gebhart/patrepeval huggingface dataset:
Self-oxygenating scaffolds for anoxic culture of adipose tissue (2016)

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Post hoc analysis of a phase III study to test the association between circulating methylated glutathione s transferase (mGSTP1) DNA levels and response to docetaxel (DTX) in metastatic castration resistant prostate cancer (mCRPC). (2017)

5014 Background: GSTP1 inactivation is associated with CpG island hypermethylation in &gt; 99% prostate cancers. Detection of circulating mGSTP1 DNA predicts response to DTX and overall survival (OS) in phase I/II mCRPC cohorts. This post hoc analysis of a phase III study aims to test the association between circulating mGSTP1 DNA levels and outcomes. Methods: The phase III SYNERGY study tested DTX +/- custirsen as 1 st line chemotherapy in mCRPC (n = 1022) with no OS benefit in the experimental arm. Serum samples were taken at baseline (BL) and preC3 of DTX +/- custirsen from 600 patients (pts) enrolled on the SYNERGY study. mGSTP1levels in free DNA were measured using a sensitive methylation specific PCR assay and correlated with PSA response, time to PSA progression (TTP) and OS. Results: On interim analysis of 300 pts, serum mGSTP1 was detectable at BL in 80% and preC3 in 44%. Undetectable preC3 mGSTP1 correlated with a ≥30% fall in PSA within 3m of starting DTX (p &lt; 0.001). Detectable BL and preC3 mGSTP1 predicted shorter TTP after DTX (BL; HR 1.6 95%CI 1.1-2.3; p = 0.01 and preC3 HR 2.2 95%CI 1.6-2.9; p &lt; 0.001). Detectable mGSTP1 at both time points predicted shorter OS (BL; median OS 18.4 vs 33.1m, HR 2.4 95%CI 1.6-3.7; p &lt; 0.001 and preC3; median OS 13.9 vs 29m, HR 2.7 95%CI 2.0-3.6; p &lt; 0.001). In those with detectable BL mGSTP1, 50% had undetectable preC3 mGSTP1 predicting &gt; 30% fall in PSA within 3m (p &lt; 0.001), improved TTP (HR 0.40 95%CI 0.29-0.57; p &lt; 0.001) and improved OS (25.2 vs 13.9 m HR 0.38 95%CI 0.28-0.51; p &lt; 0.001). On multivariable analysis including Hb, Karnofsky PS, LDH, PSA and visceral metastases, detectable preC3 mGSTP1 independently predicted shorter TTP (HR 1.9 95%CI 1.4-2.6; p &lt; 0.001). Detectable mGSTP1at both time points independently predicted OS (BL; HR1.8 95%CI 1.2-2.8; p = 0.006 and preC3; HR 2.2 95%CI 1.6-3.0; p &lt; 0.001). Results from the full cohort of 600 pts will be available for presentation at the meeting. Conclusions: This study should validate circulating mGSTP1 DNA as a marker of therapeutic benefit and prognosis in men with mCRPC receiving DTX and could be utilized for clinical management.
The E3 Ubiquitin Ligase Cbl-b Limits Nascent Th9 Differentiation (2015)

