix (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCorrectionPurification of Subunit B of Shiga Toxin Using a Synthetic Trisaccharide-Based Affinity MatrixVince Pozsgay, Loc Trinh, Joseph Shiloach, John B. Robbins, Arthur Donohue-Rolfe, and Stephen B. CalderwoodCite this: Bioconjugate Chem. 1996, 7, 4, 523Publication Date (Web):July 25, 1996Publication History Published online25 July 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/bc960192ghttps://doi.org/10.1021/bc960192gcorrectionACS PublicationsCopyright © Not subject to U.S. Copyright. Published 1996 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views234Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (22 KB) Get e-AlertscloseSUBJECTS:Purification,Toxins Get e-Alerts
Effects of a program of human interaction and alterations in diet composition on activity of the hypothalamic-pituitary-adrenal axis in dogs housed in a public animal shelter (2002)

Results suggest that both a program of human interaction and alterations in diet composition have moderating effects on activity of the HPA axis in dogs housed in an animal shelter and that activity of the HPA axis may be increased for a longer period during shelter housing than measurement of plasma cortisol concentration alone would suggest.
ChemInform Abstract: Pharmaceutical “Gold” from Neurostabilizing Agents: Topiramate and Successor Molecules (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The aerodynamic shape optimization of airfoils using unconstrained trust region methods (2009)

In this article, unconstrained trust region methods are studied and applied in aerodynamic shape optimization. Trust region methods are high-performance gradient-based optimization methods. The theory of unconstrained trust region methods is explained, and a trust region subproblem is solved using the dogleg method and the Moré–Sorensen method. After verifying the trust region methods via analytical test problems, they are applied to the aerodynamic shape design optimization for transonic and subsonic flows.
A fabrication method for the integration of vacuum microelectronic devices (1991)

The sharply pointed tip of the emitter is the only physical structure in typical field emission vacuum microelectronic devices that is not commonly produced by standard integrated circuit fabrication processes. The authors suggest the use of a cusp which naturally forms when a hole is filled with a conformal film, as a mold to create the sharply pointed emitter. Not only is this tip formation method easily integrated with standard semiconductor processes to produce cathodes, diodes, triodes, and higher number electrode devices, but it is also self-aligned to all of the electrodes within the device structure. The authors describe the basic process sequence used to create a microtriode device and then show how the process can be altered to produce different numbers of electrodes and freestanding cathode structures. Preliminary experimental results are described and estimates of process reproducibility are analyzed and discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Coordinated multiple cadaver use for minimally invasive surgical training. (2008)

The coordinated use of cadavers, which allows for multiple cadaver use for different teaching sessions, is an excellent training method that increases availability of human anatomical material for minimally invasive surgical training.
Variability of venous anatomy of rat testis: Application to experimental testicular surgery (1992)

The venous drainage of the testis of the laboratory rat was observed in 31 animals. The right testicular (internal spermatic) vein drained directly into the right common iliac vein in 77.4%, and into the inferior vena cava in 22.6% of the animals. The left testicular vein drained into the left common iliac vein in all animals, but in 90.3% there was also an accessory branch of the testicular vein draining into the left renal vein. These observations suggest that in the rat the exact anatomy of the venous drainage of each testis should be identified prior to undertaking any surgical procedure on the testis where the venous vasculature plays a major role such as testicular transplantation or the creation of an experimental varicocele.
Differential GABAergic and Glycinergic Inputs of Inhibitory Interneurons and Purkinje Cells to Principal Cells of the Cerebellar Nuclei (2014)