Abstract Introduction: Th9 cells are critical mediators of allergy and anti-cancer immunity. The E3 ubiquitin ligase Cbl-b modulates T cell activation via regulation of the T cell receptor (TCR) activation threshold as well as by inducing TGF-β sensitivity, which is a critical differentiation factor for Th9 differentiation. Even though some evidence shows that Cbl-b impairs Th9 differentiation by targeting IL-4 dependent STAT6 activation, a complete suppression of Th9 differentiation in the absence of both STAT6 and Cbl-b is not achieved, implying the involvement of additional mechanisms. In this study, we evaluate the role of Cbl-b in early stages of TGF-β dependent Th9 differentiation. Methods: Th9 cells were generated from WT and cblb-deficient naïve CD4+ T cells. After maximum 3 days in presence of IL-4, TGF-β and anti-IFN-γ antibodies, differentiation was determined by the quantification of cytokines, mainly IL-9, and that of the two required transcription factors for Th9 differentiation, namely IRF4 and PU.1. Microarray assay revealed gene candidates that were further validated by mRNA and protein expression analysis. The functional role of Cbl-b was tested in a Th9-mediated murine lung allergy model, in which mice were challenged by intratracheal injections of house dust mite (HDM) extracts. Results: cblb-deficient naïve T cells more efficiently differentiate into Th9 cells after 3 days in culture, express in parallel PU.1 more intensively compared to WT Th9 cells, while retaining similar expression levels of IRF4, another important Th9 differentiation factor. Increased IL-9 level is not based on cblb -deficient T cell hyperproliferation, as we show an increased IL-9 production per cell by using combination of CFSE with intracellular IL-9 staining. Microarray analysis revealed that RUNX1, a known transcriptional modulator of PU.1, is more rapidly down-regulated in cblb-deficient Th9 cells compared to WT Th9 cells. Accordingly, knocking down RUNX1 by siRNA in naïve CD4+ T cells and subsequently differentiating them into Th9 cells, also induces higher IL-9 expression at the mRNA and protein levels in RUNX1-depleted Th9 cells compared to control scrambled siRNA-nucleofected Th9 cells. In the HDM murine allergy model, cblb-deficient mice have a higher lung inflammation as mirrored by increased eosinophils in the BAL and in the lungs, as well as by increased IgE production in the blood. These are also paralleled by an increased IL-9 expression level in the lungs of the allergic cblb -deficient mice. Conclusions: Cbl-b critically limits Th9 differentiation and may thus be a potential target to modify Th9 cell generation in allergy or cancer. Future studies will validate the molecular link that exists between Cbl-b and the RUNX1-dependent IL-9 expression as well as the in vivo significance of increased Th9 cell differentiation in cblb-deficient animal models of lung inflammation and cancer. Disclosures No relevant conflicts of interest to declare.
Low zinc levels at clinical admission associates with poor outcomes in COVID-19 (2020)

Abstract Background Biomarkers to predict Coronavirus disease-19 (COVID-19) outcome early at infection are urgently needed to improve prognosis and treatment. Zinc balances immune responses and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with more severe COVID-19 outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression and thus might represent a useful biomarker. Methods We run a retrospective observational study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel we have studied SARS-CoV2 replication in the Vero E6 cell line modifying zinc concentrations. Findings Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dl at admission correlated with worse clinical presentation, longer time to reach stability and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV2 infected cells. Interpretation SZC is a novel biomarker to predict COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency. Funding Spanish Ministry of Science and Innovation, “Maria de Maeztu” Programme for Units of Excellence in R&amp;D and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement of the Generalitat de Catalunya. Instituto Carlos III Fondos de Investigaciones Sanitarias (FIS), CIBER on Frailty and Healthy Ageing and FEDER funds
Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach (2017)

Neoadjuvant imatinib treatment for 6-9 months is a promising treatment for large gastric GISTs, allowing a high R0 resection rate with acceptable toxicity.
A System for Aerodynamically Sizing Ultrafine Radioactive Particles (1995)

A hypersonic impactor similar to that originally developed by Fernandez de la Mora et al. (1990a) has been modified to measure the aerodynamic diameter, dae, of radioactive particles. The first application is the measurement of the size of the radiolytic particles/clusters formed in the decay of 222Rn. The particles are generated in 32-liter radon chamber under well-controlled experimental conditions. The initial system test was with the particles generated in a gas-mixture of 222Rn and high-purity nitrogen. N2, for various relative humidities, < 1%, 10%, 15%, and 25% at 22°C. The measured particle size agrees with previously measured diffusion diameters. Thus, the size-discriminating capability of the system is good if an appropriate nozzle diameter is used. A particle's d ae, unlike its diffusion coefficient, is independent of the number of charges carried by the particle. There is then the possibility of obtaining a better size distribution resolution than can be achieved with a diffusion-based measurement system for the case when the aerosol is an admixture of both neutral and charged particles. Also, the particle density information contained in the d ae will be utilized in the latter studies to estimate these particle's actual chemical composition.
Features of the SIVmac Transmembrane Glycoprotein Cytoplasmic Domain That Are Important for Env Functions (1998)

The cytoplasmic domain (CD) of the SIVmac transmembrane protein (TM) can affect viral infectivity by modulating several Env functions, notably fusogenic capacity and incorporation into virions. In addition, envelopes with a truncated CD are counterselected in primary cells in culture and in vivo in rhesus macaques, suggesting a role for this domain in viral persistence. Here, we have used mutagenesis to examine specific features of the SIVmac TM CD, including the conserved C-terminal alpha helix and the overall length of the CD. Several mutations dramatically reduced and/or delayed virus infectivity in lymphoid cell lines. Detailed analysis of mutants revealed defects in envelope stability, fusogenic capacity, and virion incorporation. The primary defect associated with an envelope containing a 64-residue CD was rapid degradation. A mutant Env lacking the C-terminal alpha helix but encoding an exceptionally long CD (373 residues) was highly fusogenic but inefficiently incorporated into virions. A third mutant, containing amino acid substitutions designed to alter the charge density of the C-terminal helix, retained cytopathic properties and showed enhanced fusogenic capacity but replicated with delayed kinetics. Taken together, these results demonstrate that CD sequence variation entails functional "tradeoffs" that can involve optimization of certain Env functions at the expense of others.
An Assessment Tool to Provide Targeted Feedback to Robotic Surgical Trainees: Development and Validation of the End-to-End Assessment of Suturing Expertise (EASE) (2022)

Purpose:\nTo create a suturing skills assessment tool that comprehensively defines criteria around relevant sub-skills of suturing and to confirm its validity.\n\nMaterials and Methods:\n5 expert surgeons and an educational psychologist participated in a cognitive task analysis (CTA) to deconstruct robotic suturing into an exhaustive list of technical skill domains and sub-skill descriptions. Using the Delphi methodology, each CTA element was systematically reviewed by a multi-institutional panel of 16 surgical educators and implemented in the final product when content validity index (CVI) reached ≥0.80. In the subsequent validation phase, 3 blinded reviewers independently scored 8 training videos and 39 vesicourethral anastomoses (VUA) using EASE; 10 VUA were also scored using Robotic Anastomosis Competency Evaluation (RACE), a previously validated, but simplified suturing assessment tool. Inter-rater reliability was measured with intra-class correlation (ICC) for normally distributed values and prevalence-adjusted bias-adjusted Kappa (PABAK) for skewed distributions. Expert (≥100 prior robotic cases) and trainee (&lt;100 cases) EASE scores from the non-training cases were compared using a generalized linear mixed model.\n\nResults:\nAfter two rounds of Delphi process, panelists agreed on 7 domains, 18 sub-skills, and 57 detailed sub-skill descriptions with CVI ≥ 0.80. Inter-rater reliability was moderately high (ICC median: 0.69, range: 0.51-0.97; PABAK: 0.77, 0.62-0.97). Multiple EASE sub-skill scores were able to distinguish surgeon experience. The Spearman’s rho correlation between overall EASE and RACE scores was 0.635 (p=0.003).\n\nConclusions:\nThrough a rigorous CTA and Delphi process, we have developed EASE, whose suturing sub-skills can distinguish surgeon experience while maintaining rater reliability.
Mapping the coherence time of far-field speckle scattered by disordered media (2013)

The polarization and temporal coherence properties of light are altered by scattering events. In this paper, we follow a far-field approach, modelizing the scattering from disordered media with the scattering matrix formalism. The degree of polarization and coherence time of the scattered light are expressed with respect to the characteristics of the incident field.
Monoclonal antibody to microtubule-associated STOP protein: affinity purification of neuronal STOP activity and comparison of antigen with activity in neuronal and nonneuronal cell extracts (1989)