The principal neurons of the cerebellar nuclei (CN), the sole output of the olivo-cerebellar system, receive a massive inhibitory input from Purkinje cells (PCs) of the cerebellar cortex. Morphological evidence suggests that CN principal cells are also contacted by inhibitory interneurons, but the properties of this connection are unknown. Using transgenic, tracing, and immunohistochemical approaches in mice, we show that CN interneurons form a large heterogeneous population with GABA/glycinergic phenotypes, distinct from GABAergic olive-projecting neurons. CN interneurons are found to contact principal output neurons, via glycine receptor (GlyR)-enriched synapses, virtually devoid of the main GABA receptor (GABAR) subunits α1 and γ2. Those clusters account for 5% of the total number of inhibitory receptor clusters on principal neurons. Brief optogenetic stimulations of CN interneurons, through selective expression of channelrhodopsin 2 after viral-mediated transfection of the flexed gene in GlyT2-Cre transgenic mice, evoked fast IPSCs in principal cells. GlyR activation accounted for 15% of interneuron IPSC amplitude, while the remaining current was mediated by activation of GABAR. Surprisingly, small GlyR clusters were also found at PC synapses onto principal CN neurons in addition to α1 and γ2 GABAR subunits. However, GlyR activation was found to account for <3% of the PC inhibitory synaptic currents evoked by electrical stimulation. This work establishes CN glycinergic neurons as a significant source of inhibition to CN principal cells, forming contacts molecularly distinct from, but functionally similar to, Purkinje cell synapses. Their impact on CN output, motor learning, and motor execution deserves further investigation.
Comparison of the National Genetics Institute (NGI) HCV Superquant and Roche COBAS Amplicor HCV Monitor, Version 2.0 Assays (2000)

METHODS: Linearity: Samples used in this study were serum and EDTA plasma samples submitted to ARUP for Hepatitis C Virus (HCV) Testing. Four samples were serially diluted in HCV seronegative normal human plasma to obtain a range of HCV RNA levels from 5,000,000 copies/mL were serially diluted in HCV seronegative normal human plasma to obtain a range of HCV RNA levels from 100,000 – 5,000,000 copies HCV RNA/mL. All dilution samples were submitted to both assays in triplicate on the same day. Comparison: Thirty clinical samples with HCV RNA levels measured in the Roche assay as 1,000 – 1,000,000 copies HCV RNA/mL were split, aliquoted for each assay, and submitted in duplicate. The aliquots of the duplicate specimens were submitted on separate weeks. Precision: The triplicate measurements from the dilution series were used to evaluate the within run precision of the methods. Duplicate values from the comparison study were used to evaluate the between run precision of the two assays. Low end detection: Seven samples with high background in the COBAS Amplicor HCV (qualitative) assay and 23 samples reported as <1,000 copies HCV RNA/mL in the COBAS Amplicor HCV Monitor V2.0 were submitted in singlet to the following assays: Roche COBAS Amplicor HCV Monitor V2.0, NGI HCV Superquant, Roche COBAS Amplicor HCV (qualitative) assay, and Bayer TMA HCV Qualitative assay.
Isolation of a Syringyl-β-O-4 Rich End-Wise Type Lignin Fraction from Birch Periodate Lignin (1992)

ABSTRACT A fraction of lignin which was almost mono-disperse was isolated from an acetylated birch periodate lignin, and its chemical structure was investigated by various NMR experiments. It was proved that the fraction was composed mainly of non-phenolic syringyl-β-0-4 structures.
A Chlorinating Reagent Yields Vinyl Chlorides with High Regioselectivity under Heterogeneous Gold Catalysis (2017)

A novel chlorinating reagent with a high concentration of HCl has enabled the highly regioselective hydrochlorination of unactivated alkynes using a commercial nanogold catalyst. No overchlorination or hydration products were formed, and various functional groups were tolerated. This hydrochlorination method could be conducted under open air.
Biology-derived synaptic dynamics and optimized system architecture for neuromorphic hardware (2010)

Neuromorphic circuits try to replicate aspects of the information processing in neural tissue. Historically, this has often meant some kind of long-term learning function which slowly adjusts the weight of a synapse to achieve a certain target network function. Recently, short-term dynamics at the synapse have also gained significant attention due to their role in dynamic and temporal information processing. However, only very few neuromorphic circuits have incorporated short term dynamics, with still fewer of these implementations being biologically realistic. We derive a circuit for biologically relevant short term dynamics, showing its accuracy with respect to biological measurements. Since this circuit significantly increases the overall complexity of the synapse, a direct integration in the synapse would be prohibitive. Thus, in addition to the short term dynamics, we also present a novel configurable topology for the neurons and synapses on chip which achieves a compact and flexible overall design while still augmenting all synapses with the new short term dynamics.
Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation (2023)

DNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of broadly acting, small molecule-based demethylating drugs with significant side-effects and toxicities. To allow for targeted DNA demethylation, we integrated two nucleic acid-based approaches: DNMT1 interacting RNA (DiR) and RNA aptamer strategy. By combining the RNA inherent capabilities of inhibiting DNMT1 with an aptamer platform, we generated a first-in-class DNMT1-targeted approach - aptaDiR. Molecular modelling of RNA-DNMT1 complexes coupled with biochemical and cellular assays enabled the identification and characterization of aptaDiR. This RNA bio-drug is able to block DNA methylation, impair cancer cell viability and inhibit tumour growth in vivo. Collectively, we present an innovative RNA-based approach to modulate DNMT1 activity in cancer or diseases characterized by aberrant DNA methylation and suggest the first alternative strategy to overcome the limitations of currently approved non-specific hypomethylating protocols, which will greatly improve clinical intervention on DNA methylation.
Change Detection from Remote Sensing to Guide OpenStreetMap Labeling (2020)

The growing amount of openly available, meter-scale geospatial vertical aerial imagery and the need of the OpenStreetMap (OSM) project for continuous updates bring the opportunity to use the former to help with the latter, e.g., by leveraging the latest remote sensing data in combination with state-of-the-art computer vision methods to assist the OSM community in labeling work. This article reports our progress to utilize artificial neural networks (ANN) for change detection of OSM data to update the map. Furthermore, we aim at identifying geospatial regions where mappers need to focus on completing the global OSM dataset. Our approach is technically backed by the big geospatial data platform Physical Analytics Integrated Repository and Services (PAIRS). We employ supervised training of deep ANNs from vertical aerial imagery to segment scenes based on OSM map tiles to evaluate the technique quantitatively and qualitatively.
Clinical Efficacy of Low Energy Cardioversion in Automatic Implantable Cardioverter Defibrillator Patients (1991)

The inclusion of low energy cardioversion capability into modern implantable antiarrhythmic devices, although an appealing idea, is nevertheless unproven with regard to its potential benefits. Moreover, since occasional reports have surfaced suggesting that ineffective application of low energy shocks may prejudice subsequent arrhythmia reversion, we examined the effectiveness and risks of this feature in a large series of patients performed as part of a US Food and Drug Administration clinical trial performed under an investigational device exemption. A total of 813 induced monomorphic ventricular tachycardias were studied in 244 patients. We found that many of the arrhythmias could be reverted to sinus rhythm with small amounts of energy. Cardioversion energy was less than or equal to 6 joules (J) for 84 (53.2%) and less than or equal to 14 joules in 105 (66.4%) of the 158 patients tested at implant and subsequently remained unchanged through greater than 4 months follow up. The incidence of noncardioversion, acceleration or both occurred in 12.7%, 5.7%, and 13.1%, respectively on a per patient basis. On a per episode basis, nonconversion occurred in 51 (6.3%) and acceleration in 61 (7.5%) of the 813 inductions. There was no correlation between the occurrence of nonconversions and accelerations. The devices were allowed to recycle in the event the arrhythmia was not reverted. The subsequent shock was almost always effective, and in any event, no patient failed to be reverted by the second 30-J rescue shock. Over the entire follow-up period as long as 17 months, there were 17 deaths. Neither the incidence nor the mode of death was correlated with nonconversion or acceleration.(ABSTRACT TRUNCATED AT 250 WORDS)
Functional and Pharmacological Characterization of the First Specific Agonist and Antagonist for the V1b Receptor in Mammals (2003)

By activating three distinct vasopressin receptor isoforms called V1a-R, V1b-R (V3-R) and V2-R, vasopressin (VP) mediates a wide number of biological effects in mammals and may be involved in several pathological states. Up to now only specific V1a and V2 receptor agonists and antagonists have been successfully designed. The role of the V1b-R still remains partially unknown, due to the lack of selective V1b-R ligands and orally-active molecules, which are crucial tools for investigating the central and peripheral functions or pathological disorders associated with this receptor. In this review, we report the biological and pharmacological properties of the first two specific V1b-R ligands: d[Cha4] AVP, a high affinity V1b-R agonist and SSR149415, a potent orally-active V1b-R antagonist with good selectivity with respect to other VP/OT receptor isoforms and able to control ACTH secretion in vitro and in vivo. Indeed, these molecules constitute invaluable tools for exploring the central and peripheral roles of VP mediated via V1b receptors. Interestingly, SSR149415 displays potent anxiolytic and antidepressant-like activities, indicating that this new class of drugs has a promising therapeutical potential in the treatment of stress-related disorders, anxiety and depression.
Modelling methodology of atrial fibrosis affects rotor dynamics and electrograms (2016)

The specific representation of fibrosis has a large effect on rotor dynamics and needs to be carefully considered for patient specific modelling.