Microtubules, ordinarily cold-labile structures, are made entirely resistant to cold temperature by the presence of substoichiometric amounts of STOP (stable tubule only polypeptide), a microtubule-associated protein. We have produced a monoclonal antibody which specifically recognizes a 145-kDa protein previously implicated in STOP activity in rat brain extracts. An antibody affinity column removes both the 145-kDa protein and STOP activity from solution. A urea eluate from the affinity column contains the 145-kDa protein and exhibits substantial STOP activity. We conclude the 145-kDa protein accounts for all measurable STOP activity in rat neuronal extracts. For this work, we have developed an assay of microtubule cold stability which is generally applicable to the detection of STOP activity in various tissues. Using this assay, we show STOP activity is most abundant in neuronal tissue but is detectable in all tissues tested, with the exception of heart muscle. In all tissues that we have examined, STOP activity elutes as a single peak from heparin affinity columns, and in common with brain STOP, all activity is Ca2+-calmodulin sensitive. The monoclonal antibody recognizes the 145-kDa STOP in rat neuronal extracts but reacts with no protein in active fractions from other tissue. A similar, but not identical, analogue of brain STOP thus appears to be widespread in mammalian tissues.
Acrylic Gonio-Subconjunctival Plates in Glaucoma Surgery (1954)

OF the numerous surgical procedures designed to the dictates of the pleo- morphic demands of glaucoma no one method can be regarded as invariably satisfactory. The very fact that so many operations have been designed for the relief of ocular hypertension suggests that a surgical procedure has yet to be evolved which would adequately restore and maintain normal pressure and save the eye from disaster. The surgeon is consequently forced to select one operation in a given case of simple glaucoma from a long list of possible methods. Sometimes he opens the filtration angle in the hope of establishing an adequate drainage channel, or where this is already obliterated or has been damaged by the pathological process he looks for the seepage of aqueous fluid into the subconjunctival tissue or the suprachoroidal space, through sclerectomies with or without cyclodialysis.
Femtosecond electron diffraction: making the "molecular movie" (2005)

The second part of this talk concerns a new type of X-ray source, betatron, based on the relativistic laser-plasma interaction in gas. This source produces a polychromatic and highly collimated X-ray beam with duration about 25 fs. Its applications in time-resolved EXAFS and Laue diffraction, together with its comparison with other existing pulsed X-ray sources, will be presented.
X‐ray reconstruction of moving morphology (XROMM): precision, accuracy and applications in comparative biomechanics research (2010)

X-Ray Reconstruction of Moving Morphology (XROMM) comprises a set of 3D X-ray motion analysis techniques that merge motion data from in vivo X-ray videos with skeletal morphology data from bone scans into precise and accurate animations of 3D bones moving in 3D space. XROMM methods include: (1) manual alignment (registration) of bone models to video sequences, i.e., Scientific Rotoscoping; (2) computer vision-based autoregistration of bone models to biplanar X-ray videos; and (3) marker-based registration of bone models to biplanar X-ray videos. Here, we describe a novel set of X-ray hardware, software, and workflows for marker-based XROMM. Refurbished C-arm fluoroscopes retrofitted with high-speed video cameras offer a relatively inexpensive X-ray hardware solution for comparative biomechanics research. Precision for our biplanar C-arm hardware and analysis software, measured as the standard deviation of pairwise distances between 1 mm tantalum markers embedded in rigid objects, was found to be +/-0.046 mm under optimal conditions and +/-0.084 mm under actual in vivo recording conditions. Mean error in measurement of a known distance between two beads was within the 0.01 mm fabrication tolerance of the test object, and mean absolute error was 0.037 mm. Animating 3D bone models from sets of marker positions (XROMM animation) makes it possible to study skeletal kinematics in the context of detailed bone morphology. The biplanar fluoroscopy hardware and computational methods described here should make XROMM an accessible and useful addition to the available technologies for studying the form, function, and evolution of vertebrate animals.
Concurrently adjusting interrelated control parameters to achieve optimal engine performance (2023)

Methods and systems for real-time engine control optimization are provided. A value of an engine performance variable is determined, a value of a first operating condition and a value of a second operating condition of a vehicle engine are detected, and initial values for a first engine control parameter and a second engine control parameter are determined based on the detected first operating condition and the detected second operating condition. The initial values for the first engine control parameter and the second engine control parameter are adjusted based on the determined value of the engine performance variable to cause the engine performance variable to approach a target engine performance variable. In order to cause the engine performance variable to approach the target engine performance variable, adjusting the initial value for the first engine control parameter necessitates a corresponding adjustment of the initial value for the second engine control parameter.
High Level of Skeletal Muscle Carnosine Contributes to the Latter Half of Exercise Performance during 30-s Maximal Cycle Ergometer Sprinting. (2002)

The histidine-containing dipeptide carnosine (beta-alanyl-L-histidine) has been shown to significantly contribute to the physicochemical buffering in skeletal muscles, which maintains acid-base balance when a large quantity of H(+) is produced in association with lactic acid accumulation during high-intensity exercise. The purpose of the present study was to examine the relations among the skeletal muscle carnosine concentration, fiber-type distribution, and high-intensity exercise performance. The subjects were 11 healthy men. Muscle biopsy samples were taken from the vastus lateralis at rest. The carnosine concentration was determined by the use of an amino acid autoanalyzer. The fiber-type distribution was determined by the staining intensity of myosin adenosinetriphosphatase. The high-intensity exercise performance was assessed by the use of 30-s maximal cycle ergometer sprinting. A significant correlation was demonstrated between the carnosine concentration and the type IIX fiber composition (r=0.646, p<0.05). The carnosine concentration was significantly correlated with the mean power per body mass (r=0.785, p<0.01) during the 30-s sprinting. When dividing the sprinting into 6 phases (0-5, 6-10, 11-15, 16-20, 21-25, 26-30 s), significant correlations were observed between the carnosine concentration and the mean power per body mass of the final 2 phases (21-25 s: r=0.694, p<0.05; 26-30 s: r=0.660, p<0.05). These results indicated that the carnosine concentration could be an important factor in determining the high-intensity exercise performance.
New insights into growth hormone action (2006)

It has been 75 years since Evans and Long identified a somatic growth-promoting substance in pituitary extracts, yet it is only in the last 20 years that the molecular basis for this action has been established. Three key elements in this elucidation were the cloning of the GH receptor, the identification of Janus kinase (JAK) 2 as the receptor-associated tyrosine kinase, and the delineation of signal transduction and activators of transcription (STAT) 5a/b as the key transcription factor(s) activated by JAK2. The interaction between these three elements results in enhanced postnatal growth and is the subject of this review. We describe a new model for GH receptor activation based on subunit rotation within a constitutive dimer, together with the phenotype and hepatic transcript profile of mice with targeted knockins to the receptor cytoplasmic domain. These support a central role for STAT5a/b in postnatal growth.
Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: Results of a phase I clinical trial (2006)

2551 Background: For patients with hormone-refractory prostate cancer (HRPC) treatment options are limited. Immunotherapies based on dendritic cells (DCs) might represent promising alternatives. In a Phase I clinical trial, we evaluated the safety and feasibility of a vaccination with monocyte-derived DCs loaded with a cocktail consisting of HLA-A*0201-restricted peptides derived from prostate cancer-associated antigens (PSA, PSMA, survivin, prostein, trp-p8). Methods: Eight HRPC patients were enrolled in this study (Table). Each patient underwent two leukaphereses, for the isolation of monocytes and subsequent generation of mature DCs. Patients received a total of four vaccinations each with peptide cocktail-loaded DCs at a dose of 1 x 10 7 cells both intradermally and intravenously every other week. Clinical response was monitored by the determination of the PSA level. The induction of a peptide-specific T-cell response was assessed by ELISPOT analysis. Results: Apart from local erythema and edema at the site of intradermal administration no side effects were noted. Four of eight patients showed a temporary PSA decline. One patient displayed a partial response with a PSA decrease &gt; 50% for seven weeks and further stabilization for five weeks. Stable PSA values or decelerated PSA increases were observed in the three remaining patients. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8 + T-cell activation against prostein, survivin and PSMA. Conclusions: The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa. [Table: see text] [Table: see text]